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Sample records for prognoosimine hpoosmootse testi

  1. Testis tumor associated to microlithiasis

    PubMed Central

    de Jesus, Lisieux Eyer; Maciel, Felipe; Monnerat, Andrea Lima C.; Fernandes, Marcia Antunes; Dekermache, Samuel

    2013-01-01

    OBJECTIVE: To discuss the relationship between testicular microlithiasis and testis tumors in children and to consider the chances of testis preserving surgery in specific cases. CASE DESCRIPTION: Pre-adolescent presenting testicular microlithiasis and a larger left testis, corresponding to a cystic testicular tumor. The tumor was excised, with ipsilateral testis preservation. Histology diagnosed a testis dermoid tumor. COMMENTS: The relationship between testis tumors and testicular microlithiasis is ill defined in children. Pediatric urologists need to develop specific follow-up protocols for pre-pubertal children. PMID:24473964

  2. Cancer of the Testis

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 8,720 % of All New Cancer Cases 0.5% Estimated Deaths in 2016 380 % of All Cancer Deaths ... of This Cancer : In 2013, there were an estimated 240,372 men living with testis cancer in ...

  3. Electroporation of the Testis

    NASA Astrophysics Data System (ADS)

    Yomogida, Kentaro

    The mature mammalian testis is a marvelous organ that produces numerous sperm cells during its reproductive phase. This biologically significant process consists of three steps: stem cell self-renewal and differentiation, meiosis and genetic recombination, and haploid cell morphogenesis into sperm (Russell et al., 1990). The first step provides a good model for investigating the molecular mechanism of stem cell regulation. Currently, the mechanism underlying sperm cell production is a very exciting topic in regenerative medicine (Lensch et al. 2007; Okita et al., 2007). The spermatogonial stem cell system has several advantages, including the easy histological identification of stem cells (Russell et al., 1990), a clear relationship between stem cells and the supporting Sertoli cells, which provide a stem cell niche (Tadokoro et al., 2002; Yomogida et al., 2003), and a transplantation assay for stem cell activity (Oatley & Brinster, 2006). Although germline stem (GS) cells derived from the gonocytes in newborn testis constitute a suitable in vitro system for investigating the properties of spermatogonial stem cells (Kanatsu-Shinohara et al., 2003, 2004), studies using living mammalian testes continue to provide information regarding the roles of the stem cell niche. In vivo electroporation of the supporting cells in the testis will expand our ability to study it.

  4. [Unclassified sex cord testis tumor].

    PubMed

    Grenha, Vânia; Serra, Paula; Coelho, Hugo; Retroz, Edson; Temido, Paulo; Mota, Alfredo

    2014-01-01

    Unclassified sex cord testis tumor is an extremely rare tumor, especially in the adult. It is characterized histologically for a nonspecific combination of testis stromal and epithelial elements, with varying degree of differentiation. Treatment usually consists of radical orchiectomy followed by clinical and imaging surveillance. The available literature about this pathology relies almost exclusively on clinical cases. It's our aim to describe the case of a 37 years old man with an unclassified sex cord testis tumor, the first case described in Portugal, and to review the literature about this issue.

  5. Congenital extrusion of testis (scrotoschisis).

    PubMed

    Kella, Nandlal; Asif, Mohammad; Kumar, Mahesh; Laghari, Farman; Qureshi, Muhammad Ali

    2014-11-01

    A one-day, full term newborn, born to a healthy mother presented with exposed right testicle out of right hemiscrotum since birth. Physical examination showed normal looking testicle and spermatic cord, which was stained with meconium. All baseline investigations and ultrasound of abdomen were within normal limits. There was no visible associated anomaly. Scrotum was explored and viable testis was repositioned. Postoperative recovery was uneventful. At three months follow-up, testicle was good in size and normal in position.

  6. Epidermoid cyst of the testis.

    PubMed

    Mak, C W; Chen, C Y; Tzeng, W S; Li, C-F

    2007-10-01

    Epidermoid cysts, though having a variable sonographic appearance, may present with an onion peel configuration, that is, concentric rings of alternating hyperechogenicities and hypoechogenicities. The absence of vascular flow on colour Doppler sonography is also consistent with the avascular nature of these lesions. By combining these two sonographic features and the absence of biochemical tumour marker, preoperative diagnosis of epidermoid cyst is possible and may prompt a testis sparing surgery rather than orchidectomy. PMID:17875166

  7. [Updated immunoregulation mechanism of the testis].

    PubMed

    Yu, Li-Li; Li, Cui-Ling; Zhang, Hui-Ping

    2013-05-01

    The testis is an immune privileged organ where germ cells are protected from autoimmune attack to ensure its reproductive function. Immune tolerance is important for the normal development and function of the testis. Notwithstanding its immune-privileged status, the imbalance between the tolerogenic and the efferent limb of the testicular immune response may lead to autoimmune damage in inflammatory or infected circumstances. Testicular immune regulation is a complex system involving multiple factors and the study of the regulation mechanisms of the testis is of great significance for access to new therapeutic targets. Currently, testicular immunoregulation is thought to be related with blood-testis barrier, Sertoli cells, immune cells, cytokines and androgen.

  8. Closing left gastroschisis with vanishing left testis.

    PubMed

    Patel, Ramnik V; Sinha, C K; More, Bharat; Rajimwale, Ashok

    2013-01-01

    We report a baby boy with gastroschisis with left non-palpable undescended testis who had a defect on the left side of an intact and normal umbilical cord and had associated testicular atrophy and abnormalities of the ductus deferens. They were successfully managed by primary repair and had uneventful recovery. Subsequent inguinal exploration confirmed blind ending vas deferens and vanishing left undescended testis. Our case confirms vascular accidents at the narrow abdominal wall defect can lead to vanishing testis following attempts at closing gastroschisis making the defect narrow and compromising the blood supply to the testis.

  9. [Aging of the human testis].

    PubMed

    Sibert, Louis; Lacarrière, Emeric; Safsaf, Athmane; Rives, Nathalie

    2014-02-01

    The morphological and histological changes related to testicular aging are: volume decrease, arteriolar sclerosis, degeneration of Leydig cells and Sertoli, depletion of germ cells and thickening of the tunica albuginea testis. The participation in testicular androgen decline in aging is related to the decrease in the number of Leydig cells associated with alterations in the functioning of the hypothalamic-pituitary axis Sperm volume, concentration and total number, motility and morphology of sperm decrease with aging male. The interindividual variability of sperm parameters, the variability of methodologies for data collection and selection of patients must be careful in interpreting the published results. Overall, the quality of sperm decreases progressively with age, without any age limit that can be individualized. Alterations of spermatogenesis do not seem significantly compromising fertility in the elderly. The clinical impact of testicular aging implies androgen production decrease and diseases associated with aging.

  10. [Endocrine tumors of the testis].

    PubMed

    Loy, V; Linke, J

    2003-07-01

    The most characteristic endocrine tumours of the testis are germ cell tumours and sex cord/gonadal stromal tumours. They include the primary carcinoid, the relation of which to teratomas is still unclear. In general, gonadal stromal tumours are rare, however, endocrine activity occurs in at least 10%-20%. Among gonadal stromal tumours, only Leydig cell tumours and Sertoli cell tumours are of practical importance. Endocrine disorders are mostly related to Leydig cell tumours (gynaecomastia, pubertas praecox). Although less frequent than the other gonadal stromal tumours, they can, in principle, occur. The large cell calcifying Sertoli cell tumour occurs in association with other complex disorders (i.e. Peutz-Jeghers syndrome). Valuable markers are: inhibin, calretinin, cytokeratin, melan-A, CD-99, Ki-67, androgen receptor and p53. As the conventional morphology and immunohistological markers frequently overlap, unclear cases should be referred to specialised centres. PMID:14513279

  11. Epidemiology and Diagnosis of Testis Cancer.

    PubMed

    Stevenson, Scott M; Lowrance, William T

    2015-08-01

    Testis cancer is the most commonly diagnosed cancer in young men. Most cases represent sporadic occurrences. Most commonly it presents at an early stage (clinical stage I) and is highly curable with radical orchiectomy. Even more advanced stages of testicular cancer are curable with a multimodality treatment approach. There are no widely accepted screening strategies for germ cell tumors. This article discusses the known risk factors and epidemiology of testis cancer, the presentation, and work up for new patients, and the prognosis and cure rates based on the staging and current treatment modalities for testis cancer patients.

  12. Metastasis of Prostate Adenocarcinoma to the Testis

    PubMed Central

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  13. Acquired undescended testis: putting the pieces together.

    PubMed

    Hack, W W M; Goede, J; van der Voort-Doedens, L M; Meijer, R W

    2012-02-01

    Acquired undescended testis is now a well-recognized disorder. It is seen in 1.5% of pre-pubertal boys and accounts for the 1-2% orchidopexy rate in older boys. Its pathogenesis remains largely unclear, but it may be caused by a fibrous remnant of the processus vaginalis. There is much controversy over its management, and the proper management awaits a randomized-controlled trial. Until now, follow-up data are available only for cases of spontaneous descent or pubertal orchidopexy. It is speculated that acquired undescended testis is in fact congenital and because of a short funiculus at birth, allowing a low-scrotal position early in life. However, as the boy grows, the testis might evolve into an undescended state. When testosterone surges at puberty, spontaneous descent occurs in three of every four cases.

  14. Rete testis adenomatous hyperplasia: our experience.

    PubMed

    Martino, Giovanni; Pasta, Vittorio; Ciardi, Antonio; Palmieri, Andrea; Marinaccio, Lucia; Malavenda, Maria Stella; Monti, Massimo

    2013-01-01

    The word "adenomatous hyperplasia of rete testis" (AHRT) was used by M. Nistal et Al. for the first time in an article about the cystic dysplasia of the testis (1976). AHRT is a benign lesion of the testis. The patient who came to our attention was studied with a testicular echo color Doppler that identified a solid, well circumscribed and hypoechoic mass of 4.5 x3.8mm as diameter, localized in the upper third of the right testicle and with a perilesional vascularization pattern. The preoperative study was based on an accurate medical history, on an ultrasound with contrast and on a RMI. The treatment consisted in an echo guided excisional biopsy of the testicular lesion, considering this as the best approach for those testicular neoformation difficult to define, with a lot of benefits for the patients, especially for those monorchid. PMID:24311150

  15. Free radicals in adolescent varicocele testis.

    PubMed

    Romeo, Carmelo; Santoro, Giuseppe

    2014-01-01

    We examine the relationship between the structure and function of the testis and the oxidative and nitrosative stress, determined by an excessive production of free radicals and/or decreased availability of antioxidant defenses, which occur in the testis of adolescents affected by varicocele. Moreover, the effects of surgical treatment on oxidative stress were provided. We conducted a PubMed and Medline search between 1980 and 2014 using "adolescent," "varicocele," "free radicals," "oxidative and nitrosative stress," "testis," and "seminiferous tubules" as keywords. Cross-references were checked in each of the studies, and relevant articles were retrieved. We conclude that increased concentration of free radicals, generated by conditions of hypoxia, hyperthermia, and hormonal dysfunction observed in adolescent affected by varicocele, can harm germ cells directly or indirectly by influencing nonspermatogenic cells and basal lamina. With regard to few available data in current literature, further clinical trials on the pre- and postoperative ROS and RNS levels together with morphological studies of the cellular component of the testis are fundamental for complete comprehension of the role played by free radicals in the pathogenesis of adolescent varicocele and could justify its pharmacological treatment with antioxidants.

  16. Cryptorchid testis with torsion: Inguinoscrotal whirlpool sign

    PubMed Central

    Indiran, Venkatraman

    2016-01-01

    Non contrast helical computed tomography (CT) study of the abdomen is frequently performed in evaluation of suspected ureteric colic. We present CT images of a young adult male patient who had torsion of an undescended, non-neoplastic testis and describe the “Inguinoscrotal whirlpool sign on CT”. PMID:27555688

  17. Cryptorchid testis with torsion: Inguinoscrotal whirlpool sign.

    PubMed

    Indiran, Venkatraman

    2016-01-01

    Non contrast helical computed tomography (CT) study of the abdomen is frequently performed in evaluation of suspected ureteric colic. We present CT images of a young adult male patient who had torsion of an undescended, non-neoplastic testis and describe the "Inguinoscrotal whirlpool sign on CT". PMID:27555688

  18. Wnt signaling in testis development: Unnecessary or essential?

    PubMed

    Dong, Wei-Lai; Tan, Fu-Qing; Yang, Wan-Xi

    2015-07-10

    Testis development is a fundamental process in sexual development and reproduction. It is under the regulation of multiple factors. Wnt signaling pathway is a classical pathway, which plays an essential role during early development. From a traditional view, Wnt signaling serves as a key regulator of female reproductive system. However, its role in testis development is relatively controversial. This paper reviews Wnt signaling's part in the major events during testis development, including primordial germ cell specification, proliferation and migration, testis determination, spermatogenesis and somatic cell regulation, and summarizes Wnt signaling's impact on testis-related disorders. We evaluate the outcomes of current studies in the field and suggest future research directions.

  19. Congenital Erythropoietic Porphyria with Undescended Testis

    PubMed Central

    Arora, Sandeep; Harith, Arun Kumar; Sodhi, Neha

    2016-01-01

    Hereditary porphyrias are a group of metabolic disorders of heme biosynthesis pathway that are characterized by acute neurovisceral symptoms, skin lesions, or both. Congenital erythropoietic porphyria (CEP) is an extremely rare disease with a mutation in the gene that codes for uroporphyrinogen III synthase leading to accumulation of porphyrin in different tissues and marked cutaneous photosensitivity. We report a case of CEP with infancy onset blistering, photosensitivity, red colored urine, and teeth along with scarring. Examination revealed an undescended testis of the left side. Mutation analysis revealed mutation in the uroporphyrinogen III synthase gene (UROS) resulting in c. 56 A > G (Tyr19Cys). The presence of undescended testis with a rare mutation in a case of CEP which itself is an extremely rare condition make the case interesting. PMID:27512208

  20. An update of the macaque testis proteome

    PubMed Central

    Zhou, Tao; Guo, Yueshuai; Zhou, Zuomin; Guo, Xuejiang; Sha, Jiahao

    2015-01-01

    The genome sequence of rhesus macaque is a draft version with many errors and is lack of Y chromosome annotation. In the present dataset, we reanalyzed the previously published macaque testis proteome. We searched for refined protein sequences, potential Y chromosome proteins and transcripts predicted proteins in addition to the latest Ensembl protein sequences of macaque. A total of 74,433 peptides corresponding to 9247 protein groups were identified, and the data are supplied in this paper. The updated version of macaque testis proteome provided evidences for predicted genes or transcripts at the peptide level. It can be used for further in-depth proteogenomic annotation of macaque genome and is useful for studying the mechanisms of macaque spermatogenesis. PMID:26484360

  1. Endocrinology of the mammalian fetal testis.

    PubMed

    O'Shaughnessy, Peter J; Fowler, Paul A

    2011-01-01

    The testes are essential endocrine regulators of fetal masculinization and male development and are, themselves, subject to hormonal regulation during gestation. This review focuses, primarily, on this latter control of testicular function. Data available suggest that, in most mammalian species, the testis goes through a period of independent function before the fetal hypothalamic-pituitary-gonadal axis develops at around 50% of gestation. This pituitary-independent phase coincides with the most critical period of fetal masculinization. Thereafter, the fetal testes appear to become pituitary hormone-dependent, concurrent with declining Leydig cell function, but increasing Sertoli cell numbers. The two orders of mammals most commonly used for these types of studies (rodents and primates) appear to represent special cases within this general hypothesis. In terms of testicular function, rodents are born 'early' before the pituitary-dependent phase of fetal development, while the primate testis is dependent upon placental gonadotropin released during the pituitary-independent phase of development.

  2. Bilateral synchronous plasmacytoma of the testis.

    PubMed

    Narayanan, Geetha; Joseph, Rona; Soman, Lali V

    2016-04-01

    Extramedullary plasmacytoma (EMP) is usually seen in the head and neck regions and in the upper respiratory, gastrointestinal, and central nervous systems. Testis is a rare site for EMP, and bilateral synchronous testicular plasmacytoma occurring as an isolated event at initial presentation has been reported only once previously. We present herein the second such report in a 70-year-old man who underwent bilateral orchidectomy. PMID:27034568

  3. The Treatment of the Incompletely Descended Testis

    PubMed Central

    Wilson, D. S. Poole

    1939-01-01

    (1) Under three years of age the diagnosis of the incompletely descended testis is uncertain. (2) The policy of awaiting spontaneous descent may be pursued until 10 years of age but, unless the testis lies in the superior scrotal position, this policy should not be persisted in thereafter. (3) Hormonal therapy may be employed before operative treatment as a means of determining testes which will descend spontaneously. It should only be used in the prepuberty period. (4) Operative treatment may be safely carried out at any age after 3 years and should be completed before puberty. The optimum period is between 8 and 11 years. The Bevan operation may be successful when the testis is very mobile but the most consistent results are obtained by the septal transposition or Keetley-Torek operations. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 8Fig. 9Fig. 10Fig. 13Fig. 14Fig. 15Fig. 16Fig. 18Fig. 19Fig. 20Fig. 21Fig. 22 PMID:19991991

  4. The undescended testis. Hormonal and surgical management.

    PubMed

    Elder, J S

    1988-10-01

    Cryptorchidism is the most common disorder of sexual differentiation in males, with an incidence of 3.4 per cent in the term newborn, decreasing to 0.8 per cent at 1 year of age. The mechanisms of normal testicular descent are multifactorial and include an intact hypothalamic-pituitary-testicular axis, as well as a normal gubernaculum and epididymis. In boys with cryptorchidism, the testes demonstrate degenerative changes histologically as early as 1 to 2 years of age. Both testes may be affected, even with a unilateral undescended testis. The most important long-term complications of cryptorchidism include infertility and testicular cancer. The risk of malignancy is 10 to 40 times higher in men with cryptorchidism than in normal men and is highest in men who have had an intra-abdominal testis and in certain intersex conditions. Orchiopexy does not appear to lessen this risk. In clinical trials in the United States, hormonal therapy with hCG or GnRH has not been effective in causing testicular descent; therefore, orchiopexy remains standard treatment. However, hCG is recommended if the clinician suspects that a testis is retractile. Orchiopexy should be performed between 12 and 18 months of age to prevent the degenerative changes that are demonstrable by 2 years.

  5. Thyroid Hormone and Leptin in the Testis

    PubMed Central

    Ramos, Cristiane Fonte; Zamoner, Ariane

    2014-01-01

    Leptin is primarily expressed in white adipose tissue; however, it is expressed in the hypothalamus and reproductive tissues as well. Leptin acts by activating the leptin receptors (Ob-Rs). Additionally, the regulation of several neuroendocrine and reproductive functions, including the inhibition of glucocorticoids and enhancement of thyroxine and sex hormone concentrations in human beings and mice are leptin functions. It has been suggested that thyroid hormones (TH) could directly regulate leptin expression. Additionally, hypothyroidism compromises the intracellular integration of leptin signaling specifically in the arcuate nucleus. Two TH receptor isoforms are expressed in the testis, TRa and TRb, with TRa being the predominant one that is present in all stages of development. The effects of TH involve the proliferation and differentiation of Sertoli and Leydig cells during development, spermatogenesis, and steroidogenesis. In this context, TH disorders are associated with sexual dysfunction. An endocrine and/or direct paracrine effect of leptin on the gonads inhibits testosterone production in Leydig cells. Further studies are necessary to clarify the effects of both hormones in the testis during hypothyroidism. The goal of this review is to highlight the current knowledge regarding leptin and TH in the testis. PMID:25505448

  6. Glycosylation pattern in the appendix testis in children with cryptorchidism.

    PubMed

    Lopez, Gerardo; Jmenez, Salvador; Martinez, Ruth; Pina, Maria del Socorro; Gallegos, Belem; Pérez-Campos, Eduardo; Zenteno, Edgar; Hernández, Pedro

    2011-01-01

    In humans, at about week 6, sex cords develop within the forming testes. Testes normally descend to the scrotum; cryptorchidism occurs when one or two testes do not descend to scrotum and in some case are accompanied by the appendix testis. The appendix testis is a small sessile or polypoid structure located at the antero superior pole of the testis, adjacent to the head of the epididymis. Glycans can be involved in development of the appendix testis and cryptorchidism. In this work, lectin histochemistry was used to evaluate glycans expression in appendix testis in children with cryptorchidism. Our results showed that lectin from Lens culinaris, Ulex europaeus I., Canavalia ensiformis, Artocarpus integrifolia, Glycine max, and Griffonia simplicifolia recognizes epithelial and estromal cells. Not interaction was observed with lectin from Amaranthus leucocarpus, while lectin from Dolichus biflorus lectin only recognizes epithelial cells. Our results suggest that O-glycans linked in some glycoproteins represent important elements in appendix testis development.

  7. Clinics in diagnostic imaging (114). Rupture of the right testis.

    PubMed

    Muttarak, M; Thinyu, S; Lojanapiwat, B

    2007-03-01

    A 22-year-old man, who was kicked in the scrotum during Thai kickboxing, presented with a painful swelling of the right hemiscrotum. Scrotal ultrasonography (US) showed an enlarged right testis with heterogeneous echogenicity and irregular contours. Colour Doppler US showed vascularity in the upper pole of the right testis and avascularity in the lower pole. Emergency exploration of the right hemiscrotum revealed laceration of the lower pole of the right testis. Debridement and repair of the right testis were performed. The clinical manifestations, role of US and US findings of scrotal trauma are discussed.

  8. Leptin in male reproduction: the testis paradigm.

    PubMed

    Tena-Sempere, M; Barreiro, M L

    2002-02-25

    Leptin, the adipocyte-derived hormone that plays a key role in body weight homeostasis, has recently emerged as a relevant neuroendocrine mediator in different systems, including the reproductive axis. Thus, compelling evidence points out a major role of leptin in the regulation of female pubertal development and fertility, both in humans and experimental animals. The contribution of leptin to the proper functioning of the male reproductive system has been less clear. However, data gathered in recent years, from independent groups and through a variety of experimental approaches, strongly suggest that leptin is able to act at different levels of the hypothalamic-pituitary-testicular axis. Herein, we review the biological effects and potential mechanisms of action of leptin upon rodent testis. Leptin appears to act as a direct inhibitory signal for testicular steroidogenesis, which may be relevant to explain the link between decreased testosterone secretion and hyperleptinaemia in obese men. Analysis of the molecular basis for leptin-induced inhibition of testosterone secretion revealed the potential involvement of decreased gene expression of several up-stream factors (e.g. SF-1, StAR and P450scc) in the steroidogenic pathway. In this context, testicular expression of leptin receptor (Ob-R) gene shows a complex pattern of alternative splicing with generation of multiple variants, including the functional leptin receptor type-b (Ob-Rb) and several short isoforms. Moreover, Ob-R mRNA expression in rat testis was regulated by homologous (leptin) as well as heterologous (gonadotropins) signals. Overall, the current data indicate that the testis is a direct target for leptin actions. Furthermore, the available evidence is suggestive of a tightly regulated, complex mode of action of leptin at different levels of the male gonadal axis that involves not only stimulatory but also inhibitory effects.

  9. Circannual Testis Changes in Seasonally Breeding Mammals.

    PubMed

    Jiménez, Rafael; Burgos, Miguel; Barrionuevo, Francisco J

    2015-01-01

    In the non-equatorial zones of the Earth, species concentrate their reproductive effort in the more favorable season. A consequence of seasonal breeding is seasonal testis regression, which implies the depletion of the germinative epithelium, permeation of the blood-testis barrier, and reduced androgenic function. This process has been studied in a number of vertebrates, but the mechanisms controlling it are not yet well understood. Apoptosis was assumed for years to be an important effector of seasonal germ cell depletion in all vertebrates, including mammals, but an alternative mechanism has recently been reported in the Iberian mole as well as in the large hairy armadillo. It is based on the desquamation of meiotic and post-meiotic germ cells as a consequence of altered Sertoli-germ cell adhesion molecule expression and distribution. Desquamated cells are either discarded alive through the epididymis, as in the mole, or subsequently die by apoptosis, as in the armadillo. Also, recent findings on the reproductive cycle of the greater white-toothed shrew at the meridional limits of its distribution area have revealed that the mechanisms controlling seasonal breeding are in fact far more plastic and versatile than initially suspected. Perhaps these higher adaptive capacities place mammals in a better position to face the ongoing climate change. PMID:26375035

  10. Methylation patterns of testis-specific genes.

    PubMed Central

    Ariel, M; McCarrey, J; Cedar, H

    1991-01-01

    The methylation patterns of genes expressed in the mouse male germ line have been examined. Int-1, Hox-2.1, and Prm-1, all of which contain 5' CpG islands, were found to be completely unmethylated at many sites in these domains, both in somatic tissues and in sperm DNA. Many other testis-specific genes have a similar structure and are probably also constitutively unmethylated. Pgk-2, a non-CpG-island gene, is similar to somatic tissue-specific genes in that it is highly methylated in nonexpressing cell types but undermethylated in pachytene spermatocytes and round spermatids, where it is actively transcribed. At later stages of spermatogenesis, however, the gene becomes remethylated and thus acquires the full modification pattern in sperm DNA. In all these cases, the sperm DNA that emerges from the testis does not contain any germ-line-specific unmethylated sites and thus carries the methylation pattern typical of that in somatic tissues. Images PMID:2006171

  11. Tight junctions in the testis: new perspectives

    PubMed Central

    Mruk, Dolores D.; Cheng, C. Y.

    2010-01-01

    In the testis, tight junctions (TJs) are found between adjacent Sertoli cells at the level of the blood–testis barrier (BTB) where they coexist with basal ectoplasmic specializations and desmosome-gap junctions. The BTB physically divides the seminiferous epithelium into two distinct compartments: a basal compartment where spermatogonia and early spermatocytes are found, and an adluminal compartment where more developed germ cells are sequestered from the systemic circulation. In order for germ cells (i.e. preleptotene spermatocytes) to enter the adluminal compartment, they must cross the BTB, a cellular event requiring the participation of several molecules and signalling pathways. Still, it is not completely understood how preleptotene spermatocytes traverse the BTB at stage VIII of the seminiferous epithelial cycle. In this review, we discuss largely how TJ proteins are exploited by viruses and cancer cells to cross endothelial and epithelial cells. We also discuss how this information may apply to future studies investigating the movement of preleptotene spermatocytes across the BTB. PMID:20403874

  12. Proteomics analysis of adult testis from Bombyx mori.

    PubMed

    Zhang, Yan; Dong, Zhaoming; Gu, Peiming; Zhang, Weiwei; Wang, Dandan; Guo, Xiaomeng; Zhao, Ping; Xia, Qingyou

    2014-10-01

    The development of the testis involves a large number of tissue-specific proteins, possibly because the sperms in it are the most divergent of all cell types. In this study, LC-MS/MS was employed to investigate the protein compositions of the adult testis of silkworm. A total of 14,431 peptides were identified in the adult testis of Bombyx mori, which were matched to 2292 proteins. Thirty-two HSPs constitute a group of most abundant proteins in the adult testis, suggesting that they are critical for the development, differentiation, and survival of germ cells. Other proteins in this analysis were also involved in testis-specific processes mainly including sperm motility, meiosis, germ cell development, and spermatogenesis. The data have been deposited to the ProteomeXchange with identifier PXD000909 (http://proteomecentral.proteomexchange.org/dataset/PXD000909). PMID:25044914

  13. Testis mediated gene transfer: in vitro transfection in goat testis by electroporation.

    PubMed

    Raina, Atish; Kumar, Subodh; Shrivastava, Rohit; Mitra, Abhijit

    2015-01-01

    Testis mediated gene transfer (TMGT) is a potential tool for making transgenic mice having more than 90% success rate. However, this method needs further standardization before it can be adapted in other species including livestock. In order to standardize the TMGT in goat, buck testes (n=20) collected from the slaughter house were injected with a vector driving green fluorescent protein (GFP) expression under a cytomegalovirus (CMV) promoter. Then, the testes were subjected to electroporation with predetermined voltage, pulse length, pulse interval and number of pulses. Seminiferous tubules were isolated from the electroporated testis and cultured in-vitro. The expression was checked at regular intervals. Green fluorescence was observed on different days in different samples. It suggests transient integration of the plasmid into the seminiferous tubules. This in-vitro transfection of seminiferous tubule using electroporation will provide valuable baseline information.

  14. Characterization and expression of trypsinogen and trypsin in medaka testis.

    PubMed

    Rajapakse, Sanath; Ogiwara, Katsueki; Takahashi, Takayki

    2014-12-01

    Previously, we reported that the medaka testis abundantly expresses the mRNA for trypsinogen, which is a well-known pancreatic proenzyme that is secreted into and activated in the intestine. Currently, we report our characterization of the medaka trypsin using a recombinant enzyme and show that this protein is a serine protease that shares properties with trypsins from other species. Two polypeptides (28- and 26-kDa) were detected in the testis extracts by Western blot analysis using antibodies that are specific for medaka trypsinogen. The 28-kDa polypeptide was shown to be trypsinogen (inactive precursor), and the 26-kDa polypeptide was shown to be trypsin (active protease). We did not detect enteropeptidase, which is the specific activator of trypsinogen, in the testis extract. Immunohistochemical analyses using the same trypsinogen-specific antibody produced a strong signal in the spermatogonia and spermatozoa of the mature medaka testis. Substantial staining was found with spermatocytes, whereas extremely weak signals were observed with spermatids. In vitro incubation of testis fragments with the trypsinogen antibody strongly inhibited the release of sperm from the testis into the medium. Trypsin activity was detected in sperm extracts using gelatin zymographic analysis. Immunocytochemistry showed that trypsinogen and trypsin were localized to the cell membranes surrounding the sperm head. Collectively, these results suggest that trypsin plays an important role in the testis function of the medaka.

  15. The Mammalian Blood-Testis Barrier: Its Biology and Regulation

    PubMed Central

    Cheng, C. Yan

    2015-01-01

    Spermatogenesis is the cellular process by which spermatogonia develop into mature spermatids within seminiferous tubules, the functional unit of the mammalian testis, under the structural and nutritional support of Sertoli cells and the precise regulation of endocrine factors. As germ cells develop, they traverse the seminiferous epithelium, a process that involves restructuring of Sertoli-germ cell junctions, as well as Sertoli-Sertoli cell junctions at the blood-testis barrier. The blood-testis barrier, one of the tightest tissue barriers in the mammalian body, divides the seminiferous epithelium into 2 compartments, basal and adluminal. The blood-testis barrier is different from most other tissue barriers in that it is not only comprised of tight junctions. Instead, tight junctions coexist and cofunction with ectoplasmic specializations, desmosomes, and gap junctions to create a unique microenvironment for the completion of meiosis and the subsequent development of spermatids into spermatozoa via spermiogenesis. Studies from the past decade or so have identified the key structural, scaffolding, and signaling proteins of the blood-testis barrier. More recent studies have defined the regulatory mechanisms that underlie blood-testis barrier function. We review here the biology and regulation of the mammalian blood-testis barrier and highlight research areas that should be expanded in future studies. PMID:26357922

  16. A new clinical classification for undescended testis.

    PubMed

    Hack, W W M; Meijer, R W; Bos, S D; Haasnoot, K

    2003-01-01

    A new classification for undescended testis (UDT), suitable for a clinical setting, is proposed. UDT is categorized into congenital and acquired forms. Congenital forms include intra-abdominal, intra-canalicular, supra-scrotal and ectopic testes. Acquired forms can be divided into primary and secondary types. Primary forms are described as either ascending testes, i.e. those which cannot be manipulated into the scrotum, or high scrotal testes, i.e. those which can still be brought through the scrotal entrance into a high scrotal (unstable) position. Secondary forms are the result of ipsilateral groin surgery and are termed "trapped testes". Congenital forms of UDT should be treated surgically at an early age, preferably at 1 year. Therapy for primary acquired forms remains controversial. Therapeutic modalities include orchidopexy, hormonal treatment (preferably with human chorionic gonadotrophin) or waiting for spontaneous descent during the peripubertal period ("laissez faire policy"). Secondary acquired forms are probably best treated surgically.

  17. [The influence of lead on testis function].

    PubMed

    Martynowicz, Helena; Andrzejak, Ryszard; Medraś, Marek

    2005-01-01

    The deterioration of male fertility, found in numerous epidemiological studies of past decades, can be connected to growing exposure to environmental toxins. Heavy metals, especially lead is widely spread and extremely toxic. The mechanism by which lead exerts toxic effects on testis is quite complex. It involves spermatogenesis, steroidogenesis, and red-ox system. The chronic lead exposure can induce functional disorder (decrease of testosterone synthesis) or morphological disorder (decrease of testicular weight and seminal vesicle, peritubular fibrosis, seminiferous tubular diameter decrease and decrease in germ cell population related to an apoptotic process). Currently existing environmental and occupational exposure to lead and increasing combined exposure to environmental toxins results in constantly increasing number of diagnosed fertility impairments.

  18. Effect of the Y chromosome on testis weight in mice.

    PubMed

    Satou, Kunio; Suto, Jun-ichi

    2015-06-01

    We investigated the effect of the Y chromosome on testis weight in (B6.Cg-A(y) × Y-consomic mouse strain) F1 male mice. We obtained the following results: (1) Mice with the Mus musculus domesticus-type Y chromosome had significantly heavier testis than those with the M. m. musculus-type Y chromosome. (2) Variations in Usp9y and the number of CAG repeats in Sry were significantly associated with testes weight. The A(y) allele was correlated with a reduced testis weight, and the extent of this reduction was significantly associated with a CAG repeat number polymorphism in Sry. These results suggest that Y chromosome genes not only influence testis weight but also modify the effect of the A(y) allele in mediating this phenomenon.

  19. Ameboid cells in spermatogenic cysts of caecilian testis.

    PubMed

    Smita, Mathew; Jancy, M George; Akbarsha, M A; Oommen, Oommen V

    2005-03-01

    Sertoli cells constitute a permanent feature of the testis lobules in caecilians irrespective of the functional state of the testis. The developing germ cells are intimately associated with the Sertoli cells, which are adherent to the basal lamina, until spermiation. There are irregularly shaped cells in the cores of the testis lobules that interact with germ cells at the face opposite to their attachment with Sertoli cells. These irregularly shaped (ameboid) cells first appear in the lumen of the cysts containing primary spermatocytes and are continually present until spermiation. We did not observe any cytoplasmic continuity between a Sertoli cell and an ameboid cell. Both light microscopic and TEM observations reveal a phagocytic role for the ameboid cells: they scavenge the residual bodies shed by spermatozoa. Organization of the ameboid cells is grossly different from that of the spermatogenic and Sertoli cells. They appear to develop from the epithelium at the juncture of the collecting ductule with the testis lobule.

  20. Organic and inorganic transporters of the testis: A review

    PubMed Central

    Klein, David M; Cherrington, Nathan J

    2014-01-01

    Transporters have a huge impact on the toxicology and pharmacological effects of xenobiotics in addition to being implicated in several diseases. While these important proteins have been well studied in organs such as the kidney or liver, characterization of transporters in the testis is still in the early stages. Knowledge of transporter function may greatly advance the field's understanding of the physiological and toxicological processes that occur in the testis. Several foundational studies involving both organic and inorganic transporters have been critical in furthering our understanding of how the testis interacts with endogenous and xenobiotic compounds. This review provides an overview of how transporters function, their clinical significance, and highlights what is known for many of the important transporters in the testis. PMID:26413398

  1. Ameboid cells in spermatogenic cysts of caecilian testis.

    PubMed

    Smita, Mathew; Jancy, M George; Akbarsha, M A; Oommen, Oommen V

    2005-03-01

    Sertoli cells constitute a permanent feature of the testis lobules in caecilians irrespective of the functional state of the testis. The developing germ cells are intimately associated with the Sertoli cells, which are adherent to the basal lamina, until spermiation. There are irregularly shaped cells in the cores of the testis lobules that interact with germ cells at the face opposite to their attachment with Sertoli cells. These irregularly shaped (ameboid) cells first appear in the lumen of the cysts containing primary spermatocytes and are continually present until spermiation. We did not observe any cytoplasmic continuity between a Sertoli cell and an ameboid cell. Both light microscopic and TEM observations reveal a phagocytic role for the ameboid cells: they scavenge the residual bodies shed by spermatozoa. Organization of the ameboid cells is grossly different from that of the spermatogenic and Sertoli cells. They appear to develop from the epithelium at the juncture of the collecting ductule with the testis lobule. PMID:15688448

  2. Torsion of the Appendix Testis in a Neonate

    PubMed Central

    Krishnan, Arvind; Rich, Mark A.; Swana, Hubert S.

    2016-01-01

    Torsion of the appendix testis is a rare cause of scrotal swelling in the neonatal period. We present a case of torsion of the appendix testis in a one-day-old male. We discuss the physical examination and radiologic studies used to make the diagnosis. Nonoperative therapy was recommended and the patient has done well. Recognition of this condition in the neonatal period can prevent surgical intervention and its associated risks. PMID:27379193

  3. Primary B-cell lymphoblastic lymphoma of the testis.

    PubMed

    Tombolini, Flavia; Lacetera, Vito; Gini, Guido; Capelli, Debora; Leoni, Pietro; Montironi, Rodolfo; Galosi, Andrea Benedetto; Muzzonigro, Giovanni

    2014-12-01

    We present a rare case of primary lymphoblastic B-cell lymphoma of the testis focusing on ultrasonographic and pathological features and clinical implications. Pathological examination revealed primary testicular lymphoblastic B-cell lymphoma which was treated with adjuvant chemotherapy, including rachicentesis with administration of chemotherapy and with radiotherapy of contralateral testis. Primary testicular lymphoblastic B cell lymphoma is an aggressive disease and it is necessary a multimodal therapy (surgery, chemotherapy and radiotherapy) to prevent metastasis. PMID:25641484

  4. The fragmented testis method: development and its advantages of a new quantitative evaluation technique for detection of testis-ova in male fish.

    PubMed

    Lin, Bin-Le; Hagino, Satoshi; Kagoshima, Michio; Iwamatsu, Takashi

    2009-02-01

    A new quantitative evaluation technique, termed the fragmented testis method, has been developed for the detection of testis-ova in genotypic male fish using the medaka (Oryzias latipes). The routine traditional histological method for detection of testis-ova in male fish exposed to estrogens or suspected endocrine-disrupting chemicals has several disadvantages, including possible oversight of testis-ova due to limited sampling of selected tissue sections. The method we have developed here allows for the accurate determination of the developmental stages and the number and the size of testis-ova in a whole testis. Each testis was removed from the fish specimen, fixed with 10% buffered formalin solution, and then divided into small fragments on a glass slide with a dissecting needle or scalpel and aciform forceps in glycerin solution containing a small amount of methylene blue or toluidine blue. If present, all developing testis-ova of various sizes in fragmented testicular tissues were clearly stained and were observable under a dissecting microscope. Testis-ova occurred in controls were ascertained, while spermatozoa were also distinguishable using this method. This proved to be a convenient and cost-effective method for quantitatively evaluating testis-ova appearance in fish, and it may help to clarify the mechanism of testis-ova formation and the biological significance of testis-ova in future studies of endocrine disruption. PMID:18824262

  5. Cancer/testis antigens and urological malignancies

    PubMed Central

    Kulkarni, Prakash; Shiraishi, Takumi; Rajagopalan, Krithika; Kim, Robert; Mooney, Steven M.; Getzenberg, Robert H.

    2012-01-01

    Cancer/testis antigens (CTAs) are a group of tumour-associated antigens (TAAs) that display normal expression in the adult testis—an immune-privileged organ—but aberrant expression in several types of cancers, particularly in advanced cancers with stem cell-like characteristics. There has been an explosion in CTA-based research since CTAs were first identified in 1991 and MAGE-1 was shown to elicit an autologous cytotoxic T-lymphocyte (CTL) response in a patient with melanoma. The resulting data have not only highlighted a role for CTAs in tumorigenesis, but have also underscored the translational potential of these antigens for detecting and treating many types of cancers. Studies that have investigated the use of CTAs for the clinical management of urological malignancies indicate that these TAAs have potential roles as novel biomarkers, with increased specificity and sensitivity compared to those currently used in the clinic, and therapeutic targets for cancer immunotherapy. Increasing evidence supports the utilization of these promising tools for urological indications. PMID:22710665

  6. Gestational bisphenol A exposure and testis development

    PubMed Central

    Williams, Cecilia; Bondesson, Maria; Krementsov, Dimitry N; Teuscher, Cory

    2015-01-01

    Virtually all humans are exposed to bisphenol A (BPA). Since BPA can act as a ligand for estrogen receptors, potential hazardous effects of BPA should be evaluated in the context of endogenous estrogenic hormones. Because estrogen is metabolized in the placenta, developing fetuses are normally exposed to very low endogenous estrogen levels. BPA, on the other hand, passes through the placenta and might have distinct adverse consequences during the sensitive stages of fetal development. Testicular gametogenesis and steroidogenesis begin early during fetal development. These processes are sensitive to estrogens and play a role in determining the number of germ stem cells, sperm count, and male hormone levels in adulthood. Although studies have shown a correlation between BPA exposure and perturbed reproduction, a clear consensus has yet to be established as to whether current human gestational BPA exposure results in direct adverse effects on male genital development and reproduction. However, studies in animals and in vitro have provided direct evidence for the ability of BPA exposure to influence male reproductive development. This review discusses the current knowledge of potential effects of BPA exposure on male reproductive health and whether gestational exposure adversely affects testis development. PMID:26167515

  7. Diethylstilbestrol affects the expression of GPER in the gubernaculum testis.

    PubMed

    Zhang, Xuan; Ke, Song; Chen, Kai-Hong; Li, Jian-Hong; Ma, Lian; Jiang, Xue-Wu

    2015-01-01

    Recent evidence suggested a positive correlation between environmental estrogens (EEs) and high incidence of abnormalities in male urogenital system. EEs are known to cause the abnormalities of testes development and testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernacular cells, and its nongenomic effects on gubernaculum testis cells may be mediated by G protein-coupled estrogen receptor (GPER). In this study, we detected the expression of GPER in mouse gubernacular testis and investigated the effects of DES on the expression of GPER in gubernaculum testis cells. RT-PCR analysis revealed that GPER mRNA was expressed in the gubernaculum. GPER protein was detected in the parenchymal cells of the gubernaculum early in development. Furthermore, we demonstrate that GPER inhibitor G15 relieved DES-induced inhibition of GPER expression in gubernaculum testis cell, but ER inhibitor ICI 182780 had the converse effects on DES-induced inhibition of GPER expression in these cells. These data suggest that the effects of DES on mouse gubernaculum testis cells are mediated at least partially by the regulation of GPER expression.

  8. Oncogenic cancer/testis antigens: prime candidates for immunotherapy.

    PubMed

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

    2015-06-30

    Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer/testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic functions, including support of growth, survival and metastasis. This novel insight into the function of cancer/testis antigens has the potential to deliver more effective cancer vaccines. Moreover, immune targeting of oncogenic cancer/testis antigens in combination with conventional cytotoxic therapies or novel immunotherapies such as checkpoint blockade or adoptive transfer, represents a highly synergistic approach with the potential to improve patient survival.

  9. Diethylstilbestrol affects the expression of GPER in the gubernaculum testis.

    PubMed

    Zhang, Xuan; Ke, Song; Chen, Kai-Hong; Li, Jian-Hong; Ma, Lian; Jiang, Xue-Wu

    2015-01-01

    Recent evidence suggested a positive correlation between environmental estrogens (EEs) and high incidence of abnormalities in male urogenital system. EEs are known to cause the abnormalities of testes development and testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernacular cells, and its nongenomic effects on gubernaculum testis cells may be mediated by G protein-coupled estrogen receptor (GPER). In this study, we detected the expression of GPER in mouse gubernacular testis and investigated the effects of DES on the expression of GPER in gubernaculum testis cells. RT-PCR analysis revealed that GPER mRNA was expressed in the gubernaculum. GPER protein was detected in the parenchymal cells of the gubernaculum early in development. Furthermore, we demonstrate that GPER inhibitor G15 relieved DES-induced inhibition of GPER expression in gubernaculum testis cell, but ER inhibitor ICI 182780 had the converse effects on DES-induced inhibition of GPER expression in these cells. These data suggest that the effects of DES on mouse gubernaculum testis cells are mediated at least partially by the regulation of GPER expression. PMID:26261617

  10. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis.

    PubMed

    DeFalco, Tony; Potter, Sarah J; Williams, Alyna V; Waller, Brittain; Kan, Matthew J; Capel, Blanche

    2015-08-18

    The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs). Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules, in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony-stimulating factor 1 (CSF1) and enzymes involved in retinoic acid (RA) biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues.

  11. [Undescended testis: current views and advice for treatment].

    PubMed

    Hack, W W M; Sijstermans, K; van der Voort-Doedens, L M; Meijer, R W; Heij, H A; Delemarre-van de Waal, H A; Pierik, F H

    2008-02-01

    --Undescended testis (UDT) is one of the most common urogenital abnormalities in boys. --UDT is defined as a testis which cannot be brought into a stable scrotal position. --At present, congenital and acquired forms of UDT are recognised. Congenital UDT is defined as a UDT which has never descended from birth. Acquired UDT is defined as a UDT which has been fully descended in the past. --Congenital UDT should be treated surgically between 6 to 12 months of age. --The treatment of acquired UDT is still disputed. As yet, awaiting spontaneous descent at early puberty seems to be the most rational treatment. --In the Netherlands, the high number of late orchidopexies is due to surgery for acquired UDT. To reduce this high number, the guidelines of the first development conference on 'non-scrotal testis' dating back to 1986 should be revised on several points.

  12. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis

    PubMed Central

    DeFalco, Tony; Potter, Sarah J.; Williams, Alyna V.; Waller, Brittain; Kan, Matthew J.; Capel, Blanche

    2015-01-01

    Summary The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs). Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony stimulating factor 1 (CSF1) and enzymes involved in retinoic acid (RA) biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis, and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues. PMID:26257171

  13. Expression and Localization of Lung Surfactant Proteins in Human Testis

    PubMed Central

    Wagner, Walter; Matthies, Cord; Ruf, Christian; Hartmann, Arndt; Garreis, Fabian; Paulsen, Friedrich

    2015-01-01

    Background Surfactant proteins (SPs) have been described in various tissues and fluids including tissues of the nasolacrimal apparatus, airways and digestive tract. Human testis have a glandular function as a part of the reproductive and the endocrine system, but no data are available on SPs in human testis and prostate under healthy and pathologic conditions. Objective The aim of the study was the detection and characterization of the surfactant proteins A, B, C and D (SP-A, SP-B, SP-C, SP-D) in human testis. Additionally tissue samples affected by testicular cancer were investigated. Results Surfactant proteins A, B, C and D were detected using RT-PCR in healthy testis. By means of Western blot analysis, these SPs were detected at the protein level in normal testis, seminoma and seminal fluid, but not in spermatozoa. Expression of SPs was weaker in seminoma compared to normal testicular tissue. SPs were localized in combination with vimentin immunohistochemically in cells of Sertoli and Leydig. Conclusion Surfactant proteins seem to be inherent part of the human testis. By means of physicochemical properties the proteins appear to play a role during immunological and rheological process of the testicular tissue. The presence of SP-B and SP-C in cells of Sertoli correlates with their function of fluid secretion and may support transportation of spermatozoa. In seminoma the expression of all SP's was generally weaker compared to normal germ cells. This could lead to a reduction of immunomodulatory and rheology processes in the germ cell tumor. PMID:26599233

  14. Segmental infarction of the testis: can frozen sections avoid orchidectomy?

    PubMed

    Pacella, E; Grillo, F; Lapetina, C; Cabiddu, F; Auriati, L; Tunesi, G; Mastracci, L

    2015-03-01

    Segmental infarction (SI) of the testis is a rare condition that can masquerade as a mass lesion, thus requiring exclusion of tumour. If clinical exams do not exclude a neoplastic lesion with certainty, orchidectomy is usually performed. A case of SI of the testis is presented; the use of frozen section of the enucleated mass demonstrated the ischaemic nature of the lesion, so avoiding orchidectomy. The 8 year follow-up was uneventful. The use of frozen section in SI could permit the selection of cases in which testicular-sparing surgery should be considered.

  15. Sex cord-gonadal stromal tumor of the rete testis.

    PubMed

    Sajadi, Kamran P; Dalton, Rory R; Brown, James A

    2009-01-01

    A 34-year-old tetraplegic patient with suppurative epididymitis was found on follow-up examination and ultrasonography to have a testicular mass. The radical orchiectomy specimen contained an undifferentiated spindled sex cord-stromal tumor arising in the rete testis. Testicular sex cord-stromal tumors are far less common than germ cell neoplasms and are usually benign. The close relationship between sex cords and ductules of the rete testis during development provides the opportunity for these uncommon tumors to arise anatomically within the rete tesis. This undifferentiated sex cord-stromal tumor, occurring in a previously unreported location, is an example of an unusual lesion mimicking an intratesticular malignant neoplasm.

  16. Transgenerational Epigenetic Programming of the Embryonic Testis Transcriptome

    PubMed Central

    Anway, Matthew D.; Rekow, Stephen S.; Skinner, Michael K.

    2008-01-01

    Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination appears to promote an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Transgenerational effects on the embryonic day 16 (E16) testis demonstrated reproducible changes in the testis transcriptome for multiple generations (F1-F3). The expression of 196 genes were found to be influenced, with the majority of gene expression being decreased or silenced. Dramatic changes in the gene expression of methyltransferases during gonadal sex determination were observed in the F1 and F2 vinclozolin generation (E16) embryonic testis, but the majority returned to control generation levels by the F3 generation. The most dramatic effects were on the germ-line associated Dnmt3A and Dnmt3L isoforms. Observations demonstrate that an embryonic exposure to vinclozolin appears to promote an epigenetic reprogramming of the male germ-line that correlates with transgenerational alterations in the testis transcriptome in subsequent generations. PMID:18042343

  17. Comparative Analysis of Testis Protein Evolution in Rodents

    PubMed Central

    Turner, Leslie M.; Chuong, Edward B.; Hoekstra, Hopi E.

    2008-01-01

    Genes expressed in testes are critical to male reproductive success, affecting spermatogenesis, sperm competition, and sperm–egg interaction. Comparing the evolution of testis proteins at different taxonomic levels can reveal which genes and functional classes are targets of natural and sexual selection and whether the same genes are targets among taxa. Here we examine the evolution of testis-expressed proteins at different levels of divergence among three rodents, mouse (Mus musculus), rat (Rattus norvegicus), and deer mouse (Peromyscus maniculatus), to identify rapidly evolving genes. Comparison of expressed sequence tags (ESTs) from testes suggests that proteins with testis-specific expression evolve more rapidly on average than proteins with maximal expression in other tissues. Genes with the highest rates of evolution have a variety of functional roles including signal transduction, DNA binding, and egg–sperm interaction. Most of these rapidly evolving genes have not been identified previously as targets of selection in comparisons among more divergent mammals. To determine if these genes are evolving rapidly among closely related species, we sequenced 11 of these genes in six Peromyscus species and found evidence for positive selection in five of them. Together, these results demonstrate rapid evolution of functionally diverse testis-expressed proteins in rodents, including the identification of amino acids under lineage-specific selection in Peromyscus. Evidence for positive selection among closely related species suggests that changes in these proteins may have consequences for reproductive isolation. PMID:18689890

  18. Simple cysts of testis with immunohistochemical evidence of mesothelial origin.

    PubMed

    Kuwamoto, Satoshi; Okuno, Keisuke; Kato, Masako; Hayashi, Kazuhiko

    2009-09-01

    Simple cysts of the testis are an uncommon lesion found in adults as well as infants. Only a few histological and immunohistochemical studies for this lesion have been reported because the lesion have rarely undergone surgical excision or histological confirmation. Herein is reported an autopsy case of simple cysts of the right testis found incidentally in an 84-year-old man who died of hepatocellular carcinoma. The cysts were multilocular, 12 x 8 mm in size, separated from the tunica albuginea and filled with transparent and colorless serous fluid. Histology and immunohistochemistry showed that the cystic lesion had flattened or cuboidal single-layered lining cells that were positive for cytokeratin AE1/AE3, calretinin, D2-40, HBME-1, mesothelin and thrombomodulin, indicating its mesothelial origin. To the authors' knowledge this is the first English-language report describing the origin of simple cysts of the testis. Although the exact pathogenesis of simple cysts of the testis is as yet unknown and there seems to be more than one etiology, at least in the present case the cysts were confirmed to correspond to mesothelial inclusions.

  19. Post-hatching development of Alligator mississippiensis ovary and testis

    PubMed Central

    Moore, Brandon C.; Hamlin, Heather J.; Botteri, Nicole L.; Lawler, Ashley N.; Mathavan, Ketan K.; Guillette, Louis J.

    2009-01-01

    We investigated ovary and testis development of Alligator mississippiensis during the first five months post-hatch. To better describe follicle assembly and seminiferous cord development, we employed histochemical techniques to detect carbohydrate-rich extracellular matrix components in one-week, one-month, three-month, and five-month-old gonads. We found profound morphological changes in both ovary and testis. During this time, oogenesis progressed up to diplotene arrest and meiotic germ cells increasingly interacted with follicular cells. Concomitant with follicles becoming invested with full complements of granulosa cells, a periodic acid Schiff’s (PAS)-positive basement membrane formed. As follicles enlarged and thecal layers were observed, basement membranes and thecal compartments gained periodic acid-methionine silver (PAMS)-reactive fibers. The ovarian medulla increased first PAS- and then PAMS-reactivity as it fragmented into wide lacunae lined with low cuboidal to squamous epithelia. During this same period, testicular germ cells found along the tubule margins were observed progressing from spermatogonia to round spermatids located within the center of tubules. Accompanying this meiotic development, interstitial Leydig cell clusters become more visible and testicular capsules thickened. During the observed testis development, the thickening tunica albuginea and widening interstitial tissues showed increasing PAS- and PAMS-reactivity. We observed putative inter-sex structures in both ovary and testis. On the coelomic aspect of testes were cell clusters with germ cell morphology and at the posterior end of ovaries, we observed “medullary rests” resembling immature testis cords. We hypothesize laboratory conditions accelerated gonad maturation due to optimum conditions, including nutrients and temperature. Laboratory alligators grew more rapidly and with increased body conditions compared to previous measured, field-caught animals. Additionally, we

  20. [Molecular cloning and expression in cryptorchid testis of SRG2 from a mouse testis spermatocyte apoptosis-related gene].

    PubMed

    Liu, Shang-Feng; Li, Lu-Yun; Mo, Ya-Qin; Fu, Jun-Jiang; Liu, Gang; Xing, Xiao-Wei; Lu, Guang-Xiu

    2003-10-01

    It was observed that the spermatogenic cells apoptosis dramatically increased in infertile man. Cloning of novel spermatogenic cell-specific gene related to apoptosis is of momentous physiological and pathological significance to illustrate the apoptosis mechanism and the biology process of spermatogenic cells. A novel mouse gene full-length cDNA sequence-SRG2 was identified (GenBank accession number AF395083), which was significantly changed in cryptorchidism, from a mouse testis cDNA library using a cDNA fragment (GenBank accession number BE644542) as an electronic probe. SRG2 was 1,088 bp in length. The putative protein encoded by this gene was 295 amino acids with a theoretical molecular weight of 33,579 kDa and isoelectric point of 9.64. The sequence shared no significant homology with any known protein in databases except TSARG2, with which its homology was 78%. RT-PCR showed that SRG2 was expressed significantly in testis. Using molecular beacon probe to examine the mRNA expression level of SRG2 gene in cryptorchid testis of various stages, we found that the gene was up-regulated distinctly. Therefore, we conclude that this gene plays an important role in cryptorchid testis.

  1. Derivation of sperm from xenografted testis cells and tissues of the peccary (Tayassu tajacu).

    PubMed

    Campos-Junior, Paulo Henrique Almeida; Costa, Guilherme Mattos Jardim; Avelar, Gleide Fernandes; Lacerda, Samyra Maria Santos Nassif; da Costa, Nathália Nogueira; Ohashi, Otávio Mitio; Miranda, Moysés dos Santos; Barcelos, Lucíola Silva; Jorge, Erika Cristina; Guimarães, Diva Anelie; de França, Luiz Renato

    2014-03-01

    Because the collared peccary (Tayassu tajacu) has a peculiar Leydig cell cytoarchitecture, this species represents a unique mammalian model for investigating testis function. Taking advantage of the well-established and very useful testis xenograft technique, in the present study, testis tissue and testis cell suspensions from immature collared peccaries (n=4; 3 months old) were xenografted in SCID mice (n=48) and evaluated at 2, 4, 6, and 8 months after grafting. Complete spermatogenesis was observed at 6 and 8 months after testis tissue xenografting. However, probably due to de novo testis morphogenesis and low androgen secretion, functionally evaluated by the seminal vesicle weight, a delay in spermatogenesis progression was observed in the testis cell suspension xenografts, with the production of fertile sperm only at 8 months after grafting. Importantly, demonstrating that the peculiar testicular cytoarchitecture of the collared peccary is intrinsically programmed, the unique Leydig cell arrangement observed in this species was re-established after de novo testis morphogenesis. The sperm collected from the xenografts resulted in diploid embryos that expressed the paternally imprinted gene NNAT after ICSI. The present study is the first to demonstrate complete spermatogenesis with the production of fertile sperm from testis cell suspension xenografts in a wild mammalian species. Therefore, due to its unique testicular cytoarchitecture, xenograft techniques, particularly testis cell suspensions, may represent a new and very promising approach to evaluate testis morphogenesis and to investigate spermatogonial stem cell physiology and niche in the collared peccary.

  2. Endocrine function and regulation of the fetal and neonatal testis.

    PubMed

    Huhtaniemi, I

    1989-03-01

    An interesting sex difference prevails in the early development of endocrine functions in the ovary and testis. The testis actively produces androgens already in utero whereas the physiologically important steroid hormone production of the ovary does not start until puberty. Likewise, the different components of the hypothalamic-pituitary-gonadal axis seem to mature earlier in the male. The hormonal regulation of the fetal testes differs in many respects from that of the adult, and these differences make it possible for the fetal testes to function in the intrauterine endocrine milieu. The purpose of this review is to summarize our findings on the development, special functional characteristics and physiological role of the fetal and neonatal pituitary-gonadal axis.

  3. FlyTED: the Drosophila Testis Gene Expression Database

    PubMed Central

    Zhao, Jun; Klyne, Graham; Benson, Elizabeth; Gudmannsdottir, Elin; White-Cooper, Helen; Shotton, David

    2010-01-01

    FlyTED, the Drosophila Testis Gene Expression Database, is a biological research database for gene expression images from the testis of the fruit fly Drosophila melanogaster. It currently contains 2762 mRNA in situ hybridization images and ancillary metadata revealing the patterns of gene expression of 817 Drosophila genes in testes of wild type flies and of seven meiotic arrest mutant strains in which spermatogenesis is defective. This database has been built by adapting a widely used digital library repository software system, EPrints (http://eprints.org/software/), and provides both web-based search and browse interfaces, and programmatic access via an SQL dump, OAI-PMH and SPARQL. FlyTED is available at http://www.fly-ted.org/. PMID:19934263

  4. Dynamics of testis-ova in a wild population of Japanese pond frogs, Rana nigromaculata.

    PubMed

    Kobayashi, Tohru; Kumakura, Masahiko; Yoshie, Sumio; Sugishima, Tomomi; Horie, Yoshifumi

    2015-02-01

    Although many studies have reported the occurrence of testis-ova in wild frog populations, the origin and trigger of testis-ova differentiation/development remain unclear. A high frequency of testis-ova has been previously reported for wild populations of the Japanese pond frog, Rana nigromaculata (cf. Iwasawa and Asai, '59). In the present study, we aimed to clarify the dynamics of testis-ova in this frog species, including the origin and artificial induction of testis-ova. Testis-ova were observed in both mature frogs and puberty-stage frogs (i.e., 0- and 1-year-old frogs). However, the early stages of testis-ova (~pachytene stage) were mostly observed in puberty-stage male frogs at the onset of spermatogenesis. The early stages of testis-ova were observed in the cysts of early secondary spermatogonia and the single cysts of the primary spermatogonium. This finding indicates that testis-ova differentiation occurs during spermatogonial proliferation and that it is correlated with the initiation of spermatogenesis. We also examined whether estrogen exposure induced testis-ova differentiation and how it is correlated with the progression of spermatogenesis. When 1-year-old frogs were exposed to estradiol-17β during spring (i.e., when spermatogenesis was initiated), testis-ova differentiation was induced in a dose-dependent manner. However, this phenomenon did not occur in 1-year-old frogs during summer, (i.e., when the transition from spermatogonia to spermatocytes mainly occurs). These results present the first evidence that testis-ova of the Japanese pond frog are derived from primary and early secondary spermatogonia, and that estrogen exposure induces testis-ova differentiation accompanied by the initiation of spermatogenesis.

  5. Adenomatoid tumor of testis: A rare cytological diagnosis

    PubMed Central

    Makkar, M; Dayal, P; Gupta, C; Mahajan, NC

    2013-01-01

    Adenomatoid tumor is a benign neoplasm of the male and female genital tracts arising from mesothelial cells. Fine needle aspiration cytology (FNAC) plays a pivotal role in its preoperative diagnosis. Therefore, it is imperative that pathologists should be well aware of its cytological features so as to avoid erroneous diagnosis and hence prevent unnecessary surgical interventions. We hereby, present a case of adenomatoid tumor of testis in a 41 year male diagnosed by FNAC and later confirmed by histopathological examination. PMID:23661947

  6. Impact of electronic-cigarette refill liquid on rat testis.

    PubMed

    El Golli, N; Rahali, D; Jrad-Lamine, A; Dallagi, Y; Jallouli, M; Bdiri, Y; Ba, N; Lebret, M; Rosa, J P; El May, M; El Fazaa, S

    2016-07-01

    Electronic cigarettes (e-cigarettes) are becoming the fashionable alternative to decrease tobacco smoking, although their impact on health has not been fully assessed yet. The present study was designed to compare the impact of e-cigarette refill liquid (e-liquid) without nicotine to e-liquid with nicotine on rat testis. For this purpose, e-liquid with nicotine and e-liquid without nicotine (0.5 mg/kg of body weight) were administered to adult male Wistar rats via the intraperitoneally route during four weeks. Results showed that e-liquid with or without nicotine leads to diminished sperm density and viability, such as a decrease in testicular lactate dehydrogenase activity and testosterone level. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis identified a reduction in cytochrome P450 side-chain cleavage (P450 scc) and 17 beta-hydroxysteroid dehydrogenase (17βHSD) mRNA level, two key enzymes of steroidogenesis. Following e-liquid exposure, histopathological examination showed alterations in testis tissue marked by germ cells desquamation, disorganization of the tubular contents of testis and cell deposits in seminiferous tubules. Finally, analysis of oxidative stress status pointed an outbreak of antioxidant enzyme activities such as superoxide dismutase, catalase and gluthatione-S-transferase, as well as an important increase in sulfhydril group content. Taken together, these results indicate that e-liquid per se induces toxicity in Wistar rat testis, similar to e-liquid with nicotine, by disrupting oxidative balance and steroidogenesis. PMID:27098213

  7. Impact of electronic-cigarette refill liquid on rat testis.

    PubMed

    El Golli, N; Rahali, D; Jrad-Lamine, A; Dallagi, Y; Jallouli, M; Bdiri, Y; Ba, N; Lebret, M; Rosa, J P; El May, M; El Fazaa, S

    2016-07-01

    Electronic cigarettes (e-cigarettes) are becoming the fashionable alternative to decrease tobacco smoking, although their impact on health has not been fully assessed yet. The present study was designed to compare the impact of e-cigarette refill liquid (e-liquid) without nicotine to e-liquid with nicotine on rat testis. For this purpose, e-liquid with nicotine and e-liquid without nicotine (0.5 mg/kg of body weight) were administered to adult male Wistar rats via the intraperitoneally route during four weeks. Results showed that e-liquid with or without nicotine leads to diminished sperm density and viability, such as a decrease in testicular lactate dehydrogenase activity and testosterone level. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) analysis identified a reduction in cytochrome P450 side-chain cleavage (P450 scc) and 17 beta-hydroxysteroid dehydrogenase (17βHSD) mRNA level, two key enzymes of steroidogenesis. Following e-liquid exposure, histopathological examination showed alterations in testis tissue marked by germ cells desquamation, disorganization of the tubular contents of testis and cell deposits in seminiferous tubules. Finally, analysis of oxidative stress status pointed an outbreak of antioxidant enzyme activities such as superoxide dismutase, catalase and gluthatione-S-transferase, as well as an important increase in sulfhydril group content. Taken together, these results indicate that e-liquid per se induces toxicity in Wistar rat testis, similar to e-liquid with nicotine, by disrupting oxidative balance and steroidogenesis.

  8. Id4 Marks Spermatogonial Stem Cells in the Mouse Testis.

    PubMed

    Sun, Feng; Xu, Qing; Zhao, Danfeng; Degui Chen, Charlie

    2015-01-01

    Mammalian spermatogenesis is a classic adult stems cell-dependent process, supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs). However, the identification of SSCs and elucidation of their behaviors in undisturbed testis has long been a big challenge. Here, we generated a knock-in mouse model, Id4-2A-CreERT2-2A-tdTomato, which allowed us to mark Id4-expressing (Id4(+)) cells at different time points in situ and track their behaviors across distinct developmental stages during steady-state and regenerating spermatogenesis. We found that Id4(+) cells continue to produce spermatogonia, spermatocytes and sperm in mouse testis, showing they are capable of self-renewal and have differentiation potential. Consistent with these findings, ablation of Id4(+) cells in mice results in a loss of spermatogenesis. Furthermore, developmental fate mapping reveals that Id4(+) SSCs originate from neonate Id4(+) gonocytes. Therefore, our results indicate that Id4 marks spermatogonial stem cells in the mouse testis.

  9. Testis-specific expression of the human MYCL2 gene.

    PubMed Central

    Robertson, N G; Pomponio, R J; Mutter, G L; Morton, C C

    1991-01-01

    We have characterized the expression of MYCL2, an intronless X-linked gene related to MYCL1. RNase protection analysis of a panel of human normal and tumor tissues has revealed that MYCL2 is expressed almost exclusively in human adult normal testis; much lower levels of transcript were detected in one human lung adenocarcinoma. No MYCL2 transcript was found in human testis RNA obtained from second trimester fetuses. This observation suggests a germ cell rather than somatic cell origin of the transcript and possible developmental regulation of MYCL2. Northern blot analysis of poly(A)+ RNA from adult human normal testis with an antisense riboprobe revealed a transcript of approximately 4.8-kb, which is in agreement with the size predicted from the MYCL2 nucleotide sequence. Antisense transcripts were found spanning regions of MYCL2 corresponding to all three exons of MYCL1. No sizable open reading frame was seen for the MYCL2 antisense transcripts suggesting that they may represent either regulatory sequences or an intron of a gene encoded by the complementary strand. RNase protection assays and the 5' RACE protocol (Rapid Amplification of cDNA Ends) were used to address the localization of the transcription start site of the MYCL2 sense transcript and different putative promoters and transcription regulatory elements have been identified. Images PMID:1711681

  10. In vitro transformation of mouse testis cells by oncogene transfection.

    PubMed

    Morimoto, Hiroko; Lee, Jiyoung; Tanaka, Takashi; Ishii, Kei; Toyokuni, Shinya; Kanatsu-Shinohara, Mito; Shinohara, Takashi

    2012-05-01

    Germ cell tumors (GCTs) are unique in that they exhibit diverse biological characteristics and pathological features. Although several in vivo GCT models are available, studies on GCTs are hampered because in vivo development of GCTs is time consuming and prevents a detailed molecular analysis of the transformation process. Here we developed a novel strategy to transform mouse testis cells in vitro. Lentivirus-mediated transfection of dominant negative Trp53, Myc, and activated Hras1 into a CD9-expressing testis cells caused tumorigenic conversion in vitro. Although these cells resembled embryonic stem (ES) cells, they were aneuploid and lacked Nanog expression, which is involved in the maintenance of the undifferentiated state in ES cells. Euploid ES-like cells were produced by transfecting the Yamanaka factors (Pou5f1, Myc, Klf4, and Sox2) into the same cell population. Although these cells expressed Nanog, they were distinct from ES cells in that they expressed CD44, a cancer stem cell antigen. Both treatments induced similar changes in the DNA methylation patterns in differentially methylated regions of imprinted genes. Moreover, despite the differences in their phenotype and karyotype, both cell types similarly produced mixed GCTs on transplantation, which were composed of teratomas, seminomas, and embryonal carcinomas. Thus, in vitro testis cell transformation facilitates an analysis of the GCT formation process, and our results also suggest the close similarity between GCT formation and reprogramming. PMID:22357549

  11. Gene expression during testis development in Duroc boars.

    PubMed

    Lervik, S; Kristoffersen, A B; Conley, L N; Oskam, I C; Hedegaard, J; Ropstad, E; Olsaker, I

    2015-11-01

    Androstenone is a steroid pheromone occurring in the pubertal Leydig cells. Breeding against androstenone can decrease pheromone odour in swine meat but appears to cause unwanted side effects such as delayed onset of puberty. To study causality, global gene expression in developing boar testes at 12, 16, 20 and 27 weeks was investigated using a porcine cDNA microarray. The morphological status and androgenic levels of the same individuals have been described in a previous publication. In the present paper, expression of genes and pathways has been analysed with reference to these findings. Nine clusters of genes with significant differential expression over time and 49 functional charts were found in the analysed testis samples. Prominent pathways in the prepubertal testis were associated with tissue renewal, cell respiration and increased endocytocis. E-cadherines may be associated with the onset of pubertal development. With elevated steroidogenesis (weeks 16 to 27), there was an increase in the expression of genes in the MAPK pathway, STAR and its analogue STARD6. A pubertal shift in genes coding for cellular cholesterol transport was observed. Increased expression of meiotic pathways coincided with the morphological onset of puberty. Puberty-related change in Ca(2+) pathway transcripts, neurosteroids, neuronal changes and signalling in redox pathways suggested a developmental-specific period of neuromorphogenesis. Several growth factors were found to increase differentially over time as the testis matured. There may be interactions between MAPK, STAR and growth factors during specific periods. In conclusion, pathways for neurogenesis, morphological pathways and several transcripts for growth factors, which have known modulating effects on steroidogenesis and gonadotropins in humans and rodents, act at specific ages and developmental stages in the boar testis. The age dependency and complexity shown for development-specific testis transcripts must be considered

  12. Germ cell transplantation and testis tissue xenografting in mice.

    PubMed

    Tang, Lin; Rodriguez-Sosa, Jose Rafael; Dobrinski, Ina

    2012-01-01

    Germ cell transplantation was developed by Dr. Ralph Brinster and colleagues at the University of Pennsylvania in 1994(1,2). These ground-breaking studies showed that microinjection of germ cells from fertile donor mice into the seminiferous tubules of infertile recipient mice results in donor-derived spermatogenesis and sperm production by the recipient animal(2). The use of donor males carrying the bacterial β-galactosidase gene allowed identification of donor-derived spermatogenesis and transmission of the donor haplotype to the offspring by recipient animals(1). Surprisingly, after transplantation into the lumen of the seminiferous tubules, transplanted germ cells were able to move from the luminal compartment to the basement membrane where spermatogonia are located(3). It is generally accepted that only SSCs are able to colonize the niche and re-establish spermatogenesis in the recipient testis. Therefore, germ cell transplantation provides a functional approach to study the stem cell niche in the testis and to characterize putative spermatogonial stem cells. To date, germ cell transplantation is used to elucidate basic stem cell biology, to produce transgenic animals through genetic manipulation of germ cells prior to transplantation(4,5), to study Sertoli cell-germ cell interaction(6,7), SSC homing and colonization(3,8), as well as SSC self-renewal and differentiation(9,10). Germ cell transplantation is also feasible in large species(11). In these, the main applications are preservation of fertility, dissemination of elite genetics in animal populations, and generation of transgenic animals as the study of spermatogenesis and SSC biology with this technique is logistically more difficult and expensive than in rodents. Transplantation of germ cells from large species into the seminiferous tubules of mice results in colonization of donor cells and spermatogonial expansion, but not in their full differentiation presumably due to incompatibility of the

  13. Pdgfr-α mediates testis cord organization and fetal Leydig cell development in the XY gonad

    PubMed Central

    Brennan, Jennifer; Tilmann, Christopher; Capel, Blanche

    2003-01-01

    During testis development, the rapid morphological changes initiated by Sry require the coordinate integration of many signaling pathways. Based on the established role of the platelet-derived growth factor (PDGF) family of ligands and receptors in migration, proliferation, and differentiation of cells in various organ systems, we have investigated the role of PDGF in testis organogenesis. Analysis of expression patterns and characterization of the gonad phenotype in Pdgfr-α−/− embryos identified PDGFR-α as a critical mediator of signaling in the early testis at multiple steps of testis development. Pdgfr-α−/− XY gonads displayed disruptions in the organization of the vasculature and in the partitioning of interstitial and testis cord compartments. Closer examination revealed severe reductions in characteristic XY proliferation, mesonephric cell migration, and fetal Leydig cell differentiation. This work identifies PDGF signaling through the α receptor as an important event downstream of Sry in testis organogenesis and Leydig cell differentiation. PMID:12651897

  14. [A case of traumatic rupture of the testis: usefulness of magnetic resonance imaging].

    PubMed

    Satake, H; Inoue, K; Sawada, K; Shuin, T

    2001-05-01

    Traumatic rupture of the testis is rare because of the protection afforded by surrounding structures. Moreover, it is difficult to accurately diagnose preoperatively. A 17-year-old man was referred to our department with the complaint of painful swelling of the left testis after being hit by a basketball. Although ultrasonography and computed tomography did not reveal the rupture of the tunica albuginea, we preoperatively diagnosed the rupture of the left testis by magnetic resonance imaging (MRI). We repaired the tunica albuginea and preserved the left testis. In this report, the advantages of MRI for preoperative diagnosis of traumatic rupture of the testis are discussed. In addition, previous cases with traumatic rupture of the testis in the Japanese literature are also reviewed.

  15. Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis

    NASA Technical Reports Server (NTRS)

    Hadley, Jill A.; Hall, Joseph C.; O'Brien, Ami; Ball, Richard

    1992-01-01

    The effect of simulated microgravity on the structure and function of the testis and epididymis cells was investigated in rats subjected to 7 days of tail suspension. Results of a histological examination revealed presence of disorganized seminiferous tubules and accumulation of large multinucleated cells and spermatids in the lumen of the epididymis. In addition, decreases in the content of testis protein and in testosterone levels in the testis, the interstitial fluid, and the epididymis were observed.

  16. Cyclosporine inhibits testosterone biosynthesis in the rat testis.

    PubMed

    Rajfer, J; Sikka, S C; Lemmi, C; Koyle, M A

    1987-08-01

    To determine whether the immunosuppressive agent cyclosporine (CsA) has an effect on testicular androgen function in the male rat, four groups of adult animals were treated daily for 28 days with either orange juice or three doses of CsA (7.5, 15, or 30 mg/kg X day). Twenty-four hours after the last dose of CsA, the animals were killed and the following parameters were measured: testis, seminal vesicle, and ventral prostate weights; serum levels of CsA, creatinine, testosterone (T), and LH; and intratesticular levels of pregnenolone, progesterone, 17 alpha-hydroxyprogesterone, androstenedione, and T. There were no differences between the control (orange juice) and the three CsA-treated groups with respect to serum creatinines and testis, seminal vesicle, and ventral prostate weights. Serum T decreased significantly in the 15 and 30 mg/kg CsA-treated groups. The intratesticular T level decreased significantly only in the 15 and 30 mg/kg CsA-treated groups. In the 15 and 30 mg/kg CsA-treated groups, the intratesticular pregnenolone, progesterone, and 17 alpha-hydroxyprogesterone levels all showed a significant decline compared to controls. There was no significant change in the androstenedione levels in any of the CsA-treated groups. To determine whether the decrease in T production by the testis exposed to CsA is via inhibition of the hypothalamic-pituitary axis, serum LH was measured in all four groups. Serum LH decreased significantly only in the 15 and 30 mg/kg CsA-treated groups. These data suggest that oral CsA administration in doses greater than 15 mg/kg X day results in diminished intratesticular T production that appears to be mediated via inhibition of pituitary LH function.

  17. Testicular microlithiasis in acquired undescended testis after orchidopexy at diagnosis.

    PubMed

    van der Plas, E; Meij-de Vries, A; Goede, J; van der Voort-Doedens, L; Zijp, G; Hack, W

    2013-11-01

    The aim of this study was to observe the prevalence of testicular microlithiasis (TM) in surgically corrected acquired undescended testis (UDT). The prevalence of TM was assessed by ultrasound. Boys and young men who had undergone orchidopexy (ORP) for acquired UDT in mid or late childhood were observed to study the long-term testicular volume. During this examination, the presence or absence of TM was also assessed. TM was defined as echogenic foci without shadowing within the testis parenchyma. We included 106 patients who had undergone ORP at the Medical Center Alkmaar (1986-1999) and 155 patients who had undergone ORP at the Juliana Children's Hospital (1996-2009). The majority of patients were white, Caucasian (82%). The median age at follow-up, 25.8 years (range 14.0-31.6 years) was higher in Medical Center Alkmaar than in Juliana Children's Hospital 13.4 years (range 5.1-26.6 years). From 2009 to 2011, these 261 patients (median age 18.9 years) underwent an ultrasound examination. Median follow-up after ORP was 11.3 years (range 1.4-23.5 years); age at ORP ranged from 2.1 to 16.2 years, with a median of 8.5 years. TM was found in 17 (6.5%) patients (median age at follow-up 20.4 years; range 11-28). No significant association was found with the incidence of TM and the operated testis, the age at ORP or the racial variance (p > 0.05). ORP at diagnosis for acquired UDT is associated with a 6.5% prevalence of TM in boys and young adults.

  18. Cyclooxygenase and prostaglandins in somatic cell populations of the testis.

    PubMed

    Frungieri, Mónica B; Calandra, Ricardo S; Mayerhofer, Artur; Matzkin, María E

    2015-04-01

    Prostaglandins (PGs) are synthesized through the action of the rate-limiting enzyme cyclooxygenase (COX) and further specific enzymes. The development of Cox-deficient mice in the 1990s gave insights into the reproductive roles of PGs. Female Cox-knockout mice were subfertile or infertile. Interestingly, fertility was not affected in male mice deficient in Cox, suggesting that PGs may not be critical for the functioning of the testis. However, this conclusion has recently been challenged by observations of important roles for PGs in both physiological and pathological processes in the testis. The two key somatic cell types in the testis, Leydig and Sertoli cells, express the inducible isoenzyme COX2 and produce PGs. Testicular COX2 expression in these somatic cells is regulated by hormonal input (FSH, prolactin (PRL), and testosterone) as well as by IL1β. PGs modulate steroidogenesis in Leydig cells and glucose uptake in Sertoli cells. Hence, the COX2/PG system in Leydig and Sertoli cells acts as a local modulator of testicular activity, and consequently may regulate spermatogenic efficiency. In addition to its expression in Leydig and Sertoli cells, COX2 has been detected in the seminiferous tubule wall, and in testicular macrophages and mast cells of infertile patients. These observations highlight the possible relevance of PGs in testicular inflammation associated with idiopathic infertility. Collectively, these data indicate that the COX2/PG system plays crucial roles not only in testicular physiology (i.e., development, steroidogenesis, and spermatogenesis), but more importantly in the pathogenesis or maintenance of infertility status in the male gonad. Further studies of these actions could lead to new therapeutic approaches to idiopathic male infertility.

  19. Testis Scintigraphy in a Patient with Acute Lymphoblastic Leukemia

    PubMed Central

    Şencan Eren, Mine; Koç, Murat; Ören, Hale; Özkal, Şermin; Durak, Hatice

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is a pediatric malignancy associated with remissions and relapses. Common relapsing sitesare meninges, testis and ovary. Testicular scintigraphy is a highly specific modality used mainly in the differential diagnosis of testicular torsion and epidydimitis/epidydimo-orchitis. There is only one interesting image on leukemic infiltration with scrotal scintigraphy in the literature. The aim of this case presentation is to report that although the scintigraphic appearance of testicular torsion was observed in a patient with the diagnosis of ALL, testicular ALL infiltration was revealed in pathologic examination. Conflict of interest:None declared. PMID:24653935

  20. Differential expression of estrogen receptor α and progesterone receptor in the normal and cryptorchid testis of a dog

    PubMed Central

    Jung, Hyo Young; Yoo, Dae Young; Jo, Young Kwang; Kim, Geon A; Chung, Jin Young; Choi, Jung Hoon

    2016-01-01

    Descending of the testes is an important process for spermatogenesis and cryptorchidism is one of the most relevant genital defects in dogs. In a previous study, we observed abnormal morphology and proliferation of Sertoli cells in a cryptorchid testis. In the present study, we investigated the expression of estrogen and progesterone receptors in the normal and cryptorchid testis of a dog. Elective orchidectomy was performed on the dog's abdominal right testis (undescended, cryptorchid) and scrotal left testis (descended, normal). In the normal testis, estrogen receptor α immunoreactivity was detected in Leydig cells alone, while estrogen receptor α immunoreactivity in the cryptorchid testis was significantly prominent in the Sertoli cells as well. In addition, progesterone receptor immunoreactivity in the control testis was detected in the spermatids, but was not detected in the cryptorchid testis. This result suggests that unilateral cryptorchidism causes increases of estrogen receptor α expression in Sertoli cells. PMID:27382382

  1. Differential expression of estrogen receptor α and progesterone receptor in the normal and cryptorchid testis of a dog.

    PubMed

    Jung, Hyo Young; Yoo, Dae Young; Jo, Young Kwang; Kim, Geon A; Chung, Jin Young; Choi, Jung Hoon; Jang, Goo; Hwang, In Koo

    2016-06-01

    Descending of the testes is an important process for spermatogenesis and cryptorchidism is one of the most relevant genital defects in dogs. In a previous study, we observed abnormal morphology and proliferation of Sertoli cells in a cryptorchid testis. In the present study, we investigated the expression of estrogen and progesterone receptors in the normal and cryptorchid testis of a dog. Elective orchidectomy was performed on the dog's abdominal right testis (undescended, cryptorchid) and scrotal left testis (descended, normal). In the normal testis, estrogen receptor α immunoreactivity was detected in Leydig cells alone, while estrogen receptor α immunoreactivity in the cryptorchid testis was significantly prominent in the Sertoli cells as well. In addition, progesterone receptor immunoreactivity in the control testis was detected in the spermatids, but was not detected in the cryptorchid testis. This result suggests that unilateral cryptorchidism causes increases of estrogen receptor α expression in Sertoli cells. PMID:27382382

  2. Primary adenocarcinoma of rete testis with distinct biphasic pattern: An extremely rare entity and diagnostic challenge.

    PubMed

    Ghosh, Prithwijit; Saha, Kaushik

    2015-01-01

    Primary adenocarcinoma of rete testis is one of the rarest intrascrotal tumors. Very few cases have been reported in the literature. In addition, presence of biphasic component creates difficulty in the diagnosis. We present here a unique third case of rete testis adenocarcinoma having distinct cytologically malignant spindle cell component in a young male who presented with recurrent hydrocele. PMID:25810664

  3. Differential expression of transforming growth factor-beta in the interstitial tissue of testis during aging.

    PubMed

    Jung, Jae-Chang; Park, Geun-Tae; Kim, Kook-Hee; Woo, Ju Hyung; An, Jung-Min; Kim, Ki-Chul; Chung, Hae Young; Bae, Young-Seuk; Park, Jeen Woo; Kang, Shin-Sung; Lee, Young-Sup

    2004-05-01

    Transforming growth factor-betas (TGF-betas) have significant effects on testis development. The pattern of TGF-beta expression in aging testis has not been established to date. We examined age-related changes in the expression of TGF-beta and its receptors in the testis using Western blot analysis. TGF-beta1 expression increased continuously in aging rat testis, whereas no age-associated changes were observed for TGF-beta3. Strong expression of TGF-beta2, as well as type I and II receptors was observed in 12-month-old testis, but following this time, expression decreased dramatically. Interestingly, TGF-beta2 and -beta3 displayed strong and similar expression patterns in liver, regardless of age, suggesting that the down-regulation of TGF-beta2 is testis-specific. We observed significant induction of p53 and p21WAF1 in 18-month-old testis that appeared to correspond with aging. Moreover, caloric restriction (CR) prevented age-related decrease in TGF-beta2 expression. Using immunohistochemistry, we showed that all TGF-beta1, -beta2, and -beta3 proteins are expressed primarily in interstitial cells, which are located in the space between adjoining seminiferous tubules. Our data collectively indicate that aging in the testis is regulated by differential expression of TGF-beta proteins, and decreased levels of TGF-beta2 contribute to the aging process.

  4. The effect of microgravity on tissue structure and function of rat testis.

    PubMed

    Ding, Ye; Tang, Jin; Zou, Jun; She, Ruiping; Wang, Yinghua; Yue, Zhuo; Tian, Jijing; Xia, Kangkang; Yin, Jun; Wang, Desheng

    2011-12-01

    To explore whether an environment of weightlessness will cause damage to the reproductive system of animals, we used the tail-suspension model to simulate microgravity, and investigated the effect of microgravity on the tissue structure and function of the testis in sexually mature male rats. Forty-eight male Wistar rats weighing 200-250 g were randomly assigned to three groups (N = 16 each): control, tail traction, and tail suspension. After the rats were suspended for 7 or 14 days, morphological changes of testis were evaluated by histological and electron microscopic methods. The expression of HSP70, bax/bcl-2 and AR (androgen receptor) in testis was measured by immunohistochemistry. Obvious pathological lesions were present in the testis after the rats were suspended for 7 or 14 days. We detected overexpression of HSP70 and an increase of apoptotic cells, which may have contributed to the injury to the testis. The expression of AR, as an effector molecule in the testis, was significantly decreased in the suspended groups compared to control (P < 0.01). We also observed that, with a longer time of suspension, the aforementioned pathological damage became more serious and some pathological injury to the testis was irreversible. The results demonstrated that a short- or medium-term microgravity environment could lead to severe irreversible damage to the structure of rat testis. PMID:22042268

  5. The vitamin D receptor localization and mRNA expression in ram testis and epididymis.

    PubMed

    Jin, Hui; Huang, Yang; Jin, Guang; Xue, Yanrong; Qin, Xiaowei; Yao, Xiaolei; Yue, Wenbing

    2015-02-01

    The objectives of present study were to investigate the presence of vitamin D receptor (VDR) in testis and epididymis of ram by polymerase chain reaction (PCR), to locate VDR in testis and epididymis by immunohistochemistry and to compare difference of VDR expression between testis and epididymis before and after sexual maturation by Real time-PCR and Western blot. The results showed that VDR exists in the testis and epididymis of ram while VDR protein in testis and epididymis was localized in Leydig cells, spermatogonial stem cells, spermatocytes, Sertoli cells and principal cells. For the adult ram, the amounts of VDR mRNA and VDR protein were less (p < 0.01) in testis than compared with caput, corpus and cauda epididymis. For prepubertal ram, the result showed the same trend (p < 0.01). However, the expression levels of VDR mRNA and VDR protein in caput, corpus, cauda epididymis and testis showed no significant difference (p > 0.05) between adult and prepubertal. In conclusion, VDR exists in testis and epididymis of ram, suggesting 1α,25-(OH)(2)VD(3) may play a role in ram reproduction.

  6. The effect of microgravity on tissue structure and function of rat testis.

    PubMed

    Ding, Ye; Tang, Jin; Zou, Jun; She, Ruiping; Wang, Yinghua; Yue, Zhuo; Tian, Jijing; Xia, Kangkang; Yin, Jun; Wang, Desheng

    2011-12-01

    To explore whether an environment of weightlessness will cause damage to the reproductive system of animals, we used the tail-suspension model to simulate microgravity, and investigated the effect of microgravity on the tissue structure and function of the testis in sexually mature male rats. Forty-eight male Wistar rats weighing 200-250 g were randomly assigned to three groups (N = 16 each): control, tail traction, and tail suspension. After the rats were suspended for 7 or 14 days, morphological changes of testis were evaluated by histological and electron microscopic methods. The expression of HSP70, bax/bcl-2 and AR (androgen receptor) in testis was measured by immunohistochemistry. Obvious pathological lesions were present in the testis after the rats were suspended for 7 or 14 days. We detected overexpression of HSP70 and an increase of apoptotic cells, which may have contributed to the injury to the testis. The expression of AR, as an effector molecule in the testis, was significantly decreased in the suspended groups compared to control (P < 0.01). We also observed that, with a longer time of suspension, the aforementioned pathological damage became more serious and some pathological injury to the testis was irreversible. The results demonstrated that a short- or medium-term microgravity environment could lead to severe irreversible damage to the structure of rat testis.

  7. Effects of hyperthermia and radiation on mouse testis stem cells

    SciTech Connect

    Reid, B.O.; Mason, K.A.; Withers, H.R.; West, J.

    1981-11-01

    The response of mouse testis stem cells to hyperthermia and combined hyperthermia-radiation treatments was assayed by spermatogenic colony regrowth, sperm head counts, testis weight loss, and fertility. With the use of spermatogenic colony assay, thermal enhancement ratios at an isosurvival level of 0.1 were 1.27 at 41 degrees, 1.80 at 42 degrees, and 3.97 at 43 degrees for testes exposed to heat for 30 min prior to irradiation. Sperm head counts were reduced by heat alone from a surviving fraction of 0.58 at 41 degrees to 0.003 at 42.5-43.5 degrees. Curves for sperm head survival measured 56 days after the testes had been heated for 30 min prior to irradiation were biphasic and showed a progressive downward displacement to lower survival with increasing temperature. The 41, 42, and 43 degrees curves were displaced downward by factors of 2, 58, and 175, respectively. The proportion of animals remaining sterile after 30 min of heat (41-43 degrees) and the median sterility period in days increased with increasing temperature. The minimum sperm count necessary to regain fertility was 13% of the normal mouse level.

  8. Fertility after homologous prepubertal testis transplantation in the dog.

    PubMed

    Pullium, J K; Milner, R; Tuma, G A; Lin, P H

    2008-10-01

    Canine models of hereditary human diseases are widely used throughout the biomedical community, particularly when no suitable rodent model exists. In several models, the homozygote dogs die prior to puberty, or have substantially reduced fertility. Prepubertal transplantation of the testes was used to propagate the genotype of a mutant dog that would not otherwise have survived until puberty. The transplant recipient remained fertile 7 years postoperatively. To begin determining the factors necessary for successful function in testis transplants, prepubertal dogs that were dog leukocyte antigen (DLA) identical and disparate were examined for fertility and compared to the original transplant recipient as well as unoperated and sham-operated dogs. Immunosuppression was maintained with cyclosporine (CyA) and prednisone in the immediate postoperative period and CyA alone thereafter. The DLA-identical dogs demonstrated initial acceptance of the transplant, whereas one of two underwent chronic rejection. Both DLA-disparate dogs had subacute rejection prior to sexual maturity. These results demonstrate that homologous transplantation of prepubertal testes can be an effective method to preserve genotype in DLA-identical dogs. This model may also be useful for studying testis development and immunobiology. PMID:18929852

  9. Human testis-specific genes are under relaxed negative selection.

    PubMed

    Pierron, Denis; Razafindrazaka, Harilanto; Rocher, Christophe; Letellier, Thierry; Grossman, Lawrence I

    2014-02-01

    Recent studies have suggested that selective forces and constraints acting on genes varied during human evolution depending on the organ in which they are expressed. To gain insight into the evolution of organ determined negative selection forces, we compared the non-synonymous SNP diversity of genes expressed in different organs. Based on a HAPMAP dataset, we determined for each SNP its frequency in 11 human populations and, in each case, predicted whether or not the change it produces is deleterious. We have shown that, for all organs under study, SNPs predicted to be deleterious are present at a significantly lower frequency than SNPs predicted to be tolerated. However, testis-specific genes contain a higher proportion of deleterious SNPs than other organs. This study shows that negative selection is acting on the whole human genome, but that the action of negative selection is relaxed on testis-specific genes. This result adds to and expands the hypothesis of a recent evolutionary change in the human male reproductive system and its behavior.

  10. High expression of NPY receptors in the human testis.

    PubMed

    Körner, Meike; Waser, Beatriche; Thalmann, George N; Reubii, Jean Claude

    2011-04-30

    NPY receptors represent novel molecular therapeutic targets in cancer and obesity. However, the extent of NPY receptor expression in normal human tissues is poorly investigated. Based on the role of NPY in reproductive functions, the NPY receptor expression was studied in 25 normal human testes and, additionally, 24 testicular tumors using NPY receptor autoradiography. In the normal testis, Leydig cells strongly expressed NPY receptor subtype Y2, and small arterial blood vessels Y1. Y2 receptors were found to be functional with agonist-stimulated [(35)S]GTPγS binding autoradiography. Full functional integrity of the NPY system was further suggested by the immunohistochemical detection of NPY peptide in nerve fibers directly adjacent to Leydig cells and arteries. Germ cell tumors expressed Y1 and Y2 on tumor cells in 33% and Y1 on intratumoral blood vessels in 50%. Based on its strong NPY receptor expression in Leydig cells and blood vessels, the normal human testis represents a potentially important physiological and pharmalogical NPY target.

  11. Cadmium-induced genetic instability in mice testis.

    PubMed

    Oliveira, Helena; Lopes, Tina; Almeida, Tânia; Pereira, Maria de Lourdes; Santos, Conceição

    2012-12-01

    Cadmium is a well recognized carcinogenic, cytotoxic and mutagenic transition metal. Recent evidence suggests that the proteins participating in the DNA repair systems, especially in excision and mismatch repair (MMR), are sensitive targets of cadmium toxicity. Microsatellite instability (MSI) is regarded as one of the phenotypes of defective DNA MMR and, consequently, as a marker of high risk for cancer. The purpose of this work is to determine whether cadmium, in the form of cadmium chloride (CdCl(2)), may induce microsatellite mutations in murine testes. For this study, 2-month-old male ICR-CD1 mice were treated by a single subcutaneous injection of 1, 2 and 3 mg CdCl(2)/kg body weight and killed after 35 days. A panel of six microsatellite markers, previously reported as being the most sensitive in detecting MSI in murine tumours, was used in this study. The results show that CdCl(2) in the doses of 2 and 3 mg/kg induced a decrease in the testis weight and severe histopathologic changes with complete disorganization of testicular structure and evidences of severe necrosis. In addition, the animals exposed to the lowest CdCl(2) dose presented MSI in the testis. The results indicate the existence of MSI in at least two nuclear loci suggesting putative genotoxic effects induced by cadmium. PMID:22699117

  12. Activins and inhibins in mammalian testis development: new models, new insights.

    PubMed

    Barakat, B; Itman, C; Mendis, S H; Loveland, K L

    2012-08-15

    The discovery of activin and inhibins as modulators of the hypothalamic-pituitary-gonadal axis has set the foundation for understanding their central importance to many facets of development and disease. This review contains an overview of the processes and cell types that are central to testis development and spermatogenesis and then provides an update focussed on information gathered over the past five years to address new concepts about how these proteins function to control testis development in fetal and juvenile life. Current knowledge about the interactive nature of the transforming growth factor-β (TGFβ) superfamily signalling network is applied to recent findings about activins and inhibins in the testis. Information about the regulated synthesis of signalling components and signalling regulators in the testis is integrated with new concepts that demonstrate their functional significance. The importance of activin bioactivity levels or dosage in controlling balanced growth of spermatogonial cells and their niche at different stages of testis development is highlighted.

  13. Biology of the Sertoli Cell in the Fetal, Pubertal, and Adult Mammalian Testis.

    PubMed

    Chojnacka, Katarzyna; Zarzycka, Marta; Mruk, Dolores D

    2016-01-01

    A healthy man typically produces between 50 × 10(6) and 200 × 10(6) spermatozoa per day by spermatogenesis; in the absence of Sertoli cells in the male gonad, this individual would be infertile. In the adult testis, Sertoli cells are sustentacular cells that support germ cell development by secreting proteins and other important biomolecules that are essential for germ cell survival and maturation, establishing the blood-testis barrier, and facilitating spermatozoa detachment at spermiation. In the fetal testis, on the other hand, pre-Sertoli cells form the testis cords, the future seminiferous tubules. However, the role of pre-Sertoli cells in this process is much less clear than the function of Sertoli cells in the adult testis. Within this framework, we provide an overview of the biology of the fetal, pubertal, and adult Sertoli cell, highlighting relevant cell biology studies that have expanded our understanding of mammalian spermatogenesis. PMID:27300181

  14. Testis-specific transcription initiation sites of rat farnesyl pyrophosphate synthetase mRNA.

    PubMed Central

    Teruya, J H; Kutsunai, S Y; Spear, D H; Edwards, P A; Clarke, C F

    1990-01-01

    A variety of rat tissues were screened at low stringency with a rat farnesyl pyrophosphate (FPP) synthetase cDNA. In testis, an FPP synthetase-related RNA was detected that was larger than the liver FPP synthetase mRNA and was present at very high levels comparable with liver FPP synthetase RNA levels obtained from rats fed diets supplemented with cholestyramine and mevinolin. Sequence analysis of testis cDNA clones, together with primer extension and S1 nuclease experiments, indicated that testis FPP synthetase transcripts contain an extended 5' untranslated region. The 5' extension contained one or two out-of-frame upstream ATGs, depending on the site of transcription initiation. Protein in vitro translation studies indicated that the extended 5' untranslated region may play a role in regulating the translation of the FPP synthetase polypeptide in rat testis. Southern blot analysis with a probe containing both testis and liver 5' untranslated sequences provided evidence that both liver and testis transcripts derive from the same gene. The data suggest that an upstream testis-specific promoter results in the abundant production of FPP synthetase transcripts that are translated at low efficiency; another promoter functions in liver and other somatic tissues and directs the regulated synthesis of shorter discrete transcripts. Images PMID:2325654

  15. Effects of plants and plant products on the testis

    PubMed Central

    D'Cruz, Shereen Cynthia; Vaithinathan, Selvaraju; Jubendradass, Rajamanickam; Mathur, Premendu Prakash

    2010-01-01

    For centuries, plants and plant-based products have been used as a valuable and safe natural source of medicines for treating various ailments. The therapeutic potential of most of these plants could be ascribed to their anticancer, antidiabetic, hepatoprotective, cardioprotective, antispasmodic, analgesic and various other pharmacological properties. However, several commonly used plants have been reported to adversely affect male reproductive functions in wildlife and humans. The effects observed with most of the plant and plant-based products have been attributed to the antispermatogenic and/or antisteroidogenic properties of one or more active ingredients. This review discusses the detrimental effects of some of the commonly used plants on various target cells in the testis. A deeper insight into the molecular mechanisms of action of these natural compounds could pave the way for developing therapeutic strategies against their toxicity. PMID:20562897

  16. Aspiration biopsy of testis: another method for histologic examination

    SciTech Connect

    Nseyo, U.O.; Englander, L.S.; Huben, R.P.; Pontes, J.E.

    1984-08-01

    The most important method for evaluating the pathogenesis of male infertility is open testicular biopsy. Herein the authors describe a method of aspiration biopsy of testis for histologic examination. Sexually mature dogs and rats treated with chemotherapeutic agents and ionizing radiation were followed with periodic testicular aspiration biopsy during and after treatment. The histologic findings from the aspiration biopsy compare with the results of routine histologic examination in assessing spermatogenetic activity and delineating pathologic changes. The puncture in the experimental animals was performed under general anesthesia. In human patients testicular biopsy could be done under local anesthesia in an outpatient clinic. The procedure would be less painful, minimally invasive, and more cost-effective.

  17. Steroidogenesis of the testis -- new genes and pathways.

    PubMed

    Flück, Christa E; Pandey, Amit V

    2014-05-01

    Defects of androgen biosynthesis cause 46,XY disorder of sexual development (DSD). All steroids are produced from cholesterol and the early steps of steroidogenesis are common to mineralocorticoid, glucocorticoid and sex steroid production. Genetic mutations in enzymes and proteins supporting the early biosynthesis pathways cause adrenal insufficiency (AI), DSD and gonadal insufficiency. The classic androgen biosynthesis defects with AI are lipoid CAH, CYP11A1 and HSD3B2 deficiencies. Deficiency of CYP17A1 rarely causes AI, and HSD17B3 or SRD5A2 deficiencies only cause 46,XY DSD and gonadal insufficiency. All androgen biosynthesis depends on 17,20 lyase activity of CYP17A1 which is supported by P450 oxidoreductase (POR) and cytochrome b5 (CYB5). Therefore 46,XY DSD with apparent 17,20 lyase deficiency may be due to mutations in CYP17A1, POR or CYB5. Illustrated by patients harboring mutations in SRD5A2, normal development of the male external genitalia depends largely on dihydrotestosterone (DHT) which is converted from circulating testicular testosterone (T) through SRD5A2 in the genital skin. In the classic androgen biosynthetic pathway, T is produced from DHEA and androstenedione/-diol in the testis. However, recently found mutations in AKR1C2/4 genes in undervirilized 46,XY individuals have established a role for a novel, alternative, backdoor pathway for fetal testicular DHT synthesis. In this pathway, which has been first elucidated for the tammar wallaby pouch young, 17-hydroxyprogesterone is converted directly to DHT by 5α-3α reductive steps without going through the androgens of the classic pathway. Enzymes AKR1C2/4 catalyse the critical 3αHSD reductive reaction which feeds 17OH-DHP into the backdoor pathway. In conclusion, androgen production in the fetal testis seems to utilize two pathways but their exact interplay remains to be elucidated. PMID:24793988

  18. Characterization of testis-specific isoenzyme of human pyruvate dehydrogenase.

    PubMed

    Korotchkina, Lioubov G; Sidhu, Sukhdeep; Patel, Mulchand S

    2006-04-01

    Pyruvate dehydrogenase (PDH), the first component of the human pyruvate dehydrogenase complex, has two isoenzymes, somatic cell-specific PDH1 and testis-specific PDH2 with 87% sequence identity in the alpha subunit of alpha(2) beta(2) PDH. The presence of functional testis-specific PDH2 is important for sperm cells generating nearly all their energy from carbohydrates via pyruvate oxidation. Kinetic and regulatory properties of recombinant human PDH2 and PDH1 were compared in this study. Site-specific phosphorylation/dephosphorylation of the three phosphorylation sites by four PDH kinases (PDK1-4) and two PDH phosphatases (PDP1-2) were investigated by substituting serines with alanine or glutamate in PDHs. PDH2 was found to be very similar to PDH1 as follows: (i) in specific activities and kinetic parameters as determined by the pyruvate dehydrogenase complex assay; (ii) in thermostability at 37 degrees C; (iii) in the mechanism of inactivation by phosphorylation of three sites; and (iv) in the phosphorylation of sites 1 and 2 by PDK3. In contrast, the differences for PDH2 were indicated as follows: (i) by a 2.4-fold increase in binding affinity for the PDH-binding domain of dihydrolipoamide acetyltransferase as measured by surface plasmon resonance; (ii) by possible involvement of Ser-264 (site 1) of PDH2 in catalysis as evident by its kinetic behavior; and (iii) by the lower activities of PDK1, PDK2, and PDK4 as well as PDP1 and PDP2 toward PDH2. These differences between PDH2 and PDH1 are less than expected from substitution of 47 amino acids in each PDH2 alpha subunit. The multiple substitutions may have compensated for any drastic alterations in PDH2 structure thereby preserving its kinetic and regulatory characteristics largely similar to that of PDH1. PMID:16436377

  19. Comparative Transcriptome Analysis of Differentially Expressed Genes and Signaling Pathways between XY and YY Testis in Yellow Catfish.

    PubMed

    Wu, Junjie; Xiong, Shuting; Jing, Jing; Chen, Xin; Wang, Weimin; Gui, Jian-Fang; Mei, Jie

    2015-01-01

    YY super-males have rarely been detected in nature and only been artificially created in some fish species including tilapia and yellow catfish (Pelteobagrusfulvidraco), which provides a promising model for testis development and spermatogenesis. In our previous study, significant differences in morphology and miRNA expression were detected between XY and YY testis of yellow catfish. Here, solexa sequencing technology was further performed to compare mRNA expression between XY and YY testis. Compared with unigenes expressed in XY testis, 1146 and 1235 unigenes have significantly higher and lower expression in YY testis, respectively. 605 differentially expressed unigenes were annotated to 1604 GO terms with 319 and 286 genes having relative higher expression in XY and YY testis. KEGG analysis suggested different levels of PI3K-AKT and G protein-coupled receptor (GPCR) signaling pathways between XY and YY testis. Down-regulation of miR-141/429 in YY testis was speculated to promote testis development and maturation, and several factors in PI3K-AKT and GPCR signaling pathways were found as predicted targets of miR-141/429, several of which were confirmed by dual-luciferase reporter assays. Our study provides a comparative transcriptome analysis between XY and YY testis, and reveals interactions between miRNAs and their target genes that are possibly involved in regulating testis development and spermatogenesis. PMID:26241040

  20. Comparative Transcriptome Analysis of Differentially Expressed Genes and Signaling Pathways between XY and YY Testis in Yellow Catfish

    PubMed Central

    Wu, Junjie; Xiong, Shuting; Jing, Jing; Chen, Xin; Wang, Weimin; Gui, Jian-Fang; Mei, Jie

    2015-01-01

    YY super-males have rarely been detected in nature and only been artificially created in some fish species including tilapia and yellow catfish (Pelteobagrusfulvidraco), which provides a promising model for testis development and spermatogenesis. In our previous study, significant differences in morphology and miRNA expression were detected between XY and YY testis of yellow catfish. Here, solexa sequencing technology was further performed to compare mRNA expression between XY and YY testis. Compared with unigenes expressed in XY testis, 1146 and 1235 unigenes have significantly higher and lower expression in YY testis, respectively. 605 differentially expressed unigenes were annotated to 1604 GO terms with 319 and 286 genes having relative higher expression in XY and YY testis. KEGG analysis suggested different levels of PI3K-AKT and G protein-coupled receptor (GPCR) signaling pathways between XY and YY testis. Down-regulation of miR-141/429 in YY testis was speculated to promote testis development and maturation, and several factors in PI3K-AKT and GPCR signaling pathways were found as predicted targets of miR-141/429, several of which were confirmed by dual-luciferase reporter assays. Our study provides a comparative transcriptome analysis between XY and YY testis, and reveals interactions between miRNAs and their target genes that are possibly involved in regulating testis development and spermatogenesis. PMID:26241040

  1. Comparative Transcriptome Analysis of Differentially Expressed Genes and Signaling Pathways between XY and YY Testis in Yellow Catfish.

    PubMed

    Wu, Junjie; Xiong, Shuting; Jing, Jing; Chen, Xin; Wang, Weimin; Gui, Jian-Fang; Mei, Jie

    2015-01-01

    YY super-males have rarely been detected in nature and only been artificially created in some fish species including tilapia and yellow catfish (Pelteobagrusfulvidraco), which provides a promising model for testis development and spermatogenesis. In our previous study, significant differences in morphology and miRNA expression were detected between XY and YY testis of yellow catfish. Here, solexa sequencing technology was further performed to compare mRNA expression between XY and YY testis. Compared with unigenes expressed in XY testis, 1146 and 1235 unigenes have significantly higher and lower expression in YY testis, respectively. 605 differentially expressed unigenes were annotated to 1604 GO terms with 319 and 286 genes having relative higher expression in XY and YY testis. KEGG analysis suggested different levels of PI3K-AKT and G protein-coupled receptor (GPCR) signaling pathways between XY and YY testis. Down-regulation of miR-141/429 in YY testis was speculated to promote testis development and maturation, and several factors in PI3K-AKT and GPCR signaling pathways were found as predicted targets of miR-141/429, several of which were confirmed by dual-luciferase reporter assays. Our study provides a comparative transcriptome analysis between XY and YY testis, and reveals interactions between miRNAs and their target genes that are possibly involved in regulating testis development and spermatogenesis.

  2. Synchronous epidermoid cyst and mature teratoma of the testis: an unusual association.

    PubMed

    Huyghe, Eric; Mazerolles, Catherine; Moran, Cesar; Khedis, Mehdi; Khoury, Elias; Nohra, Joe; Soulié, Michel; Plante, Pierre

    2007-01-01

    We describe here the first case of a synchronous epidermoid cyst and mature teratoma of the testis occurring in a young man presenting a with bilateral testicular tumor. After a clinical, biological and ultrasound evaluation, testis-sparing surgery was performed on the left testis and a total orchiectomy on the right side in accordance with oncological principles. Histopathological examination revealed a simple epidermoid cyst on the left side and a mature teratoma on the right side, following Price's criteria. No metastasis was detected, and the patient was closely followed. The patient remains disease-free and has normal postoperative testosterone levels 3 years after the surgery.

  3. [Rare tumors and tumor-like lesions of the testis and paratesticular structures].

    PubMed

    Schweyer, S

    2014-05-01

    Tumors and tumor-like lesions of the testes and paratesticular structures are rare neoplasms often documented solely in case reports but are morphologically similar to their counterparts in other organ systems. According to the World Health Organization (WHO) classification, miscellaneous tumors of the testis, tumors of collecting ducts and rete testis, tumors of paratesticular structures are differentiated from mesenchymal tumors of the spermatic cord and testicular adnexa. In the differential diagnostics of a space-occupying mass in the testis or paratesticular region, tumor-like lesions should be considered because these lesions represent a large collection pot and occur more often than was originally assumed.

  4. The emerging role of insulin-like growth factors in testis development and function.

    PubMed

    Griffeth, Richard J; Bianda, Vanessa; Nef, Serge

    2014-01-01

    The insulin-like family of growth factors (IGFs) - composed of insulin, and insulin-like growth factors I (IGF1) and II (IGF2) - provides essential signals for the control of testis development and function. In the testis, IGFs act in an autocrine-paracrine manner but the extent of their actions has been underestimated due to redundancies at both the ligand and receptor levels, and the perinatal lethality of constitutive knockout mice. This review synthesizes the current understanding of how the IGF system regulates biological processes such as primary sex determination, testis development, spermatogenesis and steroidogenesis, and highlights the questions that remain to be explored.

  5. A novel method for repair of testis rupture after gunshot trauma: repair with Tutoplast processed pericardium.

    PubMed

    Ciftci, Seyfettin; Ozkul, Bahattin; Ustuner, Murat; Nagihanlnan; Culha, Mustafa Melih

    2014-12-01

    Gunshot wound injury to the external genitalia is relatively uncommon. However, if a testis isaffected in such a case, early surgical exploration should be carried out. A 16-year-old boy presented with right testicular rupture. Tunica albugineal defect could not be closed primarily. We used a Tutoplast® processed bovine pericardium to repair the defect of tunica albuginea. At his 3-month follow-up visit, there was no complication. Doppler blood flow of testis was normal. In this case, preservation of testis tissue was obtained with early exploration and repair of the big tunica albugineal defect with Tutoplast® processed pericardium. PMID:25842593

  6. [Pure choriocarcinoma of the testis: report of a case and review of the literature].

    PubMed

    Sahraoui, S; Hassani, A T; Ouhtatou, F; Acharki, A; Benider, A; Kahlain, A

    2001-03-01

    We report a case of a young man 31 years old treated at the Ibn Rochd Oncology Center for a pure choriocarcinoma of the right testis. The first examination note a skin metastasis without another localization. The beta HCG level was 328 mu/mL. The diagnosis was confirmed by pathological examination of the testis after orchidectomy. The adjuvant treatment consisted in chemotherapy like using in germ cell neoplasm's of the testis. During the evolution, partial remission (50%) was obtained after the third course and complete remission one month after the end of treatment. The patient still alive after 20 months. PMID:11355283

  7. Expression and localization of five members of the testis-specific serine kinase (Tssk) family in mouse and human sperm and testis

    PubMed Central

    Li, Yahui; Sosnik, Julian; Brassard, Laura; Reese, Michael; Spiridonov, Nikolay A.; Bates, Tonya C.; Johnson, Gibbes R.; Anguita, Juan; Visconti, Pablo E.; Salicioni, Ana M.

    2011-01-01

    Members of the testis-specific serine/threonine kinases (Tssk) family may have a role in sperm differentiation in the testis and/or fertilization. To gain insight into the functional relevance of these kinases, their expression was examined both at the mRNA and protein levels. Quantitative PCR analysis confirmed that all five Tssk mRNAs are almost exclusively expressed postmeiotically in the testis. Recombinant mouse and human Tssks were cloned and used for validation of an array of commercial and custom-made antibodies against Tssks. Immunolocalization in mouse testis, and in mouse and human sperm, showed that Tssk1, Tssk2, Tssk4 and Tssk6, but not Tssk3, were present in mouse sperm and in germ cells from mouse testis. TSSK1, TSSK2 and TSSK6 were also detected in human sperm, while TSSK3 was absent. In both mouse and human sperm, Tssk1 was partially soluble, while Tssk2, Tssk4 and Tssk6 were insoluble in non-ionic detergents. In vitro recombinant TSSK2 activity assays showed maximum enzymatic activity at 5 mM Mg2+ and a Km for ATP of ∼10 µM. These, observations together with findings that the Tssk1/Tssk2 double knock-out as well as the Tssk6 null mice are sterile without presenting other detectable defects, suggest that these kinases could be used as targets for male contraception. PMID:20729278

  8. Reproductive Organ of Blow Fly, Chrysomya megacephala (Diptera: Calliphoridae): Ultrastructural of Testis

    PubMed Central

    Sukontason, Kabkaew L.; Chaiwong, Tarinee; Chaisri, Urai; Kurahashi, Hiromu; Sanford, Michelle; Sukontason, Kom

    2011-01-01

    This work presents the ultrastructure of testis of the medically important blow fly, Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) using light microscopy and electron microscopy. Reproductive organ of males was dissected to determine the testis in the pupal stage, 3-day-old flies and 7-day-old flies and observed under scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM displayed a smooth surface which is occasionally penetrated by tracheoles. TEM of the testis in the pupal stage presents the thick testis wall covering underdeveloped cells containing a variable size of an electron-dense globule. For the 3-day-old males, the testicular wall is formed by an external layer, a peritoneal sheath, a muscular layer, a basement membrane, and a follicular epithelium. Follicular epithelium presented developing spermatozoa. Regarding the 7-day-old males, development of spermatozoa is apparent, displaying nucleus, centriolar adjunct, axoneme, and mitochondrial derivatives, with the 9 + 9 + 2 microtubule pattern of axoneme. PMID:21845212

  9. Cavernous haemangioma of the testis mimicking testicular malignancy in an adolescent.

    PubMed

    Naveed, S; Quari, H; Sharma, H

    2013-11-01

    Haemangioma of the testis is a rare condition. This benign vascular neoplasm may arise either within the testicular parenchyma (intratesticular) as in this case or from adnexal structures of the testis (extratesticular). Intratesticular haemangioma is rarer than extratesticular form. Intratesticular vascular neoplasms are extremely rare tumours and mostly seen in children or young adults. There are 21 reported testicular haemangioma cases in the literature as indexed in PubMed. Since 2007, only 19 cases of cavernous haemangioma have been reported in the literature in PubMed and other indexed sites. We report a case of cavernous haemangioma of the testis to attract attention to testicular haemangioma and also to prevent invasive surgery of the testis.

  10. Cavernous haemangioma of the testis mimicking testicular malignancy in an adolescent.

    PubMed

    Naveed, S; Quari, H; Sharma, H

    2013-11-01

    Haemangioma of the testis is a rare condition. This benign vascular neoplasm may arise either within the testicular parenchyma (intratesticular) as in this case or from adnexal structures of the testis (extratesticular). Intratesticular haemangioma is rarer than extratesticular form. Intratesticular vascular neoplasms are extremely rare tumours and mostly seen in children or young adults. There are 21 reported testicular haemangioma cases in the literature as indexed in PubMed. Since 2007, only 19 cases of cavernous haemangioma have been reported in the literature in PubMed and other indexed sites. We report a case of cavernous haemangioma of the testis to attract attention to testicular haemangioma and also to prevent invasive surgery of the testis. PMID:24215057

  11. Nuclear Protein of the Testis Midline Carcinoma Masquerading as a Primary Mediastinal Seminoma

    PubMed Central

    Sayapina, Maria S.; Savelov, Nikita A.; Karseladze, Apollon I.; Bulanov, Anatoly A.; Tryakin, Alexey A.; Nosov, Dmitry A.; Garin, Avgust M.; Tjulandin, Sergey A.

    2016-01-01

    Nuclear protein of the testis (NUT) midline carcinomas are rare aggressive carcinomas characterized by chromosomal rearrangements that involve the gene encoding the NUT. This article reviews the clinicopathologic features and the differential diagnosis of these malignancies. PMID:27441078

  12. The total Leydig cell volume of the testis in some common mammals.

    PubMed

    Kothari, L K; Patni, M K; Jain, M L

    1978-01-01

    Total Leydig cell volume has been quantitatively determined by a histometric point-counting method in six common mammals, including man. Although the size of the testis has increased from 1.3 +/- 0.1 ml in the rat to 19.8 +/- 6.9 ml in the buffalo, the composition has remained fairly constant with the Leydig cells making up 9--16% of the testicular volume. In absolute terms, the Total Leydig Volume has increased progressively with body size, from 0.11 +/- 0.02 ml/testis in rat to 2.44 +/- 0.64 ml/testis in buffalo, the value for man being 2.21 +/- 0.40 ml/testis. The significance of these findings, from the point of view of the comparative physiology of male reproduction, has been discussed. PMID:686402

  13. Effects of subchronic samarium exposure on the histopathological structure and apoptosis regulation in mouse testis.

    PubMed

    Zhang, De-Yong; Shen, Xiu-Ying; Ruan, Qin; Xu, Xiao-Lu; Yang, San-Ping; Lu, Yin; Xu, Hui-Ying; Hao, Fei-Lin

    2014-03-01

    To evaluate the reproductive toxicity of samarium, a widely used rare earth element, male ICR mice were orally exposed to samarium nitrate for 90 days for lesion evaluation in the testis. Decreased organ coefficients, disorganized seminiferous tubules, and decreased spermatogenic cells and sperm of the testis were observed extensively in the treated groups, indicating that the testis is a target organ of samarium. Electron microscopy confirmed that the lesions inside the spermatogenic cells and sperm mainly included mitochondrial swelling, mitochondrial vacuolization, fuzzy nuclear membranes, and marginated chromatin. Increased spermatogenic cell apoptosis rate in the testis was confirmed with a TUNEL assay. And expression up-regulation of p53 and Bax, and down-regulation of Bcl-2 were observed (p<0.05), indicating the apoptosis is related to p53 mediated pathway. PMID:24561534

  14. Epidermal Cyst in the Scrotum Successfully Treated while Preserving the Testis: A Case Report

    PubMed Central

    Kondo, Takuya; Kawahara, Takashi; Matsumoto, Taro; Yamamoto, Yuko; Tsutsui, Miho; Ohtani, Masako; Ohtaka, Mari; Kumano, Yohei; Maeda, Yoko; Mochizuki, Taku; Mori, Kohei; Asai, Takuo; Kuroda, Shinnosuke; Takeshima, Teppei; Hattori, Yusuke; Teranishi, Jun-ichi; Miyoshi, Yasuhide; Yumura, Yasushi; Yao, Masahiro; Inayama, Yoshiaki; Uemura, Hiroji

    2016-01-01

    A 66-year-old male was referred to our hospital for further examination of a scrotal mass. Because of the risk of testicular cancer, we first clamped the vessels as a course of higher orchiectomy. Then, we approached the tumor through the scrotum and successfully resected it while preserving the testis. A histopathological diagnosis revealed an epidermal cyst. We herein report a rare case of an intrascrotal epidermal cyst successfully treated while preserving the testis. PMID:27194984

  15. VEGFA: Just one of multiple mechanisms for Sex-Specific Vascular Development within the testis?

    PubMed Central

    Sargent, Kevin M.; McFee, Renee M.; Spuri Gomes, Renata; Cupp, Andrea S.

    2015-01-01

    Testis development from an indifferent gonad is a critical step in embryogenesis. A hallmark of testis differentiation is sex-specific vascularization which occurs as endothelial cells migrate from the adjacent mesonephros into the testis to surround Sertoli-germ cell aggregates and induce seminiferous cord formation. Many in vitro experiments have demonstrated that Vascular Endothelial Growth Factor A (VEGFA) is a critical regulator of this process. Both inhibitors to VEGFA signal transduction and excess VEGFA isoforms in testis organ cultures impaired vascular development and seminiferous cord formation. However, in vivo models using mice which selectively eliminated all VEGFA isoforms: in Sertoli and germ cells (pDmrt1-Cre;Vegfa−/−); Sertoli and Leydig cells (Amhr2-Cre;Vegfa−/−) or Sertoli cells (Amh-Cre;Vegfa−/− and Sry-Cre;Vegfa−/−) displayed testes with observably normal cords and vasculature at postnatal day 0 and onwards. Embryonic testis development may be delayed in these mice; however, the postnatal data indicate that VEGFA isoforms secreted from Sertoli, Leydig or germ cells are not required for testis morphogenesis within the mouse. A Vegfa signal transduction array was employed on postnatal testes from Sry-Cre;Vegfa−/− versus controls. Ptgs1 (Cox1) was the only upregulated gene (5-fold). COX1 stimulates angiogenesis and upregulates, VEGFA, Prostaglandin E2 (PGE2) and PGD2. Thus, other gene pathways may compensate for VEGFA loss, similar to multiple independent mechanisms to maintain SOX9 expression. Multiple independent mechanism that induce vascular development in the testis may contribute to and safeguard the sex-specific vasculature development responsible for inducing seminiferous cord formation, thus, ensuring appropriate testis morphogenesis in the male. PMID:26562337

  16. Plastins regulate ectoplasmic specialization via its actin bundling activity on microfilaments in the rat testis

    PubMed Central

    Li, Nan; Wong, Chris KC; Cheng, C Yan

    2016-01-01

    Plastins are a family of actin binding proteins (ABPs) known to cross-link actin microfilaments in mammalian cells, creating actin microfilament bundles necessary to confer cell polarity and cell shape. Plastins also support cell movement in response to changes in environment, involved in cell/tissue growth and development. They also confer plasticity to cells and tissues in response to infection or other pathological conditions (e.g., inflammation). In the testis, the cell-cell anchoring junction unique to the testis that is found at the Sertoli cell-cell interface at the blood-testis barrier (BTB) and at the Sertoli-spermatid (e.g., 8–19 spermatids in the rat testis) is the basal and the apical ectoplasmic specialization (ES), respectively. The ES is an F-actin-rich anchoring junction constituted most notably by actin microfilament bundles. A recent report using RNAi that specifically knocks down plastin 3 has yielded some insightful information regarding the mechanism by which plastin 3 regulates the status of actin microfilament bundles at the ES via its intrinsic actin filament bundling activity. Herein, we provide a brief review on the role of plastins in the testis in light of this report, which together with recent findings in the field, we propose a likely model by which plastins regulate ES function during the epithelial cycle of spermatogenesis via their intrinsic activity on actin microfilament organization in the rat testis. PMID:26608945

  17. Tissue-Based Proteogenomics Reveals that Human Testis Endows Plentiful Missing Proteins.

    PubMed

    Zhang, Yao; Li, Qidan; Wu, Feilin; Zhou, Ruo; Qi, Yingzi; Su, Na; Chen, Lingsheng; Xu, Shaohang; Jiang, Tao; Zhang, Chengpu; Cheng, Gang; Chen, Xinguo; Kong, Degang; Wang, Yujia; Zhang, Tao; Zi, Jin; Wei, Wei; Gao, Yuan; Zhen, Bei; Xiong, Zhi; Wu, Songfeng; Yang, Pengyuan; Wang, Quanhui; Wen, Bo; He, Fuchu; Xu, Ping; Liu, Siqi

    2015-09-01

    Investigations of missing proteins (MPs) are being endorsed by many bioanalytical strategies. We proposed that proteogenomics of testis tissue was a feasible approach to identify more MPs because testis tissues have higher gene expression levels. Here we combined proteomics and transcriptomics to survey gene expression in human testis tissues from three post-mortem individuals. Proteins were extracted and separated with glycine- and tricine-SDS-PAGE. A total of 9597 protein groups were identified; of these, 166 protein groups were listed as MPs, including 138 groups (83.1%) with transcriptional evidence. A total of 2948 proteins are designated as MPs, and 5.6% of these were identified in this study. The high incidence of MPs in testis tissue indicates that this is a rich resource for MPs. Functional category analysis revealed that the biological processes that testis MPs are mainly involved in are sexual reproduction and spermatogenesis. Some of the MPs are potentially involved in tumorgenesis in other tissues. Therefore, this proteogenomics analysis of individual testis tissues provides convincing evidence of the discovery of MPs. All mass spectrometry data from this study have been deposited in the ProteomeXchange (data set identifier PXD002179).

  18. Simian immunodeficiency virus infection and immune responses in the pig-tailed macaque testis.

    PubMed

    Winnall, Wendy R; Lloyd, Sarah B; De Rose, Robert; Alcantara, Sheilajen; Amarasena, Thakshila H; Hedger, Mark P; Girling, Jane E; Kent, Stephen J

    2015-03-01

    The testis is a site of immune privilege in rodents, and there is evidence that T cell responses are also suppressed in the primate testis. Local immunosuppression is a potential mechanism for HIV persistence in tissue reservoirs that few studies have examined. The response of the pig-tailed macaque testis to SIVmac239 infection was characterized to test this possibility. Testes were surgically removed during early-chronic (10 wk) and late-chronic (24-30 wk) SIV infection in 4 animals and compared with those from 7 uninfected animals. SIV infection caused only minor disruption to the seminiferous epithelium without marked evidence of inflammation or consistent changes in total intratesticular leukocyte numbers. Infection also led to an increase in the relative proportion of testicular effector memory CD8(+) T cell numbers and a corresponding reduction in central memory CD4(+) T cells. A decrease in the relative proportion of resident-type CD163(+) macrophages and DCs was also observed. SIV-specific CD8(+) T cells were detectable in the testis, 10-11 wk after infection by staining with SIV Gag-specific or Tat-specific MHC-I tetramers. However, testicular CD8(+) T cells from the infected animals had suppressed cytokine responses to mitogen activation. These results support the possibility that local immunosuppression in the testis may be restricting the ability of T cells to respond to SIV or HIV infection. Local immunosuppression in the testis may be an underexplored mechanism allowing HIV persistence.

  19. 0610009K11Rik, a testis-specific and germ cell nuclear receptor-interacting protein

    SciTech Connect

    Zhang Heng; Denhard, Leslie A.; Zhou Huaxin; Liu Lanhsin; Lan Zijian

    2008-02-22

    Using an in silico approach, a putative nuclear receptor-interacting protein 0610009K11Rik was identified in mouse testis. We named this gene testis-specific nuclear receptor-interacting protein-1 (Tnrip-1). Tnrip-1 was predominantly expressed in the testis of adult mouse tissues. Expression of Tnrip-1 in the testis was regulated during postnatal development, with robust expression in 14-day-old or older testes. In situ hybridization analyses showed that Tnrip-1 is highly expressed in pachytene spermatocytes and spermatids. Consistent with its mRNA expression, Tnrip-1 protein was detected in adult mouse testes. Immunohistochemical studies showed that Tnrip-1 is a nuclear protein and mainly expressed in pachytene spermatocytes and round spermatids. Moreover, co-immunoprecipitation analyses showed that endogenous Tnrip-1 protein can interact with germ cell nuclear receptor (GCNF) in adult mouse testes. Our results suggest that Tnrip-1 is a testis-specific and GCNF-interacting protein which may be involved in the modulation of GCNF-mediated gene transcription in spermatogenic cells within the testis.

  20. HSL-knockout mouse testis exhibits class B scavenger receptor upregulation and disrupted lipid raft microdomains.

    PubMed

    Casado, María Emilia; Huerta, Lydia; Ortiz, Ana Isabel; Pérez-Crespo, Mirian; Gutiérrez-Adán, Alfonso; Kraemer, Fredric B; Lasunción, Miguel Ángel; Busto, Rebeca; Martín-Hidalgo, Antonia

    2012-12-01

    There is a tight relationship between fertility and changes in cholesterol metabolism during spermatogenesis. In the testis, class B scavenger receptors (SR-B) SR-BI, SR-BII, and LIMP II mediate the selective uptake of cholesterol esters from HDL, which are hydrolyzed to unesterified cholesterol by hormone-sensitive lipase (HSL). HSL is critical because HSL knockout (KO) male mice are sterile. The aim of the present work was to determine the effects of the lack of HSL in testis on the expression of SR-B, lipid raft composition, and related cell signaling pathways. HSL-KO mouse testis presented altered spermatogenesis associated with decreased sperm counts, sperm motility, and infertility. In wild-type (WT) testis, HSL is expressed in elongated spermatids; SR-BI, in Leydig cells and spermatids; SR-BII, in spermatocytes and spermatids but not in Leydig cells; and LIMP II, in Sertoli and Leydig cells. HSL knockout male mice have increased expression of class B scavenger receptors, disrupted caveolin-1 localization in lipid raft plasma membrane microdomains, and activated phospho-ERK, phospho-AKT, and phospho-SRC in the testis, suggesting that class B scavenger receptors are involved in cholesterol ester uptake for steroidogenesis and spermatogenesis in the testis.

  1. Characteristics of spermatogonial stem cells derived from neonatal porcine testis.

    PubMed

    Shi, R; Bai, Y; Li, S; Wei, H; Zhang, X; Li, L; Tian, X C; Jiang, Q; Wang, C; Qin, L; Cai, J; Zhang, S

    2015-09-01

    The aim of this study was to isolate and characterise porcine spermatogonial stem cells (PSSCs). The putative porcine germline stem cells from testis were isolated successfully by an improving way of enrichment with lymphocyte separation medium (LSM). Results from RT-PCR analyses showed that PSSCs were positive for OCT4, SOX2, NANOG, PGP9.5, c-MYC, KEL4 and PRDM-14 which are multipotent stem cell markers. At the protein level, the results of immunofluorescence analyses showed that PSSCs were positive for OCT4, PGP9.5, SOX2 and CD29. We successfully differentiated these PSSCs into adipocytes and muscle cells and then defined their characteristics, including morphology, surface stem cell markers, and mechanical properties. But the experiment of teratoma formation was negative. The results indicated the PSSCs could be multipotent. Atomic force microscopy was used to characterise the morphological and mechanical properties of undifferentiated PSSCs, as well as the differentiated adipocytes and muscle cells, which could be potentially useful for distinguishing PSSCs from differentiated cells.

  2. Testicular function following irradiation of the human prepubertal testis.

    PubMed

    Shalet, S M; Beardwell, C G; Jacobs, H S; Pearson, D

    1978-12-01

    Testicular function was studied in ten men, aged between 17 and 36 years, who had received irradiation for a nephroblastoma during childhood. The dose of scattered irradiation to the testes ranged from 268 to 983 rad. Eight subjects had either oligo- or azoospermia (0 to 5.6 million/ml), seven of whom had an elevated serum follicle-stimulating hormone (FSH) level. One subject showed evidence of Leydig cell dysfunction with a raised serum luteinizing hormone level (LH) and a low plasma testosterone concentration. A second group of eight prepubertal males, aged between 8 and 14 years, were studied. These had also been irradiated for abdominal malignancies during childhood and received a similar dose of irradiation to the testis as the first group studied. The plasma testosterone levels were within the normal range for prepubertal boys in all eight. The mean gonadotrophin levels were not significantly different from the mean levels of normal prepubertal males. Thus irradiation-induced damage to the germinal epithelium in prepubertal boys produces raised FSH levels after puberty but not before it. We conclude, therefore, that inhibition has a minor role in the control of the prepubertal hypothalamic-pituitary testicular axis and its contribution to gonadal control of gonadotrophin secretion changes with sexual maturation.

  3. Sertoliform cystadenoma: a rare benign tumour of the rete testis

    PubMed Central

    2013-01-01

    Abstract Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335 PMID:23406299

  4. Testicular Ectopia in the Anterior Abdominal Wall of a Neonate: A Rare Site of Ectopic Testis

    PubMed Central

    Siddiqui, Salman Atiq; Marei, Tamer Ibrahim; Al-Makhaita, Ghada

    2016-01-01

    Patient: Male, 3-day Final Diagnosis: Ectopic right testis in anterior abdominal wall Symptoms: — Medication: — Clinical Procedure: Testicular ultrasound and MRI abdomen Specialty: Radiology Objective: Unusual clinical course Background: Abnormal testicular descent can either be undescended or, less commonly, ectopic. Most undescended testes complete the course of descent by the first year of life only if these remain in the normal path of descent. The deviation of the testis may occur to an ectopic location during the transinguinal phase. Of the known ectopic sites, the anterior abdominal wall is the rarest site of testicular ectopia and to our knowledge only 3 cases of this nature have been reported in the available literature to date. Case Report: This rare case of testicular ectopia occurred in a 3-day-old boy in whom the right scrotal sac was empty; on abdominal ultrasound, the right testis was found in the subcutaneous tissues of the right antero-lateral abdominal wall. These findings were confirmed on abdominal MRI, where the right testis was seen beneath the skin between the subcutaneous tissues and external oblique aponeurosis. No aponeurotic or muscular defect was appreciable under the abdominal wall. The neonate underwent orchiopexy at the age of 6 months and remained uneventful postoperatively. Conclusions: Preoperative imaging is recommended to detect and confirm the ectopic site as well as the morphology of testis, thereby increasing the chance of surveillance and preservation of an ectopic testis. Imaging can serve as preoperative road mapping to localize the exact site for surgical exploration of an ectopic testis if there is no apparent or palpable swelling over the anterior abdominal wall. PMID:27411886

  5. The Type 3 Deiodinase Is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis.

    PubMed

    Martinez, M Elena; Karaczyn, Aldona; Stohn, J Patrizia; Donnelly, William T; Croteau, Walburga; Peeters, Robin P; Galton, Valerie A; Forrest, Douglas; St Germain, Donald; Hernandez, Arturo

    2016-03-01

    Timely and appropriate levels of thyroid hormone (TH) signaling are necessary to ensure normal developmental outcomes in many tissues. Studies using pharmacological models of altered TH status have revealed an influence of these hormones on testis development and size, but little is known about the role of endogenous determinants of TH action in the developing male gonads. Using a genetic approach, we demonstrate that the type 3 deiodinase (D3), which inactivates TH and protects developing tissues from undue TH action, is a key factor. D3 is highly expressed in the developing testis, and D3-deficient (D3KO) mice exhibit thyrotoxicosis and cell proliferation arrest in the neonatal testis, resulting in an approximately 75% reduction in testis size. This is accompanied by larger seminiferous tubules, impaired spermatogenesis, and a hormonal profile indicative of primary hypogonadism. A deficiency in the TH receptor-α fully normalizes testis size and adult testis gene expression in D3KO mice, indicating that the effects of D3 deficiency are mediated through this type of receptor. Similarly, genetic deficiencies in the D2 or in the monocarboxylate transporter 8 partially rescue the abnormalities in testis size and gonadal axis gene expression featured in the D3KO mice. Our study highlights the testis as an important tissue in which determinants of TH action coordinately converge to ensure normal development and identifies D3 as a critical factor in testis development and in testicular protection from thyrotoxicosis. PMID:26727108

  6. [Status quo of the researches on the biological effect of electromagnetic radiation on the testis and epididymal sperm].

    PubMed

    Gao, Xiao-fang; Wang, Shui-ming; Peng, Rui-yun

    2007-09-01

    The testis is highly sensitive to electromagnetic radiation. Sperm is the passer of male genetic material and electromagnetic radiation may cause structural and functional injury to the testis, including motility reduction, abnormality increase and ultrastructural alteration of epididymal sperm. Energy metabolism disorder in spermatogenic cells, enhancement of lipid peroxidation in the testis, excessive expression of inflammatory factors and abnormality of genetic transcription may be responsible for injury to the testis and epididymal sperm. This paper reviews the progress made in this field and the preventive measures against the injury.

  7. Genetic ablation of androgen receptor signaling in fetal Leydig cell lineage affects Leydig cell functions in adult testis.

    PubMed

    Kaftanovskaya, Elena M; Lopez, Carolina; Ferguson, Lydia; Myhr, Courtney; Agoulnik, Alexander I

    2015-06-01

    It is commonly accepted that androgen-producing fetal Leydig cells (FLC) are substituted by adult Leydig cells (ALC) during perinatal testis development. The mechanisms influencing this process are unclear. We used mice with a retinoid acid receptor 2 promoter-Cre recombinase transgene (Rarb-cre) expressed in embryonic FLC precursors, but not in postnatal testis, and a dual fluorescent Cre recombinase reporter to label FLC and ALC in vivo. All FLC in newborn testis had the recombinant, whereas the majority of LC in adult testis had the nonrecombinant reporter. Primary LC cultures from adult testis had either recombinant (20%) or nonrecombinant (80%) cells, demonstrating that the FLC survive in adult testis and their ontogeny is distinct from ALC. Conditional inactivation of androgen receptor (AR) allele using the Rarb-cre transgene resulted in a 50% increase of AR-negative LC in adult testis. The mutant males became infertile with age, with all LC in older testis showing signs of incomplete differentiation, such as a large number of big lipid droplets, an increase of finger-like protrusions, and a misexpression of steroidogenic or FLC- and ALC-specific genes. We propose that the antiandrogenic exposure during early development may similarly result in an increase of FLC in adult testis, leading to abnormal LC differentiation.

  8. The Type 3 Deiodinase Is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis.

    PubMed

    Martinez, M Elena; Karaczyn, Aldona; Stohn, J Patrizia; Donnelly, William T; Croteau, Walburga; Peeters, Robin P; Galton, Valerie A; Forrest, Douglas; St Germain, Donald; Hernandez, Arturo

    2016-03-01

    Timely and appropriate levels of thyroid hormone (TH) signaling are necessary to ensure normal developmental outcomes in many tissues. Studies using pharmacological models of altered TH status have revealed an influence of these hormones on testis development and size, but little is known about the role of endogenous determinants of TH action in the developing male gonads. Using a genetic approach, we demonstrate that the type 3 deiodinase (D3), which inactivates TH and protects developing tissues from undue TH action, is a key factor. D3 is highly expressed in the developing testis, and D3-deficient (D3KO) mice exhibit thyrotoxicosis and cell proliferation arrest in the neonatal testis, resulting in an approximately 75% reduction in testis size. This is accompanied by larger seminiferous tubules, impaired spermatogenesis, and a hormonal profile indicative of primary hypogonadism. A deficiency in the TH receptor-α fully normalizes testis size and adult testis gene expression in D3KO mice, indicating that the effects of D3 deficiency are mediated through this type of receptor. Similarly, genetic deficiencies in the D2 or in the monocarboxylate transporter 8 partially rescue the abnormalities in testis size and gonadal axis gene expression featured in the D3KO mice. Our study highlights the testis as an important tissue in which determinants of TH action coordinately converge to ensure normal development and identifies D3 as a critical factor in testis development and in testicular protection from thyrotoxicosis.

  9. TGF-β superfamily signaling in testis formation and early male germline development.

    PubMed

    Young, Julia C; Wakitani, Shoichi; Loveland, Kate L

    2015-09-01

    The TGF-β ligand superfamily contains at least 40 members, many of which are produced and act within the mammalian testis to facilitate formation of sperm. Their progressive expression at key stages and in specific cell types determines the fertility of adult males, influencing testis development and controlling germline differentiation. BMPs are essential for the interactive instructions between multiple cell types in the early embryo that drive initial specification of gamete precursors. In the nascent foetal testis, several ligands including Nodal, TGF-βs, Activins and BMPs, serve as key masculinizing switches by regulating male germline pluripotency, somatic and germline proliferation, and testicular vascularization and architecture. In postnatal life, local production of these factors determine adult testis size by regulating Sertoli cell multiplication and differentiation, in addition to specifying germline differentiation and multiplication. Because TGF-β superfamily signaling is integral to testis formation, it affects processes that underlie testicular pathologies, including testicular cancer, and its potential to contribute to subfertility is beginning to be understood.

  10. Identification of conservative microRNAs in Saanen dairy goat testis through deep sequencing.

    PubMed

    Wu, J; Zhu, H; Song, W; Li, M; Liu, C; Li, N; Tang, F; Mu, H; Liao, M; Li, X; Guan, W; Li, X; Hua, J

    2014-02-01

    MicroRNA (miRNA) is a kind of small non-coding RNA molecules that function as important gene expression regulators by targeting messenger RNAs for post-transcriptional endonucleolytic cleavage or translational inhibition. In this study, small RNA libraries were constructed based on adult dairy goat testicular tissues and sequenced using the Illumina high-throughput sequencing technology. Blasted to miRNAs of cow and sheep in miRBase 19.0, 373 conserved miRNAs were identified in dairy goat testis and 91 novel paired-miRNAs were found. Expression of miRNAs in the dairy goat testis (miR-10b, miR-126-3p, miR-126-5p, miR-34c, miR-449b and miR-1468) was confirmed by qRT-PCR. In addition, the 128 conserved miRNAs were found by comparing the miRNA expression profiles in dairy goat testis with those in cow and mouse, which all might be involved in dairy goat testis development and meiosis. This study reveals the first miRNA profile related to the biology of testis in the dairy goat. The characterization of these miRNAs could contribute to a better understanding of the molecular mechanisms of reproductive physiology and development in the dairy goat.

  11. Simulated microgravity activates apoptosis and NF-κB in mice testis

    PubMed Central

    Sharma, Chidananda S.; Sarkar, Shubhashish; Periyakaruppan, Adaikkappan; Ravichandran, Prabakaran; Sadanandan, Bindu; Ramesh, Vani; Thomas, Renard; Hall, Joseph C.; Wilson, Bobby L.

    2009-01-01

    Microgravity is known to have significant effect on all aspects of reproductive function in animal models. Recent studies have also shown that microgravity induces changes at the cellular level, including apoptosis. Our effort here was to study the effect of simulated microgravity on caspase-8 and the caspase-3 activities, the effectors of the apoptotic pathway and on the transcription factor NF-κB a signaling molecule in mouse testis. Morey-Holton hind limb suspension model was used to simulate microgravity. Caspase-8 and 3 fluorometric assays were carried out and HLS mice testis exhibited a 51% increase in caspase-8 and caspase-3 compared to the controls. A sandwich ELISA-based immunoassay was carried out for detection of NF-κB which again significantly increased in the test mice. Testosterone levels were measured using an ELISA kit and in HLS mice the decrease was significant. There was also a significant decrease in testis weight in the test mice. Simulated microgravity activates caspase 8, 3 and NF-κB necessary to stimulate the apoptotic pathway in mice testis. This may account for the drop in testis weight and testosterone level further affecting testicular physiology and function. PMID:18385949

  12. Localization and Characterization of Rat Transmembrane Protein 225 Specifically Expressed in Testis

    PubMed Central

    Yang, Shirui; Wang, Weiping; Lei, Chen; Liu, Qingmei; Xu, Fengqin; Xing, Xiaowei; Chen, Hao; Liu, Jiajia; Wu, Shiliang

    2011-01-01

    Testis is the one and only location of spermatogenesis and sexual hormone production. Spermatogenesis is a complicated physiological process regulated by many genes specifically and differentially expressed in the testis. In this study, Transmembrane Protein 225 (TMEM225), which is specifically expressed in rat testis, has been identified. TMEM225 was cloned from the testis cDNA library and was mapped to chromosome 8q22 by browsing the University of California Santa Cruz genomic database. It contains an open reading frame with a length of 696 bp, encoding a protein with four putative transmembrane helices. TMEM225 mRNA expression was evaluated by reverse transcription–polymerase chain reaction and in situ hybridization. In addition, the subcellular location of TMEM225 was evaluated. The results obtained highlighted age related specific expression of TMEM225 in testis, specifically during the adult period after age of 13 months. In situ hybridization analysis indicated that TMEM225 mRNA was mainly expressed in spermatocyte cells and round spermatids. Green fluorescence protein localization analysis showed that rat TMEM225 mainly surrounded the nuclear membrane, with a minority distribution in the cytoplasm, and the distribution of TMEM225 was affected by the deletion of N-terminal transmembrane domain. As the expression phase is not related to the first wave of spermatozoon development, our data presented here suggest that TMEM225 may play an important role in sperm degeneration but not in spermatogenesis. PMID:20979528

  13. Protective effect of Zingiber officinale extract on rat testis after cyclophosphamide treatment.

    PubMed

    Mohammadi, F; Nikzad, H; Taghizadeh, M; Taherian, A; Azami-Tameh, A; Hosseini, S M; Moravveji, A

    2014-08-01

    Decreasing the side effects of chemotherapy in testis has been the subjects of many studies. In this study, the protective effects of Zingiber officinale extract on rat testis were investigated after chemotherapy with cyclophosphamide. Histological and biochemical parameters were compared in cyclophosphamide-treated rats with or without ginger extract intake. Wistar male rats were randomly divided into four groups each 10. The control group received a single injection of 1 ml isotonic saline intraperitoneally. The Cyclophosphamide (CP) group received a single dose of cyclophosphamide (100 mg kg(-1) BW) intraperitoneally. CP + 300 and CP + 600 groups received orally 300 or 600 mg of ginger extract, respectively, for a period of 6 weeks after cyclophosphamide injection. The morphologic and histological structure of the testis was compared in different groups of the rats. Also, factors like malondialdehyde, reactive oxygen species, total antioxidant capacity and testosterone level were assessed in blood serum as well. Our results showed that although ginger extract could not change testis weight, malondialdehyde (MDA) and ROS, but antioxidant and testosterone levels in serum were increased significantly. Also, an obvious improved histological change was seen in CP + 300 and CP + 600 groups in comparison with CP group. These protective effects of ginger on rat testis after cyclophosphamide treatment could be attributed to the higher serum level of antioxidants.

  14. Dosimetry for a study of effects of 2. 45-GHz microwaves on mouse testis

    SciTech Connect

    Cairnie, A.B.; Hill, D.A.; Assenheim, H.M.

    1980-01-01

    In order to determine the effects of microwave radiation on the testis, it is necessary to express the physical insult in animal studies in a way that can be replicated elsewhere and ultimately used as a basis for extrapolation to man. However, there is conflict--especially in chronic experiments--between the desire for precise dosimetry and the need to minimise alteration of the normal physiological functions of the animals. The compromise arrangement used in this study was to house the mice singly, in cages with limited food and water, and to irradiate them for up to 30 days (16 h/day) in an anechoic chamber. The only measurements taken routinely were of power density in the positions normally occupied by the cages. In addition, a series of absorption measurements was made in mouse carcasses: Whole-body specific absorption rate (SAR); energy-deposition patterns (determined thermographically); and local SAR in testis (using a miniature electric (E)-field probe). It was concluded that the SAR in testis was considerably less than the whole-body SAR. Exposure for 16 h at 50 mW/cm2 elevated rectal but not testis temperature, thus demonstrating the ability of the conscious mouse to regulate the temperature of its testis.

  15. Trace elemental analysis in cancer-afflicted tissues of penis and testis by PIXE technique

    NASA Astrophysics Data System (ADS)

    Naga Raju, G. J.; John Charles, M.; Bhuloka Reddy, S.; Sarita, P.; Seetharami Reddy, B.; Rama Lakshmi, P. V. B.; Vijayan, V.

    2005-04-01

    PIXE technique was employed to estimate the trace elemental concentrations in the biological samples of cancerous penis and testis. A 3 MeV proton beam was employed to excite the samples. From the present results it can be seen that the concentrations of Cl, Fe and Co are lower in the cancerous tissue of the penis when compared with those in normal tissue while the concentrations of Cu, Zn and As are relatively higher. The concentrations of K, Ca, Ti, Cr, Mn, Br, Sr and Pb are in agreement within standard deviations in both cancerous and normal tissues. In the cancerous tissue of testis, the concentrations of K, Cr and Cu are higher while the concentrations of Fe, Co and Zn are lower when compared to those in normal tissue of testis. The concentrations of Cl, Ca, Ti and Mn are in agreement in both cancerous and normal tissues of testis. The higher levels of Cu lead to the development of tumor. Our results also support the underlying hypothesis of an anticopper, antiangiogenic approach to cancer therapy. The Cu/Zn ratios of both penis and testis were higher in cancer tissues compared to that of normal.

  16. Can Hypertrophy of the Contralateral Testis Predict the Absence of a Viable Testis in Infancy with Cryptorchidism: A Prospective Analysis.

    PubMed

    Son, Hee Seo; Lee, Yong Seung; Im, Young Jae; Kim, Sang Woon; Chi, Byung Hoon; Han, Sang Won

    2016-01-01

    This prospective study aimed to evaluate whether Contralateral compensatory testicular hypertrophy (CTH) is valid as a predictive tool for a non-viable testis in children aged between 6 and 18 months, and whether CTH is affected by mini-puberty. Seventy-two testes from 60 boys aged between 6 and 18 months were categorized into three groups: 24 testes contralateral to surgically removed non-viable testes (NVTs), 24 testes contralateral to surgically corrected undescended testes (UDTs), and 24 testes from a normal controls. Contralateral testicular length and volume were measured with ultrasonography and compared among the groups. Group 1 (NVT) had a significantly longer length and larger volume than group 2 (UDT). The length and volume of each group among three developmental periods (6-10, 10-14, and 14-18 months) were also analyzed. In the controls, the length was significantly larger at 6-10 months than at 10-14 months in accordance with previously reported changes in testicular size due to the effect of "mini-puberty." The volume of controls showed a similar pattern, though without statistical significance. However, this pattern was not observed in the NVT and UDT groups. A receiver operating curve revealed that a testicular length of 16.1 mm or a volume of 0.59 ml had the highest sensitivity and specificity for predicting NVTs. The CTH was also found to be valid as a predictive tool for a NVT in children of ages 6 to 18 months, as the effect of mini-puberty appeared to be absent in the NVT and UDT groups. However, the cut-off values were less than those of previous reports. The proper cut-off level according to the age and measurement method should be applied in this developmental period.

  17. Induced malignant genome reprogramming in somatic cells by testis-specific factors.

    PubMed

    Wang, Jin; Emadali, Anouk; Le Bescont, Aurore; Callanan, Mary; Rousseaux, Sophie; Khochbin, Saadi

    2011-01-01

    Germline cell differentiation is controlled by a specific set of genes whose expression is tightly locked into the repressed state in somatic cells. Large-scale epigenome alterations, now evidenced in nearly all cancers, lead to aberrant activation of these normally silenced genes, as attested by the many reports describing the expression of testis-specific factors, known as cancer-testis genes, in various cancer cells. Here, based on the literature, we argue that off-context activity of some of the testis-specific epigenome regulators can reprogram the somatic cell epigenome toward a malignant state by favoring self-renewal and sustaining cell proliferation under stressful conditions, thereby constituting a major oncogenic mechanism.

  18. Effects of silver nanoparticles on neonatal testis development in mice

    PubMed Central

    Zhang, Xi-Feng; Gurunathan, Sangiliyandi; Kim, Jin-Hoi

    2015-01-01

    Background Metal nanoparticles (MNPs) play an important role in consumer products. An increasing use of MNPs has raised concerns about potential risks for human health. Therefore, in vivo tests of MNPs are urgently required. Using mice as a model animal, the aim of the present study was designed to investigate the effect of biologically synthesized silver nanoparticles (AgNPs) on spermatogenesis in neonatal mice. Methods AgNPs were synthesized using Bacillus funiculus. The prepared nanoparticles were characterized using various analytical techniques such as UV–visible spectroscopy, X-ray diffraction, Fourier transform-infrared spectroscopy, and transmission electron microscopy. The prepared AgNPs were used to investigate testis development in neonatal mice. Institute of Cancer Research neonatal male mice were used in all experiments and were treated with different doses (0, 1, and 5 mg/kg) of AgNPs five times (interval of 3 days from postnatal day [PND] 8–21) by abdominal subcutaneous injection. Results The results showed that the sperm abnormalities such as quality and quantity were significantly increased by the synthesized AgNPs. The diameter of the convoluted tubules shrank significantly in mice treated with AgNPs on PND28 and PND42. The results of reverse transcription-quantitative polymerase chain reaction indicated that the E1f1ay, Gsta4, and Fdx1 genes were up-regulated, and the Amh, Cx43, and Claudin-11 genes were down-regulated in response to AgNPs exposure on PND28; however, these genes recovered at PND60. AgNPs had no effect on the recombination levels of chromosomes in germ cells. Conclusion These results demonstrated the adverse effects of AgNPs on the male reproductive tract, particularly spermatogenesis and the quality of sperm. This study suggests that the development of nanomaterials should be safer and non-toxic to the living organisms and the potential reprotoxicity of AgNPs should be investigated more carefully. PMID:26491295

  19. Transgenic characterization of two testis-specific promoters in the silkworm, Bombyx mori.

    PubMed

    Xu, J; Bi, H; Chen, R; Aslam, A F M; Li, Z; Ling, L; Zeng, B; Huang, Y; Tan, A

    2015-04-01

    Sex-specific regulatory elements are key components for developing insect genetic sexing systems. The current insect genetic sexing system mainly uses a female-specific modification system whereas little success was reported on male-specific genetic modification. In the silkworm Bombyx mori, a lepidopteran model insect with economic importance, a transgene-based, female-specific lethality system has been established based on sex-specific alternative splicing factors and a female-specific promoter BmVgp (vitellogenin promoter) has been identified. However, no male-specific regulatory elements have yet been identified. Here we report the transgenic identification of two promoters that drive reporter gene expression in a testis-specific manner in B. mori. Putative promoter sequences from the B. mori Radial spoke head 1 gene (BmR1) and beta-tubulin 4 gene (Bmβ4) were introduced using piggybac-based germline transformation. In transgenic silkworms, expression of the reporter gene enhanced green fluorescent protein (EGFP) directed by either BmR1 promoter (BmR1p) or Bmβ4p showed precisely testis-specific manners from the larval to adult stage. Furthermore, EGFP expression of these two transgenic lines showed different localization in the testis, indicating that BmR1p or Bmβ4p might be used as distinct regulatory elements in directing testis-specific gene expression. Identification of these testis-specific promoters not only contributes to a better understanding of testis-specific gene function in insects, but also has potential applications in sterile insect techniques for pest management.

  20. Beyond Testis Size: Links between Spermatogenesis and Sperm Traits in a Seasonal Breeding Mammal.

    PubMed

    Pintus, Eliana; Ros-Santaella, José Luis; Garde, José Julián

    2015-01-01

    Spermatogenesis is a costly process that is expected to be under selection to maximise sperm quantity and quality. Testis size is often regarded as a proxy measure of sperm investment, implicitly overlooking the quantitative assessment of spermatogenesis. An enhanced understanding of testicular function, beyond testis size, may reveal further sexual traits involved in sperm quantity and quality. Here, we first estimated the inter-male variation in testicular function and sperm traits in red deer across the breeding and non-breeding seasons. Then, we analysed the relationships between the testis mass, eight parameters of spermatogenic function, and seven parameters of sperm quality. Our findings revealed that the Sertoli cell number and function parameters vary greatly between red deer males, and that spermatogenic activity co-varies with testis mass and sperm quality across the breeding and non-breeding seasons. For the first time in a seasonal breeder, we found that not only is the Sertoli cell number important in determining testis mass (r = 0.619, p = 0.007 and r = 0.248, p = 0.047 for the Sertoli cell number assessed by histology and cytology, respectively), but also sperm function (r = 0.703, p = 0.002 and r = 0.328, p = 0.012 for the Sertoli cell number assessed by histology and cytology, respectively). Testicular histology also revealed that a high Sertoli cell number per tubular cross-section is associated with high sperm production (r = 0.600, p = 0.009). Sperm production and function were also positively correlated (r = 0.384, p = 0.004), suggesting that these traits co-vary to maximise sperm fertilisation ability in red deer. In conclusion, our findings contribute to the understanding of the dynamics of spermatogenesis, and reveal new insights into the role of testicular function and the Sertoli cell number on testis size and sperm quality in red deer.

  1. The effect of melatonin on acetylsalicylic acid-induced kidney and testis damage.

    PubMed

    Altintas, R; Polat, A; Parlakpinar, H; Vardi, N; Beytur, A; Oguz, F; Sagir, M; Yildiz, A; Duran, Z R

    2014-04-01

    The aim of this study was to evaluate the acute effect of high-dose acetylsalicylic acid (ASA) on kidney and testis, and the potential protective and therapeutic effects of melatonin on ASA-related pathology. A total of 40 rats were randomly divided into the following 5 groups (n = 8): group 1: control, not given any drug; group 2: only 200 mg/kg ASA was given; group 3: 5 mg/kg melatonin was given 45 min before administering 200 mg/kg ASA; group 4: 5 mg/kg melatonin was given 45 min after administering 200 mg/kg ASA; and group 5: only 5 mg/kg melatonin was given. The histopathological changes and the biochemical findings; such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), reduced glutathione (GSH), and blood urea nitrogen (BUN) as well as serum creatinine (Cr) levels were evaluated. ASA significantly increased MDA levels in both kidney and testis, whereas it significantly decreased the values of SOD, CAT, GPX, and GSH in kidney and CAT levels in testis. Melatonin significantly decreased MDA levels in kidney and ameliorated it in testis, whereas it caused elevation in the levels of antioxidants. BUN and Cr levels were higher after ASA, whereas these levels were diminished after melatonin administration. The improvement obtained by melatonin on ASA-induced histological alterations was more prominent when it was used after ASA in kidney and before ASA in testis. In this study, we demonstrated the beneficial effect of melatonin on high-dose ASA-related pathology of kidney and testis for the first time.

  2. Beyond Testis Size: Links between Spermatogenesis and Sperm Traits in a Seasonal Breeding Mammal

    PubMed Central

    Pintus, Eliana; Ros-Santaella, José Luis; Garde, José Julián

    2015-01-01

    Spermatogenesis is a costly process that is expected to be under selection to maximise sperm quantity and quality. Testis size is often regarded as a proxy measure of sperm investment, implicitly overlooking the quantitative assessment of spermatogenesis. An enhanced understanding of testicular function, beyond testis size, may reveal further sexual traits involved in sperm quantity and quality. Here, we first estimated the inter-male variation in testicular function and sperm traits in red deer across the breeding and non-breeding seasons. Then, we analysed the relationships between the testis mass, eight parameters of spermatogenic function, and seven parameters of sperm quality. Our findings revealed that the Sertoli cell number and function parameters vary greatly between red deer males, and that spermatogenic activity co-varies with testis mass and sperm quality across the breeding and non-breeding seasons. For the first time in a seasonal breeder, we found that not only is the Sertoli cell number important in determining testis mass (r = 0.619, p = 0.007 and r = 0.248, p = 0.047 for the Sertoli cell number assessed by histology and cytology, respectively), but also sperm function (r = 0.703, p = 0.002 and r = 0.328, p = 0.012 for the Sertoli cell number assessed by histology and cytology, respectively). Testicular histology also revealed that a high Sertoli cell number per tubular cross-section is associated with high sperm production (r = 0.600, p = 0.009). Sperm production and function were also positively correlated (r = 0.384, p = 0.004), suggesting that these traits co-vary to maximise sperm fertilisation ability in red deer. In conclusion, our findings contribute to the understanding of the dynamics of spermatogenesis, and reveal new insights into the role of testicular function and the Sertoli cell number on testis size and sperm quality in red deer. PMID:26430740

  3. Transgenic characterization of two testis-specific promoters in the silkworm, Bombyx mori.

    PubMed

    Xu, J; Bi, H; Chen, R; Aslam, A F M; Li, Z; Ling, L; Zeng, B; Huang, Y; Tan, A

    2015-04-01

    Sex-specific regulatory elements are key components for developing insect genetic sexing systems. The current insect genetic sexing system mainly uses a female-specific modification system whereas little success was reported on male-specific genetic modification. In the silkworm Bombyx mori, a lepidopteran model insect with economic importance, a transgene-based, female-specific lethality system has been established based on sex-specific alternative splicing factors and a female-specific promoter BmVgp (vitellogenin promoter) has been identified. However, no male-specific regulatory elements have yet been identified. Here we report the transgenic identification of two promoters that drive reporter gene expression in a testis-specific manner in B. mori. Putative promoter sequences from the B. mori Radial spoke head 1 gene (BmR1) and beta-tubulin 4 gene (Bmβ4) were introduced using piggybac-based germline transformation. In transgenic silkworms, expression of the reporter gene enhanced green fluorescent protein (EGFP) directed by either BmR1 promoter (BmR1p) or Bmβ4p showed precisely testis-specific manners from the larval to adult stage. Furthermore, EGFP expression of these two transgenic lines showed different localization in the testis, indicating that BmR1p or Bmβ4p might be used as distinct regulatory elements in directing testis-specific gene expression. Identification of these testis-specific promoters not only contributes to a better understanding of testis-specific gene function in insects, but also has potential applications in sterile insect techniques for pest management. PMID:25387604

  4. Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration

    PubMed Central

    Barrionuevo, Francisco J; Hurtado, Alicia; Kim, Gwang-Jin; Real, Francisca M; Bakkali, Mohammed; Kopp, Janel L; Sander, Maike; Scherer, Gerd; Burgos, Miguel; Jiménez, Rafael

    2016-01-01

    The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8 are required for postnatal male fertility, but their role in the adult testis has not been investigated. Here we show that after ablation of Sox9 in Sertoli cells of adult, fertile Sox8-/- mice, testis-to-ovary genetic reprogramming occurs and Sertoli cells transdifferentiate into granulosa-like cells. The process of testis regression culminates in complete degeneration of the seminiferous tubules, which become acellular, empty spaces among the extant Leydig cells. DMRT1 protein only remains in non-mutant cells, showing that SOX9/8 maintain Dmrt1 expression in the adult testis. Also, Sox9/8 warrant testis integrity by controlling the expression of structural proteins and protecting Sertoli cells from early apoptosis. Concluding, this study shows that, in addition to its crucial role in testis development, Sox9, together with Sox8 and coordinately with Dmrt1, also controls adult testis maintenance. DOI: http://dx.doi.org/10.7554/eLife.15635.001 PMID:27328324

  5. Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration.

    PubMed

    Barrionuevo, Francisco J; Hurtado, Alicia; Kim, Gwang-Jin; Real, Francisca M; Bakkali, Mohammed; Kopp, Janel L; Sander, Maike; Scherer, Gerd; Burgos, Miguel; Jiménez, Rafael

    2016-01-01

    The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8 are required for postnatal male fertility, but their role in the adult testis has not been investigated. Here we show that after ablation of Sox9 in Sertoli cells of adult, fertile Sox8(-/-) mice, testis-to-ovary genetic reprogramming occurs and Sertoli cells transdifferentiate into granulosa-like cells. The process of testis regression culminates in complete degeneration of the seminiferous tubules, which become acellular, empty spaces among the extant Leydig cells. DMRT1 protein only remains in non-mutant cells, showing that SOX9/8 maintain Dmrt1 expression in the adult testis. Also, Sox9/8 warrant testis integrity by controlling the expression of structural proteins and protecting Sertoli cells from early apoptosis. Concluding, this study shows that, in addition to its crucial role in testis development, Sox9, together with Sox8 and coordinately with Dmrt1, also controls adult testis maintenance. PMID:27328324

  6. A study of the rete testis epithelium in several wild birds.

    PubMed

    Barker, S G; Kendall, M D

    1984-01-01

    Material from six wild non-breeding starlings (Sturnus vulgaris), twelve adult wild quelea (Quelea quelea) in prenuptial, full and post-breeding condition and one wild puffin (Fratercula arctica) was examined by light and electron microscopy. Contrary to previous accounts of avian material, the epithelium of the rete testis was composed of a mixture of numerous non-ciliated and fewer ciliated cells. Both cell types contained many inclusions in the cytoplasm all of which indicated that the cells could modify the luminal contents. All rete testis epithelial cells showed a strong reaction with stains for alkaline phosphatase. PMID:6706832

  7. Histometric Analysis of the Effects of Reserpine on the Interstital Cells of the Rat Testis

    PubMed Central

    Dias, P. L. R.

    1982-01-01

    Reserpine is known to block luteinizing hormone (LH) release and by this action to inhibit ovulation, delay implantation and cause abortion in rats. A histometric technique was applied to estimate quantitatively the changes in the density of rat testis interstitial cells after the injection of a fixed dose of reserpine over a varying period of time. A significant decrease in the density of the interstitial cell population was observed in relation to the duration of treatment with reserpine. Reserpine appears to produce atrophy of the interstitial cells of the testis possibly due to its LH-inhibiting action. PMID:7171476

  8. Ultrastructure of the testis in rats with blood hypertension induced by long-term lead exposure.

    PubMed

    Boscolo, P; Carmignani, M; Sacchettoni-Logroscino, G; Rannelletti, F O; Artese, L; Preziosi, P

    1988-05-01

    Male Sprague-Dawley rats received 60 micrograms/ml of lead (as acetate) in drinking water for 18 months. Their blood pressure and cardiac inotropism were increased. Lead was augmented in blood, kidney and brain, but not in testis. Examination by light microscopy of the organs did not reveal alterations. Ultrastructural examination of the testis with both transmission and scanning electron microscopy (EM) did not evidence modifications in the external part of the seminiferous tubules, in the spermatogenetic cells and in the connective tissue including the Leydig cells; only Sertoli cells presented increased size of lysosomes.

  9. CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway Critical for Spermatogenesis

    PubMed Central

    Huijuan, Liao; Jiang, Xie; Ming, Yang; Huaqin, Sun; Wenming, Xu

    2016-01-01

    Cystic fibrosis is the most common genetic disease among Caucasians and affects tissues including lung, pancreas and reproductive tracts. It has been shown that Endoplasmic Reticulum (ER) stress and heat shock response are two major deregulated functional modules related to CFTR dysfunction. To identify the impact of CFTR deletion during spermatogenesis, we examined the expression of spermiogenesis-related genes in the testis of CFTR mutant mice (CF mice). We confirmed expression changes of MSY2, a germ cell specific RNA binding protein, resulting from deletion of CFTR in testis. Furthermore, real time PCR and Western blot results showed that an inflammatory response was activated in CF mice testis, as reflected by the altered expression of cytokines. We demonstrate for the first time that expression of MSY2 is decreased in CF mice. Our results suggest that CFTR deletion in testis influences inflammatory responses and these features are likely to be due to the unique environment of the seminiferous tubule during the spermatogenesis process. The current study also suggests avenues to understand the pathophysiology of CFTR during spermatogenesis and provides targets for the possible treatment of CFTR-related infertility. PMID:27483469

  10. Structure of human nucleosome containing the testis-specific histone variant TSH2B

    SciTech Connect

    Urahama, Takashi; Horikoshi, Naoki; Osakabe, Akihisa; Tachiwana, Hiroaki; Kurumizaka, Hitoshi

    2014-03-25

    The crystal structure of human nucleosome containing the testis-specific TSH2B variant has been determined. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, and induces a local structural difference between TSH2B and H2B in nucleosomes. The human histone H2B variant TSH2B is highly expressed in testis and may function in the chromatin transition during spermatogenesis. In the present study, the crystal structure of the human testis-specific nucleosome containing TSH2B was determined at 2.8 Å resolution. A local structural difference between TSH2B and canonical H2B in nucleosomes was detected around the TSH2B-specific amino-acid residue Ser85. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, but in the canonical nucleosome the H2B Asn84 residue (corresponding to the TSH2B Ser85 residue) forms water-mediated hydrogen bonds with the H4 Arg78 residue. In contrast, the other TSH2B-specific amino-acid residues did not induce any significant local structural changes in the TSH2B nucleosome. These findings may provide important information for understanding how testis-specific histone variants form nucleosomes during spermatogenesis.

  11. Comparison of ex vivo DSP and in vitro MBP Exposures on Fetal Testis Testosterone Production

    EPA Science Inventory

    In utero exposure to di‐butyl phthalate (DBP) during sex differentiation reduces androgen production and produces a characteristic profile of gene expression changes in the fetal testis. The DPB metabolite mono‐butyl phthalate (MBP) is hypothesized to produce these changes by ...

  12. Zona occludens-2 is critical for blood-testis barrier integrity and male fertility.

    PubMed

    Xu, Jianliang; Anuar, Farhana; Ali, Safiah Mohamed; Ng, Mei Yong; Phua, Dominic C Y; Hunziker, Walter

    2009-10-01

    Tight junction integral membrane proteins such as claudins and occludin are tethered to the actin cytoskeleton by adaptor proteins, notably the closely related zonula occludens (ZO) proteins ZO-1, ZO-2, and ZO-3. All three ZO proteins have recently been inactivated in mice. Although ZO-3 knockout mice lack an obvious phenotype, animals deficient in ZO-1 or ZO-2 show early embryonic lethality. Here, we rescue the embryonic lethality of ZO-2 knockout mice by injecting ZO-2(-/-) embryonic stem (ES) cells into wild-type blastocysts to generate viable ZO-2 chimera. ZO-2(-/-) ES cells contribute extensively to different tissues of the chimera, consistent with an extraembryonic requirement for ZO-2 rather than a critical role in epiblast development. Adult chimera present a set of phenotypes in different organs. In particular, male ZO-2 chimeras show reduced fertility and pathological changes in the testis. Lanthanum tracer experiments show a compromised blood-testis barrier. Expression levels of ZO-1, ZO-3, claudin-11, and occludin are not apparently affected. ZO-1 and occludin still localize to the blood-testis barrier region, but claudin-11 is less well restricted and the localization of connexin-43 is perturbed. The critical role of ZO-2 for male fertility and blood-testis barrier integrity thus provides a first example for a nonredundant role of an individual ZO protein in adult mice.

  13. Cloning of thyrotropin-releasing hormone precursor and receptor in rat thymus, adrenal gland, and testis.

    PubMed

    Montagne, J J; Ladram, A; Nicolas, P; Bulant, M

    1999-03-01

    TRH is a hypophysiotropic peptide that acts mainly via the hypothalamic-pituitary-thyroid axis, but TRH immunoreactivity is also detected in several peripheral tissues. PCR with two pairs of primers enabling amplification of three fragments of TRH complementary DNA (cDNA) was used to demonstrate local production of TRH. Products of the expected size were detected in the testis, adrenal gland, lymphoid organs, thymus, and spleen. The amplified cDNA fragments were cloned and sequenced to show that the TRH gene is expressed in the thymus, spleen, and adrenal gland. Competitive RT-PCR showed that the TRH messenger RNA content of the testis was about one third that of the hypothalamus, whereas the adrenal gland contained 2% and the thymus 6%. HPLC analysis of thymus and spleen extracts showed small amounts of TRH, with a particular processing pattern of pro-TRH in lymphoid organs. The expression of the TRH receptor gene in peripheral organs was investigated to determine whether TRH had an autocrine or a paracrine action. cDNA fragments that encompassed the coding region of the receptor were identified in the testis, adrenal gland and thymus. No signal was detected in the spleen. These findings indicate that TRH may have a biological activity in extrapituitary organs and may act locally in the testis, adrenal gland, and thymus.

  14. EXPRESSION OF THE SPERMATOGENIC CELL-SPECIFIC GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE (GAPDS) IN RAT TESTIS

    EPA Science Inventory

    The spermatogenic cell-specific variant of glyceraldehyde 3-phosphate dehydrogenase (GAPDS) has been cloned from a rat testis cDNA library and its pattern of expression determined. A 1417 nucleotide cDNA has been found to encode an enzyme with substantial homology to mouse GAPDS...

  15. CFTR Deletion in Mouse Testis Induces VDAC1 Mediated Inflammatory Pathway Critical for Spermatogenesis.

    PubMed

    Yan, Chen; Lang, Qin; Huijuan, Liao; Jiang, Xie; Ming, Yang; Huaqin, Sun; Wenming, Xu

    2016-01-01

    Cystic fibrosis is the most common genetic disease among Caucasians and affects tissues including lung, pancreas and reproductive tracts. It has been shown that Endoplasmic Reticulum (ER) stress and heat shock response are two major deregulated functional modules related to CFTR dysfunction. To identify the impact of CFTR deletion during spermatogenesis, we examined the expression of spermiogenesis-related genes in the testis of CFTR mutant mice (CF mice). We confirmed expression changes of MSY2, a germ cell specific RNA binding protein, resulting from deletion of CFTR in testis. Furthermore, real time PCR and Western blot results showed that an inflammatory response was activated in CF mice testis, as reflected by the altered expression of cytokines. We demonstrate for the first time that expression of MSY2 is decreased in CF mice. Our results suggest that CFTR deletion in testis influences inflammatory responses and these features are likely to be due to the unique environment of the seminiferous tubule during the spermatogenesis process. The current study also suggests avenues to understand the pathophysiology of CFTR during spermatogenesis and provides targets for the possible treatment of CFTR-related infertility. PMID:27483469

  16. METABOLOMIC EVALUATION OF RAT LIVER AND TESTIS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES

    EPA Science Inventory

    The effects of two triazole fungicides, myclobutanil and triadimefon, on endogenous rat metabolite profiles in blood serum, liver, and testis was assessed using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Adult male Sprague-Dawley rats were dosed daily by gavage for...

  17. DEVELOPMENT OF A 950-GENE DNA ARRAY FOR EXAMINING GENE EXPRESSION PATTERNS IN MOUSE TESTIS

    EPA Science Inventory

    Development of a 950-gene DNA array for examining gene expression patterns in mouse testis.

    Rockett JC, Christopher Luft J, Brian Garges J, Krawetz SA, Hughes MR, Hee Kirn K, Oudes AJ, Dix DJ.

    Reproductive Toxicology Division, National Health and Environmental Effec...

  18. Evolution of cadmium effects in the testis and sperm of the tropical fish Gymnotus carapo.

    PubMed

    Vergilio, C S; Moreira, R V; Carvalho, C E V; Melo, E J T

    2015-04-01

    The present study investigated the testis and sperm morphology of the tropical fish Gymnotus carapo after exposure to increasing CdCl2 concentrations (5-40 μM) for 24 and 96 h. The treatments induced Cd accumulation in the testis and a decrease in the gonadosomatic index from a 10 μM. Cd induced alterations in testis since 24h; however the extension and severity of damages increased after 96 h in all tested concentrations. Marked variations in the cysts size, proliferation of the interstitial tissue, infiltration of inflammatory cells, necrosis, reduction of germ cells and sperm aggregation was observed in 96 h treated fishes. In this time, there was a complete absence of germ cells in the testis of fish treated with 40 μM. The ultrastructural analysis allowed for the visualization of the initial damages over germ cells, such as the presence of vacuoles in the cytoplasm of spermatogonia, spermatocytes, and spermatids. Exposed fish (20 μM for 24 and 96 h) had alterations in sperm number and morphology. These results are important for establishing a direct correlation between the Cd accumulation and incidence of damages and can help characterize the mechanism of Cd-induced pathogenesis in the male reproductive system.

  19. A murine fer testis-specific transcript (ferT) encodes a truncated Fer protein.

    PubMed Central

    Fischman, K; Edman, J C; Shackleford, G M; Turner, J A; Rutter, W J; Nir, U

    1990-01-01

    A cDNA for a potential tyrosine kinase-encoding mRNA was isolated from a mouse testis cDNA library. In a survey of eight mouse tissues, a transcript of 2.4 kilobases restricted to testis tissue was found. The mRNA encodes a 453-amino-acid protein of 51,383 daltons, the smallest tyrosine kinase protein ever described. RNA synthesized from the cDNA template directs the synthesis of a 51,000-Mr protein in a cell-free translation system. The carboxy-terminal 409 amino acids are 98 and 90% identical to the carboxy halves of the rat and human Fer proteins, respectively. This suggests that the cDNA represents an alternatively spliced testis-specific fer mRNA and is therefore termed by us ferT. On the basis of the appearance time of the fer mRNA in the testis of maturing neonatal mice, we speculate on the role played by this protein in the development of this organ. Images PMID:2294399

  20. GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS

    EPA Science Inventory

    GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE (EDS) ALTERS DEVELOPMENT OF THE MOUSE TESTIS. D.K. Tarka*1,2, J.D. Suarez*2, N.L. Roberts*2, J.M. Rogers*1,2, M.P. Hardy3, and G.R. Klinefelter1,2. 1University of North Carolina, Curriculum in Toxicology, Chapel Hill, NC; 2USEPA,...

  1. Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas

    PubMed Central

    Skvortsova, Yulia V.; Zinovyeva, Marina V.; Stukacheva, Elena A.; Klimov, Alexey; Tryakin, Alexey A.; Azhikina, Tatyana L.

    2016-01-01

    PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from studying only normal testis and TGCT samples, we also analyzed an intermediate stage, i.e. preneoplastic testis tissues adjacent to TGCTs. Importantly, in this study, we minimized the contribution of patient-to-patient heterogeneity by using matched preneoplastic/TGCT samples. Surprisingly, expression of germ cell marker DDX4 suggests that spermatogenesis is retained in premalignant testis tissues adjacent to nonseminoma, but not those adjacent to seminoma. Moreover, this pattern is followed by expression of PIWI pathway genes, which impacts one of their functions: DNA methylation level over LINE-1 promoters is higher in preneoplastic testis tissues adjacent to nonseminomas than those adjacent to seminomas. This finding might imply distinct routes for development of the two types of TGCTs and could be used as a novel diagnostic marker, possibly, noninvasively. Finally, we studied the role of CpG island methylation in expression of PIWI genes in patient samples and using in vitro experiments in cell line models: a more complex interrelation between DNA methylation and expression of the corresponding genes was revealed. PMID:26843623

  2. Use of genetically engineered swine to elucidate testis function in the boar

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The second mammalian GnRH isoform (GnRH-II) and its specific receptor (GnRHR-II) are abundant within the testis, suggesting a critical role. Gene coding errors prevent their production in many species, but both genes are functional in swine. We have demonstrated that GnRHR-II localizes to porcine Le...

  3. Transcriptional changes of cytokines in rooster testis and epididymis during sexual maturation stages and Salmonella infection.

    PubMed

    Anastasiadou, M; Michailidis, G

    2016-08-01

    Infection of rooster testis and epididymis by pathogens can lead to impaired fertility, resulting in economic losses in the poultry industry. Antimicrobial protection of rooster reproductive organs is, therefore, an important aspect of reproductive physiology. Salmonellosis is one of the most important zoonotic diseases, caused by Salmonella bacteria including Salmonella Enteritidis (SE) and is usually the result of infection of the reproductive organs. Thus, knowledge of the endogenous innate immune mechanisms of the rooster testis and epididymis is an emerging aspect of reproductive physiology. Cytokines are key factors for stimulating the immune response and inflammation in chickens to Salmonella infection. In the present study the expression profile of 11 pro-inflammatory cytokine genes in the rooster testis and epididymis in vivo and transcriptional changes in these organs during sexual maturation and SE infection were investigated. Gene expression analysis data revealed that in both testis and epididymis nine cytokines namely the IL-1β, IL-6, IL-8, IL-10, IL-12, IL-15, IL-16, IL-17 and IL-18 genes were expressed, while no mRNA transcripts were detected in both organs for IL-2 and IL-4. Furthermore, the expression of various cytokine genes during sexual maturation appeared to be developmentally regulated, while SE infection resulted in a significant up-regulation of IL-1β, -6, -12 and -18 genes in the testis and an increase in the mRNA relative abundance of IL-1β, -6, -12, -16 and -18 in the epididymis of SE-infected sexually mature 28-week-old roosters. These results suggest a cytokine-mediated immune response mechanism against Salmonella infection in the rooster reproductive tract. PMID:27289435

  4. Steroidogenesis by testis and accessory glands of the Lusitanian toadfish, Halobatrachus didactylus, during reproductive season.

    PubMed

    Modesto, Teresa; Freitas, Ana M M S; Canario, Adelino V M

    2015-11-01

    In teleost fish sex steroids are essential for gonadal function and have marked effects in reproductive and agonistic behavior and in the expression of secondary sexual characteristics. The Lusitanian toadfish, Halobatrachus didactylus, has two male morphotypes: type I males are territorial nest-holders and have large accessory glands while type II males are smaller, have a relatively large testis and small accessory glands. In the present study, the steroidogenic activity of the testis and accessory testicular glands of the Lusitanian toadfish were examined in vitro as well as their presence in urine. The testis of type I males produced 11-ketotestosterone (11KT) and 11β-hydroxy-4-androstene-3,17-dione (11βA) from tritiated 17-hydroxyprogesterone, while those of type II males produced testosterone (T) and 11β,17β-dihydroxy-4-andosten-3-one (11βT), but not 11KT. Additionally, the testis and accessory glands of both morphs produced mostly 5β,3α-reduced and 17,20α-hydroxylated metabolites. Type I, but not of type II, males synthesised 5β-reduced androgens in their accessory glands. The presence of 11βA exclusively in the urine of type I males during reproductive season suggests an association with maintenance of secondary sexual characteristics and behavior in this morph. The urine of both types of males contained two 5α-androstane and 5β-pregnane glucuronides. Among the latter steroids, those that are 17,21-dihydroxylated are potentially metabolites from cortisol and were found only in type I males during the spawning season. The diversity of metabolites produced by the testis and accessory glands and the presence of some in urine is suggestive of a potential role in chemical communication and reproductive behavior.

  5. Effect of varicocelectomy on testis volume and semen parameters in adolescents: a meta-analysis.

    PubMed

    Zhou, Tie; Zhang, Wei; Chen, Qi; Li, Lei; Cao, Huan; Xu, Chuan-Liang; Chen, Guang-Hua; Sun, Ying-Hao

    2015-01-01

    Varicocele repair in adolescent remains controversial. Our aim is to identify and combine clinical trials results published thus far to ascertain the efficacy of varicocelectomy in improving testis volume and semen parameters compared with nontreatment control. A literature search was performed using Medline, Embase and Web of Science, which included results obtained from meta-analysis, randomized and nonrandomized controlled studies. The study population was adolescents with clinically palpable varicocele with or without the testicular asymmetry or abnormal semen parameters. Cases were allocated to treatment and observation groups, and testis volume or semen parameters were adopted as outcome measures. As a result, seven randomized controlled trials (RCTs) and nonrandomized controlled trials studying bilateral testis volume or semen parameters in both treatment and observation groups were identified. Using a random effect model, mean difference of testis volume between the treatment group and the observation group was 2.9 ml (95% confidence interval [CI]: 0.6, 5.2; P< 0.05) for the varicocele side and 1.5 ml (95% CI: 0.3, 2.7; P< 0.05) for the healthy side. The random effect model analysis demonstrated that the mean difference of semen concentration, total semen motility, and normal morphology between the two groups was 13.7 × 10 6 ml-1 (95% CI: -1.4, 28.8; P = 0.075), 2.5% (95% CI: -3.6, 8.6; P= 0.424), and 2.9% (95% CI: -3.0, 8.7; P= 0.336) respectively. In conclusion, although varicocelectomy significantly improved bilateral testis volume in adolescents with varicocele compared with observation cases, semen parameters did not have any statistically significant difference between two groups. Well-planned, properly conducted RCTs are needed in order to confirm the above-mentioned conclusion further and to explore whether varicocele repair in adolescents could improve subsequently spontaneous pregnancy rates.

  6. Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) - Lesson from Adjudin.

    PubMed

    Chen, Haiqi; Mruk, Dolores D; Xia, Weiliang; Bonanomi, Michele; Silvestrini, Bruno; Cheng, Chuen-Yan

    2016-01-01

    The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium of the seminiferous tubule, the functional unit of the testis, where spermatogenesis takes place, into the basal and the adluminal (apical) compartments. Functionally, the BTB provides a unique microenvironment for meiosis I/II and post-meiotic spermatid development which take place exclusively in the apical compartment, away from the host immune system, and it contributes to the immune privilege status of testis. However, the BTB also poses major obstacles in developing male contraceptives (e.g., adjudin) that exert their effects on germ cells in the apical compartment, such as by disrupting spermatid adhesion to the Sertoli cell, causing germ cell exfoliation from the testis. Besides the tight junction (TJ) between adjacent Sertoli cells at the BTB that restricts the entry of contraceptives from the microvessels in the interstitium to the adluminal compartment, drug transporters, such as P-glycoprotein and multidrug resistance-associated protein 1 (MRP1), are also present that actively pump drugs out of the testis, limiting drug bioavailability. Recent advances in drug formulations, such as drug particle micronization (<50 μm) and co-grinding of drug particles with ß-cyclodextrin have improved bioavailability of contraceptives via considerable increase in solubility. Herein, we discuss development in drug formulations using adjudin as an example. We also put emphasis on the possible use of nanotechnology to deliver adjudin to the apical compartment with multidrug magnetic mesoporous silica nanoparticles. These advances in technology will significantly enhance our ability to develop effective non-hormonal male contraceptives for men. PMID:26758796

  7. Temporal Profiling of Rat Transcriptomes in Retinol-Replenished Vitamin A-Deficient Testis

    PubMed Central

    Doyle, Timothy J.; Oudes, Asa J.; Kim, Kwan Hee

    2009-01-01

    At least in mammals, retinoic acid is a pivotal factor in maintaining the functionality of the testis, in particular, for the progression of germ cells from mitosis to meiosis. Removal of dietary vitamin A or a targeted deletion of retinoic acid receptor alpha gene (Rara), the receptor for retinoic acid, in mice, led to testicular degeneration by a dramatic loss of germ cells and a loss of control of the spermatogenic cycle. The germ cells that remained in the vitamin A deficient (VAD) rat testis were spermatogonia and a few preleptotene spermatocytes. Spermatogenesis can be reinitiated by injection of VAD rats with retinol, the metabolic precursor of retinoic acid, but to date, the functions of retinoic acid in the testis remain elusive. We have applied DNA microarray technology to investigate the time-dependent transcriptome changes that occur 4 to 24 h after retinol replenishment in the VAD rat testis. The retinol-regulated gene expression occurred both in germ cells and Sertoli cells. Bioinformatic analyses revealed time-dependent clusters of genes and canonical pathways that may have critical functions for proper progression through spermatogenesis. In particular, gene clusters that emerged dealt with: (1) cholesterol and oxysterol homeostasis, (2) the regulation of steroidogenesis, (3) glycerophospholipid metabolism, (4) the regulation of acute inflammation, (5) the regulation of the cell cycle including ubiquitin-mediated degradation of cell cycle proteins and control of centrosome and genome integrity, and (6) the control of membrane scaffolding proteins that can integrate multiple small GTPase signals within a cell. These results provide insights into the potential role of retinoic acid in the testis. PMID:19886770

  8. Effect of varicocelectomy on testis volume and semen parameters in adolescents: a meta-analysis

    PubMed Central

    Zhou, Tie; Zhang, Wei; Chen, Qi; Li, Lei; Cao, Huan; Xu, Chuan-Liang; Chen, Guang-Hua; Sun, Ying-Hao

    2015-01-01

    Varicocele repair in adolescent remains controversial. Our aim is to identify and combine clinical trials results published thus far to ascertain the efficacy of varicocelectomy in improving testis volume and semen parameters compared with nontreatment control. A literature search was performed using Medline, Embase and Web of Science, which included results obtained from meta-analysis, randomized and nonrandomized controlled studies. The study population was adolescents with clinically palpable varicocele with or without the testicular asymmetry or abnormal semen parameters. Cases were allocated to treatment and observation groups, and testis volume or semen parameters were adopted as outcome measures. As a result, seven randomized controlled trials (RCTs) and nonrandomized controlled trials studying bilateral testis volume or semen parameters in both treatment and observation groups were identified. Using a random effect model, mean difference of testis volume between the treatment group and the observation group was 2.9 ml (95% confidence interval [CI]: 0.6, 5.2; P< 0.05) for the varicocele side and 1.5 ml (95% CI: 0.3, 2.7; P< 0.05) for the healthy side. The random effect model analysis demonstrated that the mean difference of semen concentration, total semen motility, and normal morphology between the two groups was 13.7 × 106 ml−1 (95% CI: −1.4, 28.8; P = 0.075), 2.5% (95% CI: −3.6, 8.6; P= 0.424), and 2.9% (95% CI: −3.0, 8.7; P= 0.336) respectively. In conclusion, although varicocelectomy significantly improved bilateral testis volume in adolescents with varicocele compared with observation cases, semen parameters did not have any statistically significant difference between two groups. Well-planned, properly conducted RCTs are needed in order to confirm the above-mentioned conclusion further and to explore whether varicocele repair in adolescents could improve subsequently spontaneous pregnancy rates. PMID:25677136

  9. Adaptive evolution of testis-specific, recently evolved, clustered miRNAs in Drosophila

    PubMed Central

    Mohammed, Jaaved; Bortolamiol-Becet, Diane; Flynt, Alex S.; Gronau, Ilan; Siepel, Adam; Lai, Eric C.

    2014-01-01

    The propensity of animal miRNAs to regulate targets bearing modest complementarity, most notably via pairing with miRNA positions ∼2–8 (the “seed”), is believed to drive major aspects of miRNA evolution. First, minimal targeting requirements have allowed most conserved miRNAs to acquire large target cohorts, thus imposing strong selection on miRNAs to maintain their seed sequences. Second, the modest pairing needed for repression suggests that evolutionarily nascent miRNAs may generally induce net detrimental, rather than beneficial, regulatory effects. Hence, levels and activities of newly emerged miRNAs are expected to be limited to preserve the status quo of gene expression. In this study, we unexpectedly show that Drosophila testes specifically express a substantial miRNA population that contravenes these tenets. We find that multiple genomic clusters of testis-restricted miRNAs harbor recently evolved miRNAs, whose experimentally verified orthologs exhibit divergent sequences, even within seed regions. Moreover, this class of miRNAs exhibits higher expression and greater phenotypic capacities in transgenic misexpression assays than do non-testis-restricted miRNAs of similar evolutionary age. These observations suggest that these testis-restricted miRNAs may be evolving adaptively, and several methods of evolutionary analysis provide strong support for this notion. Consistent with this, proof-of-principle tests show that orthologous miRNAs with divergent seeds can distinguish target sensors in a species-cognate manner. Finally, we observe that testis-restricted miRNA clusters exhibit extraordinary dynamics of miRNA gene flux in other Drosophila species. Altogether, our findings reveal a surprising tissue-directed influence of miRNA evolution, involving a distinct mode of miRNA function connected to adaptive gene regulation in the testis. PMID:24942624

  10. Differential zinc transport into testis and brain of cadmium-sensitive and -resistant murine strains.

    PubMed

    King, L M; Banks, W A; George, W J

    2000-01-01

    Recently, we showed that murine strain differences to the testicular toxicity of cadmium (Cd) are the result of variable transport of Cd across the blood-testis barrier. Because Cd is a nonessential trace element, it must be using the transporter for an endogenous substance. The objectives for this study were to determine the natural ligand for the transport system used by Cd to enter testis and brain, and to determine whether the transport of that natural ligand also differs among Cd-sensitive and -resistant murine strains. Because zinc (Zn) and Cd are cations of similar size and charge, and because Cd has been shown to inhibit Zn uptake in a variety of systems, we hypothesized that Cd was using Zn transporters to enter tissues. In this study we characterized Zn transport into the testis and brain of Cd-sensitive and -resistant murine strains. We found that the transport of 65Zn into testis and brain of Cd-resistant A/J mice was significantly reduced compared with that in Cd-sensitive 129/J mice. In 129/J mice, unlabeled CdCl2 significantly reduced 65Zn transport by 56% in testes and by 47% in brain. Pretreatment with Zn had no significant effect on 109Cd transport rates into testes or brain of 129/J or A/J mice, but did reduce the percentage of the injected 109Cd dose in testes of 129/J mice by 44% within 60 minutes. From these results we can conclude that Cd is using transport systems that normally function to regulate Zn levels in testes and brain. Murine strain resistance to the testicular effects of Cd is associated with a concomitant attenuation of the Zn transport system in testis.

  11. CRISPR/Cas9 Promotes Functional Study of Testis Specific X-Linked Gene In Vivo

    PubMed Central

    Jiang, Xue; Chen, Yuxi; Zhang, Zhen; Zhang, Xiya; Liang, Puping; Zhan, Shaoquan; Cao, Shanbo; Songyang, Zhou; Huang, Junjiu

    2015-01-01

    Mammalian spermatogenesis is a highly regulated multistage process of sperm generation. It is hard to uncover the real function of a testis specific gene in vitro since the in vitro model is not yet mature. With the development of the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9) system, we can now rapidly generate knockout mouse models of testis specific genes to study the process of spermatogenesis in vivo. SYCP3-like X-linked 2 (SLX2) is a germ cell specific component, which contains a Cor1 domain and belongs to the XLR (X-linked, lymphocyte regulated) family. Previous studies suggested that SLX2 might play an important role in mouse spermatogenesis based on its subcellular localization and interacting proteins. However, the function of SLX2 in vivo is still elusive. Here, to investigate the functions of SLX2 in spermatogenesis, we disrupted the Slx2 gene by using the CRISPR/Cas9 system. Since Slx2 is a testis specific X-linked gene, we obtained knockout male mice in the first generation and accelerated the study process. Compared with wild-type mice, Slx2 knockout mice have normal testis and epididymis. Histological observation of testes sections showed that Slx2 knockout affected none of the three main stages of spermatogenesis: mitosis, meiosis and spermiogenesis. In addition, we further confirmed that disruption of Slx2 did not affect the number of spermatogonial stem cells, meiosis progression or XY body formation by immunofluorescence analysis. As spermatogenesis was normal in Slx2 knockout mice, these mice were fertile. Taken together, we showed that Slx2 itself is not an essential gene for mouse spermatogenesis and CRISPR/Cas9 technique could speed up the functional study of testis specific X-linked gene in vivo. PMID:26599493

  12. Regulation of drug transporters in the testis by environmental toxicant cadmium, steroids and cytokines.

    PubMed

    Su, Linlin; Mruk, Dolores D; Cheng, C Yan

    2012-10-01

    The blood-testis barrier (BTB) provides an efficient barrier to restrict paracellular and transcellular transport of substances, such as toxicants and drugs, limiting their entry to the testis to cause injury. This is achieved by the coordinated actions of efflux and influx transporters at the BTB, which are integral membrane proteins that interact with their substrates, such as drugs and toxicants. An efflux transporter (e.g., P-glycoprotein) can either restrict the entry of drugs/toxicants into the testis or actively pump drugs/toxicants out of Sertoli and/or germ cells if they have entered the seminiferous epithelium via influx pumps. This thus provides an effective mechanism to safeguard spermatogenesis. Using Sertoli cells cultured in vitro with an established tight junction (TJ)-permeability barrier which mimicked the BTB in vivo and treated with cadmium chloride (CdCl2), and also in adult rats (~300 g b.w.) treated with CdCl2 (3 mg/kg b.w., via i.p.) to induce testicular injury, cadmium was found to significantly downregulate the expression of efflux (e.g., P-glycoprotein, Mrp1, Abcg1) and influx (e.g., Oatp3, Slc15a1, Scl39a8) transporters. For instance, treatment of Sertoli cells with cadmium induced significant loss of P-glycoprotein and Oatp-3 at the cell-cell interface, which likely facilitated cadmium entry into the Sertoli cell. These findings illustrate that one of the mechanisms by which cadmium enters the testis is mediated by downregulating the expression of drug transporters at the BTB. Furthermore, cytokines and steroids were found to have differential effects in regulating the expression of drug transporters. Summary, the expression of drug transporters in the testis is regulated by toxicants, steroids and cytokines. PMID:23248770

  13. Transcriptional changes of cytokines in rooster testis and epididymis during sexual maturation stages and Salmonella infection.

    PubMed

    Anastasiadou, M; Michailidis, G

    2016-08-01

    Infection of rooster testis and epididymis by pathogens can lead to impaired fertility, resulting in economic losses in the poultry industry. Antimicrobial protection of rooster reproductive organs is, therefore, an important aspect of reproductive physiology. Salmonellosis is one of the most important zoonotic diseases, caused by Salmonella bacteria including Salmonella Enteritidis (SE) and is usually the result of infection of the reproductive organs. Thus, knowledge of the endogenous innate immune mechanisms of the rooster testis and epididymis is an emerging aspect of reproductive physiology. Cytokines are key factors for stimulating the immune response and inflammation in chickens to Salmonella infection. In the present study the expression profile of 11 pro-inflammatory cytokine genes in the rooster testis and epididymis in vivo and transcriptional changes in these organs during sexual maturation and SE infection were investigated. Gene expression analysis data revealed that in both testis and epididymis nine cytokines namely the IL-1β, IL-6, IL-8, IL-10, IL-12, IL-15, IL-16, IL-17 and IL-18 genes were expressed, while no mRNA transcripts were detected in both organs for IL-2 and IL-4. Furthermore, the expression of various cytokine genes during sexual maturation appeared to be developmentally regulated, while SE infection resulted in a significant up-regulation of IL-1β, -6, -12 and -18 genes in the testis and an increase in the mRNA relative abundance of IL-1β, -6, -12, -16 and -18 in the epididymis of SE-infected sexually mature 28-week-old roosters. These results suggest a cytokine-mediated immune response mechanism against Salmonella infection in the rooster reproductive tract.

  14. Effect of tertiary-butyl hydroperoxide (TBHP)-induced oxidative stress on mice sperm quality and testis histopathology.

    PubMed

    Fatemi, N; Sanati, M H; Jamali Zavarehei, M; Ayat, H; Esmaeili, V; Golkar-Narenji, A; Zarabi, M; Gourabi, H

    2013-08-01

    Male infertility is responsible for approximately 50% of infertility worldwide. Reactive oxygen species are one of the major causes of male infertility. In this study, the effects of oxidative stress induced by tertiary-butyl hydroperoxide (TBHP) on sperm quality and testis tissue are investigated. After determination of LD50 , TBHP with a concentration of 1 : 10 LD50 was injected in adult male mice strains Balb/c for two consecutive weeks. Their testis tissues were used for cell viability, histopathology analysis and ROS assay. The epididymis was also surveyed for sperm analysis by CASA system. The sperm motility, count and viability decreased in the TBHP-treated mice compared to the control mice. The flow cytometry analysis showed a significant increase in H2 O2 and O2 ·- levels in both testis and sperm within 2 weeks after intraperitoneal injection. Body weights revealed no treatment-related effects, but atrophy of testis and a decrease of testis cells viability were observed. The results showed that exposure to TBHP could lead to morphological changes in seminiferous tubules. TBHP-induced oxidative stress caused a decrease in sperm parameters and testis cells viability. That is due to an increase level of ROS in the testis and their deleterious effects on genomic levels.

  15. Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene*

    PubMed Central

    Thyagaraju, K.; Hemavathi, B.; Vasundhara, K.; Rao, A.D.; Devi, K.N.

    2005-01-01

    A comparative study was made on the tissue specific expression of glutathione transferases (GST) in brain and testis after exposure of rat to phenobarbitol (PB) and β-methylcholanthrene (MC). Glutathione transferases, a family of multifunctional proteins are involved in intracellular transport processes and in detoxication of electrophilic xenobiotics by catalyzing reactions such as conjugation, isomerization, reduction and thiolysis. On purification, the yield of GST proteins by affinity chromatography was 39% in testis and 32% in brain. The affinity purified testis GSTs were resolved by chromatofocusing into six anionic and four cationic isozymes, and in brain glutathione transferases were resolved into four anionic and three cationic isozymes, suggesting the presence of multiple isozymes with Yc, Yb, Yβ and Yδ in both of them. In testis and brain, these isozymes at identical pI values showed variable functions with a battery of substrates and the cationic isozymes of brain and testis showed identical properties in CHP (cumene hydroperoxide) at pH values of above 7.0. Substrate specificity studies and immunoblot analysis of testis and brain proteins revealed that they play a predominant role in the detoxication of phenobarbitol or β-methylcholanthrene. Expression of the isozymes in testis and brain on exposure to PB and MC indicated elevated subunit variation. In both testis and brain, Yδ of π class was expressed on PB treatment and Yc of α class and Yβ of μ class was expressed in MC treated testis and only Yc was predominantly expressed in MC treated brain. Thus these subunits expression is considered as markers for carcinogenesis and specific to chemical toxicity under phenobarbitol and β-methylcholanthrene stress. PMID:16052709

  16. The measurement of rectal and testis temperature in conscious mice, with observations on the effect of direct heating.

    PubMed

    Cairnie, A B; Prud'homme-Lalonde, L F; Harding, R K; Zuker, M

    1980-03-01

    The application of Newton's law of cooling to freshly killed mice was found not to measure accurately their rectal or testis temperature. Improvements in the fitting process gave satisfactory results for rectal temperature only. A diffusion model was applied to testis cooling but was of no avail. Finally a satisfactory correction factor was determined empirically. This method was applied to conscious mice whose hindquarters were immersed in a stirred oilbath at 34 to 42 degrees C for 1 h, and to controls. It was found that both rectal and testis temperatures increased with bath temperature, producing a graph with a slope of only 0.5, indicating a regulatory capacity. Conscious mice, but not anaesthetised, can maintain a testis temperature of 39 degrees C in a bath at 42 degrees C.

  17. Vascular endothelial growth factor A: just one of multiple mechanisms for sex-specific vascular development within the testis?

    PubMed

    Sargent, Kevin M; McFee, Renee M; Spuri Gomes, Renata; Cupp, Andrea S

    2015-11-01

    Testis development from an indifferent gonad is a critical step in embryogenesis. A hallmark of testis differentiation is sex-specific vascularization that occurs as endothelial cells migrate from the adjacent mesonephros into the testis to surround Sertoli-germ cell aggregates and induce seminiferous cord formation. Many in vitro experiments have demonstrated that vascular endothelial growth factor A (VEGFA) is a critical regulator of this process. Both inhibitors to VEGFA signal transduction and excess VEGFA isoforms in testis organ cultures impaired vascular development and seminiferous cord formation. However, in vivo models using mice which selectively eliminated all VEGFA isoforms: in Sertoli and germ cells (pDmrt1-Cre;Vegfa(-/-)); Sertoli and Leydig cells (Amhr2-Cre;Vegfa(-/-)) or Sertoli cells (Amh-Cre;Vegfa(-/-) and Sry-Cre;Vegfa(-/-)) displayed testes with observably normal cords and vasculature at postnatal day 0 and onwards. Embryonic testis development may be delayed in these mice; however, the postnatal data indicate that VEGFA isoforms secreted from Sertoli, Leydig or germ cells are not required for testis morphogenesis within the mouse. A Vegfa signal transduction array was employed on postnatal testes from Sry-Cre;Vegfa(-/-) versus controls. Ptgs1 (Cox1) was the only upregulated gene (fivefold). COX1 stimulates angiogenesis and upregulates, VEGFA, Prostaglandin E2 (PGE2) and PGD2. Thus, other gene pathways may compensate for VEGFA loss, similar to multiple independent mechanisms to maintain SOX9 expression. Multiple independent mechanism that induce vascular development in the testis may contribute to and safeguard the sex-specific vasculature development responsible for inducing seminiferous cord formation, thus ensuring appropriate testis morphogenesis in the male.

  18. Transcriptome Analysis of Spermatogenically Regressed, Recrudescent and Active Phase Testis of Seasonally Breeding Wall Lizards Hemidactylus flaviviridis

    PubMed Central

    Gautam, Mukesh; Mathur, Amitabh; Khan, Meraj Alam; Majumdar, Subeer S.; Rai, Umesh

    2013-01-01

    Background Reptiles are phylogenically important group of organisms as mammals have evolved from them. Wall lizard testis exhibits clearly distinct morphology during various phases of a reproductive cycle making them an interesting model to study regulation of spermatogenesis. Studies on reptile spermatogenesis are negligible hence this study will prove to be an important resource. Methodology/Principal Findings Histological analyses show complete regression of seminiferous tubules during regressed phase with retracted Sertoli cells and spermatognia. In the recrudescent phase, regressed testis regain cellular activity showing presence of normal Sertoli cells and developing germ cells. In the active phase, testis reaches up to its maximum size with enlarged seminiferous tubules and presence of sperm in seminiferous lumen. Total RNA extracted from whole testis of regressed, recrudescent and active phase of wall lizard was hybridized on Mouse Whole Genome 8×60 K format gene chip. Microarray data from regressed phase was deemed as control group. Microarray data were validated by assessing the expression of some selected genes using Quantitative Real-Time PCR. The genes prominently expressed in recrudescent and active phase testis are cytoskeleton organization GO 0005856, cell growth GO 0045927, GTpase regulator activity GO: 0030695, transcription GO: 0006352, apoptosis GO: 0006915 and many other biological processes. The genes showing higher expression in regressed phase belonged to functional categories such as negative regulation of macromolecule metabolic process GO: 0010605, negative regulation of gene expression GO: 0010629 and maintenance of stem cell niche GO: 0045165. Conclusion/Significance This is the first exploratory study profiling transcriptome of three drastically different conditions of any reptilian testis. The genes expressed in the testis during regressed, recrudescent and active phase of reproductive cycle are in concordance with the testis

  19. Blood-testis barrier and spermatogenesis: lessons from genetically-modified mice

    PubMed Central

    Jiang, Xiao-Hua; Bukhari, Ihtisham; Zheng, Wei; Yin, Shi; Wang, Zheng; Cooke, Howard J; Shi, Qing-Hua

    2014-01-01

    The blood-testis barrier (BTB) is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions (TJs), adhesion junctions and gap junctions (GJs). Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives. PMID:24713828

  20. Isolation and characterization of all-trans-retinoic acid-responsive genes in the rat testis.

    PubMed

    Gaemers, I C; Van Pelt, A M; Themmen, A P; De Rooij, D G

    1998-05-01

    By way of differential screening of testis cDNA libraries from vitamin A-deficient (VAD) rats before and after administration of all-trans retinoic acid (ATRA), genes, the transcription of which was influenced by ATRA, were isolated. Most clones with an increased transcription encoded different subunits of the same mitochondrial protein complex, cytochrome c oxidase (COX). The mRNA expression of COX increased by a factor 3.9 +/- 1.5 (mean +/- SD, n = 4). This increased expression seems to reflect an increased energy demand in the ATRA-supplemented VAD testis. Also, one gene was isolated, the transcription of which was reduced to about 70% by ATRA. This gene, sulfated glycoprotein 2 (Sgp-2), is a major secretion product of Sertoli cells, the function of which is still unknown. The effect of ATRA on Sgp-2 expression may be direct, since the promoter of Sgp-2 contains a putative ATRA-responsive element (RARE). PMID:9547504

  1. Expression of CD1d protein in human testis showing normal and abnormal spermatogenesis.

    PubMed

    Adly, Mohamed A; Abdelwahed Hussein, Mahmoud-Rezk

    2011-05-01

    CD1d is a member of CD1 family of transmembrane glycoproteins, which represent antigen-presenting molecules. Immunofluorescent staining methods were utilized to examine expression pattern of CD1d in human testicular specimens. In testis showing normal spermatogenesis, a strong CD1d cytoplasmic expression was seen the Sertoli cells, spermatogonia, and Leydig cells. A moderate expression was observed in the spermatocytes. In testes showing maturation arrest, CD1d expression was strong in the Sertoli cells and weak in spermatogonia and spermatocytes compared to testis with normal spermatogenesis. In Sertoli cell only syndrome, CD1d expression was strong in the Sertoli and Leydig cells. This preliminary study displayed testicular infertility-related changes in CD1d expression. The ultrastructural changes associated with with normal and abnormal spermatogenesis are open for further investigations.

  2. Rat Testis Damage Caused by Lead Sulfide Nanoparticles After Oral Exposure.

    PubMed

    Cao, Yanhua; Wang, Dong; Li, Qingzhao; Deng, Hongliang; Shen, Jian; Zheng, Guoying; Sun, Miao

    2016-03-01

    Lead sulfide nanoparticals (PbS NPs) is an important semiconductor material due to its unique physical and chemical properties, but its potential health hazard to reproductive system is not clear. In the current study, we systematically explored the reproductive toxicity of PbS NPs in rats by measuring the body weight and testicular coefficient, testing serum testosterone levels, and studying the sperm survival rate and sperm abnormality rate. Furthermore, in order to study the toxic mechanism we performed lead contents measurements in testis, and investigated the pathology in testis. Our results confirmed that PbS NPs showed high reproductive toxicity due to PbS NPs in rats' testicular tissue by the establishment of PbS NPs chronic exposure model. PMID:27455644

  3. A putative fourth Na+,K(+)-ATPase alpha-subunit gene is expressed in testis.

    PubMed Central

    Shamraj, O I; Lingrel, J B

    1994-01-01

    The Na+,K(+)-ATPase alpha subunit has three known isoforms, alpha 1, alpha 2 and alpha 3, each encoded by a separate gene. This study was undertaken to determine the functional status of a fourth human alpha-like gene, ATP1AL2. Partial genomic sequence analysis revealed regions exhibiting sequence similarity with exons 3-6 of the Na+,K(+)-ATPase alpha isoform genes. ATP1AL2 cDNAs spanning the coding sequence of a novel P-type ATPase alpha subunit were isolated from a rat testis library. The predicted polypeptide is 1028 amino acids long and exhibits 76-78% identity with the rat Na+,K(+)-ATPase alpha 1, alpha 2 and alpha 3 isoforms, indicating that ATP1AL2 may encode a fourth Na+,K(+)-ATPase alpha isoform. A 3.9-kb mRNA is expressed abundantly in human and rat testis. Images Fig. 2 Fig. 5 PMID:7809153

  4. Switching on sex: transcriptional regulation of the testis-determining gene Sry

    PubMed Central

    Larney, Christian; Bailey, Timothy L.; Koopman, Peter

    2014-01-01

    Mammalian sex determination hinges on the development of ovaries or testes, with testis fate being triggered by the expression of the transcription factor sex-determining region Y (Sry). Reduced or delayed Sry expression impairs testis development, highlighting the importance of its accurate spatiotemporal regulation and implying a potential role for SRY dysregulation in human intersex disorders. Several epigenetic modifiers, transcription factors and kinases are implicated in regulating Sry transcription, but it remains unclear whether or how this farrago of factors acts co-ordinately. Here we review our current understanding of Sry regulation and provide a model that assembles all known regulators into three modules, each converging on a single transcription factor that binds to the Sry promoter. We also discuss potential future avenues for discovering the cis-elements and trans-factors required for Sry regulation. PMID:24866114

  5. Rat Testis Damage Caused by Lead Sulfide Nanoparticles After Oral Exposure.

    PubMed

    Cao, Yanhua; Wang, Dong; Li, Qingzhao; Deng, Hongliang; Shen, Jian; Zheng, Guoying; Sun, Miao

    2016-03-01

    Lead sulfide nanoparticals (PbS NPs) is an important semiconductor material due to its unique physical and chemical properties, but its potential health hazard to reproductive system is not clear. In the current study, we systematically explored the reproductive toxicity of PbS NPs in rats by measuring the body weight and testicular coefficient, testing serum testosterone levels, and studying the sperm survival rate and sperm abnormality rate. Furthermore, in order to study the toxic mechanism we performed lead contents measurements in testis, and investigated the pathology in testis. Our results confirmed that PbS NPs showed high reproductive toxicity due to PbS NPs in rats' testicular tissue by the establishment of PbS NPs chronic exposure model.

  6. Repeated administrations of carbon nanotubes in male mice cause reversible testis damage without affecting fertility

    NASA Astrophysics Data System (ADS)

    Bai, Yuhong; Zhang, Yi; Zhang, Jingping; Mu, Qingxin; Zhang, Weidong; Butch, Elizabeth R.; Snyder, Scott E.; Yan, Bing

    2010-09-01

    Soluble carbon nanotubes show promise as materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, but their effects on male reproduction have not been examined. Here, we show that repeated intravenous injections of water-soluble multiwalled carbon nanotubes into male mice can cause reversible testis damage without affecting fertility. Nanotubes accumulated in the testes, generated oxidative stress and decreased the thickness of the seminiferous epithelium in the testis at day 15, but the damage was repaired at 60 and 90 days. The quantity, quality and integrity of the sperm and the levels of three major sex hormones were not significantly affected throughout the 90-day period. The fertility of treated male mice was unaffected; the pregnancy rate and delivery success of female mice that mated with the treated male mice did not differ from those that mated with untreated male mice.

  7. Persistent mullerian duct syndrome presenting as retractile testis with hypospadias: A rare entity

    PubMed Central

    Vanikar, Aruna V; Nigam, Lovelesh A; Patel, Rashmi D; Kanodia, Kamal V; Suthar, Kamlesh S; Thakkar, Umang G

    2016-01-01

    A rare entity of persistent mullerian duct syndrome usually presents with a common symptom of undescended testis (UDT) or hernia. Male pseudo-hermaphroditism with persistent internal mullerian duct structures can present with a 46, XY karyotype with normal external genitalia and. It arises due to deficiency of anti-mullerian substance, resulting from reduced production/responsiveness to mullerian duct, leading to persistence of mullerian duct along with normal development of Wolffian duct structures. Presence of mullerian structure prevents testicular descent increasing the risk of testicular vanishing syndrome. The authors here report a case of 16 years old phenotypical male who came with retractile right sided testis and left side UDT in the urology out-patient department. Explorative laparotomy was performed and an ill-defined mass was excised and sent for histopathological examination. Histopathology revealed presence of mullerian structures. The serum testosterone level was normal, buccal smear cytology and karyotyping revealed a 46, XY genotype of the patient. PMID:27326401

  8. Targeting testis-specific proteins to inhibit spermatogenesis: lesson from endocrine disrupting chemicals

    PubMed Central

    Wan, HT; Mruk, Dolores D; Wong, Chris KC; Cheng, C Yan

    2014-01-01

    Introduction Exposure to endocrine disrupting chemicals (EDCs) has recently been linked to declining fertility in men in both developed and developing countries. Since many EDCs possess intrinsic estrogenic or androgenic activities, thus, the gonad is one of the major targets of EDCs. Areas covered For the past 2 decades, studies found in the literature regarding the disruptive effects of these EDCs on reproductive function in human males and also rodents were mostly focused on oxidative stress-induced germ cell apoptosis, disruption of steroidogenesis, abnormal sperm production and disruption of spermatogenesis in particular cell adhesion function and the blood–testis-barrier (BTB) function. Herein, we highlight recent findings in the field illustrating testis-specific proteins are also targets of EDCs. Expert opinion This information should be helpful in developing better therapeutic approach to manage ECD-induced reproductive toxicity. This information is also helpful to identify potential targets for male contraceptive development. PMID:23600530

  9. Blood-testis barrier and spermatogenesis: lessons from genetically-modified mice.

    PubMed

    Jiang, Xiao-Hua; Bukhari, Ihtisham; Zheng, Wei; Yin, Shi; Wang, Zheng; Cooke, Howard J; Shi, Qing-Hua

    2014-01-01

    The blood-testis barrier (BTB) is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions (TJs), adhesion junctions and gap junctions (GJs). Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.

  10. Expression of POTE protein in human testis detected by novel monoclonal antibodies

    SciTech Connect

    Ise, Tomoko; Das, Sudipto; Nagata, Satoshi; Maeda, Hiroshi; Lee, Yoomi; Onda, Masanori; Anver, Miriam R.; Pastan, Ira

    2008-01-25

    The POTE gene family is composed of 13 highly homologous paralogs preferentially expressed in prostate, ovary, testis, and placenta. We produced 10 monoclonal antibodies (MAbs) against three representative POTE paralogs: POTE-21, POTE-2{gamma}C, and POTE-22. One reacted with all three paralogs, six MAbs reacted with POTE-2{gamma}C and POTE-22, and three MAbs were specific to POTE-21. Epitopes of all 10 MAbs were located in the cysteine-rich repeats (CRRs) motifs located at the N-terminus of each POTE paralog. Testing the reactivity of each MAb with 12 different CRRs revealed slight differences among the antigenic determinants, which accounts for differences in cross-reactivity. Using MAbs HP8 and PG5 we were able to detect a POTE-actin fusion protein in human testis by immunoprecipitation followed by Western blotting. By immunohistochemistry we demonstrated that the POTE protein is expressed in primary spermatocytes, implying a role in spermatogenesis.

  11. Unilateral orchidectomy in donkey (Equus asinus): Evaluation of different surgical techniques, histological and morphological changes on remaining testis

    PubMed Central

    Mahmoud Ali Omar, Magda; Mohamed Ahmed Hassanein, Khaled; Khalifa Abdel-Razek, Abdel-Razek; Ali Yousef Hussein, Haroon

    2013-01-01

    Unilateral orchidectomy (UO) is required when further breeding potential is important. It is sometimes necessary to remove a single testis in a matured stallion for therapeutic reasons. In this study, twelve donkeys were used to evaluate three techniques of unilateral castration, histological and morphological changes on the remaining testis. Results of the study showed that each of the surgical techniques used had its advantages and disadvantages in comparison with the other two techniques. Therefore the selection among the three techniques depends on the surgeon preferences and the environment in which the unilateral orchidectomy is performed. The volume of the remaining testis recorded at the end of the study was significantly greater than that estimated at the start of the study (p < 0.05). The percentage of sperm motility obtained from the remaining testis was significantly decreased (p < 0.05). Histological examination of the testis in open surgery (group I) (where the scrotum was left opened) revealed severe hemorrhages, edema and fibrosis. The test is showed degenerative changes in the seminiferous tubules and interstitial orchitis. Histological examination of the testes removed using a closed technique, (in groups II and III) where the scrotum wound was sutured, revealed hyperplasia of spermatogenic series and Leydig cells. In conclusion, unilateral orchidectomy had compensatory effects on the weight and volume of remaining testis. Adverse effects on sperm motility and viability can affect the fertility of the animal. PMID:25593678

  12. Unilateral orchidectomy in donkey (Equus asinus): Evaluation of different surgical techniques, histological and morphological changes on remaining testis.

    PubMed

    Mahmoud Ali Omar, Magda; Mohamed Ahmed Hassanein, Khaled; Khalifa Abdel-Razek, Abdel-Razek; Ali Yousef Hussein, Haroon

    2013-01-01

    Unilateral orchidectomy (UO) is required when further breeding potential is important. It is sometimes necessary to remove a single testis in a matured stallion for therapeutic reasons. In this study, twelve donkeys were used to evaluate three techniques of unilateral castration, histological and morphological changes on the remaining testis. Results of the study showed that each of the surgical techniques used had its advantages and disadvantages in comparison with the other two techniques. Therefore the selection among the three techniques depends on the surgeon preferences and the environment in which the unilateral orchidectomy is performed. The volume of the remaining testis recorded at the end of the study was significantly greater than that estimated at the start of the study (p < 0.05). The percentage of sperm motility obtained from the remaining testis was significantly decreased (p < 0.05). Histological examination of the testis in open surgery (group I) (where the scrotum was left opened) revealed severe hemorrhages, edema and fibrosis. The test is showed degenerative changes in the seminiferous tubules and interstitial orchitis. Histological examination of the testes removed using a closed technique, (in groups II and III) where the scrotum wound was sutured, revealed hyperplasia of spermatogenic series and Leydig cells. In conclusion, unilateral orchidectomy had compensatory effects on the weight and volume of remaining testis. Adverse effects on sperm motility and viability can affect the fertility of the animal. PMID:25593678

  13. Molecular cloning of a novel nuclear factor, TDRP1, in spermatogenic cells of testis and its relationship with spermatogenesis

    SciTech Connect

    Wang, Xuanchun; Jiang, Haowen; Zhou, Wenbai; Zhang, Zhaoyun; Yang, Zhihong; Lu, Yong; Lu, Bin; Wang, Xiang; Ding, Qiang; Hu, Renming

    2010-03-26

    We reported the identification of a novel gene termed TDRP (encoding testis development-related protein) that might be involved in spermatogenesis. The human TDRP gene had two distinct transcripts, TDRP1 and TDRP2, which encoded proteins of 183 aa and 198 aa respectively. Tdrp mRNA was predominantly expressed in testis tissue. We generated rabbit polyclonal antibodies specific against human TDRP1. Immunohistochemistry analysis showed TDRP1 was expressed in spermatogenic cells, especially with high expression in spermatocytes. We provided evidence that TDRP1 distributed in both cytoplasm and nuclei of spermatogenic cells. Expression patterns of Tdrp1 mRNA and its protein were investigated in the rat testis tissues of different developmental stages. Both Tdrp1 mRNA and its protein were barely detected in the testis of neonatal rats, increased remarkably at 3 weeks postpartum, and peaked at 2 months postpartum. We also investigated TDRP1 expressions in testis tissues of azoospermic men with defective spermatogenesis. Western blot analysis showed that TDRP1 expressions were significantly lower in the testis tissues of azoospermic men compared with normal controls. These current data demonstrated that as a nuclear factor, TDRP1 might play an important role in spermatogenesis.

  14. HSL-knockout mouse testis exhibits class B scavenger receptor upregulation and disrupted lipid raft microdomains[S

    PubMed Central

    Casado, María Emilia; Huerta, Lydia; Ortiz, Ana Isabel; Pérez-Crespo, Mirian; Gutiérrez-Adán, Alfonso; Kraemer, Fredric B.; Lasunción, Miguel Ángel; Busto, Rebeca; Martín-Hidalgo, Antonia

    2012-01-01

    There is a tight relationship between fertility and changes in cholesterol metabolism during spermatogenesis. In the testis, class B scavenger receptors (SR-B) SR-BI, SR-BII, and LIMP II mediate the selective uptake of cholesterol esters from HDL, which are hydrolyzed to unesterified cholesterol by hormone-sensitive lipase (HSL). HSL is critical because HSL knockout (KO) male mice are sterile. The aim of the present work was to determine the effects of the lack of HSL in testis on the expression of SR-B, lipid raft composition, and related cell signaling pathways. HSL-KO mouse testis presented altered spermatogenesis associated with decreased sperm counts, sperm motility, and infertility. In wild-type (WT) testis, HSL is expressed in elongated spermatids; SR-BI, in Leydig cells and spermatids; SR-BII, in spermatocytes and spermatids but not in Leydig cells; and LIMP II, in Sertoli and Leydig cells. HSL knockout male mice have increased expression of class B scavenger receptors, disrupted caveolin-1 localization in lipid raft plasma membrane microdomains, and activated phospho-ERK, phospho-AKT, and phospho-SRC in the testis, suggesting that class B scavenger receptors are involved in cholesterol ester uptake for steroidogenesis and spermatogenesis in the testis. PMID:22988039

  15. Comparative analysis of testis transcriptomes from triploid and fertile diploid cyprinid fish.

    PubMed

    Xu, Kang; Wen, Ming; Duan, Wei; Ren, Li; Hu, Fangzhou; Xiao, Jun; Wang, Jing; Tao, Min; Zhang, Chun; Wang, Jun; Zhou, Yi; Zhang, Yi; Liu, Yun; Liu, Shaojun

    2015-04-01

    The fertility of fish is a key factor in fish breeding. RNA-seq is widely used in high-throughput sequencing and provides a rapid method to examine the molecular mechanisms underlying a biological process. To probe fertility-related molecular mechanisms, we obtained testis transcriptomes from diploid and triploid cyprinid fish and tested for differentially expressed genes (DEGs) in the testis. A total of 6730 transcripts were differentially expressed between the triploid and diploid fish. In these transcripts, 2428 transcripts showed reduced expression and 4302 transcripts were overexpressed in triploid fish compared to the diploid fish. Functional analyses revealed that partial genes related to reproductive, developmental, and locomotion processes, and the axoneme, were differentially expressed in triploid fish relative to diploid fish. Pathway analysis indicated that variations in the gene expression levels of the "ubiquinone and other terpenoid-quinone biosynthesis pathway" and the "apoptotic pathway" played a central role in the sterility of triploid male fish. A series of genes (DNAHs, DNAL1, IFTs, and DNAAF1) associated with sperm flagellar assembly and motility, and testis-specific candidate markers (Tcte1, Tekt1, Tekt4, Spag17, Spag5, Spag9a, Spag1b, and Spef2), had low expression levels in the testis of triploid fish. We validated these DEGs in triploid fish using quantitative PCR to quantify expression of eight representative genes. Furthermore, 276 putative transcription factors, 6 chromatin remodeling factors, and 35 transcription cofactors exhibited differential expression in triploid compared to diploid fish. This study provides insight into the regulatory mechanisms causing sterility in male triploid fish.

  16. Necrotic seminoma of the testis: establishing the diagnosis with Masson trichrome stain and immunostains.

    PubMed

    Florentine, Barbara D; Roscher, Arno A; Garrett, Jerry; Warner, Nancy E

    2002-02-01

    We describe an infarcted mass in the testis containing "ghost" cells suspicious for neoplasm. The entire lesion was necrotic. A Masson trichrome stain greatly improved nuclear and cytologic detail, confirming the suspicion of neoplasm. Placental alkaline phosphatase revealed specific membrane staining of the neoplastic cells and established a diagnosis of seminoma. Masson trichrome plus selected immunostains offer a promising approach to the diagnosis of certain necrotic neoplasms.

  17. Juvenile granulosa cell tumor of the testis: prenatal diagnosis and prescrotal approach

    PubMed Central

    2012-01-01

    Neonatal testicular tumors are rare and should be considered in the differential diagnosis of newborn scrotal masses. Juvenile granulosa cell tumor (JGCT) accounts for about 5% of all prepubertal testis tumors. As a benign neoplasm, radical orchiectomy is sufficient for treatment. We report a case of a newborn with a prenatal diagnosis of scrotal mass. After surgery, the histological diagnosis was juvenile granulosa cell tumor. To date the patient is healthy. PMID:23217189

  18. Comparative testis morphometry and seminiferous epithelium cycle length in donkeys and mules.

    PubMed

    Neves, Elizabeth S; Chiarini-Garcia, Hélio; França, Luiz R

    2002-07-01

    The mule (Equus mulus mulus) is a sterile hybrid domestic animal that results from the breeding of a male donkey (Equus asinus) to a female horse (Equus caballus). Usually, spermatogenesis in mules does not advance beyond spermatocytes. In the present study, we performed a comparative and more accurate morphometric and functional investigation of the testis in donkeys and mules. Due to the smaller testis size, lower seminiferous tubule volume density, and fewer germ cells, the total length of seminiferous tubules in mules was significantly smaller than in donkeys. However, the percentage of seminiferous tubules containing germ cells (spermatogonia and spermatocytes) in mules was approximately 95%. The total number of Sertoli cells per testis observed in donkeys and mules was very similar. However, the total number of Leydig cells in mules was approximately 70% lower than in donkeys. At least in part, this difference was probably related to the lower number of germ cells present in mule seminiferous tubules. Although spermatogenesis in mules did not advance beyond secondary spermatocytes/newly formed round spermatids, germ cell associations in the seminiferous epithelium and pachytene spermatocytes nuclear volume in donkeys and mules were similar. The duration of spermatogenesis was estimated using intratesticular injections of tritiated thymidine. Each spermatogenic cycle in donkeys lasted 10.5 days. A similar value was found in mules ( approximately 10.1 days). Considering that the entire spermatogenic process takes approximately 4.5 cycles to be completed, its total duration in donkeys was estimated to last 47.2 days. The results found for mules suggest that the mechanisms involved in the determination of testis structure and function are probably originated from donkeys. Also, the data found for mules suggest that their seminiferous tubules are able to sustain complete spermatogenesis. In this regard, this species is a potential model for transplants of germ

  19. CSD mRNA expression in rat testis and the effect of taurine on testosterone secretion.

    PubMed

    Yang, Jiancheng; Wu, Gaofeng; Feng, Ying; Sun, Changmian; Lin, Shumei; Hu, Jianmin

    2010-06-01

    In the present study, the cysteine sulfinate decarboxylase (CSD) mRNA expression was detected in rat testis by RT-PCR. The results showed that CSD mRNA was expressed in rat testis, and the putative encoded-amino acid sequence was exactly the same as that in rat liver which was already known. At the same time, the effects of taurine on testosterone secretion were investigated both in vivo and in vitro. In vivo, taurine were administered to male rats by tap water. The results showed that taurine obviously stimulated the secretion of FSH, LH and testosterone in serum, but showed no significant effect on the secretion of estradiol. Taurine administered in water could significantly increase the concentration of taurine in the blood and testis of rats. In vitro, cultured Leydig cells were treated with taurine independently or incubated with human chorionic gonadotropin (HCG) and progesterone. The results showed that taurine had biphasic effects on basal testosterone secretion in cultured Leydig cells. Low concentrations of taurine (0.1-100 microg/ml) could stimulate testosterone secretion, whereas high concentration of taurine (400 microg/ml) could inhibit testosterone secretion. Testosterone secretion stimulated by HCG was significantly increased by 10 and 100 microg/ml of taurine administration, and obviously decreased by treating with 400 microg/ml of taurine. Testosterone secretion induced by progesterone was significantly stimulated by treating with 1.0 and 10 microg/ml of taurine, however, it was significantly inhibited when treated with 400 microg/ml of taurine. Meanwhile, the effect of silencing CSD mRNA by siRNA on testosterone secretion was analyzed. The results showed that testosterone secretion was obviously decreased after the inhibition of CSD mRNA expression in cultured Leydig cells. These results indicated that taurine can be synthesized in rat testis by CSD pathway, and it plays important roles in testosterone secretion both in vivo and in vitro which

  20. Acidic glycosphingolipids of cock testis elucidated by mass spectrometry and NMR spectroscopy.

    PubMed

    Iga, D P; Iga, S; Larsson, T; Angström, J; Soussi, B; Rakotonirainy, O; Miller-Podraza, H

    1998-12-01

    The main acidic glycosphingolipids (GSLs) of cock testis were identified as GalCer I3-sulfate and gangliosides GM4, GM3, GD3 and GT3. They contained N-acetylneuraminic acid as the major sialic acid, and ceramides composed mainly of sphingosine (dl8:1) and C18-24 non-hydroxy fatty acids. Appreciable amounts of hydroxy fatty acids were detected only in the GM4 preparation.

  1. Assessment of morphological and functional changes in neonate vitrified testis grafts after host treatment with melatonin.

    PubMed

    Hemadi, M; Zargar, M; Sobhani, A; Sobhani, A

    2011-05-01

    This study was conducted to assess the effect of melatonin on the structure of testis and spermatogenesis dynamics in neonate vitrified testis grafts. Neonate vitrified testes, candidates for transplantation heterotopically to experiment or control groups, were warmed in thawing media which had or did not have a supplement of 100 μM melatonin, respectively. Following transplantation, melatonin (20 mg/ /kg/day) or saline solution was intraperitoneally injected into the treated and the non-treated groups, respectively. The initiating spermatogenesis, spermatogonia survival, and structure of tissue in the testis graft were examined. Cell apoptosis (TUNEL assay) and proliferation (Brdu assay) in germ cells were determined. Histological studies revealed the dynamic of the spermatogenesis process in the vitrified testis graft. However, dilation of the lumen accompanied by a disorganised epithelium in the non-treated group was higher than in the treated group. Furthermore, the proportion of apoptotic germ cells together with a reduced proportion of proliferated germ cells was higher in the non-treated group than in the treated group. Overall, the number of seminiferous tubules in the testes grafts of both groups remained steady. However, the non-treated testes grafts contained more damaged seminiferous tubules than the treated ones. The thickness of the seminiferous tubules was greater in the melatonin treated group than in the non-treated group. In fact, the thickness of germinal epithelium was significantly higher in the treated group than in the non-treated group. The study may show a positive effect from melatonin resulting in more grafts restoring puberty. Furthermore, the associated increase in the healthy number of seminiferous tubules suggests that melatonin may have a preventative ischaemia/antioxidant role and in fact may be useful to initiate the spermatogenesis process.

  2. RBPJ in mouse Sertoli cells is required for proper regulation of the testis stem cell niche.

    PubMed

    Garcia, Thomas Xavier; Farmaha, Jaspreet Kaur; Kow, Sean; Hofmann, Marie-Claude

    2014-12-01

    Stem cells are influenced by their surrounding microenvironment, or niche. In the testis, Sertoli cells are the key niche cells directing the population size and differentiation fate of spermatogonial stem cells (SSCs). Failure to properly regulate SSCs leads to infertility or germ cell hyperplasia. Several Sertoli cell-expressed genes, such as Gdnf and Cyp26b1, have been identified as being indispensable for the proper maintenance of SSCs in their niche, but the pathways that modulate their expression have not been identified. Although we have recently found that constitutively activating NOTCH signaling in Sertoli cells leads to premature differentiation of all prospermatogonia and sterility, suggesting that there is a crucial role for this pathway in the testis stem cell niche, a true physiological function of NOTCH signaling in Sertoli cells has not been demonstrated. To this end, we conditionally ablated recombination signal binding protein for immunoglobulin kappa J region (Rbpj), a crucial mediator of NOTCH signaling, in Sertoli cells using Amh-cre. Rbpj knockout mice had: significantly increased testis sizes; increased expression of niche factors, such as Gdnf and Cyp26b1; significant increases in the number of pre- and post-meiotic germ cells, including SSCs; and, in a significant proportion of mice, testicular failure and atrophy with tubule lithiasis, possibly due to these unsustainable increases in the number of germ cells. We also identified germ cells as the NOTCH ligand-expressing cells. We conclude that NOTCH signaling in Sertoli cells is required for proper regulation of the testis stem cell niche and is a potential feedback mechanism, based on germ cell input, that governs the expression of factors that control SSC proliferation and differentiation.

  3. Temperature-induced elevation of basal metabolic rate does not affect testis growth in great tits.

    PubMed

    Caro, Samuel P; Visser, Marcel E

    2009-07-01

    The timing of reproduction varies from year to year in many bird species. To adjust their timing to the prevailing conditions of that year, birds use cues from their environment. However, the relative importance of these cues, such as the initial predictive (e.g. photoperiod) and the supplemental factors (e.g. temperature), on the seasonal sexual development are difficult to distinguish. In particular, the fine-tuning effect of temperature on gonadal growth is not well known. One way temperature may affect timing is via its strong effect on energy expenditure as gonadal growth is an energy-demanding process. To study the interaction of photoperiod and temperature on gonadal development, we first exposed 35 individually housed male great tits (Parus major) to mid-long days (after 6 weeks of 8 h L:16 h D at 15 degrees C, photoperiod was set to 13 h L:11 h D at 15 degrees C). Two weeks later, for half of the males the temperature was set to 8 degrees C, and for the other half to 22 degrees C. Unilateral laparotomies were performed at weeks 5 (i.e one week before the birds were transferred to mid-long days), 8 and 11 to measure testis size. Two measures of basal metabolic rate (BMR) were performed at the end of the experiment (weeks 11 and 12). Testis size increased significantly during the course of the experiment, but independently of the temperature treatment. BMR was significantly higher in birds exposed to the cold treatment. These results show that temperature-related elevation of BMR did not impair the long-day-induced testis growth in great tits. As a consequence, temperature may not be a crucial cue and/or constraint factor in the fine-tuning of the gonadal recrudescence in male great tits, and testis growth is not a high energy-demanding seasonal process. PMID:19525424

  4. The effect of zinc supplementation on the effects of lead on the rat testis.

    PubMed

    Batra, N; Nehru, B; Bansal, M P

    1998-01-01

    With increasing concerns about environmental pollution, the interaction of micronutrients with toxic metals is of great interest. The present study was designed to investigate testicular effects of lead following concomitant administration of zinc. Lead was administered orally as lead acetate (50 mg/kg b.w.) daily for 3 months to male Portan rats with or without zinc (1 mg/kg b.w. as zinc sulphate). The control group was given the same volume of distilled water. Endpoints included lead concentration in various body organs as well as in the reproductive system, including testicular subfractions; the testicular enzymes superoxide dismutase (SOD) and catalase; the marker enzyme delta-aminolevulinic acid dehydratase (delta-ALAD); and testicular histoarchitecture. The concentrations of lead in bone, kidney, prostate, testis, liver, epididymis, spleen, seminal vesicles, and blood were significantly higher in lead-treated rats. Lead deposition was reduced in animals that received supplemental zinc. There was a 30% reduction in lead deposition in the testis when zinc was coadministered. At the subcellular level, there was differential accumulation of lead; the nucleus preferentially took up the metal after lead treatment alone, while zinc coadministration shifted lead accumulation to the mitochondria. A significant decrease in delta-ALAD and in SOD activity was seen in the testis with lead treatment. Coadministration of zinc prevented these decreases, at least partially. Zinc coadministration did not prevent the inhibition of catalase observed with lead treatment. Histologically, the alterations in the testis with lead treatment alone were more pronounced compared to animals in which zinc was supplemented. Improvement in the inhibition of delta-ALAD and in the ubiquitous cellular enzyme SOD suggests less testicular tissue damage due to detoxification of free radicals. In conclusion, zinc supplementation ameliorates lead-induced testicular damage both at the cellular and

  5. Gene expression profiling in liver and testis of rats to characterize the toxicity of triazole fungicides

    SciTech Connect

    Tully, Douglas B.; Bao Wenjun; Goetz, Amber K.; Blystone, Chad R.; Ren, Hongzu; Schmid, Judith E.; Strader, Lillian F.; Wood, Carmen R.; Best, Deborah S.; Narotsky, Michael G.; Wolf, Douglas C.; Rockett, John C.; Dix, David J. . E-mail: dix.david@epa.gov

    2006-09-15

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected for hormone measurements, and liver and testes were collected for histology, enzyme biochemistry, or gene expression profiling. Body and testis weights were unaffected, but liver weights were significantly increased by all four triazoles, and hepatocytes exhibited centrilobular hypertrophy. Myclobutanil exposure increased serum testosterone and decreased sperm motility, but no treatment-related testis histopathology was observed. We hypothesized that gene expression profiles would identify potential mechanisms of toxicity and used DNA microarrays and quantitative real-time PCR (qPCR) to generate profiles. Triazole fungicides are designed to inhibit fungal cytochrome P450 (CYP) 51 enzyme but can also modulate the expression and function of mammalian CYP genes and enzymes. Triazoles affected the expression of numerous CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a isoforms as well as other xenobiotic metabolizing enzyme (XME) and transporter genes. For some genes, such as Ces2 and Udpgtr2, all four triazoles had similar effects on expression, suggesting possible common mechanisms of action. Many of these CYP, XME and transporter genes are regulated by xeno-sensing nuclear receptors, and hierarchical clustering of CAR/PXR-regulated genes demonstrated the similarities of toxicogenomic responses in liver between all four triazoles and in testis between myclobutanil and triadimefon. Triazoles also affected expression of multiple genes involved in steroid hormone metabolism in the two tissues. Thus, gene expression profiles helped identify possible toxicological mechanisms of the triazole fungicides.

  6. The effect of zinc supplementation on the effects of lead on the rat testis.

    PubMed

    Batra, N; Nehru, B; Bansal, M P

    1998-01-01

    With increasing concerns about environmental pollution, the interaction of micronutrients with toxic metals is of great interest. The present study was designed to investigate testicular effects of lead following concomitant administration of zinc. Lead was administered orally as lead acetate (50 mg/kg b.w.) daily for 3 months to male Portan rats with or without zinc (1 mg/kg b.w. as zinc sulphate). The control group was given the same volume of distilled water. Endpoints included lead concentration in various body organs as well as in the reproductive system, including testicular subfractions; the testicular enzymes superoxide dismutase (SOD) and catalase; the marker enzyme delta-aminolevulinic acid dehydratase (delta-ALAD); and testicular histoarchitecture. The concentrations of lead in bone, kidney, prostate, testis, liver, epididymis, spleen, seminal vesicles, and blood were significantly higher in lead-treated rats. Lead deposition was reduced in animals that received supplemental zinc. There was a 30% reduction in lead deposition in the testis when zinc was coadministered. At the subcellular level, there was differential accumulation of lead; the nucleus preferentially took up the metal after lead treatment alone, while zinc coadministration shifted lead accumulation to the mitochondria. A significant decrease in delta-ALAD and in SOD activity was seen in the testis with lead treatment. Coadministration of zinc prevented these decreases, at least partially. Zinc coadministration did not prevent the inhibition of catalase observed with lead treatment. Histologically, the alterations in the testis with lead treatment alone were more pronounced compared to animals in which zinc was supplemented. Improvement in the inhibition of delta-ALAD and in the ubiquitous cellular enzyme SOD suggests less testicular tissue damage due to detoxification of free radicals. In conclusion, zinc supplementation ameliorates lead-induced testicular damage both at the cellular and

  7. Immunolocalisation of ghrelin and obestatin in human testis, seminal vesicles, prostate and spermatozoa.

    PubMed

    Moretti, E; Vindigni, C; Tripodi, S A; Mazzi, L; Nuti, R; Figura, N; Collodel, G

    2014-01-01

    The role of ghrelin and obestatin in male reproduction has not completely been clarified. We explored ghrelin and obestatin localisation in the male reproductive system. Polyclonal antibodies anti-ghrelin and anti-obestatin were used to detect the expression of these hormones in human testis, prostate and seminal vesicles by immunocytochemistry, while in ejaculated and swim up selected spermatozoa by immunofluorescence. Sertoli cells were positive for both peptides and Leydig cells for ghrelin; germ cells were negative for both hormones. Mild signals for ghrelin and obestatin were observed in rete testis; efferent ductules were the most immune reactive region for both peptides. Epididymis was moderately positive for ghrelin; vas deferens and seminal vesicles showed intense obestatin and moderate ghrelin labelling; prostate tissue expressed obestatin alone. Ejaculated and selected spermatozoa were positive for both peptides in different head and tail regions. This study confirms ghrelin localisation in Leydig and Sertoli cells; the finding that ghrelin is expressed in rete testis, epididymis, vas deferens and seminal vesicles is novel, as well as the localisation of obestatin in almost all tracts of the male reproductive system. This research could offer insights for stimulating other studies, particularly on the role of obestatin in sperm physiology, which is still obscure.

  8. Cancer/testis antigen NY-SAR-35 enhances cell proliferation, migration, and invasion.

    PubMed

    Song, Myung-Ha; Kim, Ye-Rin; Lee, Jun-Won; Lee, Chang-Hun; Lee, Sang-Yull

    2016-02-01

    The cancer/testis antigen NY-SAR-35 is aberrantly expressed in various cancer tissues and cancer cell lines but not in normal tissues except for the testis. A previous study demonstrated that the expression of NY-SAR-35 is activated by hypomethylation in cancer cells. However, the functions of this antigen remain unexplored. In the present study, we investigated the role of NY-SAR‑35 in human embryonic kidney (HEK) 293 cells using exogenous expression system of the gene. NY-SAR‑35 was predominantly expressed at the cytoplasm and was mainly observed in spermatogonia and spermatocytes. Expression of NY-SAR-35 in stable HEK293 transfectant clones was 2-fold higher than the control cells promoting cell growth and proliferation. NY-SAR-35 overexpression also enhanced cell migration and invasion ~2-fold and 4-fold more than the control, respectively. In contrast, small interfering RNA-mediated knockdown of NY-SAR-35 suppressed cell proliferation, migration, and invasion in HEK293 stable transfectants. We concluded that NY-SAR-35 as a cancer/testis antigen enhanced cell proliferation and invasion.

  9. In-depth proteomic analysis of whole testis tissue from the adult rhesus macaque.

    PubMed

    Wang, Jing; Xia, Yankai; Wang, Gaigai; Zhou, Tao; Guo, Yueshuai; Zhang, Chao; An, Xia; Sun, Yujie; Guo, Xuejiang; Zhou, Zuomin; Sha, Jiahao

    2014-06-01

    The rhesus macaque is similar to humans both anatomically and physiologically as a primate, and has therefore been used extensively in medical and biological research, including reproductive physiology. Despite sequencing of the macaque genome, limited postgenomic studies have been performed to date. In studies aimed at characterizing spermatogenesis, we successfully identified 9078 macaque testis proteins corresponding to 8662 genes, using advanced MS and an optimized proteomics platform, indicative of complex protein compositions during macaque spermatogenesis. Immunohistochemistry analysis further revealed the presence of proteins from different types of testicular cells, including Sertoli cells, Leydig cells, and various stages of germ cells. Our data provide expression evidence at protein level of 3010 protein-coding genes in 8662 identified testis genes for the first time. We further identified 421 homologous genes from the proteome already known to be essential for male infertility in mouse. Comparative analysis of the proteome showed high similarity with the published human testis proteome, implying that macaque and human may use similar proteins to regulate spermatogenesis. Our in-depth analysis of macaque spermatogenesis provides a rich resource for further studies, and supports the utility of macaque as a suitable model for the study of human reproduction.

  10. Cloning and Characterization of Novel Testis-Specific Diacylglycerol Kinase η Splice Variants 3 and 4.

    PubMed

    Murakami, Eri; Shionoya, Takao; Komenoi, Suguru; Suzuki, Yuji; Sakane, Fumio

    2016-01-01

    Diacylglycerol kinase (DGK) phosphorylates DG to generate phosphatidic acid. Recently, we found that a new alternative splicing product of the DGKη gene, DGKη3, which lacks exon 26 encoding 31 amino acid residues, was expressed only in the secondary spermatocytes and round spermatids of the testis. In this study, we cloned the full length DGKη3 gene and confirmed the endogenous expression of its protein product. During the cloning procedure, we found a new testis-specific alternative splicing product of the DGKη gene, DGKη4, which lacks half of the catalytic domain. We examined the DGK activity and subcellular localization of DGKη3 and η4. DGKη3 had almost the same activity as DGKη1, whereas the activity of DGKη4 was not detectable. In resting NEC8 cells (human testicular germ cell tumor cell line), DGKη1, η3 and η4 were broadly distributed in the cytoplasm. When osmotically shocked, DGKη1 and η4 were distributed in punctate vesicles in the cytoplasm. In contrast, DGKη3 was partly translocated to the plasma membrane and co-localized with the actin cytoskeleton. These results suggest that DGKη3 and η4 have properties different from those of DGKη1 and that they play roles in the testis in a different manner. PMID:27643686

  11. Phthalate esters affect maturation and function of primate testis tissue ectopically grafted in mice.

    PubMed

    Rodriguez-Sosa, Jose R; Bondareva, Alla; Tang, Lin; Avelar, Gleide F; Coyle, Krysta M; Modelski, Mark; Alpaugh, Whitney; Conley, Alan; Wynne-Edwards, Katherine; França, Luiz R; Meyers, Stuart; Dobrinski, Ina

    2014-12-01

    Di-n-Butyl (DBP) and Di-(2-EthylHexyl) (DEHP) phthalates can leach from daily-use products resulting in environmental exposure. In male rodents, phthalate exposure results in reproductive effects. To evaluate effects on the immature primate testis, testis fragments from 6-month-old rhesus macaques were grafted subcutaneously to immune-deficient mice, which were exposed to 0, 10, or 500 mg/kg of DBP or DEHP for 14 weeks or 28 weeks (DBP only). DBP exposure reduced the expression of key steroidogenic genes, indicating that Leydig cell function was compromised. Exposure to 500 mg/kg impaired tubule formation and germ cell differentiation and reduced numbers of spermatogonia. Exposure to 10 mg/kg did not affect development, but reduced Sertoli cell number and resulted in increased expression of inhibin B. Exposure to DEHP for 14 week also affected steroidogenic genes expression. Therefore, long-term exposure to phthalate esters affected development and function of the primate testis in a time and dosage dependent manner.

  12. Comprehensive functional characterization of cancer–testis antigens defines obligate participation in multiple hallmarks of cancer

    PubMed Central

    Maxfield, Kimberly E.; Taus, Patrick J.; Corcoran, Kathleen; Wooten, Joshua; Macion, Jennifer; Zhou, Yunyun; Borromeo, Mark; Kollipara, Rahul K.; Yan, Jingsheng; Xie, Yang; Xie, Xian-Jin; Whitehurst, Angelique W.

    2015-01-01

    Tumours frequently activate genes whose expression is otherwise biased to the testis, collectively known as cancer–testis antigens (CTAs). The extent to which CTA expression represents epiphenomena or confers tumorigenic traits is unknown. In this study, to address this, we implemented a multidimensional functional genomics approach that incorporates 7 different phenotypic assays in 11 distinct disease settings. We identify 26 CTAs that are essential for tumor cell viability and/or are pathological drivers of HIF, WNT or TGFβ signalling. In particular, we discover that Foetal and Adult Testis Expressed 1 (FATE1) is a key survival factor in multiple oncogenic backgrounds. FATE1 prevents the accumulation of the stress-sensing BH3-only protein, BCL-2-Interacting Killer (BIK), thereby permitting viability in the presence of toxic stimuli. Furthermore, ZNF165 promotes TGFβ signalling by directly suppressing the expression of negative feedback regulatory pathways. This action is essential for the survival of triple negative breast cancer cells in vitro and in vivo. Thus, CTAs make significant direct contributions to tumour biology. PMID:26567849

  13. Modulating testicular mass in xenografting: a model to explore testis development and endocrine function.

    PubMed

    Schlatt, Stefan; Gassei, Kathrin; Westernströer, Birgit; Ehmcke, Jens

    2010-08-01

    The hypothalamic-pituitary-gonadal (HPG) axis is involved in both the regulation of growth of the developing testis and in controlling spermatogenic and steroidogenic activity in the adult testis. Here, we develop a novel testicular xenografting model to examine to which degree testicular growth and function are controlled by intra- and extratesticular factors. Two or eight halves of neonatal Djungarian hamster testes were implanted into intact, hemicastrated, or castrated nude mouse recipients, and the development of the grafts under reduced or increased competition of testicular tissue was monitored and analyzed. We hypothesized that the outgrowth of the testicular grafts is influenced by the total amount of testicular tissue present in a host and that less testicular tissue in a host would result in more extended outgrowth of the grafts. Our results reveal that the hypothesis is wrong, because implanted hamster testis tissue irrespectively of the grafting condition grows to a similar size revealing an intrinsic mechanism for testicular growth. In contrast, similar size of seminal vesicle as bio-indicator of androgen levels in all hosts revealed that the steroidogenic activity is independent from the mass of testicular tissue and that steroid levels are extrinsically regulated by the recipient's HPG axis. We propose that the model of testicular xenografting provides highly valuable options to explore testicular growth and endocrine regulation of the HPG axis.

  14. Testosterone and estradiol are co-secreted episodically by the human testis.

    PubMed Central

    Winters, S J; Troen, P

    1986-01-01

    In spite of a striking pulsatile pattern of luteinizing hormone (LH) secretion, testosterone (T) fluctuations in peripheral blood in normal adult men are irregular and of low amplitude. To determine whether T secretion by the human testis is episodic, T was measured in blood samples drawn at 15-min intervals for 4 h through a catheter placed in the testicular vein of six men with varicocele-associated infertility. Estradiol (E2) concentrations were also determined in each sample. Each subject released testosterone in well-defined pulses. Gonadal vein T levels ranged from 1 to 1,540 ng/ml. Mean (+/- SE) pulse amplitude was 176 +/- 42 ng/ml, with a frequency of 4.0 +/- 0.3 pulses per 4 h. Testicular vein E2 levels ranged from 0.01 to 6.8 ng/ml. E2 secretory episodes were generally coincident with T pulses, and their amplitudes were highly positively correlated (r = 0.90, P less than 0.01). These results indicate that T secretion by the adult human testis is pulsatile, and suggest a functional relationship between intermittent LH secretion and normal testicular steroidogenesis in men. The failure to appreciate these fluctuations as hormone pulses in peripheral blood may relate to their absolute amplitude and frequency. The concordance between E2 and T pulses suggests that the Leydig cell, under LH control, is the source of most of the E2 secreted by the adult human testis. PMID:3760188

  15. (56)Fe ion irradiation induced apoptosis through Nrf2 pathway in mouse testis.

    PubMed

    Zhao, Qiuyue; Mao, Aihong; Yan, Jiawei; Si, Jing; Zhou, Rong; Gan, Lu; Liu, Yang; Zhang, Hong

    2016-07-15

    The phenomenon has raised the concerns about the safety of an extended manned mission into deep space due to the high potential for exposure to high-LET radiation during space missions. Heavy ions such as (56)Fe are main radiation sources in deep space, which could pose a significant hazard to space flight crews during and after missions. Since the testis is a radiosensitive organ, which may be susceptible to space radiation-induced changes. In this study, we investigated the effect and potential mechanisms of (56)Fe irradiation on mouse testis. Pathological characteristics were measured following whole-body irradiation with 0.5 and 1Gy (56)Fe irradiation. Flow cytometry and terminal dUTP nick end-labeling (TUNEL) were performed to detect apoptotic cells. Western blot was applied to identify potential biomarkers. Immunofluorescence was used to investigate protein localization. We found that pathologic changes and apoptosis cells were significantly higher in 1Gy group than those in 0Gy groups. In addition, protein expression and localization studies confirmed Nrf2 was involved in this acute injury. Nrf2 and its target genes HO-1 and NQO1 were up-regulated in the irradiated testis in a dose-dependent manner. Nrf2 may be useful molecular markers in radiation-induced cellular responses and is important for detecting abnormal spermatogenesis following exposure to space radiation. PMID:27259810

  16. Sodium fluoride and sulfur dioxide affected male reproduction by disturbing blood-testis barrier in mice.

    PubMed

    Zhang, Jianhai; Li, Zhihui; Qie, Mingli; Zheng, Ruibo; Shetty, Jagathpala; Wang, Jundong

    2016-08-01

    Fluoride and sulfur dioxide (SO2), two well-known environmental toxicants, have been implicated to have adverse effects on male reproductive health in humans and animals. The objective of this study to investigate if the BTB is one of the pathways that lead to reproductive toxicity of sodium fluoride and sulfur dioxide alone or in combination, in view of the key role of blood testis barrier (BTB) in testis. The results showed that a marked decrease in sperm quality, and altered morphology and ultrastructure of BTB in testis of mice exposure to fluoride (100 mg NaF/L in drinking water) or/and sulfur dioxide (28 mg SO2/m(3), 3 h/day). Meanwhile, the mRNA expression levels of some vital BTB-associated proteins, including occluding, claudin-11, ZO-1, Ncadherin, α-catenin, and connexin-43 were all strikingly reduced after NaF exposure, although only the reduction of DSG-2 was statistically significant in all treatment groups. Moreover, the proteins expressions also decreased significantly in claudin-11, N-cadherin, α-catenin, connexin-43 and desmoglein-2 in mice treated with fluoride and/or SO2. These changes in BTB structure and constitutive proteins may therefore be connected with the low sperm quality in these mice. The role of fluoride should deserves more attention in this process. PMID:27237588

  17. Prophylactic efficacy of Coriandrum sativum (Coriander) on testis of lead-exposed mice.

    PubMed

    Sharma, Veena; Kansal, Leena; Sharma, Arti

    2010-09-01

    Lead poisoning is a worldwide health problem, and its treatment is under investigation. The aim of this study was to access the efficacy of Coriandrum sativum (coriander) in reducing lead-induced changes in mice testis. Animal exposed to lead nitrate showed significant decrease in testicular SOD, CAT, GSH, total protein, and tissue lead level. This was accompanied by simultaneous increase in the activities of LPO, AST, ALT, ACP, ALP, and cholesterol level. Serum testosterone level and sperm density were suppressed in lead-treated group compared with the control. These influences of lead were prevented by concurrent daily administration of C. sativum extracts to some extent. Treating albino mice with lead-induced various histological changes in the testis and treatment with coriander led to an improvement in the histological testis picture. The results thus led us to conclude that administration of C. sativum significantly protects against lead-induced oxidative stress. Further work need to be done to isolate and purify the active principle involved in the antioxidant activity of this plant.

  18. Distribution of the sex chromosome during mouse spermatogenesis in testis tissue sections.

    PubMed

    Otaka, Kosuke; Hiradate, Yuuki; Kobayashi, Norio; Shirakata, Yoshiki; Tanemura, Kentaro

    2015-01-01

    During mammalian spermatogenesis, spermatogenic cells undergo mitotic division and are subsequently divided into haploid spermatids by meiotic division, but the dynamics of sex chromosomes during spermatogenesis are unclear in vivo. To gain insight into the distribution of sex chromosomes in the testis, we examined the localization of sex chromosomes before and after meiosis in mouse testis sections. Here, we developed a method of fluorescence in situ hybridization (FISH) using specific probes for the X and Y chromosomes to obtain their positional information in histological testis sections. FISH analysis revealed the sex chromosomal position during spermatogenesis in each stage of seminiferous epithelia and in each spermatogenic cell. In the spermatogonia and leptotene spermatocytes, sex chromosomes were distantly positioned in the cell. In the zygotene and pachytene spermatocytes at prophase I, X and Y chromosomes had a random distribution. After meiosis, the X and Y spermatids were random in every seminiferous epithelium. We also detected aneuploidy of sex chromosomes in spermatogenic cells using our developed FISH analysis. Our results provide further insight into the distribution of sex chromosomes during spermatogenesis, which could help to elucidate a specific difference between X and Y spermatids and sex chromosome-specific behavior.

  19. Sodium fluoride and sulfur dioxide affected male reproduction by disturbing blood-testis barrier in mice.

    PubMed

    Zhang, Jianhai; Li, Zhihui; Qie, Mingli; Zheng, Ruibo; Shetty, Jagathpala; Wang, Jundong

    2016-08-01

    Fluoride and sulfur dioxide (SO2), two well-known environmental toxicants, have been implicated to have adverse effects on male reproductive health in humans and animals. The objective of this study to investigate if the BTB is one of the pathways that lead to reproductive toxicity of sodium fluoride and sulfur dioxide alone or in combination, in view of the key role of blood testis barrier (BTB) in testis. The results showed that a marked decrease in sperm quality, and altered morphology and ultrastructure of BTB in testis of mice exposure to fluoride (100 mg NaF/L in drinking water) or/and sulfur dioxide (28 mg SO2/m(3), 3 h/day). Meanwhile, the mRNA expression levels of some vital BTB-associated proteins, including occluding, claudin-11, ZO-1, Ncadherin, α-catenin, and connexin-43 were all strikingly reduced after NaF exposure, although only the reduction of DSG-2 was statistically significant in all treatment groups. Moreover, the proteins expressions also decreased significantly in claudin-11, N-cadherin, α-catenin, connexin-43 and desmoglein-2 in mice treated with fluoride and/or SO2. These changes in BTB structure and constitutive proteins may therefore be connected with the low sperm quality in these mice. The role of fluoride should deserves more attention in this process.

  20. Repeated Duplication of Argonaute2 Is Associated with Strong Selection and Testis Specialization in Drosophila

    PubMed Central

    Lewis, Samuel H.; Webster, Claire L.; Salmela, Heli; Obbard, Darren J.

    2016-01-01

    Argonaute2 (Ago2) is a rapidly evolving nuclease in the Drosophila melanogaster RNA interference (RNAi) pathway that targets viruses and transposable elements in somatic tissues. Here we reconstruct the history of Ago2 duplications across the D. obscura group and use patterns of gene expression to infer new functional specialization. We show that some duplications are old, shared by the entire species group, and that losses may be common, including previously undetected losses in the lineage leading to D. pseudoobscura. We find that while the original (syntenic) gene copy has generally retained the ancestral ubiquitous expression pattern, most of the novel Ago2 paralogs have independently specialized to testis-specific expression. Using population genetic analyses, we show that most testis-specific paralogs have significantly lower genetic diversity than the genome-wide average. This suggests recent positive selection in three different species, and model-based analyses provide strong evidence of recent hard selective sweeps in or near four of the six D. pseudoobscura Ago2 paralogs. We speculate that the repeated evolution of testis specificity in obscura group Ago2 genes, combined with their dynamic turnover and strong signatures of adaptive evolution, may be associated with highly derived roles in the suppression of transposable elements or meiotic drive. Our study highlights the lability of RNAi pathways, even within well-studied groups such as Drosophila, and suggests that strong selection may act quickly after duplication in RNAi pathways, potentially giving rise to new and unknown RNAi functions in nonmodel species. PMID:27535930

  1. Phthalate esters affect maturation and function of primate testis tissue ectopically grafted in mice

    PubMed Central

    Rodriguez-Sosa, Jose R; Bondareva, Alla; Tang, Lin; Avelar, Gleide F.; Coyle, Krysta M.; Modelski, Mark; Alpaugh, Whitney; Conley, Alan; Wynne-Edwards, Katherine; França, Luiz R; Meyers, Stuart; Dobrinski, Ina

    2014-01-01

    Di-n-Butyl (DBP) and Di-(2-EthylHexyl) (DEHP) phthalates can leach from daily-use products resulting in environmental exposure. In male rodents, phthalate exposure results in reproductive effects. To evaluate effects on the immature primate testis, testis fragments from 6-month-old rhesus macaques were grafted subcutaneously to immune-deficient mice, which were exposed to 0, 10, or 500 mg/kg of DBP or DEHP for 14 weeks or 28 weeks (DBP only). DBP exposure reduced the expression of key steroidogenic genes, indicating that Leydig cell function was compromised. Exposure to 500 mg/kg impaired tubule formation and germ cell differentiation and reduced numbers of spermatogonia. Exposure to 10 mg/kg did not affect development, but reduced Sertoli cell number and resulted in increased expression of inhibin B. Exposure to DEHP for 14 week also affected steroidogenic genes expression. Therefore, long-term exposure to phthalate esters affected development and function of the primate testis in a time and dosage dependent manner. PMID:25450860

  2. Cloning and Characterization of Novel Testis-Specific Diacylglycerol Kinase η Splice Variants 3 and 4

    PubMed Central

    Murakami, Eri; Shionoya, Takao; Komenoi, Suguru; Suzuki, Yuji; Sakane, Fumio

    2016-01-01

    Diacylglycerol kinase (DGK) phosphorylates DG to generate phosphatidic acid. Recently, we found that a new alternative splicing product of the DGKη gene, DGKη3, which lacks exon 26 encoding 31 amino acid residues, was expressed only in the secondary spermatocytes and round spermatids of the testis. In this study, we cloned the full length DGKη3 gene and confirmed the endogenous expression of its protein product. During the cloning procedure, we found a new testis-specific alternative splicing product of the DGKη gene, DGKη4, which lacks half of the catalytic domain. We examined the DGK activity and subcellular localization of DGKη3 and η4. DGKη3 had almost the same activity as DGKη1, whereas the activity of DGKη4 was not detectable. In resting NEC8 cells (human testicular germ cell tumor cell line), DGKη1, η3 and η4 were broadly distributed in the cytoplasm. When osmotically shocked, DGKη1 and η4 were distributed in punctate vesicles in the cytoplasm. In contrast, DGKη3 was partly translocated to the plasma membrane and co-localized with the actin cytoskeleton. These results suggest that DGKη3 and η4 have properties different from those of DGKη1 and that they play roles in the testis in a different manner. PMID:27643686

  3. Prophylactic efficacy of Coriandrum sativum (Coriander) on testis of lead-exposed mice.

    PubMed

    Sharma, Veena; Kansal, Leena; Sharma, Arti

    2010-09-01

    Lead poisoning is a worldwide health problem, and its treatment is under investigation. The aim of this study was to access the efficacy of Coriandrum sativum (coriander) in reducing lead-induced changes in mice testis. Animal exposed to lead nitrate showed significant decrease in testicular SOD, CAT, GSH, total protein, and tissue lead level. This was accompanied by simultaneous increase in the activities of LPO, AST, ALT, ACP, ALP, and cholesterol level. Serum testosterone level and sperm density were suppressed in lead-treated group compared with the control. These influences of lead were prevented by concurrent daily administration of C. sativum extracts to some extent. Treating albino mice with lead-induced various histological changes in the testis and treatment with coriander led to an improvement in the histological testis picture. The results thus led us to conclude that administration of C. sativum significantly protects against lead-induced oxidative stress. Further work need to be done to isolate and purify the active principle involved in the antioxidant activity of this plant. PMID:19902160

  4. Screening targeted testis-specific genes for molecular assessment of aberrant sperm quality

    PubMed Central

    Liu, Xue Xia; Shen, Xiao Fang; Liu, Fu-Jun

    2016-01-01

    Teratospermia is a heterogeneous and complex disorder, which is closely associated with male fertility. Genes and gene products associated with teratospermia may serve as targeted biomarkers that help understand the underlying mechanisms of male infertility; however, systematic information on the subject remains to be elucidated. The present study performed a comparative bioinformatics analysis to identify biomarkers associated with sperm quality, particular focusing on testis-specific biomarkers. A stepwise screening approach identified 1,085 testis/epididymis-specific genes and 3,406 teratospermia-associated genes, resulting in 348 testis-specific genes associated with aberrant sperm quality. These genes were functionally associated with the reproduction process. Gene products corresponding to heat shock protein family A (Hsp70) member 4 like (HSPA4L) and phosphoglycerate kinase 2 were characterized at the cellular level in human testes and ejaculated spermatozoa. HSPA4L expression in sperm was revealed to be associated with sperm quality. The present study provided a novel insight into the understanding of sperm quality, and a potential method for the diagnosis and assessment of sperm quality in the event of male infertility. PMID:27356588

  5. CETN1 is a cancer testis antigen with expression in prostate and pancreatic cancers

    PubMed Central

    2013-01-01

    Background The Cancer Testis Antigens (CTAs) are a group of genes that are highly expressed in the normal testis and several types of cancer. Due to their restricted expression in normal adult tissues, CTAs have been attractive targets for immunotherapy and biomarker development. In this work, we discovered that Centrin 1 (CETN1) which is found in the centrosome of all eukaryotes, may be a member of this group and is highly expressed in prostate and pancreatic cancer. Three members of the centrin family of calcium binding proteins (CETN) are localized to the centrosome in all eukaryotes with CDC31 being the sole yeast homolog. CETN1 is a retrogene that probably arose from a retrotransposition of CETN2, an X-linked gene. A previous mouse study shows that CETN1 is expressed solely in the testis, while CETN2 is expressed in all organs. Results In this work, we show that CETN1 is a new member of the growing group of CTAs. Through the mining of publicly available microarray data, we discovered that human CETN1 expression but not CETN2 or CETN3 is restricted to the testis. In fact, CETN1 is actually down-regulated in testicular malignancies compared to normal testis. Using q-PCR, CETN1 expression is shown to be highly up-regulated in cancer of the prostate and in pancreatic xenografts. Unexpectedly however, CETN1 expression was virtually absent in various cell lines until they were treated with the DNA demethylation agent 5’AZA-2’Deoxycytidine (AZA) but showed no increased expression upon incubation with Histone deacetylase inhibitor Trichostatin-A (TSA) alone. Additionally, like most CTAs, CETN1 appears to be an intrinsically disordered protein which implies that it may occupy a hub position in key protein interaction networks in cancer. Neither CETN1 nor CETN2 could compensate for loss of CDC31 expression in yeast which is analogous to published data for CETN3. Conclusions This work suggests that CETN1 is a novel CTA with expression in cancer of the prostate and

  6. Effect of methoxychlor on the antioxidant system in mitochondrial and microsome-rich fractions of rat testis.

    PubMed

    Latchoumycandane, C; Mathur, P P

    2002-07-01

    Methoxychlor, an environmental contaminant, which is widely used as a pesticide in many countries, has been shown to induce reproductive abnormalities in male rats. The precise nature and mechanism of action of methoxychlor on the male reproductive system is not clear. In the present study, we have sought to investigate the induction of oxidative stress in the testis of rat after exposure to methoxychlor. Methoxychlor (1, 10, and 100 mg kg(-1) body weight per day) was administered orally to the rats for 45 days. After 24 h of the last treatment the animals were killed using anesthetic ether. The body weight of the animals administered with methoxychlor did not show any significant change. The weights of the testis, epididymis, seminal vesicles and ventral prostate decreased significantly in 100 mg dose but remained unchanged in 1 and 10 mg doses. Mitochondrial and microsome-rich fractions of the testis were obtained by the method of differential centrifugation. The activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase decreased significantly in the animals treated with methoxychlor in a dose-dependent manner in the mitochondrial and microsome-rich fractions of rat testis. The levels of hydrogen peroxide generation (H(2)O(2)) and lipid peroxidation increased in mitochondrial and microsome-rich fractions of the testis of the rats treated with methoxychlor. The results suggested that the low to medium doses of methoxychlor elicit depletion of antioxidant enzymes and concomitant increase in the levels of H(2)O(2) and lipid peroxidation differentially in mitochondrial and microsome-rich fractions of rat testis. In conclusion, the adverse effect of methoxychlor on male reproduction could be due to the induction of oxidative stress in testis.

  7. Activation of GPER-1 Estradiol Receptor Downregulates Production of Testosterone in Isolated Rat Leydig Cells and Adult Human Testis

    PubMed Central

    Vaucher, Laurent; Funaro, Michael G.; Mehta, Akanksha; Mielnik, Anna; Bolyakov, Alexander; Prossnitz, Eric R.; Schlegel, Peter N.; Paduch, Darius A.

    2014-01-01

    Purpose Estradiol (E2) modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. Materials and Methods Isolated Leydig cells (LC) from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. Results GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20–30% as compared to estradiol-naïve LC. The exposure to G-1 does not affect viability of isolated LCs. Conclusions Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men. PMID:24736568

  8. Histological evaluation of the testicular nubbins in patients with nonpalpable testis: assessment of etiology and surgical approach.

    PubMed

    Emir, Haluk; Ayik, Bekir; Eliçevik, Mehmet; Büyükünal, Cenk; Danişmend, Nur; Dervişoğlu, Sergülen; Söylet, Yunus

    2007-01-01

    There is a controversy in the literature whether testicular nubbins carry malignancy risk and excision of the nubbin is necessary in patients with nonpalpable testis. It is also controversial whether vanishing testis has the same etiopathogenesis and risk with true undescended testis. The aim of this study is to investigate the histological findings of testicular nubbins in patients with nonpalpable testis and to question etiology and surgical indications for vanishing testis. We reviewed the histopathological results of 44 testicular nubbins in 40 patients (mean age: 4.1 years, range 1-13 years) with nonpalpable testis between 1992 and 2004, retrospectively. Exploration revealed 5 intraabdominal and 39 inguinal testicular nubbins. Of 44 specimens only 5 (11.3%) from inquinal testicular nubbins were found to have seminiferous tubules. Two of the five had seminiferous tubule structures with viable germ cells showing maturation correlating with age. The other two with scarce seminiferous tubules were seen on only a single area and one had Sertoli cells only. None of the excised tissue had malignant degeneration. The vas deferens was identified in 23 (52.2%), vessels in 26 (59%), calcification in 14 (31.8%) and hemosiderin in 12 (27.2%) of excised tissue. Presence of calcification in one-third of the nubbins supports vascular accident thesis in the etiopathogenesis of vanishing testis. The possibility for the presence of seminiferous tubules and viable germ cells in the testicular nubbin is low. These facts decrease theoritical risk of malingnancy. Therefore, an inguinal exploration for testicular nubbin in patients with vas deferens and vessels entering into the inquinal canal diagnosed at laparoscopy can be postponed untill testicular prosthesis implantation and the nubbin can be removed at this operation.

  9. A testis-specific and testis developmentally regulated tumor protein D52 (TPD52)-like protein TPD52L3/hD55 interacts with TPD52 family proteins

    SciTech Connect

    Cao Qinhong; Chen Jie; Zhu Li; Liu Yun; Zhou Zuomin; Sha Jiahao; Wang Shui; Li Jianmin . E-mail: jianminli@njmu.edu.cn

    2006-06-09

    Tumor protein D52-like proteins (TPD52) are small coiled-coil motif bearing proteins that were first identified in breast cancer. TPD52 and related proteins have been implicated in cell proliferation, apoptosis, and vesicle trafficking. To date, three human TPD52 members had been identified, named hD52 (TPD52), hD53 (TPD52L1), and hD54 (TPD52L2). The most important characteristic of the protein family is a highly conserved coiled-coil motif that is required for homo- and heteromeric interaction with other TPD52-like proteins. Herein, we identified a novel TPD52-like sequence (TPD52L3, or hD55) in human testis using cDNA microarray. Sequence analysis of the deduced protein suggests that hD55 contains a coiled-coil motif and is highly conserved compared with other TPD52-like sequences. Yeast two-hybrid and GST pull-down assays revealed that hD55 interacts with hD52, hD53, hD54, and itself. cDNA microarray detection found that hD55 was expressed at 5.6-fold higher levels in adult testis than in fetal testis. Additionally, the expression profile shows that hD55 is testis-specific, indicating a potential role for hD55 in testis development and spermatogenesis.

  10. Nodavirus Colonizes and Replicates in the Testis of Gilthead Seabream and European Sea Bass Modulating Its Immune and Reproductive Functions.

    PubMed

    Valero, Yulema; Arizcun, Marta; Esteban, M Ángeles; Bandín, Isabel; Olveira, José G; Patel, Sonal; Cuesta, Alberto; Chaves-Pozo, Elena

    2015-01-01

    Viruses are threatening pathogens for fish aquaculture. Some of them are transmitted through gonad fluids or gametes as occurs with nervous necrosis virus (NNV). In order to be transmitted through the gonad, the virus should colonize and replicate inside some cell types of this tissue and avoid the subsequent immune response locally. However, whether NNV colonizes the gonad, the cell types that are infected, and how the immune response in the gonad is regulated has never been studied. We have demonstrated for the first time the presence and localization of NNV into the testis after an experimental infection in the European sea bass (Dicentrarchus labrax), and in the gilthead seabream (Sparus aurata), a very susceptible and an asymptomatic host fish species, respectively. Thus, we localized in the testis viral RNA in both species using in situ PCR and viral proteins in gilthead seabream by immunohistochemistry, suggesting that males might also transmit the virus. In addition, we were able to isolate infective particles from the testis of both species demonstrating that NNV colonizes and replicates into the testis of both species. Blood contamination of the tissues sampled was discarded by completely fish bleeding, furthermore the in situ PCR and immunocytochemistry techniques never showed staining in blood vessels or cells. Moreover, we also determined how the immune and reproductive functions are affected comparing the effects in the testis with those found in the brain, the main target tissue of the virus. Interestingly, NNV triggered the immune response in the European sea bass but not in the gilthead seabream testis. Regarding reproductive functions, NNV infection alters 17β-estradiol and 11-ketotestosterone production and the potential sensitivity of brain and testis to these hormones, whereas there is no disruption of testicular functions according to several reproductive parameters. Moreover, we have also studied the NNV infection of the testis in vitro to

  11. Nodavirus Colonizes and Replicates in the Testis of Gilthead Seabream and European Sea Bass Modulating Its Immune and Reproductive Functions.

    PubMed

    Valero, Yulema; Arizcun, Marta; Esteban, M Ángeles; Bandín, Isabel; Olveira, José G; Patel, Sonal; Cuesta, Alberto; Chaves-Pozo, Elena

    2015-01-01

    Viruses are threatening pathogens for fish aquaculture. Some of them are transmitted through gonad fluids or gametes as occurs with nervous necrosis virus (NNV). In order to be transmitted through the gonad, the virus should colonize and replicate inside some cell types of this tissue and avoid the subsequent immune response locally. However, whether NNV colonizes the gonad, the cell types that are infected, and how the immune response in the gonad is regulated has never been studied. We have demonstrated for the first time the presence and localization of NNV into the testis after an experimental infection in the European sea bass (Dicentrarchus labrax), and in the gilthead seabream (Sparus aurata), a very susceptible and an asymptomatic host fish species, respectively. Thus, we localized in the testis viral RNA in both species using in situ PCR and viral proteins in gilthead seabream by immunohistochemistry, suggesting that males might also transmit the virus. In addition, we were able to isolate infective particles from the testis of both species demonstrating that NNV colonizes and replicates into the testis of both species. Blood contamination of the tissues sampled was discarded by completely fish bleeding, furthermore the in situ PCR and immunocytochemistry techniques never showed staining in blood vessels or cells. Moreover, we also determined how the immune and reproductive functions are affected comparing the effects in the testis with those found in the brain, the main target tissue of the virus. Interestingly, NNV triggered the immune response in the European sea bass but not in the gilthead seabream testis. Regarding reproductive functions, NNV infection alters 17β-estradiol and 11-ketotestosterone production and the potential sensitivity of brain and testis to these hormones, whereas there is no disruption of testicular functions according to several reproductive parameters. Moreover, we have also studied the NNV infection of the testis in vitro to

  12. Nodavirus Colonizes and Replicates in the Testis of Gilthead Seabream and European Sea Bass Modulating Its Immune and Reproductive Functions

    PubMed Central

    Valero, Yulema; Arizcun, Marta; Esteban, M. Ángeles; Bandín, Isabel; Olveira, José G.; Patel, Sonal; Cuesta, Alberto; Chaves-Pozo, Elena

    2015-01-01

    Viruses are threatening pathogens for fish aquaculture. Some of them are transmitted through gonad fluids or gametes as occurs with nervous necrosis virus (NNV). In order to be transmitted through the gonad, the virus should colonize and replicate inside some cell types of this tissue and avoid the subsequent immune response locally. However, whether NNV colonizes the gonad, the cell types that are infected, and how the immune response in the gonad is regulated has never been studied. We have demonstrated for the first time the presence and localization of NNV into the testis after an experimental infection in the European sea bass (Dicentrarchus labrax), and in the gilthead seabream (Sparus aurata), a very susceptible and an asymptomatic host fish species, respectively. Thus, we localized in the testis viral RNA in both species using in situ PCR and viral proteins in gilthead seabream by immunohistochemistry, suggesting that males might also transmit the virus. In addition, we were able to isolate infective particles from the testis of both species demonstrating that NNV colonizes and replicates into the testis of both species. Blood contamination of the tissues sampled was discarded by completely fish bleeding, furthermore the in situ PCR and immunocytochemistry techniques never showed staining in blood vessels or cells. Moreover, we also determined how the immune and reproductive functions are affected comparing the effects in the testis with those found in the brain, the main target tissue of the virus. Interestingly, NNV triggered the immune response in the European sea bass but not in the gilthead seabream testis. Regarding reproductive functions, NNV infection alters 17β-estradiol and 11-ketotestosterone production and the potential sensitivity of brain and testis to these hormones, whereas there is no disruption of testicular functions according to several reproductive parameters. Moreover, we have also studied the NNV infection of the testis in vitro to

  13. Testis hormone-sensitive lipase expression in spermatids is governed by a short promoter in transgenic mice.

    PubMed

    Blaise, R; Guillaudeux, T; Tavernier, G; Daegelen, D; Evrard, B; Mairal, A; Holm, C; Jégou, B; Langin, D

    2001-02-16

    A testicular form of hormone-sensitive lipase (HSL(tes)), a triacylglycerol lipase, and cholesterol esterase, is expressed in male germ cells. Northern blot analysis showed HSL(tes) mRNA expression in early spermatids. Immunolocalization of the protein in human and rodent seminiferous tubules indicated that the highest level of expression occurred in elongated spermatids. We have previously shown that 0.5 kilobase pairs of the human HSL(tes) promoter directs testis-specific expression of a chloramphenicol acetyltransferase reporter gene in transgenic mice and determined regions binding nuclear proteins expressed in testis but not in liver (Blaise, R., Grober, J., Rouet, P., Tavernier, G., Daegelen, D., and Langin, D. (1999) J. Biol. Chem. 274, 9327-9334). Mutation of a SRY/Sox-binding site in one of the regions did not impair in vivo testis-specific expression of the reporter gene. Further transgenic analyses established that 95 base pairs upstream of the transcription start site were sufficient for correct testis expression. In gel retardation assays using early spermatid nuclear extracts, a germ cell-specific DNA-protein interaction was mapped between -46 and -29 base pairs. The DNA binding nuclear protein showed properties of zinc finger transcription factors. Mutation of the region abolished reporter gene activity in transgenic mice, showing that it is necessary for testis expression of HSL(tes). PMID:11076952

  14. Xenografting of testis tissue from bison calf donors into recipient mice as a strategy for salvaging genetic material.

    PubMed

    Abbasi, Sepideh; Honaramooz, Ali

    2011-09-01

    The objective was to evaluate the long-term outcome of testis tissue xenografting from neonatal bison calves as a model for closely related rare or endangered ungulates. Testis tissue was collected postmortem from two newborn bison calves (Bison bison bison) and small fragments of the tissue were grafted under the back skin of immunodeficient recipient mice (n = 15 mice; eight fragments/mouse). Single xenograft samples were removed from representative recipient mice every 2 mo after grafting (for up to 16 mo). The retrieved xenografts were evaluated for seminiferous tubular density, tubular diameter, seminiferous tubular morphology, and identification of the most advanced germ cell type. Overall, 69% of the grafted testis fragments were recovered as xenografts. Xenografts weight increased (P < 0.02) approximately four-fold by 2 mo and 10-fold by 16 mo post-grafting. In testis xenografts, gradual maturational changes were evident, manifested as the first detection of the following at the times specified: seminiferous tubule expansion, 2 mo; spermatocytes, 6 mo; round spermatids, 12 mo; and elongated spermatids, 16 mo. Furthermore, there were differences between the two donor calves regarding the efficiency of spermatogenesis in xenografts. The timing of complete spermatogenesis approximately corresponded to the reported timing of sexual maturation in bison. This study demonstrated, apparently for the first time, that testis tissue xenografting from neonatal bison donors into recipient mice resulted in testicular maturation and complete development of spermatogenesis in the grafts.

  15. Novel noncoding RNA from human Y distal heterochromatic block (Yq12) generates testis-specific chimeric CDC2L2

    PubMed Central

    Jehan, Zeenath; Vallinayagam, Sambandam; Tiwari, Shrish; Pradhan, Suman; Singh, Lalji; Suresh, Amritha; Reddy, Hemakumar M.; Ahuja, Y.R.; Jesudasan, Rachel A.

    2007-01-01

    The human Y chromosome, because it is enriched in repetitive DNA, has been very intractable to genetic and molecular analyses. There is no previous evidence for developmental stage- and testis-specific transcription from the male-specific region of the Y (MSY). Here, we present evidence for the first time for a developmental stage- and testis-specific transcription from MSY distal heterochromatic block. We isolated two novel RNAs, which localize to Yq12 in multiple copies, show testis-specific expression, and lack active X-homologs. Experimental evidence shows that one of the above Yq12 noncoding RNAs (ncRNAs) trans-splices with CDC2L2 mRNA from chromosome 1p36.3 locus to generate a testis-specific chimeric β sv13 isoform. This 67-nt 5′UTR provided by the Yq12 transcript contains within it a Y box protein-binding CCAAT motif, indicating translational regulation of the β sv13 isoform in testis. This is also the first report of trans-splicing between a Y chromosomal and an autosomal transcript. PMID:17095710

  16. Cancer/testis antigens trigger epithelial-mesenchymal transition and genesis of cancer stem-like cells.

    PubMed

    Yang, Ping; Huo, Zihe; Liao, Huaidong; Zhou, Quansheng

    2015-01-01

    Malignant tumors aberrantly overexpress various embryonic genes and proto-oncogenes, including a variety of cancer-testis antigens (CTAs). CTAs belong to a class of testis-derived proteins which are only expressed in germ cells in the male testis, and the expression of CTA genes is entirely silenced in the adult somatic tissues. They are, however, aberrantly overexpressed in a variety of malignant tumor tissues. Emerging evidence shows that a number of CTAs promote epithelialmesenchymal transition (EMT) and genesis of cancer stem like cells, escalating tumorigenesis, invasion, and metastasis. The can cer-testis antigens, such as SSX, MAGE-D4B, CAGE, piwil2, and CT45A1, upregulate EMT and metastatic genes, promoting EMT and tumor dissemination. In addition, certain members of CTAs, including Piwil2, DNAJB8, CT45A1, MAGE-A, GAGE, and SPANX, are implicated in the initiation or maintenance, of cancer stem-like cells, promoting tumorigenesis and malignant progression. Clinically CTAs are closely associated with poor prognosis in cancer patients. Intriguely, CTAs are strongly immunogenic and normally restricted to the male testis after birth, however, these proteins are aberrantly overexpressed in cancer stem-like cells and in a variety of cancers, suggesting their target potential for cancer immunotherapy, as diagnostic biomarkers, and as targets for novel anticancer drug discovery. Thus, the targeting of tumorigenic CTAs is a promising strategy to eradicate cancer stem-like cells and inhibit tumorigenesis for effective cancer treatment.

  17. Adenocarcinoma of the rete testis with prominent papillary structure and clear neoplastic cells: morphologic and immunohistochemical findings and differential diagnosis.

    PubMed

    Huang, Pei-Wen; Chang, Kuo-Ming

    2015-01-01

    Adenocarcinoma of the rete testis is rare, and its etiology is unknown. The definite diagnosis merely depends on the exclusion of other tumors and histological features. We first describe a 38-year-old man with a carcinoma arising in the rete testis. The tumor was characterized by clear neoplastic cells and branching papillary growth. Focal stromal invasion and transition of normal rete epithelium to neoplastic cells were seen. The neoplastic cells were positive for epithelial membrane antigen, Ber-Ep4, vimentin, renal cell carcinoma marker, and CD10, while negative for Wilms' tumor 1, thyroid transcription factor-1, estrogen receptor, prostate specific antigen, placental alkaline phosphate, CD117, and alpha-1-fetoprotein. According to the above features, we diagnosed this tumor as adenocarcinoma of the rete testis. To our best knowledge, this is the first reported case of adenocarcinoma of the rete testis with prominently papillary structure and clear neoplastic cells. The rarity of adenocarcinoma of the rete testis and the unique features in our case cause diagnostic pitfalls. A complete clinicopathological study and thorough differential diagnosis are crucial for the correct result. PMID:25885143

  18. Subchronic exposure to lead acetate inhibits spermatogenesis and downregulates the expression of Ddx3y in testis of mice.

    PubMed

    Wang, Xiaoxu; Wang, Man; Dong, Wei; Li, Yachen; Zheng, Xiaomei; Piao, Fengyuan; Li, Sheng

    2013-12-01

    Male mice were given drinking water alone or containing 0.5, 1.0 and 1.5g/L Pb acetate for 60 days. After the treatment, the concentrations of Pb were determined in the serum and testis of mice by ICP-MS. The gene transcription of Usp9y, Ddx3y and Uty and their protein levels in the testis were examined by real-time PCR, Western blotting and immunohistochemistry. The sperm quality, spermatogenesis, and histological alteration of the testis and epididymis were observed by microscope. The probability of impregnating female mice by lead-exposed male was evaluated. It was shown that the concentrations of Pb in serum and testis of mice significantly increased in the groups exposed to Pb in a dose-dependent manner. The male fertility significantly decreased in the groups exposed to 1.0 and 1.5g/L Pb acetate. Moreover, exposure to Pb also inhibited spermatogenesis and sperm development, and significantly downregulated expressions of Ddx3y gene expression in testis of mice, but Usp9y and Uty expressions unaffected.

  19. Characterization of the equine blood-testis barrier during tubular development in normal and cryptorchid stallions.

    PubMed

    Rode, K; Sieme, H; Richterich, P; Brehm, R

    2015-09-15

    The formation of the blood-testis barrier (BTB) is defined as occurring with the first appearance of spermatocytes at around puberty and is vital for normal spermatogenesis. This barrier between two adjacent Sertoli cells (SCs) consists of a cell junctional protein complex, which includes tight junctions (TJs), adherens junctions, and gap junctions. In many mammalian species, BTB composition has already been investigated, whereas little is known about the equine BTB. In the present study, immunohistochemistry and qualitative Western Blot analysis were used to assess the expression and distribution patterns of the junctional proteins claudin-11 (TJ), zonula occludens-1 (TJ associated), N-cadherin (adherens junctions), and connexin 43 (gap junctions) in equine testes during tubular development and in testes of stallions exhibiting unilateral cryptorchidism. Therefore, testes of 21 warmblood stallions (aged 12 months-11 years) were obtained during routine surgical castration. In the normal adult equine testis, the junctional proteins are localized at the basolateral region of the seminiferous tubules forming a circumferential seal corresponding to the known BTB localization. N-cadherin is additionally expressed along the lateral SC surface. In immature seminiferous cords still lacking a lumen, a diffuse distribution pattern of the junctional proteins throughout the SC cytoplasm is visible. As lumen formation advances, the immunolocalization shifts progressively toward the basolateral SC membranes. Additionally, apoptotic germ cells were detected and quantified in prepubertal stallions using terminal deoxynucleotidyl transferase dUTP nick end labeling assay and correlated with junctional protein localization. In the retained testis of cryptorchid stallions, which exhibit an aberrant testicular morphology, a deviating expression of the junctional proteins is visible. The present data show for the first time that (1) the equine SC junctional complex contains claudin-11

  20. Damage of the mouse testis by tritiated water and 137Cs-gamma-rays.

    PubMed

    Kashiwabara, Shoji; Kashimoto, Naoki; Sanoh, Seigo; Uesaka, Toshihiro; Katoh, Osamu; Watanabe, Hiromitsu

    2003-09-01

    Tritiated water at 23.2, 46.3 or 92.5 MBq/animal and 137Cs-gamma-rays at 9.5 Gy (equivalent 370 MBq) or lower doses were administered to 6-week old male C3H/HeNCrj and C57BL/6NCrj mice, as well as F1 Crj: B6C3F1 (C3H x C57BL) progeny. Each set of six to ten animals were autopsied 30 days after the first irradiation. Testis weights were decreased dose dependently, relative values being highest in the C3H and lowest in the C57BL case, with B6C3F1 intermediate. Vacuolization in seminiferous tubules appeared in the 23.2 MBq group and increased with the dose. Focal pyknosis and karyomegaly were found at 46.3 MBq, while primary and secondary spermatocytes and spermatids disappeared with 92.5 MBq. Only a few spermatogonia and Sertoli cells remained after exposure to 9.5 Gy 137Cs-gamma-rays. Sizes of seminiferous tubules were decreased dose dependently, with no strain differences. When male B6C3F1 mice were irradiated with Cs-gamma-rays at 0.119 (equivalent 4.63 MBq tritiated water) or 2.38 Gy (equivalent 92.5 MBq tritiated water), body weights and size of the seminiferous tubules were decreased at both doses, and the larger dose also caused reduction of testis weight and abnormal sperm. However, all changes except for the alteration in weights had disappeared 1 month after the final irradiation. It is considered that the size of seminiferous tubules may be a good parameter for radiation damage in the testis.

  1. Effects of 2,2,2-trifluoroethanol on the testis of the rat

    SciTech Connect

    Wilkenfeld, R.M.

    1981-01-01

    The effects of xenobiotics on the male reproductive system have become a growing concern. During an investigation into the acute toxicity of the volatile solvent 2,2,2-trifluoroethanol (TFE) following inhalation, it was noted that testicular damage was a consistent effect. Single intraperitoneal doses of TFE as low as 25 mg/kg produced damage to spermatogonia and spermatocytes, but had no effect on postmeiotic germ cells or interstitial structures. Damage to the testis was rapid, first being detectable by light microscopy 8 hours following a single i.p. dose. In order to determine the effects of subchronic inhalation exposre on male reproductive function, rats were exposed to trifluoroethanol at concentrations of 0, 100 ppM and 200 ppM, for 6 hours/day, 5 days/week for two weeks. The absorption, distribution, and excretion of intraperitoneally injected trifluoroethanol (5 mg/kg and 100 mg/kg was studied using 2-/sup 14/C-TFE. Testicular and epididymal blood flow, as determined using 15 ..mu..m /sup 57/Co-microspheres, was not altered 15 minutes, 1, 3, or 6 hours following 100 mg TFE/kg. In vivo protein incorporation of /sup 14/C-leucine in the testis was not altered 6 hours after TFE. It appears that TFE-induced testicular damage is not due to decreased blood flow, as has been suggested for cadmium-induced damage. Alteration of the redox state of the testis may be suggested by the decrease in lactate concentration. 114 references, 16 figures, 25 tables.

  2. Extreme divergence of Wolbachia tropism for the stem-cell-niche in the Drosophila testis.

    PubMed

    Toomey, Michelle E; Frydman, Horacio M

    2014-12-01

    Microbial tropism, the infection of specific cells and tissues by a microorganism, is a fundamental aspect of host-microbe interactions. The intracellular bacteria Wolbachia have a peculiar tropism for the stem cell niches in the Drosophila ovary, the microenvironments that support the cells producing the eggs. The molecular underpinnings of Wolbachia stem cell niche tropism are unknown. We have previously shown that the patterns of tropism in the ovary show a high degree of conservation across the Wolbachia lineage, with closely related Wolbachia strains usually displaying the same pattern of stem cell niche tropism. It has also been shown that tropism to these structures in the ovary facilitates both vertical and horizontal transmission, providing a strong selective pressure towards evolutionary conservation of tropism. Here we show great disparity in the evolutionary conservation and underlying mechanisms of stem cell niche tropism between male and female gonads. In contrast to females, niche tropism in the male testis is not pervasive, present in only 45% of niches analyzed. The patterns of niche tropism in the testis are not evolutionarily maintained across the Wolbachia lineage, unlike what was shown in the females. Furthermore, hub tropism does not correlate with cytoplasmic incompatibility, a Wolbachia-driven phenotype imprinted during spermatogenesis. Towards identifying the molecular mechanism of hub tropism, we performed hybrid analyses of Wolbachia strains in non-native hosts. These results indicate that both Wolbachia and host derived factors play a role in the targeting of the stem cell niche in the testis. Surprisingly, even closely related Wolbachia strains in Drosophila melanogaster, derived from a single ancestor only 8,000 years ago, have significantly different tropisms to the hub, highlighting that stem cell niche tropism is rapidly diverging in males. These findings provide a powerful system to investigate the mechanisms and evolution of

  3. Hormonal changes in relation to lunar periodicity in the testis of the forktail rabbitfish, Siganus argenteus.

    PubMed

    Rahman, Md Saydur; Morita, Masaya; Takemura, Akihiro; Takano, Kazunori

    2003-05-01

    Correlation of hormonal changes in the testis and the lunar periodicity was studied using the forktail rabbitfish, Siganus argenteus, which spawns synchronously around the last quarter moon. Weekly change in sperm motility peaked around the last quarter moon. The pH and osmolality in the seminal fluid increased and decreased around the same lunar phase, respectively. These results suggest that the testis of this species develops toward the specific lunar phase. Human chorionic gonadotropin (hCG) stimulated in vitro production of 11-ketotestosterone (11-KT) in the testicular fragments around the full moon. When the testicular fragments and the sperm preparations were incubated, respectively, with testosterone (T) and 17alpha-hydroxyprogesterone (17alpha-OHP), conversion of T to 11-KT in the testicular fragments decreased and, alternatively, that of 17alpha-OHP to 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP) in the sperm preparations increased from the full moon to the last quarter moon. Administration of the fish with hCG or DHP prior to the predicted spawning lunar day resulted in increases in the sperm motility and the seminal fluid pH. Plasma level of DHP, but not T and 11-KT, increased after hCG injection. These results indicate that gonadotropin (GtH) and DHP are related to the final stage of testicular maturation, and that GtH acts through production of DHP in the testis. Moreover, the present study shows that use of the lunar cue(s) in the rabbitfish occurs in the higher part of the hypothalamus-pituitary-gonadal axis.

  4. Extreme Divergence of Wolbachia Tropism for the Stem-Cell-Niche in the Drosophila Testis

    PubMed Central

    Toomey, Michelle E.; Frydman, Horacio M.

    2014-01-01

    Microbial tropism, the infection of specific cells and tissues by a microorganism, is a fundamental aspect of host-microbe interactions. The intracellular bacteria Wolbachia have a peculiar tropism for the stem cell niches in the Drosophila ovary, the microenvironments that support the cells producing the eggs. The molecular underpinnings of Wolbachia stem cell niche tropism are unknown. We have previously shown that the patterns of tropism in the ovary show a high degree of conservation across the Wolbachia lineage, with closely related Wolbachia strains usually displaying the same pattern of stem cell niche tropism. It has also been shown that tropism to these structures in the ovary facilitates both vertical and horizontal transmission, providing a strong selective pressure towards evolutionary conservation of tropism. Here we show great disparity in the evolutionary conservation and underlying mechanisms of stem cell niche tropism between male and female gonads. In contrast to females, niche tropism in the male testis is not pervasive, present in only 45% of niches analyzed. The patterns of niche tropism in the testis are not evolutionarily maintained across the Wolbachia lineage, unlike what was shown in the females. Furthermore, hub tropism does not correlate with cytoplasmic incompatibility, a Wolbachia-driven phenotype imprinted during spermatogenesis. Towards identifying the molecular mechanism of hub tropism, we performed hybrid analyses of Wolbachia strains in non-native hosts. These results indicate that both Wolbachia and host derived factors play a role in the targeting of the stem cell niche in the testis. Surprisingly, even closely related Wolbachia strains in Drosophila melanogaster, derived from a single ancestor only 8,000 years ago, have significantly different tropisms to the hub, highlighting that stem cell niche tropism is rapidly diverging in males. These findings provide a powerful system to investigate the mechanisms and evolution of

  5. Parallel Functional Changes in Independent Testis-Specific Duplicates of Aldehyde dehydrogenase in Drosophila

    PubMed Central

    Chakraborty, Mahul; Fry, James D.

    2015-01-01

    A large proportion of duplicates, originating from ubiquitously expressed genes, acquire testis-biased expression. Identifying the underlying cause of this observation requires determining whether the duplicates have altered functions relative to the parental genes. Typically, statistical methods are used to test for positive selection, signature of which in protein sequence of duplicates implies functional divergence. When assumptions are violated, however, such tests can lead to false inference of positive selection. More convincing evidence for naturally selected functional changes would be the occurrence of structural changes with similar functional consequences in independent duplicates of the same gene. We investigated two testis-specific duplicates of the broadly expressed enzyme gene Aldehyde dehydrogenase (Aldh) that arose in different Drosophila lineages. The duplicates show a typical pattern of accelerated amino acid substitutions relative to their broadly expressed paralogs, with statistical evidence for positive selection in both cases. Importantly, in both duplicates, width of the entrance to the substrate binding site, known a priori to influence substrate specificity, and otherwise conserved throughout the genus Drosophila, has been reduced, resulting in narrowing of the entrance. Protein structure modeling suggests that the reduction of the size of the enzyme’s substrate entry channel, which is likely to shift substrate specificity toward smaller aldehydes, is accounted for by the positively selected parallel substitutions in one duplicate but not the other. Evolution of the testis-specific duplicates was accompanied by reduction in expression of the ancestral Aldh in males, supporting the hypothesis that the duplicates may have helped resolve intralocus sexual conflict over Aldh function. PMID:25564519

  6. Testis follicles ultrastructure of three species of terrestrial isopods (Crustacea, Isopoda Oniscidea).

    PubMed

    Mazzei, V; Longo, G; Brundo, M V

    2015-10-01

    The aim of the research, carried out on three species of terrestrial isopods - Armadillidium granulatum, Halophiloscia hirsuta and Trichoniscus alexandrae - is to bring a first consistent contribution to the knowledge of the ultrastructural organization of the testis follicles. The testis follicles are seat of a remarkable dynamic activity of their cell components (somatic cells and germ cells) that results in a continuous variation, related to the trend of spermatogenesis, of their morphology, organization and of the relationships between the two cell populations. The somatic cells, known in literature as follicular cells, nurse cells or Sertoli cells, are arranged at the periphery of the follicle to form an epithelial layer of variable thickness resting on a thin basal lamina in turn surrounded by a discontinuous network of muscle cells. In A. granulatum and H. hirsuta, two types of Sertoli cells are present: a first type, the nurse cells, envelop the spermatids in cavities within their cytoplasm and through their secretion activity play a fundamental role in the formation of the spermatophores; moreover, they phagocytizes the residual cytoplasm of spermatids. A second type of Sertoli cells shows features that leave clearly identify its supporting role to the spermatophores in formation. In T. alexandrae, instead, only one type of Sertoli cells, the nurse cell, is present, whose features are widely superimposable to those observed in the other two species. Moreover, two septa of Sertoli cells depart from the periphery of the testis follicle to constitute an articulated compartmentalization of the follicle itself, probably targeted to realize at its inside a series of microenvironments functionally diversified in order to meets the needs of the different stages of the spermatogenic cycle.

  7. Parallel functional changes in independent testis-specific duplicates of Aldehyde dehydrogenase in Drosophila.

    PubMed

    Chakraborty, Mahul; Fry, James D

    2015-04-01

    A large proportion of duplicates, originating from ubiquitously expressed genes, acquire testis-biased expression. Identifying the underlying cause of this observation requires determining whether the duplicates have altered functions relative to the parental genes. Typically, statistical methods are used to test for positive selection, signature of which in protein sequence of duplicates implies functional divergence. When assumptions are violated, however, such tests can lead to false inference of positive selection. More convincing evidence for naturally selected functional changes would be the occurrence of structural changes with similar functional consequences in independent duplicates of the same gene. We investigated two testis-specific duplicates of the broadly expressed enzyme gene Aldehyde dehydrogenase (Aldh) that arose in different Drosophila lineages. The duplicates show a typical pattern of accelerated amino acid substitutions relative to their broadly expressed paralogs, with statistical evidence for positive selection in both cases. Importantly, in both duplicates, width of the entrance to the substrate binding site, known a priori to influence substrate specificity, and otherwise conserved throughout the genus Drosophila, has been reduced, resulting in narrowing of the entrance. Protein structure modeling suggests that the reduction of the size of the enzyme's substrate entry channel, which is likely to shift substrate specificity toward smaller aldehydes, is accounted for by the positively selected parallel substitutions in one duplicate but not the other. Evolution of the testis-specific duplicates was accompanied by reduction in expression of the ancestral Aldh in males, supporting the hypothesis that the duplicates may have helped resolve intralocus sexual conflict over Aldh function.

  8. Changes in testosterone concentration in the fetal rabbit testis after removal of the hypothalamus (encephalectomy)

    SciTech Connect

    Proshlyakova, E.V.; Rumyantseva, O.N.; Mitskevich, M.S.

    1986-10-01

    The aim of this investigation was to obtain direct data on the role of the hypothalamus in regulation of the adrogen function of the testes in rabbit fetuses. Testosterone was determined by radioimmunoassay. Changes in testostereone concentration in rabbit fetal testis after encephalectomy and after injection of luteinizing hormone releasing hormone (LHRH) into encephalectomized fetuses is shown. Results obtained are evidence that the hypothalamus, pituitary and testes in the rabbit aged 23-25 days of prenatal development constitute a single functional system. It is concluded that in both rabbit and hog fetuses, the hypothalamus begins to regulate pituitary gonadotrophic activity after LHRH can be detected in the hypothalamus itself.

  9. Cancer/testis antigens and obligate participation in multiple hallmarks of cancer: an update

    PubMed Central

    Mooney, Steven M; Rajagopalan, Krithika; Rangarajan, Govindan; Kulkarni, Prakash

    2016-01-01

    The Cancer/Testis Antigens (CTAs) are a group of so-called tumor antigens that exhibit provocative expression patterns in most types of cancer. However, because most CTAs appear to be intrinsically disordered, they are recalcitrant to classical structural studies. Thus, the functions of most, if not all, CTAs have remained elusive and their potential as pharmacological targets in cancer has remained largely unexplored. In this viewpoint, we suggest that perhaps, an integrative approach applying dynamical systems theory and a system-level perspective rather a merely reductionist view, may shine new light on these enigmatic molecules. PMID:26908068

  10. Cancer-testis genes as candidates for immunotherapy in breast cancer.

    PubMed

    Ghafouri-Fard, Soudeh; Shamsi, Roshanak; Seifi-Alan, Mahnaz; Javaheri, Mona; Tabarestani, Sanaz

    2014-01-01

    Cancer-testis (CT) antigens are tumor-associated antigens attracting immunologists for their possible application in the immunotherapy of cancer. Several clinical trials have assessed their therapeutic potentials in cancer patients. Breast cancers, especially triple-negative cancers are among those with significant expression of CT genes. Identification of CT genes with high expression in cancer patients is the prerequisite for any immunotherapeutic approach. CT genes have gained attention not only for immunotherapy of cancer patients, but also for immunoprevention in high-risk individuals. Many CT genes have proved to be immunogenic in breast cancer patients suggesting the basis for the development of polyvalent vaccines.

  11. The zone of mature spermatozoa in the testis of Salamandra salamandra (L.) (Amphibia, Urodela).

    PubMed

    Bergmann, M; Schindelmeiser, J; Greven, H

    1982-01-01

    The zone of mature spermatozoa in the testis of the european fire salamander, Salamandra salamandra, consists of numerous lobules embedded in a vascularized connective tissue. Most of the lobule boundary cells show features of SH-secreting cells (an increased amount of smooth ER, globular mitochondria with tubular cristae), whereas other retain a fibrocytic appearance. The mature spermatozoa within the lobules seem to be at least partly phagocytized and digested by the often highly vacuolized Sertoli cells. Lobules open into efferent ductules lined by a monolayered epithelium, whose cells are highly interdigitated. The capillaries of the interlobular connective tissue possess enlarged luminal and basal surfaces.

  12. Role of PACAP on testosterone and 17β-estradiol production in the testis of wall lizard Podarcis sicula.

    PubMed

    Rosati, Luigi; Prisco, Marina; Di Fiore, Maria Maddalena; Santillo, Alessandra; Valiante, Salvatore; Andreuccetti, Piero; Agnese, Marisa

    2016-01-01

    Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide that in mammalian testis is involved in the control of testosterone and 17β-estradiol synthesis. A similar involvement was recently postulated in the testis of a nonmammalian vertebrate, the wall lizard Podarcis sicula. Indeed, we reported the presence of PACAP and its receptors throughout the reproductive cycle within both germ and somatic cells. Now, we investigated the effects of PACAP on steroidogenesis in significant periods of Podarcis reproductive cycle: winter stasis, reproductive period and summer stasis. Using different in vitro treatments, in the absence or presence of receptor antagonists, we demonstrated that in P. sicula testis PACAP is involved in the control of testosterone and 17β-estradiol production. In particular we demonstrated that treatment with PACAP induced a testosterone increase only in stasis periods (winter and summer stasis); differently they induced a 17β-estradiol production in all periods analyzed (summer stasis, winter stasis and reproductive period).

  13. Identification, localization and developmental studies of rat prepro thyrotropin-releasing hormone mRNA in the testis.

    PubMed

    Feng, P; Gu, J; Kim, U J; Carnell, N E; Wilber, J F

    1993-02-01

    Thyrotropin-releasing hormone (TRH) plays the central regulatory role in the hypothalamic-pituitary-thyroid axis, but is also present in many extra-hypothalamic loci. The adult rat testis has been identified previously as a source of hypothalamic neuropeptides including TRH. To investigate whether the TRH gene is transcribed in testis, the identification and localization of prepro(pp) TRH mRNA and TRH were studied. Northern blot analyses of ppTRH mRNA in the adult rat testis showed a 2.0 kb band, hybridized with a ppTRH cRNA probe. This band was 0.4 kb greater than the 1.6 kb hypothalamic band. The concentration of ppTRH mRNA in the adult testis was approximately 13% of that found in the hypothalamus. Developmental studies of testicular ppTRH mRNA revealed that no ppTRH mRNA could be detected at the earliest stage (day 8). However, hybridization signals were detected on day 20 and increased progressively on days 35, 45 and 70 by 5.8, 6.4, and 9.8-fold, respectively. In addition, ppTRH mRNA was determined in Leydig cells by Northern analyses of elutriated testicular cell fractions. TRH was also measured in the rat testes at different developmental stages by RIA. TRH concentrations paralleled ppTRH mRNA during development. TRH was localized to Leydig cells by immunohistochemistry. These results indicate that ppTRH mRNA and TRH are present in the rat testis, especially in the Leydig cells. The changes of ppTRH gene expression and the concentration of TRH in the rat testis are developmentally dependent. TRH may function as a new paracrine or autocrine regulator of testicular function.

  14. Protective role of garlic oil against oxidative damage induced by furan exposure from weaning through adulthood in adult rat testis.

    PubMed

    El-Akabawy, Gehan; El-Sherif, Neveen M

    2016-06-01

    Furan is produced in a wide variety of heat-treated foods via thermal degradation. Furan contamination is found to be relatively high in processed baby foods, cereal products, fruits juices, and canned vegetables. Several studies have demonstrated that furan is a potent hepatotoxin and hepatocarcinogen in rodents. However, few studies have investigated the toxic effects of furan in the testis. In addition, the exact mechanism(s) by which furan exerts toxicity in the testis has not been fully elucidated. In this study, we investigated the potential of furan exposure from weaning through adulthood to induce oxidative stress in adult rat testis, as well as the potential of garlic oil (GO) to ameliorate the induced toxicity. Our results reveal that furan administration significantly reduced serum testosterone levels and increased the levels of malondialdehyde (MDA); furthermore, furan administration decreased significantly the enzymatic activity of testicular antioxidants, including glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) and induced histopathological alterations in the testis. GO co-administration ameliorated the reduction in testosterone levels and dramatically attenuated the furan-induced oxidative and histopathological changes. In addition, Go significantly down-regulated the increased caspase-3 and cytochrome P450 2E1 (CYP2E1) expression in the furan-treated testis. To the best of our knowledge, this study is the first to demonstrate the furan-induced oxidative changes in the adult rat testis and the protective role of GO to ameliorate these changes through its antioxidant effects and its ability to inhibit CYP2E1 production. PMID:27130490

  15. Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

    PubMed

    Chen, Yao-Tseng; Panarelli, Nicole C; Piotti, Kathryn C; Yantiss, Rhonda K

    2014-05-01

    Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions.

  16. ACTIONS OF THE ENDOCRINE DISRUPTOR METHOXYCHLOR AND ITS ESTROGENIC METABOLITE ON IN VITRO EMBRYONIC RAT SEMINIFEROUS CORD FORMATION AND PERINATAL TESTIS GROWTH. (R827405)

    EPA Science Inventory

    Abstract

    The current study examines the actions of methoxychlor and its estrogenic metabolite, 2, 2-bis-(p-hydroxyphenyl)-1, 1, 1-trichloroethane (HPTE), on seminiferous cord formation and growth of the developing rat testis. The developing testis in the embryonic and ...

  17. Identification and comparison of gonadal transcripts of testis and ovary of adult common carp Cyprinus carpio using suppression subtractive hybridization.

    PubMed

    Chen, Jian-Jun; Xia, Xiao-Hua; Wang, Li-Fang; Jia, Yong-Fang; Nan, Ping; Li, Li; Chang, Zhong-Jie

    2015-06-01

    The limited number of gonad-specific and gonad-related genes that have been identified in fish represents a major obstacle in the study of fish gonad development and sex differentiation. In common carp Cyprinus carpio from China's Yellow River, the ovary and testis differ in volume and weight in adult fish of the same age. Comparing sperm, egg, and somatic cell transcripts in this carp may provide insight into the mechanisms of its gonad development and sex differentiation. In the present work, gene expression patterns in the carp ovary and testis were compared using suppression subtractive hybridization. Two bidirectional subtracted complementary DNA (cDNA) libraries were analyzed in parallel using testis or ovary as testers. Eighteen nonredundant clones were identified in the male library, including 15 known cDNAs. The expression patterns of selected genes in testis and ovary were analyzed using reverse transcriptase polymerase chain reaction. Tektin-1, GAPDS, FGFIBP, IGFBP-5, and an unknown gene from the Ccmg4 clone were observed to be expressed only in testis. GSDF, BMI1b, Wt1a, and an unknown gene from the Ccme2 clone were expressed at higher levels in testis than in ovary at sexual maturity. Thirty functional expressed sequence tags (ESTs) were identified in 43 sequenced clones in the female library, including 28 known cDNAs, one uncharacterized cDNA (EST clone), and one novel sequence. Eight identified ESTs showed significant differences in expression between the testis and the ovary. ZP3C and Psmb2 were expressed exclusively in ovary, whereas the expression levels of IFIPGL-1, Setd6, ATP-6, CDC45, AIF-1, and an unknown gene from the Ccfh2 clone were more strongly expressed in ovary than in testis. In addition, the expression of ZP3C, Wt1a, and Setd6 was analyzed in male and female gonads, heart, liver, kidney, and brain. ZP3C was expressed only in ovary. Setd6 expression was significantly stronger in female tissues than that in the male, except in the liver

  18. [Morphological verification problems of Chernobyl factor influence on the testis of coal miners of Donbas-liquidators of Chernobyl accident].

    PubMed

    Danylov, Iu V; Motkov, K V; Shevchenko, T I

    2013-01-01

    Problem of a diagnostic of Chernobyl factor influences on different organs and systems of Chernobyl accident liquidators are remain actually until now. Though morbidly background which development at unfavorable work conditions in underground coalminers prevents from objective identification features of Chernobyl factor influences. The qualitative and quantitative histological and immunohistochemical law of morphogenesis changes in testis of Donbas's coalminer - non-liquidators Chernobyl accident in comparison with the group of Donbas's coalminers-liquidators Chernobyl accident, which we were stationed non determined problem. This reason stipulates to development and practical use of mathematical model of morphogenesis of a testis changes.

  19. Protective effects of propolis on methotrexate-induced testis injury in rat.

    PubMed

    Sönmez, Mehmet Fatih; Çilenk, Kübra Tuğçe; Karabulut, Derya; Ünalmış, Sunay; Deligönül, Erkan; Öztürk, İsmet; Kaymak, Emin

    2016-04-01

    Propolis is an adhesive substance which is collected and used by honeybees. Propolis is a potent antioxidant and a free radical scavenger. This study was designed to determine whether propolis could protect against dysfunction and oxidative stress induced by methotrexate-induced injury in rat testis. A total of 40 male Wistar albino rats were divided into four groups: group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20mg/kg. Groups 3 and 4 received 100mg/kg/day propolis (by oral gavage) for 15 days by the first day of the experimental protocol. Then the rats were decapitated under anesthesia, and their testes were removed. The histopathological and biochemical analysis along with apoptosis assessment of testis tissues were compared. Immunohistochemical analysis of Heat shock protein-70 (HSP-70) and Proliferating Cell Nuclear Antigen (PCNA) were performed. The phenolic characterization of propolis was performed by Liquid chromatography-mass spectrometry (LC-MS/MS). Methotrexate caused tended to increase in malondialdehyde level and in the number of apoptotic cells; it also caused a decrease in MSTD and JTBS, PCNA and HSP-70 expression and xanthine oxidase levels in group 2. Propolis prevented the rise in malondialdehyde, xanthine oxidase levels and HSP-70 expression and improved testicular morphology and JTBS. It was found that, methorexate gives rise to serious damage in the testes and propolis is a potent antioxidant agent in preventing testicular injury. PMID:27044811

  20. Functional constraint underlies 60 million year stasis of Dipteran testis-specific beta-tubulin.

    PubMed

    Nielsen, Mark G; Caserta, Justin M; Kidd, Sarah J; Phillips, Christopher M

    2006-01-01

    How do proteins evolve while maintaining their function? Previous studies find a highly stringent structure/function relationship between the Drosophila melanogaster testis-specific tubulin beta2 and the spermtail axoneme, such that small changes in the beta2 protein render it unable to generate a motile axoneme. This raises the question, how does beta2 evolve while maintaining its function? To address this question we cloned full- and partial-length beta2 sequences from 17 species of Drosophila and Hirtodrosophila flies spanning 60 Myr of evolution. Not a single amino acid difference is coded among them-beta2 maintains its function by not evolving. We also performed gene genealogical analyses to determine ortholog/paralog relationships among insect tubulins. We find that the Lepidopteran and Dipteran testis-specific beta-tubulins are likely orthologs, and surprisingly, despite functioning in the same structure, the Lepidopteran orthologs are evolving rapidly. We argue that differences in tubulin isoform use in the testes cause the Dipteran axoneme to be less evolvable than the Lepidopteran axoneme, which has facilitated the evolution of a unique amino acid synergism in Drosophila and Hirtodrosophilabeta2 that is resistant to change, contributing to its evolutionary stasis.

  1. Diethylstilbestrol Regulates the Expression of LGR8 in Mouse Gubernaculum Testis Cells

    PubMed Central

    Duan, Shouxing; Jiang, Xuewu; Zhang, Xuan; Xie, Lei; Sun, Zongbo; Ma, Shuhua; Li, Jianhong

    2016-01-01

    Background Hormonal effects on the gubernaculum can affect testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the outgrowth of gubernaculums, leading to testis maldescent. However, the underlying mechanisms remain elusive. Material/Methods The gubernaculum were removed from 3-day-old mice and cultured. The subcultured cells were randomly divided into a normal control group and experimental groups. The DES groups were administered 10 μg/ml, 1 μg/ml, 0.1 μg/ml, 0.01 μg/ml of diethylstilbestrol dissolved in dimethyl sulfoxide (DMSO) respectively. The cell morphology was observed under an inverted microscope, and leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8) was localized by immunofluorescence. The expressions of LGR8 gene and protein in gubernaculum cells were quantified by RT-PCR and Flow Cytometer respectively. Results DES treatment converted cells from a normal fibroblast-like morphology into a more refractile, spindle-shaped morphology or irregular elliptical shapes along with cytoplasmic shrinkage. LGR8 was expressed in the cytoplasmic membrane, DES dose-dependently downregulated LGR8 expression at low doses (≤1.0 μg/ml), but upregulated LGR8 at high doses (10 μg/ml) at both the mRNA and protein levels. Conclusions These results suggest that DES causes testicular maldescent by altering the LGR8 pathway in mouse gubernaculum testis cells. PMID:26855023

  2. Long-term effect of yolk carotenoid levels on testis size in a precocial bird.

    PubMed

    Giraudeau, Mathieu; Ziegler, Ann-Kathrin; Tschirren, Barbara

    2016-04-01

    Conditions experienced during prenatal development can have long-lasting organizational effects on offspring. Maternal carotenoids deposited in the eggs of birds and other oviparous species play an important role during fast embryonic growth and chick development through their antioxidant properties. However, the long-term consequences of variation in maternal carotenoid transfer for the offspring have seldom been considered. Since plasma carotenoid levels at adulthood are known to influence testis size and yolk carotenoid levels influence the ability to extract carotenoids later in life, we hypothesized that maternally transmitted carotenoids might influence gonad size at adulthood. Here, we showed that male Japanese quail (Coturnix japonica) originating from a carotenoid-enriched egg had smaller testes than control individuals at adulthood. This result shows that yolk carotenoids have long-term organizational effects. In addition, given that carotenoid intake at sexual maturity increases sperm quality and that a decreased testis size is associated with a lower sperm production, we propose that carotenoid exposure during embryo development might influence a trade-off between ejaculate size and sperm quality. PMID:27122006

  3. Silver nanoparticles disrupt germline stem cell maintenance in the Drosophila testis

    NASA Astrophysics Data System (ADS)

    Ong, Cynthia; Lee, Qian Ying; Cai, Yu; Liu, Xiaoli; Ding, Jun; Yung, Lin-Yue Lanry; Bay, Boon-Huat; Baeg, Gyeong-Hun

    2016-02-01

    Silver nanoparticles (AgNPs), one of the most popular nanomaterials, are commonly used in consumer products and biomedical devices, despite their potential toxicity. Recently, AgNP exposure was reported to be associated with male reproductive toxicity in mammalian models. However, there is still a limited understanding of the effects of AgNPs on spermatogenesis. The fruit fly Drosophila testis is an excellent in vivo model to elucidate the mechanisms underlying AgNP-induced defects in spermatogenesis, as germ lineages can be easily identified and imaged. In this study, we evaluated AgNP-mediated toxicity on spermatogenesis by feeding Drosophila with AgNPs at various concentrations. We first observed a dose-dependent uptake of AgNPs in vivo. Concomitantly, AgNP exposure caused a significant decrease in the viability and delay in the development of Drosophila in a dose-dependent manner. Furthermore, AgNP-treated male flies showed a reduction in fecundity, and the resulting testes contained a decreased number of germline stem cells (GSCs) compared to controls. Interestingly, testes exposed to AgNPs exhibited a dramatic increase in reactive oxygen species levels and showed precocious GSC differentiation. Taken together, our study suggests that AgNP exposure may increase ROS levels in the Drosophila testis, leading to a reduction of GSC number by promoting premature GSC differentiation.

  4. Protection of Pentoxifylline against Testis Injury Induced by Intermittent Hypobaric Hypoxia.

    PubMed

    Yao, Chen; Li, Gang; Qian, Yeyong; Cai, Ming; Yin, Hong; Xiao, Li; Tang, Wei; Guo, Fengjie; Shi, Bingyi

    2016-01-01

    To investigate the effect of pentoxifylline (PTX) on spermatogenesis dysfunction induced by intermittent hypobaric hypoxia (IHH) and unveil the underlying mechanism, experimental animals were assigned to Control, IHH+Vehicle, and IHH+PTX groups and exposed to 4 cycles of 96 h of hypobaric hypoxia followed by 96 h of normobaric normoxia for 32 days. PTX was administered for 32 days. Blood and tissue samples were collected 7 days thereafter. Serum malondialdehyde levels were used to assess lipid peroxidation; ferric-reducing antioxidant power (FRAP), superoxide dismutase, and catalase and glutathione peroxidase enzyme activities were assessed to determine antioxidant capacity in various samples. Testis histopathology was assessed after hematoxylin-eosin staining by Johnsen's testicular scoring system. Meanwhile, testosterone synthase and vimentin amounts were assessed by immunohistochemistry. Sperm count, motility, and density were assessed to determine epididymal sperm quality. IHH treatment induced significant pathological changes in testicular tissue and enhanced serum lipid peroxide levels, while reducing serum FRAP, antioxidant enzyme activities, and testosterone synthase expression. Moreover, IHH impaired epididymal sperm quality and vimentin structure in Sertoli cells. Oral administration of PTX improved the pathological changes in the testis. IHH may impair spermatogenesis function of testicular tissues by inducing oxidative stress, but this impairment could be attenuated by administration of PTX. PMID:27642493

  5. The effects of nanoparticles on mouse testis Leydig cells in vitro.

    PubMed

    Komatsu, Tomoko; Tabata, Masako; Kubo-Irie, Miyoko; Shimizu, Takahisa; Suzuki, Ken-Ichiro; Nihei, Yoshimasa; Takeda, Ken

    2008-12-01

    We have indicated the possibility that nanoparticles such as diesel exhaust particles (DEP) and titanium dioxide (TiO(2)) may impair the male mouse reproductive system. In this study, to evaluate the direct effect of nanoparticles on testis-constituent cells, we examined the effect of DEP, TiO(2) and carbon black (CB) on mouse Leydig TM3 cells, the testosterone-producing cells of the testis. The uptake of three nanoparticles into Leydig cells was detected using transmission electron microscopy (TEM) or field emission type scanning electron microscopy/energy-dispersive X-ray spectroscopy (FE-SEM/EDS). We examined the cytotoxicity and the effect on gene expression by treatment with nanoparticles. TiO(2) was more cytotoxic to Leydig cells than other nanoparticles. The proliferation of Leydig cells was suppressed transiently by treatment with TiO(2) or DEP. The expression of heme oxygenase-1 (HO-1), a sensitive marker for oxidative stress, was induced remarkably by treatment with DEP. Furthermore, CB and DEP slightly increased the gene expression of the steroidogenic acute regulatory (StAR) protein, the factor that controls mitochondrial cholesterol transfer. In this study, we found that DEPs, TiO(2) and CB nanoparticles were taken up by Leydig cells, and affected the viability, proliferation and gene expression. The patterns were unique for each nanoparticle. PMID:18805477

  6. Temporally controlled site-specific mutagenesis in the germ cell lineage of the mouse testis.

    PubMed

    Weber, Philipp; Schuler, Michael; Gérard, Christelle; Mark, Manuel; Metzger, Daniel; Chambon, Pierre

    2003-02-01

    We have obtained a PrP-Cre-ER(T) transgenic mouse line (28.8) that selectively expresses in testis the tamoxifen-inducible Cre-ER(T) recombinase under the control of a mouse Prion protein (PrP) promoter-containing genomic fragment. Cre-ER(T) is expressed in spermatogonia and spermatocytes, but not in Sertoli and Leydig cells. We also established reporter PrP-L-EGFP-L transgenic mice harboring a LoxP-flanked enhanced green fluorescent protein (EGFP) Cre reporter cassette under the control of the same PrP promoter-containing genomic fragment that exhibits prominent EGFP expression in brain and testis. Using the PrP-L-EGFP-L as well as other Cre-reporter mice, we demonstrate that tamoxifen administration efficiently and selectively induces Cre-mediated recombination in the germ cell lineage. The established PrP-Cre-ER(T) line should provide a valuable tool for studying functions of germ cell-expressed genes involved in spermatogenesis. PMID:12533419

  7. Silver nanoparticles disrupt germline stem cell maintenance in the Drosophila testis

    PubMed Central

    Ong, Cynthia; Lee, Qian Ying; Cai, Yu; Liu, Xiaoli; Ding, Jun; Yung, Lin-Yue Lanry; Bay, Boon-Huat; Baeg, Gyeong-Hun

    2016-01-01

    Silver nanoparticles (AgNPs), one of the most popular nanomaterials, are commonly used in consumer products and biomedical devices, despite their potential toxicity. Recently, AgNP exposure was reported to be associated with male reproductive toxicity in mammalian models. However, there is still a limited understanding of the effects of AgNPs on spermatogenesis. The fruit fly Drosophila testis is an excellent in vivo model to elucidate the mechanisms underlying AgNP-induced defects in spermatogenesis, as germ lineages can be easily identified and imaged. In this study, we evaluated AgNP-mediated toxicity on spermatogenesis by feeding Drosophila with AgNPs at various concentrations. We first observed a dose-dependent uptake of AgNPs in vivo. Concomitantly, AgNP exposure caused a significant decrease in the viability and delay in the development of Drosophila in a dose-dependent manner. Furthermore, AgNP-treated male flies showed a reduction in fecundity, and the resulting testes contained a decreased number of germline stem cells (GSCs) compared to controls. Interestingly, testes exposed to AgNPs exhibited a dramatic increase in reactive oxygen species levels and showed precocious GSC differentiation. Taken together, our study suggests that AgNP exposure may increase ROS levels in the Drosophila testis, leading to a reduction of GSC number by promoting premature GSC differentiation. PMID:26847594

  8. Regulation of blood-testis barrier by actin binding proteins and protein kinases

    PubMed Central

    Li, Nan; Tang, Elizabeth I.; Cheng, C. Yan

    2016-01-01

    The blood-testis barrier (BTB) is an important ultrastructure in the testis since the onset of spermatogenesis coincides with the establishment of a functional barrier in rodents and humans. It is also noted that a delay in the assembly of a functional BTB following treatment of neonatal rats with drugs such as diethylstilbestrol or adjudin also delays the first wave of spermiation. While the BTB is one of the tightest blood-tissue barriers, it undergoes extensive remodeling, in particular at stage VIII of the epithelial cycle to facilitate the transport of preleptotene spermatocytes connected in clones across the immunological barrier. Without this timely transport of preleptotene spermatocytes derived from type B spermatogonia, meiosis will be arrested, causing aspermatogenesis. Yet the biology and regulation of the BTB remains largely unexplored since the morphological studies in the 1970s. Recent studies, however, have shed new light on the biology of the BTB. Herein, we critically evaluate some of these findings, illustrating that the Sertoli cell BTB is regulated by actin binding proteins (ABPs), likely supported by non-receptor protein kinases, to modulate the organization of actin microfilament bundles at the site. Furthermore, microtubule (MT)-based cytoskeleton is also working in concert with the actin-based cytoskeleton to confer BTB dynamics. This timely review provides an update on the unique biology and regulation of the BTB based on the latest findings in the field, focusing on the role of ABPs and non-receptor protein kinases. PMID:26628556

  9. [Traumatic luxation of the testis due to self-mutilation: a case report].

    PubMed

    Ishibiki, Yuji; Matsumura, Tsutomu

    2006-01-01

    A 16-year-old male patient was admitted to our hospital with traumatic luxation of right testis due to self-mutilation with a retractable knife on Apr. 20, 2004. He had been followed as temporal lobe epilepsy and suspicions of gender identify disorder by a pediatrician. He was fully oriented with a clear sensory and normal perception, but had no memory of what he had done. His parents were free of psychiatric disease, and he was the youngest in siblings of two older brothers. The laboratory examination showed no abnormal findings. Under general anesthesia, right testis was replaced in the scrotum and the scrotal wound was closed at the emergency operation. He had an attack of epilepsy and recovered by itself on the next day. He was discharged on the eighth postoperative day. After the operation, no recurrence has been seen until now. To our knowledge, this is the 37th case of male genital self-mutilation reported in the Japanese literature.

  10. Three-dimensional structure of Drosophila testis tip: the spatial relation between dividing cells.

    PubMed

    Lee, Kyung Eun; Han, Sung Sik; Jeon, Hyesung

    2013-08-01

    At the apical tip of Drosophila testis, there is a stem cell niche known as the proliferation center, where the stem cells are maintained by hub cell cluster for the regulation of differentiation and proliferation. Germline stem cells go through mitosis four times from one primary spermatogonial cell to the 16-cell stage before the maturation. The cells derived from the same germline stem cell are located within one cyst, an enclosed system by two cyst cells, and they are connected by the intercellular bridges called ring canals. In this study, the three-dimensional (3D) structure of Drosophila testis tip was reconstructed from serial sections. The size of cells at each stage was compared in volume from the 3D structure. The stages of cells in a cyst could be distinguishable exactly by counting the cells linked with intercellular bridges in 3D-reconstructed structure. The cysts containing the same stage cells appeared in the horizontal plane. Both the germline stem cell directly attached to the hub cell and the spermatogonial cells detached from the hub cell were divided at the almost perpendicular direction to the spermatogonial cell layers. The dividing phase in one cyst was delayed gradually through the cytoplasmic region of intercellular bridge.

  11. The biology of cancer testis antigens: putative function, regulation and therapeutic potential.

    PubMed

    Fratta, Elisabetta; Coral, Sandra; Covre, Alessia; Parisi, Giulia; Colizzi, Francesca; Danielli, Riccardo; Nicolay, Hugues Jean Marie; Sigalotti, Luca; Maio, Michele

    2011-04-01

    Cancer testis antigens (CTA) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA-based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigenetic events, particularly DNA methylation, appear to be the primary mechanism regulating CTA expression in both normal and transformed cells, as well as in cancer stem cells. In view of the growing interest in CTA biology, the aim of this review is to provide the most recent information on their expression, regulation and function, together with a brief summary of the major clinical trials involving CTA as therapeutic agents. The pharmacologic modulation of CTA expression profiles on neoplastic cells by DNA hypomethylating drugs will also be discussed as a feasible approach to design new combination therapies potentially able to improve the clinical efficacy of currently adopted CTA-based immunotherapeutic regimens in cancer patients.

  12. Protection of Pentoxifylline against Testis Injury Induced by Intermittent Hypobaric Hypoxia

    PubMed Central

    Yao, Chen; Li, Gang; Qian, Yeyong; Cai, Ming; Yin, Hong; Xiao, Li; Tang, Wei; Guo, Fengjie

    2016-01-01

    To investigate the effect of pentoxifylline (PTX) on spermatogenesis dysfunction induced by intermittent hypobaric hypoxia (IHH) and unveil the underlying mechanism, experimental animals were assigned to Control, IHH+Vehicle, and IHH+PTX groups and exposed to 4 cycles of 96 h of hypobaric hypoxia followed by 96 h of normobaric normoxia for 32 days. PTX was administered for 32 days. Blood and tissue samples were collected 7 days thereafter. Serum malondialdehyde levels were used to assess lipid peroxidation; ferric-reducing antioxidant power (FRAP), superoxide dismutase, and catalase and glutathione peroxidase enzyme activities were assessed to determine antioxidant capacity in various samples. Testis histopathology was assessed after hematoxylin-eosin staining by Johnsen's testicular scoring system. Meanwhile, testosterone synthase and vimentin amounts were assessed by immunohistochemistry. Sperm count, motility, and density were assessed to determine epididymal sperm quality. IHH treatment induced significant pathological changes in testicular tissue and enhanced serum lipid peroxide levels, while reducing serum FRAP, antioxidant enzyme activities, and testosterone synthase expression. Moreover, IHH impaired epididymal sperm quality and vimentin structure in Sertoli cells. Oral administration of PTX improved the pathological changes in the testis. IHH may impair spermatogenesis function of testicular tissues by inducing oxidative stress, but this impairment could be attenuated by administration of PTX. PMID:27642493

  13. In vitro maintenance of spermatogenesis in Xenopus laevis testis explants cultured in serum-free media

    SciTech Connect

    Risley, M.S.; Miller, A.; Bumcrot, D.A.

    1987-05-01

    Spermatogenesis has been maintained for extended periods in Xenopus laevis testis explants cultured in serum-free media supplemented with bovine serum albumin, insulin, transferrin, follicle-stimulating hormone, dihydrotestosterone, testosterone, retinol, ascorbate, and tocopherol. The organization of the testis fragments was maintained for 28 days, and all stages of development were present throughout the culture period. /sup 3/H-Thymidine-labeled secondary (Type B) spermatogonia developed in 28 days into spermatids at the acrosomal vesicle stage whereas labeled zygotene spermatocytes became mature spermatids in 28 days. Spermatogonial proliferation also continued in vitro for 28 days. Germ cell differentiation was not dependent upon exogenous testosterone, ascorbate, or tocopherol since /sup 3/H-labeled spermatogonia became mature spermatids in testes cultured 35 days in media lacking these supplements. Autoradiography demonstrated that 55% of the luminal sperm present in explants cultured 10 days had differentiated in vitro. Sperm from testes cultured 10-35 days were similar to sperm from freshly dissected testes with regard to motility and fecundity, and eggs fertilized with sperm from explant cultures developed normally into swimming tadpoles. The results demonstrate the feasibility of maintaining vertebrate spermatogenesis in culture and suggest that in vitro analysis of Xenopus spermatogenesis using defined media may provide important insights into the evolution of regulatory mechanisms in spermatogenesis.

  14. Effects of Subchronic Exposure to Cadmium and Diazinon on Testis and Epididymis in Rats

    PubMed Central

    Cabaj, Michal; Massanyi, Peter; Martiniakova, Monika; Omelka, Radoslav; Krajcovicova, Vladimira; Duranova, Hana

    2014-01-01

    The present study aimed to elucidate the structural changes in testis and epididymis of adult rats following subchronic peroral administration of cadmium at 30 mg/L, diazinon at 40 mg/L, cadmium at 30 mg/L, and diazinon at 40 mg/L, respectively. At the end of 90-day experiment, the samples of the testes and epididymis were assayed by qualitative and quantitative histological methods. The testis and epididymis weights increased following exposure to cadmium and simultaneous exposure to cadmium and diazinon. Testicular damage following cadmium and diazinon coexposure was significantly less expressive than in groups with individual administration of these compounds. Cadmium caused a significant thickening of seminiferous epithelium, cellular degeneration, and necrosis. Desquamation of immature germ cells resulted in a significant increase of intraepithelial spaces and reduced tubule volume in all experimental groups. Vascular dilation and congestion were detected in the interstitial tissue. The changes in epididymal histology in the group exposed to cadmium and group exposed simultaneously included a reduction of epithelium, necrotic epithelial cells, vasoconstriction, and interstitial edema together with mononuclear cell infiltration. Results did not indicate a synergistic or any additional effect from the simultaneous administration of both toxicants. Further research is needed to determine the significance and the mechanism of the adverse effects. PMID:25548789

  15. Long-term ex vivo maintenance of testis tissues producing fertile sperm in a microfluidic device

    PubMed Central

    Komeya, Mitsuru; Kimura, Hiroshi; Nakamura, Hiroko; Yokonishi, Tetsuhiro; Sato, Takuya; Kojima, Kazuaki; Hayashi, Kazuaki; Katagiri, Kumiko; Yamanaka, Hiroyuki; Sanjo, Hiroyuki; Yao, Masahiro; Kamimura, Satoshi; Inoue, Kimiko; Ogonuki, Narumi; Ogura, Atsuo; Fujii, Teruo; Ogawa, Takehiko

    2016-01-01

    In contrast to cell cultures, particularly to cell lines, tissues or organs removed from the body cannot be maintained for long in any culture conditions. Although it is apparent that in vivo regional homeostasis is facilitated by the microvascular system, mimicking such a system ex vivo is difficult and has not been proved effective. Using the culture system of mouse spermatogenesis, we addressed this issue and devised a simple microfluidic device in which a porous membrane separates a tissue from the flowing medium, conceptually imitating the in vivo relationship between the microvascular flow and surrounding tissue. Testis tissues cultured in this device successfully maintained spermatogenesis for 6 months. The produced sperm were functional to generate healthy offspring with micro-insemination. In addition, the tissue kept producing testosterone and responded to stimulation by luteinizing hormone. These data suggest that the microfluidic device successfully created in vivo-like conditions, in which testis tissue maintained its physiologic functions and homeostasis. The present model of the device, therefore, would provide a valuable foundation of future improvement of culture conditions for various tissues and organs, and revolutionize the organ culture method as a whole. PMID:26892171

  16. Expression, Localization, and Binding Activity of the Ezrin/Radixin/Moesin Proteins in the Mouse Testis

    PubMed Central

    Wakayama, Tomohiko; Nakata, Hiroki; Kurobo, Miho; Sai, Yoshimichi; Iseki, Shoichi

    2009-01-01

    The ezrin, radixin, and moesin (ERM) proteins represent a family of adaptor proteins linking transmembrane proteins to the cytoskeleton. The seminiferous epithelium undergoes extensive changes in cellular composition, location, and shape, implicating roles of the membrane–cytoskeleton interaction. It remains unknown, however, whether the ERM proteins are expressed and play significant roles in the testis. In the present study, we examined the spatiotemporal expression of ERM proteins in the mouse testis by Western blotting and immunohistochemistry. Ezrin immunoreactivity was demonstrated in the cytoplasm of steps 15 and 16 spermatids from 5 weeks postpartum through adulthood, whereas radixin immunoreactivity was in the apical cytoplasm of Sertoli cells from 1 week through 2 weeks postpartum. No immunoreactivity for moesin was detected at any age. Immunoprecipitation demonstrated that ezrin was bound to the cytoskeletal component actin, whereas radixin was bound to both actin and tubulin. Of the transmembrane proteins known to interact with ERM proteins, only cystic fibrosis transmembrane conductance regulator, a chloride transporter, was bound to ezrin in elongated spermatids. These results suggest that ezrin is involved in spermiogenesis whereas radixin is involved in the maturation of Sertoli cells, through interaction with different sets of membrane proteins and cytoskeletal components. (J Histochem Cytochem 57:351–362, 2009) PMID:19064715

  17. Profiling cancer testis antigens in non–small-cell lung cancer

    PubMed Central

    Djureinovic, Dijana; Hallström, Björn M.; Horie, Masafumi; Mattsson, Johanna Sofia Margareta; La Fleur, Linnea; Brunnström, Hans; Madjar, Katrin; Rahnenführer, Jörg; Ekman, Simon; Koyi, Hirsh; Brandén, Eva; Edlund, Karolina; Hengstler, Jan G.; Lambe, Mats; Saito, Akira; Botling, Johan; Uhlén, Mathias

    2016-01-01

    Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non–small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.

  18. Recent adverse trends in semen quality and testis cancer incidence among Finnish men

    PubMed Central

    Jørgensen, N; Vierula, M; Jacobsen, R; Pukkala, E; Perheentupa, A; Virtanen, H E; Skakkebæk, N E; Toppari, J

    2011-01-01

    Impaired semen quality and testicular cancer may be linked through a testicular dysgenesis syndrome of foetal origin. The incidence of testis cancer has been shown to increase among Finnish men, whereas there is no recent publication describing temporal trends in semen quality. Therefore, we carried out a prospective semen quality study and a registry study of testis cancer incidence among Finnish men to explore recent trends. A total of 858 men were investigated in the semen quality study during 1998–2006. Median sperm concentrations were 67 (95% CI 57–80) million/mL, 60 (51–71) and 48 (39–60) for birth cohorts 1979–81, 1982–83 and 1987; total sperm counts 227 (189–272) million, 202 (170–240) and 165 (132–207); total number of morphologically normal spermatozoa 18 (14–23) million, 15 (12–19) and 11 (8–15). Men aged 10–59 years at the time of diagnosis with testicular cancer during 1954–2008 were included in the registry study, which confirmed the increasing incidence of testicular cancer in recent cohorts. These simultaneous and rapidly occurring adverse trends suggest that the underlying causes are environmental and, as such, preventable. Our findings necessitate not only further surveillance of male reproductive health but also research to detect and remove the underlying factors. PMID:21366607

  19. Testis tissue explantation cures spermatogenic failure in c-Kit ligand mutant mice

    PubMed Central

    Sato, Takuya; Yokonishi, Tetsuhiro; Komeya, Mitsuru; Katagiri, Kumiko; Kubota, Yoshinobu; Matoba, Shogo; Ogonuki, Narumi; Ogura, Atsuo; Yoshida, Shosei; Ogawa, Takehiko

    2012-01-01

    Male infertility is most commonly caused by spermatogenic defects or insufficiencies, the majority of which are as yet cureless. Recently, we succeeded in cultivating mouse testicular tissues for producing fertile sperm from spermatogonial stem cells. Here, we show that one of the most severe types of spermatogenic defect mutant can be treated by the culture method without any genetic manipulations. The Sl/Sld mouse is used as a model of such male infertility. The testis of the Sl/Sld mouse has only primitive spermatogonia as germ cells, lacking any sign of spermatogenesis owing to mutations of the c-kit ligand (KITL) gene that cause the loss of membrane-bound-type KITL from the surface of Sertoli cells. To compensate for the deficit, we cultured testis tissues of Sl/Sld mice with a medium containing recombinant KITL and found that it induced the differentiation of spermatogonia up to the end of meiosis. We further discovered that colony stimulating factor-1 (CSF-1) enhances the effect of KITL and promotes spermatogenesis up to the production of sperm. Microinsemination of haploid cells resulted in delivery of healthy offspring. This study demonstrated that spermatogenic impairments can be treated in vitro with the supplementation of certain factors or substances that are insufficient in the original testes. PMID:22984182

  20. US of the tunica vaginalis testis: anatomic relationships and pathologic conditions.

    PubMed

    Garriga, Victoria; Serrano, Angel; Marin, Anna; Medrano, Santiago; Roson, Nuria; Pruna, Xavier

    2009-11-01

    Extratesticular lesions are common incidental findings at ultrasonography (US) among men and boys. Most lesions originate from or depend on the tunica vaginalis, a mesothelium-lined sac with a visceral layer and a parietal layer. The tunica vaginalis is formed when the superior portion of the processus vaginalis closes during embryologic development. Abnormal closure of the processus vaginalis leads to congenital anomalies of the tunica vaginalis, such as complete or partial patency of the processus vaginalis, spermatic cord hydrocele, and inguinoscrotal hernia. The proximity of the visceral layer to the testis explains the reactive involvement seen in epididymo-orchitis, with resultant pyocele or abscess formation. The tunica vaginalis also may be affected by inflammatory and traumatic disorders such as scrotal calculi, fibrous pseudotumor, or hematocele. These lesions manifest as solid or heterogeneous tumorlike masses. Lesions of mesothelial origin, such as adenomatoid tumor, tunica cyst, and mesothelioma, may involve the tunica vaginalis. Entrapped mesenchymal cells can lead to lipoma, leiomyoma, or sarcoma, although these tumors are uncommon in the tunica vaginalis. US is not useful for differentiating between benign and malignant tumors; however, some characteristic findings may help in planning the best surgical approach. Knowledge of the embryologic development, anatomic relationships, and pathologic disorders of the tunica vaginalis is essential to narrow the differential diagnosis of an extratesticular lesion. In most cases, US findings in combination with clinical assessment can indicate whether nonsurgical management or testis-sparing surgery is warranted.

  1. Expression profiling of long noncoding RNAs in neonatal and adult mouse testis.

    PubMed

    Sun, Jin; Wu, Ji

    2015-09-01

    In recent years, advancements in genome-wide analyses of the mammalian transcriptome have revealed that long noncoding RNAs (lncRNAs) is pervasively transcribed in the genome and an increasing number of studies have demonstrated lncRNAs as a new class of regulatory molecules are involved in mammalian development (Carninci et al. (2005); Fatica and Bozzoni (2014)), but very few studies have been conducted on the potential roles of lncRNAs in mammalian testis development. To get insights into the expression patterns of lncRNA during mouse testis development, we investigated the lncRNAs expression profiles of neonatal and adult mouse testes using microarray platform and related results have been published (Sun et al., PLoS One 8 (2013) e75750.). Here, we describe in detail the experimental system, methods and validation for the generation of the microarray data associated with our recent publication (Sun et al., PLoS One 8 (2013) e75750.). Data have been deposited to the Gene Expression Omnibus (GEO) database repository with the dataset identifier GSE43442. PMID:26217809

  2. Profiling of androgen response in rainbow trout pubertal testis: relevance to male gonad development and spermatogenesis.

    PubMed

    Rolland, Antoine D; Lardenois, Aurélie; Goupil, Anne-Sophie; Lareyre, Jean-Jacques; Houlgatte, Rémi; Chalmel, Frédéric; Le Gac, Florence

    2013-01-01

    The capacity of testicular somatic cells to promote and sustain germ cell differentiation is largely regulated by sexual steroids and notably androgens. In fish species the importance of androgens is emphasized by their ability to induce sex reversal of the developing fries and to trigger spermatogenesis. Here we studied the influence of androgens on testicular gene expression in trout testis using microarrays. Following treatment of immature males with physiological doses of testosterone or 11-ketotestosterone, 418 genes that exhibit changes in expression were identified. Interestingly, the activity of testosterone appeared stronger than that of 11-ketotestosterone. Expression profiles of responsive genes throughout testis development and in isolated germ cells confirmed androgens to mainly affect gene expression in somatic cells. Furthermore, specific clusters of genes that exhibit regulation coincidently with changes in the natural circulating levels of androgens during the reproductive cycle were highlighted, reinforcing the physiological significance of these data. Among somatic genes, a phylogenetic footprinting study identified putative androgen response elements within the proximal promoter regions of 42 potential direct androgen target genes. Finally, androgens were also found to alter the germ line towards meiotic expression profiles, supporting the hypothesis of a role for the somatic responsive genes in driving germ cell fate. This study significantly increases our understanding of molecular pathways regulated by androgens in vertebrates. The highly cyclic testicular development in trout together with functions associated with regulated genes reveal potential mechanisms for androgen actions in tubule formation, steroid production, germ cell development and sperm secretion. PMID:23301058

  3. Congenital adrenal hyperplasia and vanishing testis: rare case of male pseudohermaphroditism

    PubMed Central

    Ghanei, Azam; Mohammadzade, Golnaz; Zarepur, Ehsan; Soheilikhah, Sedigheh

    2016-01-01

    Background: Congenital adrenal hyperplasia (CAH) and vanishing testes are uncommon diseases that can result from hormonal and mechanical factors. Classic CAH is determined by ambiguous genitalia and increase in amount of 17-Hydroxyprogesterone. Simultaneous occurrence of CAH and vanishing testes is a rare condition. Case: A 22-year-old boy, known case of CAH who was diagnosed as female pseudohermaphroditism due to ambiguous genitalia, was referred to Shahid Sadoughi Hospital, Yazd, Iran with colicky abdominal pain and hematuria. Ultrasonography has been performed and prostate tissue was reported. Karyotyping was done because of uncertainty in primary diagnosis, which revealed 46XY. For finding location of testes, ultrasonography and MRI were done and nothing was found in abdomen, inguinal canal or scrotum. Inhibin B serum level was measured to find out whether testis tissue was present in the body, which was <1 pg/ml and vanishing testis was confirmed. Conclusion: Early diagnosis and treatment are essential to prevent further sequels and karyotyping for all patients with CAH is recommended. Lifelong treatment with synthetic glucocorticoid replacement is necessary. PMID:27294221

  4. Expression of growth differentiation factor 9 (GDF9) and its receptor in adult cat testis.

    PubMed

    Zhao, Li; He, JunPing; Guo, QingYun; Wen, XueXue; Zhang, XueJing; Dong, ChangSheng

    2011-12-01

    Oocyte-secreted growth differentiation factor (GDF) 9 plays an essential role during follicle maturation through actions on granulosa cells. Despite its critical role in female reproduction, GDF9 expression, signalling and function are less well characterized during spermatogenesis. The purpose of this study was to investigate temporal and spatial expression and potential cellular targets of GDF9 in the adult cat testis. Our result confirmed that GDF9 is stage-specifically localized in the cytoplasm of round spermatids and pachytene spermatocytes of the cat seminiferous epithelium. In particular, activin receptor-like kinase (ALK) 5, the type I receptor of GDF9, is principally localized in the cytoplasm of round spermatids. Smad2/3, signal transducers for GDF9 signalling pathway, is mainly immunolocalized in the cytoplasm of germ cells, Sertoli cells and Leydig cells, but the expression in germ cells are weaker than in Sertoli cells. The expression pattern of ALK5 and Smad2/3 show that GDF9-ALK5-Smad2/3 may not be the only signalling pathway for testicular cell to respond to GDF9. Overall, our results demonstrate that GDF9 is a germ cell-specific factor in the adult cat testis, and that GDF9 regulates the tight junctions of Sertoli cells by paracrine secretion, and regulates the germ cells by autocrine secretion.

  5. Ultrastructural interrelationship between the pineal gland and the testis in the male rat.

    PubMed

    Kuş, I; Sarsilmaz, M; Ogetürk, M; Yilmaz, B; Keleştimur, H; Oner, H

    2000-01-01

    The ultrastructural interrelationship between the pineal gland and testis was evaluated in the rat. Wistar rats were divided into 6 groups. Groups I and II were sham-orchidectomized and orchidectomized rats, respectively. Rats in group III were orchidectomized and daily injected with testosterone propionate (TP) for 1 month. Groups IV and V were sham-pinealectomized and pinealectomized, respectively. Group VI was pinealectomized and daily injected with melatonin for 2 months. All animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II, and III and the testes of groups IV, V, and VI were removed and weighed. All specimens were examined by electron microscopy. Orchidectomy caused an increase of lipid droplets, cytoplasmic dense bodies, and lysosomes. Rough endoplasmic reticulum, Golgi apparatus, and mitochondria were extensive in the cytoplasm. TP administration to orchidectomized rats resulted in formation of less extensive lipid droplets and mitochondria. In pinealectomized rats, golgi complex, mitochondria, and enlarged smooth endoplasmic reticulum were extensive in the cytoplasm of Leydig cells. Formation of cytoplasmic secretory granules and osmiophilic bodies was observed. Testicular weight increased compared to group IV. Melatonin decreased testicular weight in comparison to group V and prevented ultrastructural changes. Pinealectomy and orchidectomy caused hyperactivity in Leydig cells and pinealocytes, respectively, which suggests a mutual relationship between the pineal gland and testis in the rat.

  6. Protection of Pentoxifylline against Testis Injury Induced by Intermittent Hypobaric Hypoxia

    PubMed Central

    Yao, Chen; Li, Gang; Qian, Yeyong; Cai, Ming; Yin, Hong; Xiao, Li; Tang, Wei; Guo, Fengjie

    2016-01-01

    To investigate the effect of pentoxifylline (PTX) on spermatogenesis dysfunction induced by intermittent hypobaric hypoxia (IHH) and unveil the underlying mechanism, experimental animals were assigned to Control, IHH+Vehicle, and IHH+PTX groups and exposed to 4 cycles of 96 h of hypobaric hypoxia followed by 96 h of normobaric normoxia for 32 days. PTX was administered for 32 days. Blood and tissue samples were collected 7 days thereafter. Serum malondialdehyde levels were used to assess lipid peroxidation; ferric-reducing antioxidant power (FRAP), superoxide dismutase, and catalase and glutathione peroxidase enzyme activities were assessed to determine antioxidant capacity in various samples. Testis histopathology was assessed after hematoxylin-eosin staining by Johnsen's testicular scoring system. Meanwhile, testosterone synthase and vimentin amounts were assessed by immunohistochemistry. Sperm count, motility, and density were assessed to determine epididymal sperm quality. IHH treatment induced significant pathological changes in testicular tissue and enhanced serum lipid peroxide levels, while reducing serum FRAP, antioxidant enzyme activities, and testosterone synthase expression. Moreover, IHH impaired epididymal sperm quality and vimentin structure in Sertoli cells. Oral administration of PTX improved the pathological changes in the testis. IHH may impair spermatogenesis function of testicular tissues by inducing oxidative stress, but this impairment could be attenuated by administration of PTX.

  7. Profiling cancer testis antigens in non–small-cell lung cancer

    PubMed Central

    Djureinovic, Dijana; Hallström, Björn M.; Horie, Masafumi; Mattsson, Johanna Sofia Margareta; La Fleur, Linnea; Brunnström, Hans; Madjar, Katrin; Rahnenführer, Jörg; Ekman, Simon; Koyi, Hirsh; Brandén, Eva; Edlund, Karolina; Hengstler, Jan G.; Lambe, Mats; Saito, Akira; Botling, Johan; Uhlén, Mathias

    2016-01-01

    Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non–small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies. PMID:27699219

  8. Toxic effects of cadmium on testis of birds and mammals: a review.

    PubMed

    Marettová, E; Maretta, M; Legáth, J

    2015-04-01

    In humans and other mammals, cadmium (Cd) causes various damages to different organs and tissues of the body. This review presents a comprehensive overview on the effect of Cd on the structure of seminiferous tubules, Leydig cells and blood vessels in the testis. The main observation of the effect of Cd is destruction of the seminiferous tubules with severe necrotic areas. Damage is to all stages of developing germ cells by inducing their structural changes and the apoptotic cell death. Sertoli supporting cells are considered the most vulnerable cells. Their damage results in cytoplasmic rearrangement and disruption of inter-Sertoli tight junctions resulting in increased permeability of the blood-testis barrier, structural changes in the Leydig cells and decreased testosterone secretion. After long time of Cd exposure an increase of the amount of interstitial connective tissue occurs. In blood vessels Cd exposure causes various morphological and physiological changes in vascular endothelial cells and smooth muscle cells. In humans and other mammals, the range of effect depends on the dose, route, ways, and duration of exposure. After necrosis of the sensitive cells Cd produced lesions in surrounding tissue and activate free cells. Atrophy of the seminiferous tubules is followed by Leydig cell regeneration and interstitial revascularization. In birds, spermatogenic cells underwent irreversible degeneration or atrophy of seminiferous tubules in the absence of significant vascular lesions.

  9. Pseudoephedrine induces sperm abnormalities, lower sperm counts and increased apoptosis in rat testis.

    PubMed

    Nudmamud-Thanoi, Sutisa; Thanoi, Samur

    2012-08-01

    Pseudoephedrine, an over-the-counter drug, is commonly used for the treatments of asthma, nasal congestion, and obesity. Furthermore, it can be used as a psychostimulant drug if taken in large doses; however, there have been no reports on its effects on reproduction. The aim of this study was therefore to investigate the effects of pseudoephedrine administration on sperm morphology, sperm concentration and apoptotic activity in the rat testis. Rats were administered intraperitoneally (IP) with pseudoephedrine at 120 mg/kg for the acute group and 80 mg/kg, IP, once daily for 15 days for the chronic group, while a control group was treated with vehicle. The percentages of normal sperm morphology were significantly decreased in both acute and chronic groups when compared with controls while the total sperm count was significantly decreased in the acute group. Apoptotic activities were increased significantly in both pseudoephedrine-treated groups. The results indicate that pseudoephedrine can induce sperm abnormalities, decrease sperm numbers and increase apoptotic activity in the testis of rats if taken at high doses. The results of this study suggest that the users of pseudoephedrine in medical treatments need to be aware of its potential toxicity involving spermatogenesis.

  10. Chronic lead exposure effects in the cynomolgus monkey (Macaca fascicularis) testis.

    PubMed

    Foster, W G; Singh, A; McMahon, A; Rice, D C

    1998-01-01

    Although reproductive consequences of high circulating blood lead levels (> or = 60 micrograms/dL) have been reported, potential adverse effects of chronic lead exposure in males that result in low to moderate blood lead levels (10-25 and 26-60 micrograms/dL, respectively) are unknown. Effects of chronic lead exposure to testis ultrastructure were determined in the cynomolgus monkey after oral administration of lead acetate (1500 micrograms/kg BW/day) in a vehicle in the following groups: from birth to 10 years (lifetime), postnatal day 300 to 10 years (postinfancy), and postnatal day 0-400 (infancy); monkeys in the control group received only the vehicle (95% glycerol and 5% distilled water). At age 10 years, circulating lead concentrations in lifetime and postinfancy-dosed monkeys were approximately 35 micrograms/dL, and in control and infancy animals the concentrations were < 1.0 microgram/dL. Sertoli and spermatogenic cells of dosed monkeys from the infancy and lifetime groups revealed injuries. Chronic exposure to lead that results in moderate blood lead concentrations induced persistent ultrastructural alterations in the cynomolgus monkey testis. Results of this study on the primate, following extrapolation to humans, could influence further refining of the impact of environmental lead contamination concentrations vis-à-vis the health of children, adults, and aged human beings.

  11. Profiling microRNAs in the testis during sexual maturation stages in Eriocheir sinensis.

    PubMed

    He, Lin; Wang, Yuan-Li; Li, Qing; Yang, Hong-Dan; Duan, Ze-Lin; Wang, Qun

    2015-11-01

    MicroRNAs (miRNAs) have been implicated in several cellular processes of reproductive tissues through post-transcriptional regulation of protein coding genes. The presence of miRNAs, their expression patterns and processing machinery genes in different stages of testicular and ovarian cellular development have demonstrated the potential role of miRNAs in testicular and ovarian physiology. The Chinese mitten crab (Eriocheir sinensis) is one of the most important aquaculture species in China and has high commercial value as a food source. The molecular mechanisms underlying testis development in these and other crustaceans, which migrate to a new habitat to breed, remain poorly understood. We focus on the gonad of E. sinensis and systematically examined the expression profile of miRNAs in testes during sexual maturation stages using the Illumina Solexa sequencing technology. We found that the microRNA transcriptome exhibited dynamic expression during crab testis development. Subsequent bioinformatic analysis on both conserved and 15 novel miRNAs illustrated that some miRNAs demonstrated a tissue-specific expression pattern and were associated with target genes involved in reproductive function. Our study illustrates how detailed profiling of miRNA expression during stages of sexual maturation and in different tissues can lead to elucidate the role of miRNAs in regulating the development and differentiation of reproductive organs.

  12. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability.

    PubMed

    Nielsen, Aaraby Yoheswaran; Gjerstorff, Morten Frier

    2016-01-01

    Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies.

  13. Mutations in the FOG2/ZFPM2 gene are associated with anomalies of human testis determination.

    PubMed

    Bashamboo, Anu; Brauner, Raja; Bignon-Topalovic, Joelle; Lortat-Jacob, Stephen; Karageorgou, Vasiliki; Lourenco, Diana; Guffanti, Alessandro; McElreavey, Ken

    2014-07-15

    In recent years, considerable advances have been made in our understanding of genetics of mammalian gonad development; however, the underlying genetic aetiology in the majority of patients with 46,XY disorders of sex development (DSD) still remains unknown. Based on mouse models, it has been hypothesized that haploinsufficiency of the Friend of GATA 2 (FOG2) gene could lead to 46,XY gonadal dysgenesis on specific inbred genetic backgrounds. Using whole exome sequencing, we identified independent missense mutations in FOG2 in two patients with 46,XY gonadal dysgenesis. One patient carried a non-synonymous heterozygous mutation (p.S402R), while the other patient carried a heterozygous p.R260Q mutation and a homozygous p.M544I mutation. Functional studies indicated that the failure of testis development in these cases could be explained by the impaired ability of the mutant FOG2 proteins to interact with a known regulator of early testis development, GATA4. This is the first example of mutations in the coding sequence of FOG2 associated with 46,XY DSD in human and adds to the list of genes in the human known to be associated with DSD.

  14. Sox100B, a Drosophila group E Sox-domain gene, is required for somatic testis differentiation.

    PubMed

    Nanda, S; DeFalco, T J; Loh, S Hui Yong; Phochanukul, N; Camara, N; Van Doren, M; Russell, S

    2009-01-01

    Sex determination mechanisms are thought to evolve rapidly and show little conservation among different animal species. For example, the critical gene on the Y chromosome, SRY, that determines sex in most mammals, is not found in other animals. However, a related Sox domain transcription factor, SOX9, is also required for testis development in mammals and exhibits male-specific gonad expression in other vertebrate species. Previously, we found that the Drosophila orthologue of SOX9, Sox100B, is expressed male-specifically during gonad development. We now investigate the function of Sox100B and find, strikingly, that Sox100B is essential for testis development in Drosophila. In Sox100B mutants, the adult testis is severely reduced and fails to interact with other parts of the reproductive tract, which are themselves unaffected. While a testis initially forms in Sox100B mutants, it fails to undergo proper morphogenesis during pupal stages, likely due to defects in the pigment cells. In contrast, no substantive defects are observed in ovary development in Sox100B mutant females. Thus, as is observed in mammals, a Sox9 homolog is essential for sex-specific gonad development in Drosophila, suggesting that the molecular mechanisms regulating sexually dimorphic gonad development may be more conserved than previously suspected.

  15. Induction of oxidative stress in the rat testis after short-term exposure to the organochlorine pesticide methoxychlor.

    PubMed

    Latchoumycandane, C; Mathur, P P

    2002-12-01

    Methoxychlor is one of the environmental contaminants that has been shown to induce reproductive abnormalities in male rats. The mechanism of action of methoxychlor on the male reproductive system remains unclear. In the present study we have sought to investigate whether short-term administration of methoxychlor induces oxidative stress in the testis of adult rats. Methoxychlor (50, 100, or 200 mg/kg body weight per day) was administered orally for 1, 4, or 7 days. The animals were killed using anesthetic ether on the day following the last dosing. The weights of epididymides, seminal vesicles, and ventral prostate decreased after 50, 100, or 200 mg/kg per day for 7 days but remained unchanged after 1 and 4 days of treatment. The production of superoxide anion and hydrogen peroxide increased in the animals that received methoxychlor for 4 and 7 days. The activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase decreased, while the level of lipid peroxidation increased in the testis after 4 or 7 days of treatment. The results indicated that short-term exposure to methoxychlor induces oxidative stress in the testis by decreasing antioxidant enzymes and increasing lipid peroxidation, possibly by inducing reactive oxygen species. In conclusion, the adverse effect of methoxychlor on the male reproduction could be due to induction of oxidative stress in testis.

  16. CHANGES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS INDUCED IN MALE OFFSPRING AFTER MATERNAL TREATMENT WITH PHTHALATE ESTERS

    EPA Science Inventory

    Targeted inactivation of the insulin-like hormone 3 (insl3) gene in male mice results in altered gubernacular development, disrupted testis decent, and cryptorchidism. Cryptorchidism is a fairly common human malformation, being displayed in 1-3% of males at birth. Since only a s...

  17. RFX1 maintains testis cord integrity by regulating the expression of Itga6 in male mouse embryos.

    PubMed

    Wang, Bo; Qi, Tao; Chen, Shi-Qin; Ye, Lei; Huang, Zhan-Sen; Li, Hao

    2016-07-01

    Formation and maintenance of testis cords during embryogenesis are essential for establishing testicular structure and function in adults. At least five genes (Wt1, Dhh, Sox8/Sox9, and Dax1) appear to be required for the maintenance of testis cord integrity in mice. Here, we report that RFX1 is specifically expressed in fetal Sertoli cells. Mouse embryos conditionally deficient in Rfx1 (Rfx1(flox/flox) , Amh-Cre) possessed disrupted testis cords, as the basal lamina lining was fragmented or completely absent in some areas of the testes. Spermatogenesis was blocked, leading to complete infertility. Expression of integrin alpha-6 was significantly decreased in Rfx1-deficient testes compared to control testes; indeed, luciferase and chromatin immunoprecipitation assays indicated that RFX1 directly activates transcription of Itga6 (the gene coding for integrin alpha-6). Taken together, RFX1 transcriptionally targets Itga6 in Sertoli cells, thereby, helping maintain the integrity of the basal lamina during testis cord development. Mol. Reprod. Dev. 83: 606-614, 2016. © 2016 Wiley Periodicals, Inc. PMID:27228460

  18. Histologic and histomorphometric changes of testis following oral exposure to methyl tertiary-butyl ether in adult rat.

    PubMed

    Gholami, S; Ansari-Lari, M; Khalili, L

    2015-01-01

    Methyl tertiary-butyl ether (MTBE) is used to reduce carbon monoxide and ozone in urban air and to boost fuel octane. There is a lack of knowledge in the literature about the histomorphometric changes of the testis following exposure to MTBE. Therefore, this experimental study was performed to determine the effect of oral exposure to MTBE on histologic and histomorphometric changes of testis in adult rat. A total of 25 adult male Sprague-Dawley rats were randomly divided into five equal experimental groups: control, almond oil and three treatment groups which received 400, 800 and 1600 mg/kg/day MTBE in almond oil by gavages for 30 consecutive days. Histomorphometric analysis showed no significant difference in absolute and relative testis weight, connective tissue thickness, germinal epithelium height, tunica albuginea thickness and Sertoli cell numbers between experimental groups (P>0.05). However, trend analysis showed that the seminiferous tubule diameter increased and interstitial cell numbers as well as spermatocyte and spermatid cell numbers decreased significantly in MTBE treated groups (P<0.05). It may be concluded that MTBE could exert adverse effects on spermatogenic cells in adult rat. Whether the observed changes in the present study are due to the direct effect of MTBE via passing blood-testis barrier or its indirect effect through another mechanism should be elucidated in future studies. PMID:27175191

  19. Advantage of Guaraná (Paullinia cupana Mart.) supplementation on cadmium-induced damages in testis of adult Wistar rats.

    PubMed

    Leite, Rodrigo P; Predes, Fabrícia S; Monteiro, Juliana C; Freitas, Karine M; Wada, Ronaldo S; Dolder, Heidi

    2013-01-01

    Paullinia cupana is an Amazonian bush whose seeds have long been used in folk medicine. However, most of the therapeutic properties attributed to this plant are broad and nonspecific, although an antioxidant activity has been reported.  On the other hand, cadmium is a heavy metal known for increasing free radicals, hence resulting in cellular oxidative damages. This study was designed to evaluate whether Paullinia cupana is able to reduce cadmium-induced morphological impairment in Wistar rat testis. Adult male Wistar rats 110 days old were ip injected with cadmium (1.15 mg/kg BW [body weight]) and subsequently treated with P. cupana during 56 days.  Furthermore, groups receiving either P. cupana extract or cadmium are mentioned. After the treatment period, testis samples were subjected to histological and stereological analyses. Moderate to severe testicular impairments were shown by the animals exposed to cadmium. However, the animals supplemented with P. cupana after cadmium exposure showed a significant decrease in the proportion of damaged seminiferous tubules. Also, P. cupana supplementation was effective in maintaining the number of Leydig cells per testis in the animals exposed to cadmium. In conclusion, P. cupana supplementation was partially efficient in preventing cadmium from damaging the testis of adult Wistar rats. PMID:22659242

  20. Gene expression profile analysis of testis and ovary of oriental river prawn, Macrobrachium nipponense, reveals candidate reproduction-related genes.

    PubMed

    Qiao, H; Xiong, Y W; Jiang, S F; Fu, H T; Sun, S M; Jin, S B; Gong, Y S; Zhang, W Y

    2015-01-01

    This study utilized high-throughput RNA sequencing technology to identify reproduction- and development-related genes of Macrobrachium nipponense by analyzing gene expression profiles of testis and ovary. More than 20 million 1 x 51-bp reads were obtained by Illumina sequencing, generating more than 7.7 and 11.7 million clean reads in the testis and ovary library, respectively. As a result, 10,018 unitags were supposed to be differentially expressed genes (DEGs) between ovary and testis. Compared to the ovary library, 4563 (45.5%) of these DEGs exhibited at least 6-fold upregulated expression, while 5455 (54.5%) DEGs exhibited at least 2-fold downregulated expression in the testis. The Gene Ontology (GO) enrichment analysis showed that 113 GO terms had potential molecular functions in reproduction. The Kyoto Encyclopedia of Genes and Genomes results revealed that the most important pathways may be relevant to reproduction and included 7 pathways. Forty-two genes were identified as reproduction-, development-, and sex-related genes based on GO classification and sequence comparison with other publications, including male reproductive-related LIM protein, spermatogenesis-associated protein, gametocyte-specific factor 1, VASA-like protein, vitellogenin, sex-determining protein fem-1, and other potential candidates. These results will advance research in the field of molecular genetics in M. nipponense and offer a valuable resource for further research related to reproduction in crustaceans. PMID:25867350

  1. Testis-specific expression of a metallothionein I-driven transgene correlates with undermethylation of the locus in testicular DNA.

    PubMed Central

    Salehi-Ashtiani, K; Widrow, R J; Markert, C L; Goldberg, E

    1993-01-01

    Mice carrying a chimeric transgene of the human testis-specific lactate dehydrogenase cDNA driven by mouse metallothionein I promoter have been reported to express the transgene in a testis-specific manner in six founder lines. To study the mechanism by which this testis-specific expression is mediated, we have examined genomic placement, expression pattern, and methylation status of the transgene. Our results indicate that transgene expression is repressed in all somatic tissues examined even when heavy metals are administered. Nuclear run-on assays indicate that failure of expression in the liver (in which the metallothionein I promoter is highly active) occurs at the transcriptional level. In contrast, the transgene mRNA is transcribed in male germ cells and is developmentally regulated during spermatogenesis. Examination of the transgene methylation status reveals that expression is inversely correlated with hypermethylation of the locus; all CpG dinucleotides examined in the promoter region were found to be fully methylated in kidney and liver but were undermethylated in testis. Since methylation of the murine metallothionein I promoter is sufficient to inhibit its activity, it is likely that suppression of the transgene in somatic tissues is mediated by methylation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8415626

  2. PHTHALATE ESTER-INDUCED GUBERNACULAR LESIONS ARE ASSOCIATED WITH REDUCED INSL-3 GENE EXPRESSION IN THE FETAL RAT TESTIS

    EPA Science Inventory

    Phthalate ester-induced gubernacular ligament lesions are associated with reduced Insl3 gene expression in the fetal rat testis during sexual differentiation.
    VS Wilson, C Lambright, J Furr, J Ostby, C Wood, G Held, LE Gray Jr.
    U.S. EPA, ORD, NHEERL, Reproductive Toxicology...

  3. Advantage of Guaraná (Paullinia cupana Mart.) supplementation on cadmium-induced damages in testis of adult Wistar rats.

    PubMed

    Leite, Rodrigo P; Predes, Fabrícia S; Monteiro, Juliana C; Freitas, Karine M; Wada, Ronaldo S; Dolder, Heidi

    2013-01-01

    Paullinia cupana is an Amazonian bush whose seeds have long been used in folk medicine. However, most of the therapeutic properties attributed to this plant are broad and nonspecific, although an antioxidant activity has been reported.  On the other hand, cadmium is a heavy metal known for increasing free radicals, hence resulting in cellular oxidative damages. This study was designed to evaluate whether Paullinia cupana is able to reduce cadmium-induced morphological impairment in Wistar rat testis. Adult male Wistar rats 110 days old were ip injected with cadmium (1.15 mg/kg BW [body weight]) and subsequently treated with P. cupana during 56 days.  Furthermore, groups receiving either P. cupana extract or cadmium are mentioned. After the treatment period, testis samples were subjected to histological and stereological analyses. Moderate to severe testicular impairments were shown by the animals exposed to cadmium. However, the animals supplemented with P. cupana after cadmium exposure showed a significant decrease in the proportion of damaged seminiferous tubules. Also, P. cupana supplementation was effective in maintaining the number of Leydig cells per testis in the animals exposed to cadmium. In conclusion, P. cupana supplementation was partially efficient in preventing cadmium from damaging the testis of adult Wistar rats.

  4. GENE EXPRESSION PROFILING IN TESTIS AND LIVER OF MICE TO IDENTIFY MODES OF ACTION OF CONAZOLE TOXICITIES

    EPA Science Inventory

    Gene Expression Profiling in Testis and Liver of Mice to Identify MODES OF ACTION OF Conazole TOXICITies

    Amber K. Goetz1, Wenjun Bao2, Judith E. Schmid2, Carmen Wood2, Hongzu Ren2, Deborah S. Best2, Rachel N. Murrell1, John C. Rockett2, Michael G. Narotsky2, Douglas C. Wol...

  5. Characterization of mouse lysophosphatidic acid acyltransferase 3: an enzyme with dual functions in the testis1s⃞

    PubMed Central

    Yuki, Koichi; Shindou, Hideo; Hishikawa, Daisuke; Shimizu, Takao

    2009-01-01

    Glycerophospholipids are structural and functional components of cellular membranes as well as precursors of various lipid mediators. Using acyl-CoAs as donors, glycerophospholipids are formed by the de novo pathway (Kennedy pathway) and modified in the remodeling pathway (Lands' cycle). Various acyltransferases, including two lysophosphatidic acid acyltransferases (LPAATs), have been discovered from a 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) family. Proteins of this family contain putative acyltransferase motifs, but their biochemical properties and physiological roles are not completely understood. Here, we demonstrated that mouse LPAAT3, previously known as mouse AGPAT3, possesses strong LPAAT activity and modest lysophosphatidylinositol acyltransferase activity with a clear preference for arachidonoyl-CoA as a donor. This enzyme is highly expressed in the testis, where CDP-diacylglycerol synthase 1 preferring 1-stearoyl-2-arachidonoyl-phosphatidic acid as a substrate is also highly expressed. Since 1-stearoyl-2-arachidonoyl species are the main components of phosphatidylinositol, mouse LPAAT3 may function in both the de novo and remodeling pathways and contribute to effective biogenesis of 1-stearoyl-2-arachidonoyl-phosphatidylinositol in the testis. Additionally, the expression of this enzyme in the testis increases significantly in an age-dependent manner, and β-estradiol may be an important regulator of this enzyme's induction. Our findings identify this acyltransferase as an alternative important enzyme to produce phosphatidylinositol in the testis. PMID:19114731

  6. Gene expression profile analysis of testis and ovary of oriental river prawn, Macrobrachium nipponense, reveals candidate reproduction-related genes.

    PubMed

    Qiao, H; Xiong, Y W; Jiang, S F; Fu, H T; Sun, S M; Jin, S B; Gong, Y S; Zhang, W Y

    2015-03-20

    This study utilized high-throughput RNA sequencing technology to identify reproduction- and development-related genes of Macrobrachium nipponense by analyzing gene expression profiles of testis and ovary. More than 20 million 1 x 51-bp reads were obtained by Illumina sequencing, generating more than 7.7 and 11.7 million clean reads in the testis and ovary library, respectively. As a result, 10,018 unitags were supposed to be differentially expressed genes (DEGs) between ovary and testis. Compared to the ovary library, 4563 (45.5%) of these DEGs exhibited at least 6-fold upregulated expression, while 5455 (54.5%) DEGs exhibited at least 2-fold downregulated expression in the testis. The Gene Ontology (GO) enrichment analysis showed that 113 GO terms had potential molecular functions in reproduction. The Kyoto Encyclopedia of Genes and Genomes results revealed that the most important pathways may be relevant to reproduction and included 7 pathways. Forty-two genes were identified as reproduction-, development-, and sex-related genes based on GO classification and sequence comparison with other publications, including male reproductive-related LIM protein, spermatogenesis-associated protein, gametocyte-specific factor 1, VASA-like protein, vitellogenin, sex-determining protein fem-1, and other potential candidates. These results will advance research in the field of molecular genetics in M. nipponense and offer a valuable resource for further research related to reproduction in crustaceans.

  7. Puberty stage and spontaneous descent of acquired undescended testis: implications for therapy?

    PubMed

    Sijstermans, K; Hack, W W M; van der Voort-Doedens, L M; Meijer, R W; Haasnoot, K

    2006-12-01

    We assessed spontaneous descent of acquired undescended testis (UDT) at puberty. 299 Boys (aged 1.2-16.5 years, mean 9.4) with 350 acquired-UDT were examined annually during a 12.6-year period (mean 3.1). An acquired-UDT was defined as a previously intrascrotal testis which can no longer be manipulated into a stable scrotal position. Each year, position of the testis and pubertal development according to Tanner's stages were assessed. Early puberty was defined as puberty stage G2 (testicular volume 4-9 mL), mid-puberty as puberty stages G3 (testicular volume 10 mL) and G4 (testicular volume 11-15 mL), and late puberty as puberty stage G5 (testicular volume >15 mL). Follow-up was completed if spontaneous descent had occurred, if mid-pubertal orchidopexy (ORP) had to be performed, if the boy was lost for follow-up, or if pre-pubertal ORP was performed in another hospital. In 139 boys with 164 acquired-UDT follow-up was meanwhile completed. Twelve boys with 14 UDT were lost for follow-up. In an additional 16 boys with 21 UDT, ORP was performed in another hospital. In 98 of the remaining 129 (76.0%) acquired-UDT spontaneous descent at puberty occurred. Mean follow-up was 2.5 years (range 0.2-8.5). In 70 of 98 testes (71.4%) descent occurred in early puberty, in 26 of 98 testes (26.5%) in mid-puberty, and in two testes in late puberty. In 31 of 129 testes (24.0%) ORP had to be performed at mid (30 cases) or late (one case) puberty. In this series, 98 of 129 acquired-UDT (76.0%) descended spontaneously at puberty, whereas in 31 of 129 (24.0%) pubertal ORP was performed. If ORP is postponed until puberty stage G3 (testicular volume of 10 mL) three of four acquired-UDT will descend spontaneously.

  8. Identification and Localization of the Cyclic Nucleotide Phosphodiesterase 10A in Bovine Testis and Mature Spermatozoa.

    PubMed

    Goupil, Serge; Maréchal, Loïze; El Hajj, Hassan; Tremblay, Marie-Ève; Richard, François J; Leclerc, Pierre

    2016-01-01

    In mammals, adenosine 3', 5'-cyclic monophosphate (cAMP) is known to play highly important roles in sperm motility and acrosomal exocytosis. It is known to act through protein phosphorylation via PRKA and through the activation of guanine nucleotide exchange factors like EPAC. Sperm intracellular cAMP levels depend on the activity of adenylyl cyclases, mostly SACY, though transmembrane-containing adenylyl cyclases are also present, and on the activity of cyclic nucleotide phosphodiesterases (PDE) whose role is to degrade cAMP into 5'-AMP. The PDE superfamily is subdivided into 11 families (PDE1 to 11), which act on either cAMP or cGMP, or on both cAMP and cGMP although with different enzymatic properties. PDE10, which is more effective on cAMP than cGMP, has been known for almost 15 years and is mostly studied in the brain where it is associated with neurological disorders. Although a high level of PDE10A gene expression is observed in the testis, information on the identity of the isoforms or on the cell type that express the PDE10 protein is lacking. The objective of this study was to identify the PDE10A isoforms expressed in the testis and germ cells, and to determine the presence and localization of PDE10A in mature spermatozoa. As a sub-objective, since PDE10A transcript variants were reported strictly through analyses of bovine genomic sequence, we also wanted to determine the nucleotide and amino acid sequences by experimental evidence. Using RT-PCR, 5'- and 3'-RACE approaches we clearly show that PDE10A transcript variants X3 and X5 are expressed in bovine testis as well as in primary spermatocytes and spermatids. We also reveal using a combination of immunological techniques and proteomics analytical tools that the PDE10A isoform X4 is present in the area of the developing acrosome of spermatids and of the acrosome of mature spermatozoa. PMID:27548062

  9. Gene expression profiles in testis of pigs with extreme high and low levels of androstenone

    PubMed Central

    Moe, Maren; Meuwissen, Theo; Lien, Sigbjørn; Bendixen, Christian; Wang, Xuefei; Conley, Lene Nagstrup; Berget, Ingunn; Tajet, Håvard; Grindflek, Eli

    2007-01-01

    Background: Boar taint is a major obstacle when using uncastrated male pigs for swine production. One of the main compounds causing this taint is androstenone, a pheromone produced in porcine testis. Here we use microarrays to study the expression of thousands of genes simultaneously in testis of high and low androstenone boars. The study allows identification of genes and pathways associated with elevated androstenone levels, which is essential for recognising potential molecular markers for breeding purposes. Results: Testicular tissue was collected from 60 boars, 30 with extreme high and 30 with extreme low levels of androstenone, from each of the two breeds Duroc and Norwegian Landrace. The samples were hybridised to porcine arrays containing 26,877 cDNA clones, detecting 563 and 160 genes that were differentially expressed (p < 0.01) in Duroc and Norwegian Landrace, respectively. Of these significantly up- and down-regulated clones, 72 were found to be common for the two breeds, suggesting the possibility of both general and breed specific mechanisms in regulation of, or response to androstenone levels in boars. Ten genes were chosen for verification of expression patterns by quantitative real competitive PCR and real-time PCR. As expected, our results point towards steroid hormone metabolism and biosynthesis as important biological processes for the androstenone levels, but other potential pathways were identified as well. Among these were oxidoreductase activity, ferric iron binding, iron ion binding and electron transport activities. Genes belonging to the cytochrome P450 and hydroxysteroid dehydrogenase families were highly up-regulated, in addition to several genes encoding different families of conjugation enzymes. Furthermore, a number of genes encoding transcription factors were found both up- and down-regulated. The high number of clones belonging to ferric iron and iron ion binding suggests an importance of these genes, and the association between

  10. Identification and Localization of the Cyclic Nucleotide Phosphodiesterase 10A in Bovine Testis and Mature Spermatozoa

    PubMed Central

    Goupil, Serge; Maréchal, Loïze; El Hajj, Hassan; Tremblay, Marie-Ève; Richard, François J.

    2016-01-01

    In mammals, adenosine 3’, 5’-cyclic monophosphate (cAMP) is known to play highly important roles in sperm motility and acrosomal exocytosis. It is known to act through protein phosphorylation via PRKA and through the activation of guanine nucleotide exchange factors like EPAC. Sperm intracellular cAMP levels depend on the activity of adenylyl cyclases, mostly SACY, though transmembrane-containing adenylyl cyclases are also present, and on the activity of cyclic nucleotide phosphodiesterases (PDE) whose role is to degrade cAMP into 5’-AMP. The PDE superfamily is subdivided into 11 families (PDE1 to 11), which act on either cAMP or cGMP, or on both cAMP and cGMP although with different enzymatic properties. PDE10, which is more effective on cAMP than cGMP, has been known for almost 15 years and is mostly studied in the brain where it is associated with neurological disorders. Although a high level of PDE10A gene expression is observed in the testis, information on the identity of the isoforms or on the cell type that express the PDE10 protein is lacking. The objective of this study was to identify the PDE10A isoforms expressed in the testis and germ cells, and to determine the presence and localization of PDE10A in mature spermatozoa. As a sub-objective, since PDE10A transcript variants were reported strictly through analyses of bovine genomic sequence, we also wanted to determine the nucleotide and amino acid sequences by experimental evidence. Using RT-PCR, 5’- and 3’-RACE approaches we clearly show that PDE10A transcript variants X3 and X5 are expressed in bovine testis as well as in primary spermatocytes and spermatids. We also reveal using a combination of immunological techniques and proteomics analytical tools that the PDE10A isoform X4 is present in the area of the developing acrosome of spermatids and of the acrosome of mature spermatozoa. PMID:27548062

  11. Characterization of the equine blood-testis barrier during tubular development in normal and cryptorchid stallions.

    PubMed

    Rode, K; Sieme, H; Richterich, P; Brehm, R

    2015-09-15

    The formation of the blood-testis barrier (BTB) is defined as occurring with the first appearance of spermatocytes at around puberty and is vital for normal spermatogenesis. This barrier between two adjacent Sertoli cells (SCs) consists of a cell junctional protein complex, which includes tight junctions (TJs), adherens junctions, and gap junctions. In many mammalian species, BTB composition has already been investigated, whereas little is known about the equine BTB. In the present study, immunohistochemistry and qualitative Western Blot analysis were used to assess the expression and distribution patterns of the junctional proteins claudin-11 (TJ), zonula occludens-1 (TJ associated), N-cadherin (adherens junctions), and connexin 43 (gap junctions) in equine testes during tubular development and in testes of stallions exhibiting unilateral cryptorchidism. Therefore, testes of 21 warmblood stallions (aged 12 months-11 years) were obtained during routine surgical castration. In the normal adult equine testis, the junctional proteins are localized at the basolateral region of the seminiferous tubules forming a circumferential seal corresponding to the known BTB localization. N-cadherin is additionally expressed along the lateral SC surface. In immature seminiferous cords still lacking a lumen, a diffuse distribution pattern of the junctional proteins throughout the SC cytoplasm is visible. As lumen formation advances, the immunolocalization shifts progressively toward the basolateral SC membranes. Additionally, apoptotic germ cells were detected and quantified in prepubertal stallions using terminal deoxynucleotidyl transferase dUTP nick end labeling assay and correlated with junctional protein localization. In the retained testis of cryptorchid stallions, which exhibit an aberrant testicular morphology, a deviating expression of the junctional proteins is visible. The present data show for the first time that (1) the equine SC junctional complex contains claudin-11

  12. [Effectiveness of blood-testis and blood-epididymis barriers for lead].

    PubMed

    Marchlewicz, M

    1994-01-01

    Over the period of the last 30 years there was a marked decrease in the number of spermatozoa produced by the gonads of men. It is felt that this observation is due to the influence of environmental pollution, wherein the lead plays quite an important role. In sperms of men, who are professionally exposed to lead compounds, oligo-, asteno-, and teratospermia is disclosed. Studies were performed on sexually mature male rats after 9-month-long exposure to lead acetate (II) as well as a group of animals after 3-month-long interval in the exposure. The changes provoked by the lead were evaluated by employing a number of study techniques, namely: morphological examination of testes with taking into account the stages of seminiferous epithelial cycle, and epididymis, giving due consideration to zones; electron microscopic examination of seminiferous cells and interstitial tissue, as well as the cells in the wall of epididymis and spermatozoa; X-ray microanalysis determining the presence and type of elements on ultrathin section; spectrophotometrical determination of Pb content in blood, testes and epididymides; determination of testosterone concentration (T) in blood serum. It has been revealed that the blood-testis barrier protects seminiferous epithelium against the toxic action of the lead. No deposits of Pb were observed either in germinal cells or Sertoli cells. The endocrine testicular cells outside the barrier had also unchanged ultrastructure, and contained no Pb. That finding was expressed by normal T level in blood serum. The only cells in the area of the testis, in whose cytoplasm there was Pb confirmed by X-ray microanalysis, were macrophages in the interstitial tissue of the testis. Apart from that, it has been disclosed that the blood-epididymis barrier does not provide a barrier against this element. Pb deposits were seen in smooth myocytes, epithelial cells and in the lumen of epididymal duct. That correlated with a marked decrease in the number of

  13. Effects of sexual maturation and Salmonella infection on the expression of avian β-defensin genes in the chicken testis.

    PubMed

    Anastasiadou, M; Theodoridis, A; Michailidis, G

    2014-06-01

    Rooster infertility is a major concern in the poultry industry and protection of the male reproductive organs from pathogens is an essential aspect of reproductive physiology. During the last years, research on antimicrobial protection has elucidated the critical role of the antimicrobial peptides avian β-defensins (AvBDs) in the innate immunity in chickens. AvBDs have been reported to be expressed in the hen reproductive organs, providing protection against microbial pathogens including Salmonella Enteritidis (SE). However, mechanisms of antimicrobial protection of rooster reproductive organs and especially the testis, mediated by AvBDs are poorly understood. The aim of this study was to investigate the expression of the complete family of the 14 AvBD genes, in the rooster testis in vivo, to determine whether sexual maturation affects their testicular mRNA abundance and to investigate whether SE infection alters their expression. Expression analysis revealed that 9 members of the AvBD family, namely AvBD1, 2, 4, 5, 6, 9, 10, 12 and 14 were expressed in the testis. Quantitative real-time PCR analysis revealed that the mRNA abundance of three AvBDs was up regulated and of three AvBDs was down regulated with respect to sexual maturation. In addition, SE infection resulted in a significant induction of AvBD4, 10, 12 and 14 in the testis of sexually mature roosters. These findings provide strong evidence to suggest that an AvBD-mediated immune response mechanism exists in the rooster testis providing protection against bacterial pathogens including Salmonella species. PMID:24469393

  14. Changes in the expression of Toll-like receptors in the chicken testis during sexual maturation and Salmonella infection.

    PubMed

    Anastasiadou, M; Theodoridis, A; Avdi, M; Michailidis, G

    2011-10-01

    Rooster infertility is a major concern in the poultry industry and chicken male reproductive organs are the infectious tissues of various pathogenic microorganisms. Protection of the chicken male reproductive organs from pathogens is therefore an essential aspect of reproductive physiology. Recently Toll-like receptors (TLRs) have been identified as one of the key components of innate immunity in vertebrate species and have been reported to be expressed in the reproductive organs in various female species, including the chicken. However, mechanisms of antimicrobial protection of male reproductive organs mediated by TLRs are poorly understood. The objectives of this study were to determine the expression profile of the entire family of the ten chicken TLR genes in the chicken testis, to investigate whether sexual maturation affects their testicular mRNA abundance and to determine the changes in their expression levels in response to Salmonella enteritidis (SE) infection. RNA was extracted from the testis of healthy pre-pubertal, sexually mature and aged birds, and from sexually mature SE infected birds. RT-PCR analysis revealed that all TLRs, apart from TLR1-1 (TLR6), were expressed in the chicken testis. Quantitative real-time PCR analysis revealed that the testicular mRNA abundance of certain TLRs was developmentally regulated with respect to sexual maturation, while SE infection resulted in a significant induction of TLR2-1, 4, 5, 15 and 21 in the testis of sexually mature birds compared, to healthy birds of the same age. These findings provide strong evidence to suggest a key role of TLRs in the innate immune responses of chicken testis against Salmonella colonization. PMID:21975303

  15. Expressions of Sox9, Sox5, and Sox13 transcription factors in mice testis during postnatal development.

    PubMed

    Daigle, Mikella; Roumaud, Pauline; Martin, Luc J

    2015-09-01

    SRY-related box (Sox) transcription factors are conserved among vertebrate species. These proteins regulate multiple processes including sex determination and testis differentiation of the male embryo. Although members of the Sox family have been identified in pre- and postnatal Sertoli cells, they have never been characterized in adult Leydig cells. The objectives of this research were to identify expressions of Sox9, Sox5, and Sox13 in mice Leydig cell cultures and to establish their expression profiles in postnatal mice testes at different developmental stages. Methods used include Western blots and qPCR of stimulated MA-10 cell cultures and whole mice testes. Sox9, Sox5, and Sox13 proteins were detected in MA-10 cells as well as whole mouse testis. Although Sox9, Sox5, and Sox13 mRNA levels from whole mice testes tended to increase according to postnatal development, these results were not significant. Sox members were also detected in whole mice testis by Western Blot. However, Sox9, Sox5, and Sox13 protein expressions remained relatively constant during postnatal development from postnatal (P) day 60 to P365. Being newly characterized in the mouse testis, Sox13 was mainly localized by immunofluorescence within the nuclei of cells from seminiferous tubules, possibly spermatocytes and Sertoli cells. In addition, Sox9, Sox5, and Sox13 proteins were characterized in the nuclei of MA-10 Leydig cell cultures. Their expressions and transcriptional activities remained unaffected by activators of the cAMP/PKA pathway. Thus, Sox9, Sox5, and Sox13 transcription factors are expressed in postnatal testis and may regulate multiple functions such as steroidogenesis and spermatogenesis.

  16. RNA Deep Sequencing Reveals Novel Candidate Genes and Polymorphisms in Boar Testis and Liver Tissues with Divergent Androstenone Levels

    PubMed Central

    Gunawan, Asep; Sahadevan, Sudeep; Neuhoff, Christiane; Große-Brinkhaus, Christine; Gad, Ahmed; Frieden, Luc; Tesfaye, Dawit; Tholen, Ernst; Looft, Christian; Uddin, Muhammad Jasim; Schellander, Karl; Cinar, Mehmet Ulas

    2013-01-01

    Boar taint is an unpleasant smell and taste of pork meat derived from some entire male pigs. The main causes of boar taint are the two compounds androstenone (5α-androst-16-en-3-one) and skatole (3-methylindole). It is crucial to understand the genetic mechanism of boar taint to select pigs for lower androstenone levels and thus reduce boar taint. The aim of the present study was to investigate transcriptome differences in boar testis and liver tissues with divergent androstenone levels using RNA deep sequencing (RNA-Seq). The total number of reads produced for each testis and liver sample ranged from 13,221,550 to 33,206,723 and 12,755,487 to 46,050,468, respectively. In testis samples 46 genes were differentially regulated whereas 25 genes showed differential expression in the liver. The fold change values ranged from −4.68 to 2.90 in testis samples and −2.86 to 3.89 in liver samples. Differentially regulated genes in high androstenone testis and liver samples were enriched in metabolic processes such as lipid metabolism, small molecule biochemistry and molecular transport. This study provides evidence for transcriptome profile and gene polymorphisms of boars with divergent androstenone level using RNA-Seq technology. Digital gene expression analysis identified candidate genes in flavin monooxygenease family, cytochrome P450 family and hydroxysteroid dehydrogenase family. Moreover, polymorphism and association analysis revealed mutation in IRG6, MX1, IFIT2, CYP7A1, FMO5 and KRT18 genes could be potential candidate markers for androstenone levels in boars. Further studies are required for proving the role of candidate genes to be used in genomic selection against boar taint in pig breeding programs. PMID:23696805

  17. Decreased spermatogenesis led to alterations of testis-specific gene expression in male mice following nano-TiO2 exposure.

    PubMed

    Hong, Fashui; Zhao, Xiaoyang; Si, Wenhui; Ze, Yuguan; Wang, Ling; Zhou, Yingjun; Hong, Jie; Yu, Xiaohong; Sheng, Lei; Liu, Dong; Xu, Bingqing; Zhang, Jianhao

    2015-12-30

    Although TiO2 nanoparticles (NPs) exposure has been demonstrated to cross blood-testis barrier and accumulate in the testis resulting in the reduction of sperm numbers, limited data with respect to the molecular mechanism of decreased spermatogenesis caused by TiO2 NP exposure. In this research, testicular damage, sperm number and alterations in testis-specific gene expressions in male mice induced by intragastric administration with TiO2 NPs for six months were investigated. It was found out that TiO2 NPs could migrate to cells, deposit in the testis and epididymis and thus cause damages to relevant organs, which are, to be more specific, the reductions of total sperm concentrations and sperm motility and an enhancement in the number of abnormal sperms in the cauda epididymis. Furthermore, the individual expression regarding to the mRNAs and proteins of testis-specific genes, including Cdc2, Cyclin B1, Dmcl, TERT, Tesmin, TESP-1, XPD and XRCCI, were significantly declined, whereas Gsk3-β and PGAM4 expressions were greatly elevated in mouse testis due to the exposures, which in fact implied that the reduced spermatogenesis may be involved in the alternated testis-specific gene expressions in those exposed male mice.

  18. Characteristics of PCR-SSCP and RAPD-HPCE methods for identifying authentication of Penis et testis cervi in Traditional Chinese Medicine based on cytochrome b gene.

    PubMed

    Li, Mingcheng; Gao, Lijun; Qu, Li; Sun, Jingyu; Yuan, Guangxin; Xia, Wei; Niu, Jiamu; Fu, Guilian; Zhang, Lihua

    2016-07-01

    The use of Penis et testis cervi, as a kind of precious Traditional Chinese Medicine (TCM), which is derived from dry deer's testis and penis, has been recorded for many years in China. There are abundant species of deer in China, the Penis et testis from species of Cervus Nippon and Cervus elaphusL were authentic, others species were defined as adulterant (different subspecies of deer) or counterfeits (different species). Identification of their origins or authenticity becomes a key in controlling the herbal products. A modified column chromatography was used to extract mitochondrial DNA of dried deer's testis and penis from sika deer (C. Nippon) and red deer (C. elaphusL) in addition to adulterants and counterfeits. Column chromatography requires for a short time to extract mitochondrial DNA of high purity with little damage of DNA molecules, which provides the primary structure of guarantee for the specific PCR; PCR-SSCP method showed a clear intra-specific difference among patterns of single-chain fragments, and completely differentiate Penis et testis origins from C. Nippon and C. elaphusL. RAPD-HPCE was based on the standard electropherograms to compute a control spectrum curve as similarity reference (R) among different samples. The similarity analysis indicated that there were significant inter-species differences among Penis et testis' adulterant or counterfeits. Both techniques provide a fast, simple, and accurate way to directly identify among inter-species or intra-species of Penis et testis.

  19. Characteristics of PCR-SSCP and RAPD-HPCE methods for identifying authentication of Penis et testis cervi in Traditional Chinese Medicine based on cytochrome b gene.

    PubMed

    Li, Mingcheng; Gao, Lijun; Qu, Li; Sun, Jingyu; Yuan, Guangxin; Xia, Wei; Niu, Jiamu; Fu, Guilian; Zhang, Lihua

    2016-07-01

    The use of Penis et testis cervi, as a kind of precious Traditional Chinese Medicine (TCM), which is derived from dry deer's testis and penis, has been recorded for many years in China. There are abundant species of deer in China, the Penis et testis from species of Cervus Nippon and Cervus elaphusL were authentic, others species were defined as adulterant (different subspecies of deer) or counterfeits (different species). Identification of their origins or authenticity becomes a key in controlling the herbal products. A modified column chromatography was used to extract mitochondrial DNA of dried deer's testis and penis from sika deer (C. Nippon) and red deer (C. elaphusL) in addition to adulterants and counterfeits. Column chromatography requires for a short time to extract mitochondrial DNA of high purity with little damage of DNA molecules, which provides the primary structure of guarantee for the specific PCR; PCR-SSCP method showed a clear intra-specific difference among patterns of single-chain fragments, and completely differentiate Penis et testis origins from C. Nippon and C. elaphusL. RAPD-HPCE was based on the standard electropherograms to compute a control spectrum curve as similarity reference (R) among different samples. The similarity analysis indicated that there were significant inter-species differences among Penis et testis' adulterant or counterfeits. Both techniques provide a fast, simple, and accurate way to directly identify among inter-species or intra-species of Penis et testis. PMID:26309015

  20. Antioxidant enzymes activity, lipid peroxidation, oxidative damage in the testis and epididymis, and steroidogenesis in rats after co-exposure to atrazine and ethanol.

    PubMed

    Abarikwu, S O; Duru, Q C; Chinonso, O V; Njoku, R-C

    2016-06-01

    Concomitant alcohol use and exposure to xenobiotics can adversely affect gonadal functions. This study investigated the oxidative status of the testis and epididymis and steroidogenesis of rats co-exposed to ethanol (EtoH, 5 mg kg(-1) b.wt.) and atrazine (ATZ, 50, 100, 300 mg kg(-1) b.wt.) for 3 weeks. The activities of catalase, superoxide dismutase, glutathione peroxidase, as well as the concentrations of glutathione and malondialdehyde, as indicators of oxidative stress were measured in the homogenates of the testis and epididymis. Testosterone and cholesterol concentrations as well as 17β-hydroxysteroid dehydrogenase (17β-HSD) activity were assayed in the plasma and testis respectively. After the administration of EtoH alone, or in combination with different doses of ATZ, oxidative damage as evident by malondialdehyde level was not observed in both the testis and epididymis. The combine exposure group showed dose-dependent decrease in plasma testosterone and testis cholesterol level and increase in testis 17β-HSD activity compared to the EtoH group. Furthermore, the testes and epididymis of the EtoH-exposed rats treated with high dose of ATZ had severe histopathological damage. Therefore, ATZ-exposed alcohol-treated rats have histological damage of the testis and epididymis and lower testosterone level than EtoH-treated rats. PMID:26364937

  1. [Diffuse large B-cell lymphoma of the testis relapsed 16 years after achieving complete response].

    PubMed

    Nagasaka, Isao; Mitsui, Takeki; Ishizaki, Takuma; Koiso, Hiromi; Yokohama, Akihiko; Saitoh, Takayuki; Hirato, Junko; Igarashi, Tadahiko; Kojima, Masaru; Tsukamoto, Norifumi; Nojima, Yoshihisa; Murakami, Hirokazu; Handa, Hiroshi

    2015-12-01

    Testicular lymphoma is a rare disease, accounting for 1-2% of non-Hodgkin lymphoma and 5-9% of all testicular tumors, and has a high relapse rate with a poor prognosis. We report a patient with testicular diffuse large B-cell lymphoma (DLBCL) who relapsed after being in remission for 16 years. He had undergone orchiectomy of the right testis and was diagnosed as having DLBCL (stage IAE) at 49 years of age. After 3 cycles of CHOP, he achieved a complete remission. Orchiectomy was performed because of a left testicular tumor, and he was again diagnosed with DLBCL at the age of 65. VH3-21 was detected in lymphoma cells at the times of both the first diagnosis and the relapse based on analysis of the variable region of the immunoglobulin heavy chain. Accordingly, the lymphoma cells at relapse were confirmed to be the same clone as that which had been documented at the first diagnosis.

  2. Paracrine Wnt/β-catenin signaling mediates proliferation of undifferentiated spermatogonia in the adult mouse testis.

    PubMed

    Takase, Hinako M; Nusse, Roeland

    2016-03-15

    Spermatogonial stem cells (SSCs) fuel the production of male germ cells but the mechanisms behind SSC self-renewal, proliferation, and differentiation are still poorly understood. Using the Wnt target gene Axin2 and genetic lineage-tracing experiments, we found that undifferentiated spermatogonia, comprising SSCs and transit amplifying progenitor cells, respond to Wnt/β-catenin signals. Genetic elimination of β-catenin indicates that Wnt/β-catenin signaling promotes the proliferation of these cells. Signaling is likely initiated by Wnt6, which is uniquely expressed by neighboring Sertoli cells, the only somatic cells in the seminiferous tubule that support germ cells and act as a niche for SSCs. Therefore, unlike other stem cell systems where Wnt/β-catenin signaling is implicated in self-renewal, the Wnt pathway in the testis specifically contributes to the proliferation of SSCs and progenitor cells.

  3. Metastatic Granulosa Cell Tumor of the Testis: Clinical Presentation and Management

    PubMed Central

    Han, Min; Figenshau, Robert S.

    2016-01-01

    Granulosa cell tumors (GCTs) of the testis are rare sex cord-stromal tumors that are present in both juvenile and adult subtypes. While most adult GCTs are benign, those that present with distant metastases manifest a grave prognosis. Treatments for aggressive GCTs are not well established. Options that have been employed in previous cases include retroperitoneal lymph node dissection (RPLND), radiation, chemotherapy, or a combination thereof. We describe the case of a 57-year-old man who presented with a painless left testicular mass and painful gynecomastia. Serum tumor markers (alpha fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase) and computed tomography of the chest and abdomen were negative. The patient underwent left radical orchiectomy. Immunohistochemical staining was consistent with a testicular GCT. He underwent a left-template laparoscopic RPLND which revealed 2/19 positive lymph nodes. Final pathological stage was IIA. He remains free of disease 32 months after surgery. PMID:27293952

  4. Localization and expression of selenoprotein S in the testis of Psammomys obesus.

    PubMed

    Windmill, Kelly; Tenne-Brown, Janette; Bayles, Richard; Trevaskis, James; Gao, Yuan; Walder, Ken; Collier, Greg R

    2007-03-01

    Selenium is an essential trace element and selenoprotein S is a member of the selenoprotein family that has the non-standard amino acid selenocysteine incorporated into the polypeptide. Dietary selenium has been shown to play an important protective role in a number of diseases including cancer, immune function and the male reproductive system. In this study, we have observed high levels of selenoprotein S gene expression in the testis from Psammomys obesus. Real-time PCR and immunofluorescence demonstrate that selenoprotein S expression is low in testes from 4-week-old animals but increases significantly by 8 weeks of age and remains high until 17 weeks of age. Selenoprotein S protein is detected in primary spermatocytes, Leydig and Sertoli cells of 8, 12 and 17-week-old animals. These results suggest that selenoprotein S may play a role in spermatogenesis.

  5. Pharmacology of Free Radicals and the Impact of Reactive Oxygen Species on the Testis

    PubMed Central

    Aprioku, Jonah Sydney

    2013-01-01

    The role of free radicals in normal cellular functions and different pathological conditions has been a focus of pharmacological studies in the recent past. Reactive oxygen species (ROS) and free radicals in general are essential for cell signaling and other vital physiological functions; however, excessive amounts can cause alteration in cellular reduction-oxidation (redox) balance, and disrupt normal biological functions. When there is an imbalance between activities of ROS and antioxidant/scavenging defense systems, oxidative stress (OS) occurs. A good number of studies have shown OS is involved in the development of several disease conditions, including male infertility. In the present article, generation of free radicals and their effects, as well as the mechanisms of antioxidant/scavenging defense systems are discussed, with particular focus on the testis. The review also discusses the contribution of OS on testicular dysfunction and briefly focuses on some OS-induced conditions that will alter testicular function. PMID:24551570

  6. Torsion of undescended testis in a 14-month-old child refusing to bear weight.

    PubMed

    Knight, Ryan M; Cuenca, Peter J

    2011-11-01

    In this report, we discuss a case of a 14-month-old male presenting in the emergency department with refusal to bear weight on his left leg. Plain radiographic studies revealed no evidence of effusion, fracture, or dislocation. Laboratory studies were significant for an elevated white blood cell count, erythrocyte sedimentation rate, and C-reactive protein. Further studies included unremarkable ultrasound of the left hip and normal magnetic resonance imaging (MRI) of both hips. An incidental finding on MRI was a left inguinal mass concerning an incarcerated hernia. Ultrasound of this mass demonstrated a left undescended testis within the inguinal canal and possible incarcerated paratesticular inguinal hernia. The final pathologic diagnosis of a torsed gangrenous left testicle within the inguinal canal was confirmed during surgery.

  7. Undescended testis – current trends and guidelines: a review of the literature

    PubMed Central

    Oszukowska, Elżbieta; Słowikowska-Hilczer, Jolanta

    2016-01-01

    The best mode of undescended testis (UDT) treatment remains controversial. However, knowledge gained from randomized controlled studies and meta-analyses allowed different groups of researchers to set out guidelines on management of patients with UDT. The authors reviewed recent literature and came to the following conclusions: (1) Hormonal treatment is not recommended, considering both the immediate results (only 15–20% of retained testes descend) and the possible long-term adverse effects on spermatogenesis. (2) Surgery is the treatment of choice; orchiopexy is successful in about 95% of UDT, with a low rate of complications (about 1%). (3) Orchiopexy should be performed between 12 and 18 months of age, or at first contact if diagnosed later. PMID:27279862

  8. Pseudogenization of testis-specific Lfg5 predates human/Neanderthal divergence.

    PubMed

    Mariotti, Marco; Smith, Temple F; Sudmant, Peter H; Goldberger, Gabriel

    2014-05-01

    Recent reviews discussed the critical roles of apoptosis in human spermatogenesis and infertility. These reviews highlight the FasL-induced caspase cascade in apoptosis lending importance to our discovery of the pseudogene status of the Lfg5 gene in modern humans, Neanderthal and the Denisovan. This gene is a member of the ancient and highly conserved apoptosis Lifeguard family. This pseudogenization is the result of a premature stop codon at the 3'-end of exon 8 not found in any other ortholog. With the current exception of the domesticated bovine and buffalo, Lfg5's expression in mammals is testis-specific. A full analysis of this gene, its phylogenetic context and its recent hominin changes suggest its inactivation was likely under selection in human evolution.

  9. PIWI-interacting RNAs (piRNAs) - a mouse testis perspective.

    PubMed

    Bortvin, A

    2013-06-01

    Over the past decade, PIWI-interacting RNAs (piRNAs) have emerged as the most intriguing class of small RNAs. Almost every aspect of piRNA biology defies established rules of the RNA interference world while the scope of piRNA functional potential spans from transcriptional gene silencing to genome defense to transgenerational epigenetic phenomena. This review will focus on the genomic origins, biogenesis, and function of piRNAs in the mouse testis - an exceptionally robust experimental system amenable to genetic, cell-biological, molecular, and biochemical studies. Aided and frequently guided by knowledge obtained in insect, worm, and fish germ cells, mouse spermatogenesis has emerged as the primary model in understanding the role of this conserved pathway in mammals. PMID:23980886

  10. Perinatal malnutrition programs gene expression of leptin receptors isoforms in testis and prostate of adult rats.

    PubMed

    Gombar, Flavia Meireles; Ramos, Cristiane Fonte

    2013-06-10

    The aim of this paper was to evaluate if maternal malnutrition during lactation programs the expression of leptin receptor isoforms in the testes and prostate ventral lobe of adult rats. At delivery, Wistar rats were separated into 3 groups: control group (C) with free access to a standard laboratory diet containing 22% protein; protein-energy restricted group (PER) with free access to an isoenergy and protein-restricted diet containing 8% protein; and energy-restricted group (ER) receiving standard laboratory diet in restricted quantities, which were calculated according to the mean ingestion of the PER group. All animals were sacrificed at 90 days of age. Both PER and ER groups presented low body weight from the first days after birth, however, while the ER group reached the control weight around day 80, the body weight of PER group was significantly lower compared to controls until the day the animals were killed. In relation to tissue weight, only the relative testis weight of the ER group presented an alteration compared to the control group (p<0.03). There was also no alteration in the leptin serum levels among the groups. The main leptin receptors isoforms, OBRa and OBRb were significantly increased in the testis (OBRa: C=0.71±0.10; PER=1.14±0.17; ER=1.92±0.70, p<0.0007, OBRb: C=0.87±0.04; PER=1.20±0.05; ER=1.44±0.17, p<0.001) and prostate (OBRa: C=0.70±0.18; PER=1.30±0.14; ER=1.65±0.22, p<0.014, OBRb: C=0.77±0.14; PER=1.16±0.04; ER=1.30±0.13, p<0.027) of both malnourished groups. However, the testis OBRc (C=1.52±0.06; PER=1.35±0.23; ER=3.50±0.72, p<0.023) and OBRf (C=1.31±0.12; PER=1.66±0.27; ER=3.47±0.55, p<0.009) and prostate OBRc (C=0.48±0.13; ER=1.18±0.34, p<0.01) and OBRf (C=0.73±0.15; PER=0.99±0.11; ER=1.83±0.30, p<0.016) isoforms were significantly increased only in the ER group. The results presented here show for the first time that both testis and prostate leptin receptor isoforms gene expression are programmed by perinatal

  11. Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function

    PubMed Central

    Alves, Marco G.; Martins, Ana D.; Cavaco, José E.; Socorro, Sílvia; Oliveira, Pedro F.

    2013-01-01

    Blood testis barrier (BTB) is one of the tightest blood-barriers controlling the entry of substances into the intratubular fluid. Diabetes Mellitus (DM) is an epidemic metabolic disease concurrent with falling fertility rates, which provokes severe detrimental BTB alterations. It induces testicular alterations, disrupting the metabolic cooperation between the cellular constituents of BTB, with dramatic consequences on sperm quality and fertility. As Sertoli cells are involved in the regulation of spermatogenesis, providing nutritional support for germ cells, any metabolic alteration in these cells derived from DM may be responsible for spermatogenesis disruption, playing a crucial role in fertility/subfertility associated with this pathology. These cells have a glucose sensing machinery that reacts to hormonal fluctuations and several mechanisms to counteract hyper/hypoglycemic events. The role of DM on Sertoli/BTB glucose metabolism dynamics and the metabolic molecular mechanisms through which DM and insulin deregulation alter its functioning, affecting male reproductive potential will be discussed. PMID:24665384

  12. Paracrine Wnt/β-catenin signaling mediates proliferation of undifferentiated spermatogonia in the adult mouse testis

    PubMed Central

    Takase, Hinako M.; Nusse, Roeland

    2016-01-01

    Spermatogonial stem cells (SSCs) fuel the production of male germ cells but the mechanisms behind SSC self-renewal, proliferation, and differentiation are still poorly understood. Using the Wnt target gene Axin2 and genetic lineage-tracing experiments, we found that undifferentiated spermatogonia, comprising SSCs and transit amplifying progenitor cells, respond to Wnt/β-catenin signals. Genetic elimination of β-catenin indicates that Wnt/β-catenin signaling promotes the proliferation of these cells. Signaling is likely initiated by Wnt6, which is uniquely expressed by neighboring Sertoli cells, the only somatic cells in the seminiferous tubule that support germ cells and act as a niche for SSCs. Therefore, unlike other stem cell systems where Wnt/β-catenin signaling is implicated in self-renewal, the Wnt pathway in the testis specifically contributes to the proliferation of SSCs and progenitor cells. PMID:26929341

  13. [Role of chemotherapy in the treatment of cancer of the testis in adults].

    PubMed

    Le Duc, A; Gisselbrecht, C; Le Doze, H; Mignot, L

    1985-02-01

    Owing to its considerable effectiveness, modern multiple chemotherapy ranks first in the treatment of non-seminoma metastatic tumours of the testis. Its side-effects in short-term treatment are recognized and acceptable in view of the results obtained, but they remain imperfectly known in long-term treatments. Fort this reason, the present tendency in clinical stage I non-seminoma tumours is to reserve chemotherapy for patients who relapsed after orchidectomy. Advanced seminomas with or without high levels of human chorionic gonadotrophin (subunit beta) already benefit from chemotherapy, and this treatment is likely to be extended to less disseminated forms of cancer. Pure or predominant choriocarcinomas still respond poorly to the cytotoxic drugs at present available.

  14. Vitamin E modifies the ultrastructure of testis and epididymis in mice exposed to lead intoxication.

    PubMed

    Fahim, Mohamed A; Tariq, Saeed; Adeghate, Ernest

    2013-05-01

    Lead (Pb) is known to cause abnormal function of several systems including the male reproductive system, where it has been shown to reduce sperm count. In order to examine the morphological basis of the reduction in sperm count and a possible effect of vitamin E, lead acetate (1 mg/kg body weight) was given to control and vitamin E-treated mice daily, intraperitoneally for 3 weeks. The testis and body of epididymis of the mice were subjected to electron microscopy study. Pb caused degenerative changes in spermatids inducing vacuolization and a reduction in the number of cytoplasmic organelles in Leydig cells. Pb also destroyed the stereocilia of epididymal epithelium. The addition of vitamin E ameliorated the severity of these morphological changes. In conclusion, Pb-induced reduction in sperm count may be due to changes in the ultrastructure of spermatids, epididymal epithelia and Leydig cells. These changes can be reduced by vitamin E.

  15. Stage-specific control of niche positioning and integrity in the Drosophila testis.

    PubMed

    Schardt, Lisa; Ander, Janina-Jacqueline; Lohmann, Ingrid; Papagiannouli, Fani

    2015-11-01

    A fundamental question is how complex structures are maintained after their initial specification. Stem cells reside in a specialized microenvironment, called niche, which provides essential signals controlling stem cell behavior. We addressed this question by studying the Drosophila male stem cell niche, called the hub. Once specified, the hub cells need to maintain their position and architectural integrity through embryonic, larval and pupal stages of testis organogenesis and during adult life. The Hox gene Abd-B, in addition to its described role in male embryonic gonads, maintains the architecture and positioning of the larval hub from the germline by affecting integrin localization in the neighboring somatic cyst cells. We find that the AbdB-Boss/Sev cascade affects integrin independent of Talin, while genetic interactions depict integrin as the central downstream player in this system. Focal adhesion and integrin-adaptor proteins within the somatic stem cells and cyst cells, such as Paxillin, Pinch and Vav, also contribute to proper hub integrity and positioning. During adult stages, hub positioning is controlled by Abd-B activity in the outer acto-myosin sheath, while Abd-B expression in adult spermatocytes exerts no effect on hub positioning and integrin localization. Our data point at a cell- and stage-specific function of Abd-B and suggest that the occurrence of new cell types and cell interactions in the course of testis organogenesis made it necessary to adapt the whole system by reusing the same players for male stem cell niche positioning and integrity in an alternative manner.

  16. Formin 1 Regulates Ectoplasmic Specialization in the Rat Testis Through Its Actin Nucleation and Bundling Activity.

    PubMed

    Li, Nan; Mruk, Dolores D; Wong, Chris K C; Han, Daishu; Lee, Will M; Cheng, C Yan

    2015-08-01

    During spermatogenesis, developing spermatids and preleptotene spermatocytes are transported across the adluminal compartment and the blood-testis barrier (BTB), respectively, so that spermatids line up near the luminal edge to prepare for spermiation, whereas preleptotene spermatocytes enter the adluminal compartment to differentiate into late spermatocytes to prepare for meiosis I/II. These cellular events involve actin microfilament reorganization at the testis-specific, actin-rich Sertoli-spermatid and Sertoli-Sertoli cell junction called apical and basal ectoplasmic specialization (ES). Formin 1, an actin nucleation protein known to promote actin microfilament elongation and bundling, was expressed at the apical ES but limited to stage VII of the epithelial cycle, whereas its expression at the basal ES/BTB stretched from stage III to stage VI, diminished in stage VII, and was undetectable in stage VIII tubules. Using an in vitro model of studying Sertoli cell BTB function by RNA interference and biochemical assays to monitor actin bundling and polymerization activity, a knockdown of formin 1 in Sertoli cells by approximately 70% impeded the tight junction-permeability function. This disruptive effect on the tight junction barrier was mediated by a loss of actin microfilament bundling and actin polymerization capability mediated by changes in the localization of branched actin-inducing protein Arp3 (actin-related protein 3), and actin bundling proteins Eps8 (epidermal growth factor receptor pathway substrate 8) and palladin, thereby disrupting cell adhesion. Formin 1 knockdown in vivo was found to impede spermatid adhesion, transport, and polarity, causing defects in spermiation in which elongated spermatids remained embedded into the epithelium in stage IX tubules, mediated by changes in the spatiotemporal expression of Arp3, Eps8, and palladin. In summary, formin 1 is a regulator of ES dynamics.

  17. The frequency of undescended testis from birth to adulthood: a review.

    PubMed

    Sijstermans, K; Hack, W W M; Meijer, R W; van der Voort-Doedens, L M

    2008-02-01

    We performed a systematic review and critique of the literature on the frequency of undescended testis (UDT) among boys from birth to adolescence. Special attention was given to whether previous testicular position was taken into account to distinguish between congenital and acquired UDT. We searched Medline, Embase, Cinahl and the Cochrane Library. Any study reporting on the frequency of UDT was included. Study population age, number of boys studied, period of examination, primary examiner, area of study, study design, ethnicity, definitions used and previous testicular position were analysed. A total of 46 studies met the inclusion criteria. Twenty-three of the 46 (50%) studies involved newborns. Definitions were described in half of the studies; however, the definitions used were heterogeneous. Previous testis position was described in 11% (5/46) of the studies. At birth, in term and/or birth weight >2.5 kg infants, the UDT rate ranged from 1.0 to 4.6%, and in premature and/or birth weight <2.5 kg infants from 1.1 to 45.3%. At the age of 1 year UDT in term and/or birth weight >2.5 kg infants was seen in 1.0-1.5%, at 6 years in 0.0-2.6%, at 11 years in 0.0-6.6% and at 15 years in 1.6-2.2% of boys. The frequency of UDT shows variable figures in the literature. The actual frequency of acquired UDT essentially remains unclear because of the shortage of studies performed at an older age, and of studies reporting on previous testicular position.

  18. Expression analysis of HSP70 in the testis of Octopus tankahkeei under thermal stress.

    PubMed

    Long, Ling-Li; Han, Ying-Li; Sheng, Zhang; Du, Chen; Wang, You-Fa; Zhu, Jun-Quan

    2015-09-01

    The gene encoding heat shock protein 70 (HSP70) was identified in Octopus tankahkeei by homologous cloning and rapid amplification of cDNA ends (RACE). The full-length cDNA (2471 bp) consists of a 5'-untranslated region (UTR) (89 bp), a 3'-UTR (426 bp), and an open reading frame (1956 bp) that encodes 651 amino acid residues with a predicted molecular mass of 71.8 kDa and an isoelectric point of 5.34. Based on the amino acid sequence analysis and multiple sequence alignment, this cDNA is a member of cytoplasmic hsp70 subfamily of the hsp70 family and was designated as ot-hsp70. Tissue expression analysis showed that HSP70 expression is highest in the testes when all examined organs were compared. Immunohistochemistry analysis, together with hematoxylin-eosin staining, revealed that the HSP70 protein was expressed in all spermatogenic cells, but not in fibroblasts. In addition, O. tankahkeei were heat challenged by exposure to 32 °C seawater for 2 h, then returned to 13 °C for various recovery time (0-24 h). Relative expression of ot-hsp70 mRNA in the testes was measured at different time points post-challenge by quantitative real-time PCR. A clear time-dependent mRNA expression of ot-hsp70 after thermal stress indicates that the HSP70 gene is inducible. Ultrastructural changes of the heat-stressed testis were observed by transmission electron microscopy. We suggest that HSP70 plays an important role in spermatogenesis and testis protection against thermal stress in O. tankahkeei. PMID:26033497

  19. Is prnt a pseudogene? Identification of ram Prt in testis and ejaculated spermatozoa.

    PubMed

    Pimenta, Jorge; Domingos, Ana; Santos, Pedro; Marques, Carla C; Cantante, Cátia; Santos, Ana; Barbas, João P; Baptista, Maria C; Horta, António E M; Viegas, Aldino; Mesquita, Patrícia; Gonçalves, João; Fontes, Carlos A; Prates, José A M; Pereira, Rosa M L N

    2012-01-01

    A hallmark of prion diseases or transmissible spongiform encephalopaties is the conversion of the cellular prion protein (PrP(C)), expressed by the prion gene (prnp), into an abnormally folded isoform (PrP(Sc)) with amyloid-like features that causes scrapie in sheep among other diseases. prnp together with prnd (which encodes a prion-like protein designated as Doppel), and prnt (that encodes the prion protein testis specific--Prt) with sprn (shadow of prion protein gene, that encodes Shadoo or Sho) genes, constitute the "prion gene complex". Whereas a role for prnd in the proper functioning of male reproductive system has been confirmed, the function of prnt, a recently discovered prion family gene, comprises a conundrum leading to the assumption that ruminant prnt is a pseudogene with no protein expression. The main objective of the present study was to identify Prt localization in the ram reproductive system and simultaneously to elucidate if ovine prnt gene is transcribed into protein-coding RNA. Moreover, as Prt is a prnp-related protein, the amyloid propensity was also tested for ovine and caprine Prt. Recombinant Prt was used to immunize BALB/c mice, and the anti-Prt polyclonal antibody (APPA) immune response was evaluated by ELISA and Western Blot. When tested by indirect immunofluorescence, APPA showed high avidity to the ram sperm head apical ridge subdomain, before and after induced capacitation, but did not show the same behavior against goat spermatozoa, suggesting high antibody specificity against ovine-Prt. Prt was also found in the testis when assayed by immunohistochemistry during ram spermatogenesis, where spermatogonia, spermatocytes, spermatids and spermatozoa, stained positive. These observations strongly suggest ovine prnt to be a translated protein-coding gene, pointing to a role for Prt protein in the ram reproductive physiology. Besides, caprine Prt appears to exhibit a higher amyloid propensity than ovine Prt, mostly associated with its

  20. The RHOX Homeodomain Proteins Regulate the Expression of Insulin and Other Metabolic Regulators in the Testis*

    PubMed Central

    MacLean, James A.; Hu, Zhiying; Welborn, Joshua P.; Song, Hye-Won; Rao, Manjeet K.; Wayne, Chad M.; Wilkinson, Miles F.

    2013-01-01

    Defects in cellular metabolism have been widely implicated in causing male infertility, but there has been little progress in understanding the underlying mechanism. Here we report that several key metabolism genes are regulated in the testis by Rhox5, the founding member of a large X-linked homeobox gene cluster. Among these Rhox5-regulated genes are insulin 2 (Ins2), resistin (Retn), and adiponectin (Adipoq), all of which encode secreted proteins that have profound and wide-ranging effects on cellular metabolism. The ability of Rhox5 to regulate their levels in the testis has the potential to dictate metabolism locally in this organ, given the existence of the blood-testes barrier. We demonstrate that Ins2 is a direct target of Rhox5 in Sertoli cells, and we show that this regulation is physiologically significant, because Rhox5-null mice fail to up-regulate Ins2 expression during the first wave of spermatogenesis and have insulin-signaling defects. We identify other Rhox family members that induce Ins2 transcription, define protein domains and homeodomain amino acid residues crucial for this property, and demonstrate that this regulation is conserved. Rhox5-null mice also exhibit altered expression of other metabolism genes, including those encoding the master transcriptional regulators of metabolism, PPARG and PPARGC1A, as well as SCD1, the rate-limiting enzyme for fatty acid metabolism. These results, coupled with the known roles of RHOX5 and its target metabolism genes in spermatogenesis in vivo, lead us to propose a model in which RHOX5 is a central transcription factor that promotes the survival of male germ cells via its effects on cellular metabolism. PMID:24121513

  1. Antioxidant and protective effects of Royal jelly on histopathological changes in testis of diabetic rats

    PubMed Central

    Ghanbari, Elham; Nejati, Vahid; Khazaei, Mozafar

    2016-01-01

    Background: Diabetes is the most common endocrine disease. It has adverse effects on male reproductive function. Royal Jelly (RJ) has antioxidant and anti-diabetic effects and show protective effects against diabetes. Objective: This study was conducted to evaluate the effect of RJ on histopathological alterations of the testicular tissue in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: In this experimental study, 28 adult Wistar rats were randomly divided into control (C), royal jelly (R), diabetic (D) and RJ-treated diabetic (D+R) groups. Diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg body weight (BW). The rats from the R and D+R groups received daily RJ (100 mg/kg BW) for 6 wks orally. Hematoxylin-Eosin staining was used to analyze histopathological changes including: tunica albuginea thickness (TAT), seminiferous tubules diameter (STsD), Johnsen’s score, tubular differentiation index (TDI), spermiogenesis index (SPI), Sertoli cell index (SCI), meiotic index (MI), and mononuclear immune cells (MICs) in testes. The antioxidant status was examined by evaluating testicular levels of ferric reducing antioxidant power (FRAP) and catalase (CAT) activity. Results: Histological results of the testis from diabetic rats showed significant decrease in STsD, Johnsen’s score, TDI, SPI, SCI and MI, and significant increase in TAT and MICs, while administration of RJ significantly reverted these changes (p<0.05). RJ treatment markedly increased activity of CAT and FRAP. There were significant differences in FRAP levels among C (13.0±0.5), RJ (13.4±0.3), D (7.8±0.6) and D+R (12.4±0.7) groups (p<0.05). Conclusion: RJ improved diabetes-induced impairment in testis, probably through its antioxidant property. PMID:27679827

  2. Expression analysis of HSP70 in the testis of Octopus tankahkeei under thermal stress.

    PubMed

    Long, Ling-Li; Han, Ying-Li; Sheng, Zhang; Du, Chen; Wang, You-Fa; Zhu, Jun-Quan

    2015-09-01

    The gene encoding heat shock protein 70 (HSP70) was identified in Octopus tankahkeei by homologous cloning and rapid amplification of cDNA ends (RACE). The full-length cDNA (2471 bp) consists of a 5'-untranslated region (UTR) (89 bp), a 3'-UTR (426 bp), and an open reading frame (1956 bp) that encodes 651 amino acid residues with a predicted molecular mass of 71.8 kDa and an isoelectric point of 5.34. Based on the amino acid sequence analysis and multiple sequence alignment, this cDNA is a member of cytoplasmic hsp70 subfamily of the hsp70 family and was designated as ot-hsp70. Tissue expression analysis showed that HSP70 expression is highest in the testes when all examined organs were compared. Immunohistochemistry analysis, together with hematoxylin-eosin staining, revealed that the HSP70 protein was expressed in all spermatogenic cells, but not in fibroblasts. In addition, O. tankahkeei were heat challenged by exposure to 32 °C seawater for 2 h, then returned to 13 °C for various recovery time (0-24 h). Relative expression of ot-hsp70 mRNA in the testes was measured at different time points post-challenge by quantitative real-time PCR. A clear time-dependent mRNA expression of ot-hsp70 after thermal stress indicates that the HSP70 gene is inducible. Ultrastructural changes of the heat-stressed testis were observed by transmission electron microscopy. We suggest that HSP70 plays an important role in spermatogenesis and testis protection against thermal stress in O. tankahkeei.

  3. Pit-1w may regulate prolactin gene expression in mouse testis.

    PubMed

    Maeda, Kazuki; Taniuchi, Shusuke; Takahashi, Sumio; Takeuchi, Sakae

    2012-09-01

    Pit-1 is a POU-domain transcription factor that promotes growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone β subunit (TSHβ) gene expression in the pituitary gland. Alternative splicing of Pit-1 gene transcripts has been shown to give rise to several variants with discrete transactivation properties. Recently, we identified a mouse Pit-1 w that is generated by alternative promoter usage and is expressed in a variety of tissues including the testis. Using a combination of reverse-transcription polymerase chain reaction analyses and luciferase reporter gene assays, we investigated the possible role of Pit-1 w in the mouse testis. In postnatal testicular development, the expression of Pit-1 w mRNA was significantly up-regulated between 18 and 20 days after birth when the numbers of secondary spermatocytes and spermatids have been reported to increase in mice. The PRL mRNA, but not the mRNAs for GH or TSHβ, showed intratesticular expression patterns that were similar to those of the Pit-1 w mRNA. In experimental unilaterally cryptorchid testes of adult mice, spermatid numbers were extremely low and the expression levels of both the Pit-1 w and PRL mRNAs dropped dramatically. Furthermore, in the luciferase reporter gene assays, we found that Pit-1 w specifically transactivated the PRL promoter but had no effect on the promoters of GH or TSHβ. These results suggested that Pit-1 w could be involved in the paracrine/autocrine system in mice and may be necessary for normal testicular function via its possible role in regulating PRL expression in testicular germ cells. This is the first report demonstrating the possible role of Pit-1 w in mammals. PMID:22634956

  4. Protective effects of different antioxidants against cadmium induced oxidative damage in rat testis and prostate tissues.

    PubMed

    Jahan, Sarwat; Zahra, Asia; Irum, Umaira; Iftikhar, Natasha; Ullah, Hizb

    2014-08-01

    The present study was performed to determine the effects of different antioxidants on testicular histopathology and oxidative damage induced by cadmium (Cd) in rat testis and prostate. Twenty five rats were equally divided into five groups (n = 5/group). The control group was injected subcutaneously with saline while the Cd alone treated group received a subcutaneous injection of 0.2 mg/kg CdCl(2). Other groups were treated with sulphoraphane (25 µg/rat), vitamin E (75 mg/kg), and Ficus Religiosa plant extract (100 mg/kg) orally along with subcutaneous injections of 0.2 mg/kg CdCl(2) for fifteen days. Oxidative damage in the testicular and prostate tissues were assessed by the estimation of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and glutathione reductase (GSR) activity. Lipid peroxidation (TBARS), protein estimation, and histomorphology were also assessed. Cadmium exposure caused a significant decrease in antioxidant enzymes like CAT, POD, SOD, GSR, protein concentrations, and a marked increase in TBARS activity in rat testis and prostate. Histological examination of adult male rat testes showed a disruption in the arrangement of seminiferous tubules along with a reduction in the number of germ cells, Leydig cells, tunica albuginea thickness, diameter of seminiferous tubules, and height of germinal epithelium. Co-treatment with vitamin E, sulphoraphane, and Ficus religiosa were found to be effective in reversing Cd induced toxicity, representing potential therapeutic options to protect the reproductive tissues from the detrimental effects of Cd toxicity. PMID:24758558

  5. Toxicants target cell junctions in the testis: Insights from the indazole-carboxylic acid model

    PubMed Central

    Cheng, C Yan

    2014-01-01

    There are numerous types of junctions in the seminiferous epithelium which are integrated with, and critically dependent on the Sertoli cell cytoskeleton. These include the basal tight junctions between Sertoli cells that form the main component of the blood–testis barrier, the basal ectoplasmic specializations (basal ES) and basal tubulobulbar complexes (basal TBC) between Sertoli cells; as well as apical ES and apical TBC between Sertoli cells and the developing spermatids that orchestrate spermiogenesis and spermiation. These junctions, namely TJ, ES, and TBC interact with actin microfilament-based cytoskeleton, which together with the desmosomal junctions that interact with the intermediate filament-based cytoskeleton plus the highly polarized microtubule-based cytoskeleton are working in concert to move spermatocytes and spermatids between the basal and luminal aspect of the seminiferous epithelium. In short, these various junctions are structurally complexed with the actin- and microtubule-based cytoskeleton or intermediate filaments of the Sertoli cell. Studies have shown toxicants (e.g., cadmium, bisphenol A (BPA), perfluorooctanesulfonate (PFOS), phthalates, and glycerol), and some male contraceptives under development (e.g., adjudin, gamendazole), exert their effects, at least in part, by targeting cell junctions in the testis. The disruption of Sertoli–Sertoli cell and Sertoli–germ cell junctions, results in the loss of germ cells from the seminiferous epithelium. Adjudin, a potential male contraceptive under investigation in our laboratory, produces loss of spermatids from the seminiferous tubules through disruption of the Sertoli cell spermatid junctions and disruption of the Sertoli cell cytoskeleton. The molecular and structural changes associated with adjudin administration are described, to provide an example of the profile of changes caused by disturbance of Sertoli-germ cell and also Sertoli cell-cell junctions. PMID:26413399

  6. Impact of diabetes in blood-testis and blood-brain barriers: resemblances and differences.

    PubMed

    Alves, Marco G; Oliveira, Pedro F; Socorro, Silvia; Moreira, Paula I

    2012-11-01

    Blood-tissue barriers prevent an uncontrolled exchange of large molecules between adjacent but metabolically separated compartments. There are several known barriers and two of the most important and tightest blood-tissue barriers are the blood-testis barrier (BTB) and the blood-brain barrier (BBB). Under normal conditions these barriers, formed by tight junctions between adjacent cells, control the entry of substances and metabolites. However, hyperglycemia and other diabetes-related complications, such as hypertension, impair the function of these biological barriers with dramatic consequences. Although both, BBB and BTB, are responsible for the maintenance of different biological processes, they have some remarkable similarities not always explored when looking at metabolic-related diseases such as diabetes. These barriers possess their own glucose sensing machinery, suffer a tied hormonal control and have specific mechanisms to counteract hyper- and hypoglycemia. In BBB and BTB the insulin signaling is also distinct from other tissues and organs thus evidencing their importance in protecting against or exacerbating the effects of diabetes on glucose metabolism. The control of glucose and lactate levels in brain and testis highlights the role of these barriers in protecting against peripheral glucose and lactate fluctuations that occur in the diabetic individual. We review the role of BBB and BTB in the control of glucose and metabolic dysfunction caused by diabetes in the brain and seminiferous epithelium. Gaining a better understanding of the molecular mechanisms through which glucose metabolism disrupts BBB and BTB function may highlight new opportunities for the treatment of diabetic complications in brain and male reproductive function. PMID:22934551

  7. Study of the potential spermatogonial stem cell compartment in dogfish testis, Scyliorhinus canicula L.

    PubMed

    Loppion, Geraldine; Crespel, Amélie; Martinez, Anne-Sophie; Auvray, Pierrïck; Sourdaine, Pascal

    2008-06-01

    In the lesser-spotted dogfish (Scyliorhinus canicula), spermatogenesis takes place within spermatocysts made up of Sertoli cells associated with stage-synchronized germ cells. As shown in testicular cross sections, cysts radiate in maturational order from the germinative area, where they are formed, to the opposite margin of the testis, where spermiation occurs. In the germinative zone, which is located in a specific area between the tunica albuginea of the testis and the dorsal testicular vessel, individual large spermatogonia are surrounded by elongated somatic cells. The aim of this study has been to define whether these spermatogonia share characteristics with spermatogonial stem cells described in vertebrate and non-vertebrate species. We have studied their ultrastructure and their mitotic activity by 5'-bromo-2'-deoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) immunodetection. Additionally, immunodetection of c-Kit receptor, a marker of differentiating spermatogonia in rodents, and of alpha- and beta-spectrins, as constituents of the spectrosome and the fusome, has been performed. Ultrastructurally, nuclei of stage I spermatogonia present the same mottled aspect in dogfish as undifferentiated spermatogonia nuclei in rodents. Moreover, intercellular bridges are not observed in dogfish spermatogonia, although they are present in stage II spermatogonia. BrdU and PCNA immunodetection underlines their low mitotic activity. The presence of a spectrosome-like structure, a cytological marker of the germline stem cells in Drosophila, has been observed. Our results constitute the first step in the study of spermatogonial stem cells and their niche in the dogfish. PMID:18340468

  8. Jak-STAT regulation of cyst stem cell development in the Drosophila testis

    PubMed Central

    Sinden, D.; Badgett, M.; Fry, J.; Jones, T.; Palmen, R.; Sheng, X.; Simmons, A.; Matunis, E.; Wawersik, M.

    2012-01-01

    Establishment and maintenance of functional stem cells is critical for organ development and tissue homeostasis. Little is known about the mechanisms underlying stem establishment during organogenesis. Drosophila testes are among the most thoroughly characterized systems for studying stem cell behavior, with germline stem cells (GSCs) and somatic cyst stem cells (CySCs) cohabiting a discrete stem cell niche at the testis apex. GSCs and CySCs are arrayed around hub cells that also comprise the niche and communication between hub cells, GSCs, and CySCs regulates the balance between stem cell maintenance and differentiation. Recent data has shown that functional, asymmetrically dividing GSCs are first established at ~23 hrs after egg laying during Drosophila testis morphogenesis (Sheng et al., 2009). This process correlates with coalescence of the hub, but development of CySCs from somatic gonadal precursors (SGPs) was not examined. Here, we show that functional CySCs are present at the time of GSC establishment, and that Jak-STAT signaling is necessary and sufficient for CySC maintenance shortly thereafter. Furthermore, hyper-activation of Jak in CySCs promotes expansion of the GSC population, while ectopic Jak activation in the germline induces GSC gene expression in GSC daughter cells but does not prevent spermatogenic differentiation. Together, these observations indicate that, similar to adult testes, Jak-STAT signaling from the hub acts on both GSCs and CySC to regulate their development and differentiation, and that additional signaling from CySCs to the GSCs play a dominant role in controlling GSC maintenance during niche formation. PMID:23010510

  9. Morphometric study of the testis and reproductive tract (including sperm granuloma) after vasectomy in mature rats

    PubMed Central

    Ma, Li; Guo, Yang; Yuan, Yong; Li, Yu-Gen; Deng, Xian-Zhong; Yang, Zheng-Wei

    2016-01-01

    By utilizing the rabbit model, previous studies have found good evidence indicating that vasectomy-induced spermatogenic damage is pressure-mediated: the damage occurs when the occluded reproductive tract is unable to accommodate additional spermatozoa produced by the testis. More studies with the more commonly used rat model have shown, however, controversial results on whether and why the damage occurs. In this study, 12 mature male Sprague-Dawley rats were subjected to unilateral vasectomy: double ligation (without severing) of the vas deferens exposed via a small inguinal incision; 37 days after the operation, the testes, epididymides, vasa deferentia (juxta-epididymal segments), and sperm granulomas (at the vasectomy site) were removed to obtain methacrylate resin-embedded sections and morphometric studies carried out with light microscopy. Marked spermatogenic damage with spermatids and spermatocytes depleted in the seminiferous epithelium in 43% of the seminiferous tubule profiles was demonstrated in 5 of the 12 testes on the vasectomized side, and the damage was associated with smaller or absent sperm granulomas; in the other 7 testes with essentially normal spermatogenesis, there was an increase (by 111% on average) in the volume of the tubule lumen, associated with larger granulomas or granulomas containing more spermatozoa. There was an overall increase (by 66%) in the thickness of the rete testis in the 12 testes; the epididymis or vas deferens showed no distension. It seems therefore that the spermatogenic damage induced by vasectomy in rats is pressure-mediated as well, and that variation in the damage depends mainly on the postoperative development of the sperm granuloma. PMID:25791731

  10. Seasonal changes and regulation of the glucocorticoid receptor in the testis of the toad Rhinella arenarum.

    PubMed

    Regueira, Eleonora; Sassone, Alina Grisel; Scaia, María Florencia; Volonteri, María Clara; Ceballos, Nora Raquel

    2013-01-01

    Several studies indicate that wild free-living vertebrates seasonally regulate plasma glucocorticoids. However, not only glucocorticoids but also the amount of receptors is important in determining biological responses. In this context, seasonal regulation of glucocorticoid receptor (GR) is crucial to modulate the response to glucocorticoids. Rhinella arenarum is an anuran exhibiting seasonal variations in plasma glucocorticoids and also in the number of binding sites (B(max)) of the testicular cytosolic GR. In this work, we evaluated if the annual pattern of GR protein in the testis varies seasonally and, by an in vitro approach, the role of glucocorticoids, androgens, and melatonin in the regulation of the GR B(max) and protein level. For this purpose, testes were treated with two physiological concentrations of melatonin (40 and 200 pg/ml), with or without luzindole (melatonin-receptor antagonist); with testosterone, cyanoketone (inhibitor of steroidogenesis) or casodex (androgen-receptor antagonist); or with dexamethasone or RU486 (GR antagonist). After treatments, B(max) and protein level were determined by the binding of [(3)H]dexamethasone and Western blot, respectively. Results showed that GR protein decreases in the winter. The in vitro treatment with melatonin produced a biphasic effect on the B(max) with the lowest concentration decreasing this parameter by a receptor-mediated mechanism. However, melatonin had no effect on the GR protein level. Conversely, a high concentration of dexamethasone up-regulated the GR protein and androgens neither changed the B(max) nor the protein level. These findings suggest that seasonal changes in plasma melatonin and glucocorticoids modulate the effect of glucocorticoids in the testis of R. arenarum. PMID:23203422

  11. The RHOX homeodomain proteins regulate the expression of insulin and other metabolic regulators in the testis.

    PubMed

    MacLean, James A; Hu, Zhiying; Welborn, Joshua P; Song, Hye-Won; Rao, Manjeet K; Wayne, Chad M; Wilkinson, Miles F

    2013-11-29

    Defects in cellular metabolism have been widely implicated in causing male infertility, but there has been little progress in understanding the underlying mechanism. Here we report that several key metabolism genes are regulated in the testis by Rhox5, the founding member of a large X-linked homeobox gene cluster. Among these Rhox5-regulated genes are insulin 2 (Ins2), resistin (Retn), and adiponectin (Adipoq), all of which encode secreted proteins that have profound and wide-ranging effects on cellular metabolism. The ability of Rhox5 to regulate their levels in the testis has the potential to dictate metabolism locally in this organ, given the existence of the blood-testes barrier. We demonstrate that Ins2 is a direct target of Rhox5 in Sertoli cells, and we show that this regulation is physiologically significant, because Rhox5-null mice fail to up-regulate Ins2 expression during the first wave of spermatogenesis and have insulin-signaling defects. We identify other Rhox family members that induce Ins2 transcription, define protein domains and homeodomain amino acid residues crucial for this property, and demonstrate that this regulation is conserved. Rhox5-null mice also exhibit altered expression of other metabolism genes, including those encoding the master transcriptional regulators of metabolism, PPARG and PPARGC1A, as well as SCD1, the rate-limiting enzyme for fatty acid metabolism. These results, coupled with the known roles of RHOX5 and its target metabolism genes in spermatogenesis in vivo, lead us to propose a model in which RHOX5 is a central transcription factor that promotes the survival of male germ cells via its effects on cellular metabolism.

  12. Gonadotropin Signaling in Zebrafish Ovary and Testis Development: Insights From Gene Knockout Study.

    PubMed

    Chu, Lianhe; Li, Jianzhen; Liu, Yun; Cheng, Christopher H K

    2015-12-01

    Using the transcription activator-like effectors nucleases-mediated gene knockout technology, we have previously demonstrated that LH signaling is required for oocyte maturation and ovulation but is dispensable for testis development in zebrafish. Here, we have further established the fshb and fshr knockout zebrafish lines. In females, fshb mutant is subfertile, whereas fshr mutant is infertile. Folliculogenesis is partially affected in the fshb mutant but is completely arrested at the primary growth stage in the fshr mutant. In males, fshb and fshr mutant are fertile. The fertilization rate and histological structure of the testis is not affected. However, double knockout of fshb;lhb or fshr;lhr leads to all infertile male offspring. The key steroid hormones and steroidogenic genes are dramatically decreased in double knockout mutant (fshb;lhb and fshr;lhr) but not in single knockout mutant (fshb, lhb, fshr, and lhr) males. Furthermore, we have also demonstrated the constitutive activities of both FSH receptor (FSHR) and LH receptor in zebrafish and the compensatory role of LH by cross-reacting with FSHR in the fshb;lhr double mutant, thus explaining the phenotypic discrepancy observed among the ligand/receptor mutant lines. Taken together, our data established the following models on the roles of gonadotropin signaling in zebrafish gonad development. In females, FSH signaling is mainly responsible for promoting follicular growth, whereas LH signaling is mainly responsible for stimulating oocyte maturation and ovulation. In males, the functions of FSH and LH signaling overlap, and only disruption of both FSH and LH signaling could lead to the infertile phenotype. In the absence of FSH, LH could play a compensatory role by cross-reacting with FSHR in both male and female.

  13. Antioxidant and protective effects of Royal jelly on histopathological changes in testis of diabetic rats

    PubMed Central

    Ghanbari, Elham; Nejati, Vahid; Khazaei, Mozafar

    2016-01-01

    Background: Diabetes is the most common endocrine disease. It has adverse effects on male reproductive function. Royal Jelly (RJ) has antioxidant and anti-diabetic effects and show protective effects against diabetes. Objective: This study was conducted to evaluate the effect of RJ on histopathological alterations of the testicular tissue in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: In this experimental study, 28 adult Wistar rats were randomly divided into control (C), royal jelly (R), diabetic (D) and RJ-treated diabetic (D+R) groups. Diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg body weight (BW). The rats from the R and D+R groups received daily RJ (100 mg/kg BW) for 6 wks orally. Hematoxylin-Eosin staining was used to analyze histopathological changes including: tunica albuginea thickness (TAT), seminiferous tubules diameter (STsD), Johnsen’s score, tubular differentiation index (TDI), spermiogenesis index (SPI), Sertoli cell index (SCI), meiotic index (MI), and mononuclear immune cells (MICs) in testes. The antioxidant status was examined by evaluating testicular levels of ferric reducing antioxidant power (FRAP) and catalase (CAT) activity. Results: Histological results of the testis from diabetic rats showed significant decrease in STsD, Johnsen’s score, TDI, SPI, SCI and MI, and significant increase in TAT and MICs, while administration of RJ significantly reverted these changes (p<0.05). RJ treatment markedly increased activity of CAT and FRAP. There were significant differences in FRAP levels among C (13.0±0.5), RJ (13.4±0.3), D (7.8±0.6) and D+R (12.4±0.7) groups (p<0.05). Conclusion: RJ improved diabetes-induced impairment in testis, probably through its antioxidant property.

  14. High expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice.

    PubMed

    Chen, Yu-Chia; Chang, Jan-Gowth; Jong, Yuh-Jyh; Liu, Ting-Yuan; Yuo, Chung-Yee

    2015-01-01

    Spinal muscular atrophy (SMA) is an inherited neuromuscular disease caused by deletion or mutation of SMN1 gene. All SMA patients carry a nearly identical SMN2 gene, which produces low level of SMN protein due to mRNA exon 7 exclusion. Previously, we found that the testis of SMA mice (smn-/- SMN2) expresses high level of SMN2 full-length mRNA, indicating a testis-specific mechanism for SMN2 exon 7 inclusion. To elucidate the underlying mechanism, we established primary cultures of testis cells from SMA mice and analyzed them for SMN2 exon 7 splicing. We found that primary testis cells after a 2-hour culture still expressed high level of SMN2 full-length mRNA, but the level decreased after longer cultures. We then compared the protein levels of relevant splicing factors, and found that the level of Tra2-β1 also decreased during testis cell culture, correlated with SMN2 full-length mRNA downregulation. In addition, the testis of SMA mice expressed the highest level of Tra2-β1 among the many tissues examined. Furthermore, overexpression of Tra2-β1, but not ASF/SF2, increased SMN2 minigene exon 7 inclusion in primary testis cells and spinal cord neurons, whereas knockdown of Tra2-β1 decreased SMN2 exon 7 inclusion in primary testis cells of SMA mice. Therefore, our results indicate that high expression level of Tra2-β1 is responsible for increased SMN2 exon 7 inclusion in the testis of SMA mice. This study also suggests that the expression level of Tra2-β1 may be a modifying factor of SMA disease and a potential target for SMA treatment.

  15. Differences in cadmium transport to the testis, epididymis, and brain in cadmium-sensitive and -resistant murine strains 129/J and A/J.

    PubMed

    King, L M; Banks, W A; George, W J

    1999-05-01

    Although most animals with scrotal testes are susceptible to cadmium-induced testicular toxicity, strain-related differences are seen in mice. Resistant murine strains demonstrate a decreased cadmium concentration in the testis and also in the epididymis and seminal vesicle. In this study we analyzed cadmium transport into tissues with a vascular barrier, the testis, epididymis, and brain, in an attempt to characterize the mechanisms of strain resistance to cadmium-induced testicular toxicity. In the resistant murine strain A/J, 109Cd transport (administered as 109CdCl2) was significantly attenuated in the testis, epididymis, and brain, when compared to the sensitive murine strain 129/J. The unidirectional influx constant (Ki, in microliter g-1 min-1) for 109Cd was 0.01929 in the A/J testis as compared with 1.174 in the 129/J testis (P <.0001). The percentage of a 109Cd dose that reached the A/J testis by 60 min was over 10 times less than that which reached the 129/J testis. The transport system used by cadmium in the 129/J testis was saturable, with 20 microM unlabeled cadmium chloride inhibiting transport by over 60%. The transporter was competitively inhibited by zinc (P =. 00017), but not by calcium, indicating a specificity in ion transport. Studies with isolated tubules and analysis of testicular fluid compartments demonstrated no significant difference in cadmium uptake or efflux between the strains when corrected for the amount of 109Cd entering the testis. Therefore, murine strain differences in testicular sensitivity to cadmium appear to be related to the variable presence of a transport system for cadmium in the testicular vasculature. PMID:10215659

  16. Role of P-Glycoprotein at the blood-testis barrier on adjudin distribution in the Testis: a revisit of recent data

    PubMed Central

    Su, Linlin; Jenardhanan, Pranitha; Mruk, Dolores D.; Mathur, Premendu P.; Cheng, Yan-ho; Mok, Ka-Wai; Bonanomi, Michele; Silvestrini, Bruno; Cheng, C. Yan

    2014-01-01

    The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in mammals including rodents and humans. It is used to sequester meiosis I and II, postmeiotic spermatid development via spermiogenesis and the release of sperm at spermiation from the systemic circulation, such that these events take place in an immune-privileged site in the adluminal (apical) compartment behind the BTB, segregated from the host immune system. Additionally, drug transporters, namely efflux (e.g., P-glycoprotein) and influx (e.g., Oatp3) pumps, many of which are integral membrane proteins in Sertoli cells at the BTB also work cooperatively to restrict the entry of drugs, toxicants, chemicals, steroids and other xenobiotics into the adluminal compartment. As such, the BTB that serves as an important physiological and selective barrier to protect germ cell development also poses a “hurdle” in male contraceptive development. For instance, adjudin, 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide, a potential nonhormonal male contraceptive that exerts its effects on germ cell adhesion, most notably at the Sertoli cell-spermatid interface, to induce “premature” germ cell loss from the seminiferous epithelium mimicking spermiation, has a relatively poor bioavailability largely because of the BTB. Since male contraceptives (e.g., adjudin) will be used by healthy men for an extended period of his life span after puberty, a better understanding on the BTB is necessary in order to effectively deliver drugs across this blood-tissue barrier in particular if these compounds exert their effects on developing germ cells in the adluminal compartment. This can also reduce long-term toxicity and health risk if the effective dosing can be lowered in order to widen the margin between its safety and efficacy. Herein, we summarize latest findings in this area of research, we also provide a critical evaluation on research areas that deserve attention in future studies. PMID:23397632

  17. Queen Conch (Strombus gigas) Testis Regresses during the Reproductive Season at Nearshore Sites in the Florida Keys

    PubMed Central

    Spade, Daniel J.; Griffitt, Robert J.; Liu, Li; Brown-Peterson, Nancy J.; Kroll, Kevin J.; Feswick, April; Glazer, Robert A.; Barber, David S.; Denslow, Nancy D.

    2010-01-01

    Background Queen conch (Strombus gigas) reproduction is inhibited in nearshore areas of the Florida Keys, relative to the offshore environment where conchs reproduce successfully. Nearshore reproductive failure is possibly a result of exposure to environmental factors, including heavy metals, which are likely to accumulate close to shore. Metals such as Cu and Zn are detrimental to reproduction in many mollusks. Methodology/Principal Findings Histology shows gonadal atrophy in nearshore conchs as compared to reproductively healthy offshore conchs. In order to determine molecular mechanisms leading to tissue changes and reproductive failure, a microarray was developed. A normalized cDNA library for queen conch was constructed and sequenced using the 454 Life Sciences GS-FLX pyrosequencer, producing 27,723 assembled contigs and 7,740 annotated transcript sequences. The resulting sequences were used to design the microarray. Microarray analysis of conch testis indicated differential regulation of 255 genes (p<0.01) in nearshore conch, relative to offshore. Changes in expression for three of four transcripts of interest were confirmed using real-time reverse transcription polymerase chain reaction. Gene Ontology enrichment analysis indicated changes in biological processes: respiratory chain (GO:0015992), spermatogenesis (GO:0007283), small GTPase-mediated signal transduction (GO:0007264), and others. Inductively coupled plasma-mass spectrometry analysis indicated that Zn and possibly Cu were elevated in some nearshore conch tissues. Conclusions/Significance Congruence between testis histology and microarray data suggests that nearshore conch testes regress during the reproductive season, while offshore conch testes develop normally. Possible mechanisms underlying the testis regression observed in queen conch in the nearshore Florida Keys include a disruption of small GTPase (Ras)-mediated signaling in testis development. Additionally, elevated tissue levels of Cu (34

  18. DEHP (DI-N-ETHYLHEXYL PHTHALATE), WHEN ADMINISTERED DURING SEXUAL DIFFERENTIATION, INDUCES DOSE DEPENDENT DECREASES IN FETAL TESTIS GENE EXPRESSION AND STEROID HORMONE SYNTHESIS

    EPA Science Inventory

    DEHP (di-n-ethylhexyl phthalate), when administered during sexual differentiation, induces dose dependent decreases in fetal testis gene expression and steroid hormone synthesis.
    Vickie S. Wilson, Christy Lambright, Johnathan Furr, Kathy Bobseine, Carmen Wood, Gary Held, and ...

  19. An examination of the characteristics, concentration, and distribution of androgen receptor in rat testis during sexual maturation

    SciTech Connect

    Buzek, S.W.

    1989-01-01

    In these studies a nuclear exchange assay was established in rat testis in which exchange after 86 hours at 4{degree}C was greater than 85% complete and receptor was stable. Receptor concentration per DNA measured by exchange declined between 15 and 25 days of age in the rat testis, then increased 4-fold during sexual maturation. Proliferation of germ cells which had low receptor concentration appeared to account for the early decline in testicular receptor concentration, whereas increase in receptor number per Sertoli cell between 25 and 35 days of age contributed to the later increase. Detailed studies showed that other possible explanations for changes in receptor number were not likely. Androgen receptor dynamics in testicular cells showed rapid, specific uptake of ({sup 3}H)-testosterone that was easily blocked by unlabeled testosterone, and medroxyprogesterone acetate, but not as well as by the anti-androgens cyproterone acetate and hydroxyflutamide.

  20. [Testicular tumor with opposite inguinal lymph node metastasis in a patient with prior orchiopexy for undescended testis].

    PubMed

    Hayashi, Keiichiro; Fukagai, Takashi; Morita, Masashi; Igarashi, Atsushi; Kushima, Miki

    2015-01-01

    The patient was a 54-year-old man. At age 6 years, he had undergone orchiopexy for left undescended testis. Six months prior to the current presentation, he visited our hospital with a chief complaint of painless enlargement of the left testis. Left high orchiectomy was performed under a diagnosis of left testicular tumor. Histopathological examination determined the tumor to be a seminoma (pT2). Postoperatively, the patient was placed on surveillance without preventive radiation treatment. He visited our hospital six months after surgery due to a painless mass in the right inguinal region. All tumor markers (AFP, HCG-β, and LDH) were within normal ranges. However, based on ultrasound and CT scan findings, lymph node metastasis was suspected and a right inguinal lymph node excision was thus performed. Histopathological examination led to the diagnosis of seminoma. PMID:25656016

  1. Protective role of zinc against the toxicity induced by exposure to cadmium during gestation and lactation on testis development.

    PubMed

    Chemek, Marouane; Mimouna, Safa Ben; Boughammoura, Sana; Delbès, Géraldine; Messaoudi, Imed

    2016-08-01

    To assess the effects of exposure to Cd and Zn on rat testicular development, offspring, from mothers receiving either tap water, Cd, Zn or Cd+Zn during gestation and lactation periods, were observed on gestational day (GD) 20 and on postnatal days (PND) 12, 21 and 35. During gestation, Cd induced maternal hypozincemia and less transfer of Zn to the fetus. During lactation, progressive Cd accumulation and Zn depletion in testis at PND12 and PND21 were noted. An increase of abnormal seminiferous tubules and a decrease in testis weight and plasmatic testosterone concentration were also observed at PND21 and PND35 respectively. Interestingly, Zn supply induced a significant protection against Cd toxicity. These results suggest that the toxic effects of Cd observed during development are mediated by the disruption of Zn metabolism, which is established in mothers during pregnancy causing Zn deficiency in fetuses and continues to become more pronounced during lactation. PMID:27288891

  2. The blood-testis barrier and its implications for male contraception.

    PubMed

    Cheng, C Yan; Mruk, Dolores D

    2012-01-01

    The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium into the basal and the apical (adluminal) compartments. Meiosis I and II, spermiogenesis, and spermiation all take place in a specialized microenvironment behind the BTB in the apical compartment, but spermatogonial renewal and differentiation and cell cycle progression up to the preleptotene spermatocyte stage take place outside of the BTB in the basal compartment of the epithelium. However, the BTB is not a static ultrastructure. Instead, it undergoes extensive restructuring during the seminiferous epithelial cycle of spermatogenesis at stage VIII to allow the transit of preleptotene spermatocytes at the BTB. Yet the immunological barrier conferred by the BTB cannot be compromised, even transiently, during the epithelial cycle to avoid the production of antibodies against meiotic and postmeiotic germ cells. Studies have demonstrated that some unlikely partners, namely adhesion protein complexes (e.g., occludin-ZO-1, N-cadherin-β-catenin, claudin-5-ZO-1), steroids (e.g., testosterone, estradiol-17β), nonreceptor protein kinases (e.g., focal adhesion kinase, c-Src, c-Yes), polarity proteins (e.g., PAR6, Cdc42, 14-3-3), endocytic vesicle proteins (e.g., clathrin, caveolin, dynamin 2), and actin regulatory proteins (e.g., Eps8, Arp2/3 complex), are working together, apparently under the overall influence of cytokines (e.g., transforming growth factor-β3, tumor necrosis factor-α, interleukin-1α). In short, a "new" BTB is created behind spermatocytes in transit while the "old" BTB above transiting cells undergoes timely degeneration, so that the immunological barrier can be maintained while spermatocytes are traversing the BTB. We also discuss recent findings regarding the molecular mechanisms by which environmental toxicants (e.g., cadmium, bisphenol A) induce testicular injury via their initial actions at the BTB to elicit

  3. The Blood-Testis Barrier and Its Implications for Male Contraception

    PubMed Central

    Mruk, Dolores D.

    2012-01-01

    The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. It divides the seminiferous epithelium into the basal and the apical (adluminal) compartments. Meiosis I and II, spermiogenesis, and spermiation all take place in a specialized microenvironment behind the BTB in the apical compartment, but spermatogonial renewal and differentiation and cell cycle progression up to the preleptotene spermatocyte stage take place outside of the BTB in the basal compartment of the epithelium. However, the BTB is not a static ultrastructure. Instead, it undergoes extensive restructuring during the seminiferous epithelial cycle of spermatogenesis at stage VIII to allow the transit of preleptotene spermatocytes at the BTB. Yet the immunological barrier conferred by the BTB cannot be compromised, even transiently, during the epithelial cycle to avoid the production of antibodies against meiotic and postmeiotic germ cells. Studies have demonstrated that some unlikely partners, namely adhesion protein complexes (e.g., occludin-ZO-1, N-cadherin-β-catenin, claudin-5-ZO-1), steroids (e.g., testosterone, estradiol-17β), nonreceptor protein kinases (e.g., focal adhesion kinase, c-Src, c-Yes), polarity proteins (e.g., PAR6, Cdc42, 14-3-3), endocytic vesicle proteins (e.g., clathrin, caveolin, dynamin 2), and actin regulatory proteins (e.g., Eps8, Arp2/3 complex), are working together, apparently under the overall influence of cytokines (e.g., transforming growth factor-β3, tumor necrosis factor-α, interleukin-1α). In short, a “new” BTB is created behind spermatocytes in transit while the “old” BTB above transiting cells undergoes timely degeneration, so that the immunological barrier can be maintained while spermatocytes are traversing the BTB. We also discuss recent findings regarding the molecular mechanisms by which environmental toxicants (e.g., cadmium, bisphenol A) induce testicular injury via their initial actions at the BTB to

  4. Developmentally distinct in vivo effects of FSH on proliferation and apoptosis during testis maturation.

    PubMed

    Meachem, Sarah J; Ruwanpura, Saleela M; Ziolkowski, Jessica; Ague, Jacquelyn M; Skinner, Michael K; Loveland, Kate L

    2005-09-01

    The critical influence of follicle stimulating hormone (FSH) on male fertility relates both to its impact on Sertoli cell proliferation in perinatal life and to its influence on the synthesis of Sertoli cell-derived products essential for germ cell survival and function in the developing adult testis. The nature and timing of this shift of germ cells to their reliance on specific Sertoli cell-derived products are not defined. Based on existing data, it is apparent that the dominant function of FSH shifts between 9 and 18 day postpartum (dpp) during the first wave of spermatogenesis from driving Sertoli cell proliferation to support germ cells. To enable comprehensive analysis of the impact of acute in vivo FSH suppression on Sertoli and germ cell development, FSH was selectively suppressed in Sprague-Dawley rats by passive immunisation for 2 days and/or 4 days prior to testis collection at 3, 9 and 18 dpp. The 3 dpp samples displayed no measurable changes, while 4 days of FSH suppression decreased Sertoli cell proliferation and numbers in 9 dpp, but not 18 dpp, animals. In contrast, germ cell numbers were unaffected at 9 dpp but decreased at 18 dpp following FSH suppression, with a corresponding increase in germ cell apoptosis measured at 18 dpp. Sixty transcripts were measured as changed at 18 dpp in response to 4 days of FSH suppression, as assessed using Affymetrix microarrays. Some of these are known as Sertoli cell-derived FSH-responsive genes (e.g. StAR, cathepsin L, insulin-like growth factor binding protein-3), while others encode proteins involved in cell cycle and survival regulation (e.g. cyclin D1, scavenger receptor class B 1). These data demonstrate that FSH differentially affects Sertoli and germ cells in an age-dependent manner in vivo, promoting Sertoli cell mitosis at day 9, and supporting germ cell viability at day 18. This model has enabled identification of candidate genes that contribute to the FSH-mediated pathway by which Sertoli cells

  5. Dual functions in response to heat stress and spermatogenesis: characterization of expression profile of small heat shock proteins 9 and 10 in goat testis.

    PubMed

    Xun, Wenjuan; Shi, Liguang; Cao, Ting; Zhao, Chunping; Yu, Ping; Wang, Dingfa; Hou, Guanyu; Zhou, Hanlin

    2015-01-01

    Small heat shock proteins 9 and 10 (HSPB9 and HSPB10) are two testis-specific expressed sHsps. The objective of this study was to investigate the mRNA expression profile of HSPB9 and HSPB10 in goat testis among the different seasons, ages, and environmental temperatures. Allocation of the two sHsps was also performed by immunohistochemistry. The results showed that the transcript levels of HSPB9 and HSPB10 were extremely high in the testis (P < 0.01). The relative expression of HSBP9 and HSPB10 in testis showed a tendency to increase with age and then is maintained at the constant level after sexual maturity. HSPB9 and HSPB10 have significantly higher expression in the breeding season  (P < 0.05) and hot season (P < 0.01). Both HSPB9 and HSPB10 were found to be upregulated by high-temperature stress in testis (P < 0.05), and the expressions of Hsp70 and Hsp90 were also increased simultaneously (P < 0.01). Immunohistochemistry analysis localized HSPB9 expressed in spermatogonia, spermatocytes, and round spermatids and HSPB10 expressed in the elongate spermatids. In epididymis, strongly staining signal of HSPB10 was detected in pseudostratified columnar epithelium. In conclusion, the two testis-specific sHsps are closely related to male reproduction and heat tolerance. The results could provide valuable data for the further studies on HSPB9 and HSPB10.

  6. Claudin 11 inter-sertoli tight junctions in the testis of the korean soft-shelled turtle (Pelodiscus maackii).

    PubMed

    Park, Chan Jin; Ha, Cheol Min; Lee, Jae Eun; Gye, Myung Chan

    2015-04-01

    Expression of claudin 11 (CLDN11), a tight junction (TJ) protein, was examined in the Korean soft-shelled turtle (Pelodiscus maackii) testis. Spermatogenesis began during the breeding season and peaked at the end of the breeding season. Spermiation started in summer and peaked in autumn. The deduced amino acid sequence of P. maackii CLDN11 was similar to those of avian and mammalian species. During the nonbreeding season when spermatogenesis and testosterone production were active, testicular Cldn11 levels were high. In the seminiferous epithelium, strong, wavy CLDN11 strands parallel to the basement membrane delaminate the spermatogonia, and early spermatocytes are in the open compartment. Otherwise, CLDN11 was found beneath the early spermatocytes and in the Sertoli cell cytoplasm. Punctate zonula occludens 1 (ZO-1) immunoreactivity was found within the CLDN11 strands parallel to the basement membrane or at the outermost periphery of the seminiferous epithelium close to the basal lamina. During the breeding season, when circulating testosterone levels and spermatogenic activity was low, testicular CLDN11 level was lower than those during the nonbreeding season. CLDN11 was found at apicolateral contact sites between adjacent Sertoli cells devoid of the postmeiotic germ cells. At this time, lanthanum tracer diffused to the adluminal compartment of seminiferous epithelium. In cultured testis tissues, testosterone propionate significantly increased the level of Cldn11 mRNA. In P. maackii testis, CLDN11 participates in the development of the blood-testis barrier (BTB), where the CLDN11 expression was coupled with spermatogenic activity and circulating androgen levels, indicating the conserved nature of TJs expressing CLDN11 at the BTB in amniotes.

  7. Fascin 1 is an actin filament-bundling protein that regulates ectoplasmic specialization dynamics in the rat testis.

    PubMed

    Gungor-Ordueri, N Ece; Celik-Ozenci, Ciler; Cheng, C Yan

    2014-11-01

    In the testis, spermatids are polarized cells, with their heads pointing toward the basement membrane during maturation. This polarity is crucial to pack the maximal number of spermatids in the seminiferous epithelium so that millions of sperms can be produced daily. A loss of spermatid polarity is detected after rodents are exposed to toxicants (e.g., cadmium) or nonhormonal male contraceptives (e.g., adjudin), which is associated with a disruption on the expression and/or localization of polarity proteins. In the rat testis, fascin 1, an actin-bundling protein found in mammalian cells, was expressed by Sertoli and germ cells. Fascin 1 was a component of the ectoplasmic specialization (ES), a testis-specific anchoring junction known to confer spermatid adhesion and polarity. Its expression in the seminiferous epithelium was stage specific. Fascin 1 was localized to the basal ES at the Sertoli cell-cell interface of the blood-testis barrier in all stages of the epithelial cycle, except it diminished considerably at late stage VIII. Fascin 1 was highly expressed at the apical ES at stage VII-early stage VIII and restricted to the step 19 spermatids. Its knockdown by RNAi that silenced fascin 1 by ~70% in Sertoli cells cultured in vitro was found to perturb the tight junction-permeability barrier via a disruption of F-actin organization. Knockdown of fascin 1 in vivo by ~60-70% induced defects in spermatid polarity, which was mediated by a mislocalization and/or downregulation of actin-bundling proteins Eps8 and palladin, thereby impeding F-actin organization and disrupting spermatid polarity. In summary, these findings provide insightful information on spermatid polarity regulation.

  8. Characterization of the annual regulation of reproductive and immune parameters on the testis of European sea bass.

    PubMed

    Valero, Yulema; Sánchez-Hernández, Miriam; García-Alcázar, Alicia; García-Ayala, Alfonsa; Cuesta, Alberto; Chaves-Pozo, Elena

    2015-10-01

    The European sea bass, Dicentrarchus labrax L., is a seasonal gonochoristic species, the males of which are generally mature during their second year of life. It has been demonstrated that cytokines and immune cells play a key role in the testicular development. This reproductive-immune interaction might be very important in the sea bass since several pathogens are able to colonise the gonad and persist in this tissue, altering further reproductive functions and spreading disease. This study aims to investigate the reproductive cycle of 1-year European sea bass males by analysing cell proliferation and apoptosis and the expression profile of some reproductive and immune-related genes in the testis, as well as the serum sex steroid levels. Our data demonstrate that, in 1-year-old European sea bass males, the testis undergoes the spermatogenesis process and that the reproductive and immune parameters analysed varied during the reproductive cycle. In the testis, the highest proliferative rates were recorded at the spermatogenesis stage, while the highest apoptotic rates were recorded at the spawning stage. We have also analysed, for the first time in European sea bass males, the serum levels of 17β-estradiol (E2) and dihydrotestosterone and the gene expression profile of the enzymes implied in their production, determining that at least E2 might be involved in the regulation of the reproductive cycle. Some immune relevant genes, including cytokines, lymphocyte receptors, and anti-viral and anti-bacterial molecules were detected in the testis of naïve European sea bass specimens, and their expression profile was related to the stages of the reproductive cycle, suggesting an important role for the defence of the reproductive tissues.

  9. Sertoli cells in the testis of caecilians, Ichthyophis tricolor and Uraeotyphlus cf. narayani (Amphibia: Gymnophiona): light and electron microscopic perspective.

    PubMed

    Smita, Mathew; Oommen, Oommen V; George, Jancy M; Akbarsha, M A

    2003-12-01

    The caecilians have evolved a unique pattern of cystic spermatogenesis in which cysts representing different stages in spermatogenesis coexist in a testis lobule. We examined unsettled issues relating to the organization of the caecilian testis lobules, including the occurrence of a fatty matrix, the possibility of both peripheral and central Sertoli cells, the origin of Sertoli cells from follicular cells, and the disengagement of older Sertoli cells to become loose central Sertoli cells. We subjected the testis of Ichthyophis tricolor (Ichthyophiidae) and Uraeotyphlus cf. narayani (Uraeotyphliidae) from the Western Ghats of Kerala, India, to light and transmission electron microscopic studies. Irrespective of the functional state of the testis, whether active or regressed, Sertoli cells constitute a permanent feature of the lobules. The tall Sertoli cells adherent to the basal lamina with basally located pleomorphic nuclei extend deeper into the lobule to meet at the core. There they provide for association of germ cells at different stages of differentiation, an aspect that has earlier been misconceived as the fatty matrix. Germ cells up to the 4-cell stage remain in the intercalating region of the Sertoli cells and they are located at the apices of the Sertoli cells from the 8-cell stage onwards. The developing germ cells are intimately associated with the Sertoli cell adherent to the basal lamina until spermiation. There are ameboid cells in the core of the lobules that appear to interact with the germ cells at the face opposite to their attachment with the Sertoli cells. Adherence of the Sertoli cells to the basal lamina is a permanent feature of the caecilian testicular lobules. The ameboid cells in the core are neither Sertoli cells nor their degeneration products.

  10. Fascin 1 is an actin filament-bundling protein that regulates ectoplasmic specialization dynamics in the rat testis

    PubMed Central

    Gungor-Ordueri, N. Ece; Celik-Ozenci, Ciler

    2014-01-01

    In the testis, spermatids are polarized cells, with their heads pointing toward the basement membrane during maturation. This polarity is crucial to pack the maximal number of spermatids in the seminiferous epithelium so that millions of sperms can be produced daily. A loss of spermatid polarity is detected after rodents are exposed to toxicants (e.g., cadmium) or nonhormonal male contraceptives (e.g., adjudin), which is associated with a disruption on the expression and/or localization of polarity proteins. In the rat testis, fascin 1, an actin-bundling protein found in mammalian cells, was expressed by Sertoli and germ cells. Fascin 1 was a component of the ectoplasmic specialization (ES), a testis-specific anchoring junction known to confer spermatid adhesion and polarity. Its expression in the seminiferous epithelium was stage specific. Fascin 1 was localized to the basal ES at the Sertoli cell-cell interface of the blood-testis barrier in all stages of the epithelial cycle, except it diminished considerably at late stage VIII. Fascin 1 was highly expressed at the apical ES at stage VII–early stage VIII and restricted to the step 19 spermatids. Its knockdown by RNAi that silenced fascin 1 by ∼70% in Sertoli cells cultured in vitro was found to perturb the tight junction-permeability barrier via a disruption of F-actin organization. Knockdown of fascin 1 in vivo by ∼60–70% induced defects in spermatid polarity, which was mediated by a mislocalization and/or downregulation of actin-bundling proteins Eps8 and palladin, thereby impeding F-actin organization and disrupting spermatid polarity. In summary, these findings provide insightful information on spermatid polarity regulation. PMID:25159326

  11. Benzo(a)pyrene induces similar gene expression changes in testis of DNA repair proficient and deficient mice

    PubMed Central

    2010-01-01

    Background Benzo [a]pyrene (B[a]P) exposure induces DNA adducts at all stages of spermatogenesis and in testis, and removal of these lesions is less efficient in nucleotide excision repair deficient Xpc-/- mice than in wild type mice. In this study, we investigated by using microarray technology whether compromised DNA repair in Xpc-/- mice may lead to a transcriptional reaction of the testis to cope with increased levels of B[a]P induced DNA damage. Results Two-Way ANOVA revealed only 4 genes differentially expressed between wild type and Xpc-/- mice, and 984 genes between testes of B[a]P treated and untreated mice irrespective of the mouse genotype. However, the level in which these B[a]P regulated genes are expressed differs between Wt and Xpc-/- mice (p = 0.000000141), and were predominantly involved in the regulation of cell cycle, translation, chromatin structure and spermatogenesis, indicating a general stress response. In addition, analysis of cell cycle phase dependent gene expression revealed that expression of genes involved in G1-S and G2-M phase arrest was increased after B[a]P exposure in both genotypes. A slightly higher induction of average gene expression was observed at the G2-M checkpoint in Xpc-/- mice, but this did not reach statistical significance (P = 0.086). Other processes that were expected to have changed by exposure, like apoptosis and DNA repair, were not found to be modulated at the level of gene expression. Conclusion Gene expression in testis of untreated Xpc-/- and wild type mice were very similar, with only 4 genes differentially expressed. Exposure to benzo(a)pyrene affected the expression of genes that are involved in cell cycle regulation in both genotypes, indicating that the presence of unrepaired DNA damage in testis blocks cell proliferation to protect DNA integrity in both DNA repair proficient and deficient animals. PMID:20504355

  12. Pro-opiomelanocortin-derived peptides in the testis: evidence for a possible role in Leydig and Sertoli cell function.

    PubMed

    Boitani, C; Chen, C L; Margioris, A N; Gerendai, I; Morris, P L; Bardin, C W

    1986-01-01

    Pro-opiomelanocortin (POMC)-derived peptides such as beta-endorphin, ACTH, and MSHs were identified in the testis where they were exclusively localized in Leydig cells. Examination of testicular extracts by a variety of physicochemical and immunological techniques indicates that the processing of the POMC in the testis is very similar to that in the brain. By using a cDNA probe, the POMC-like mRNA present in total testis and cultured Leydig cells was 150-200 bases shorter than that in the hypothalamus and pituitary. In addition, POMC mRNA was localized to Leydig cells using in situ hybridization. The expression of the POMC-like gene and the accumulation of POMC-derived peptides in Leydig cell were shown to be under the control of gonadotropin. As the testis contains low concentrations of POMC-derived peptides, we suggested that they may be implicated in local regulatory events within this organ. This postulate was supported by results from in vivo and in vitro experiments suggesting that different portions of the POMC-molecule may have opposite effects on Sertoli cell functions. For example, MSHs increased cAMP accumulation and aromatase activity in these cells, while opioids inhibited Sertoli cell proliferation and androgen binding protein (ABP) secretion. Furthermore, following intratesticular administration of opiate antagonists, testosterone production was reduced, suggesting that Leydig cell function may be also modulated by beta-endorphin and/or other related peptides. Taken together, these studies support the hypothesis of a possible role of POMC-derived peptides in testicular function. PMID:2939305

  13. Six mouse alpha-tubulin mRNAs encode five distinct isotypes: testis-specific expression of two sister genes.

    PubMed Central

    Villasante, A; Wang, D; Dobner, P; Dolph, P; Lewis, S A; Cowan, N J

    1986-01-01

    Five mouse alpha-tubulin isotypes are described, each distinguished by the presence of unique amino acid substitutions within the coding region. Most, though not all of these isotype-specific amino acids, are clustered at the carboxy terminus. One of the alpha-tubulin isotypes described is expressed exclusively in testis and is encoded by two closely related genes (M alpha 3 and M alpha 7) which have homologous 3' untranslated regions but which differ at multiple third codon positions and in their 5' untranslated regions. We show that a subfamily of alpha-tubulin genes encoding the same testis-specific isotype also exists in humans. Thus, we conclude that the duplication event leading to a pair of genes encoding a testis-specific alpha-tubulin isotype predated the mammalian radiation, and both members of the duplicated sequence have been maintained since species divergence. A second alpha-tubulin gene, M alpha 6, is expressed ubiquitously at a low level, whereas a third gene, M alpha 4, is unique in that it does not encode a carboxy-terminal tyrosine residue. This gene yields two transcripts: a 1.8-kilobase (kb) mRNA that is abundant in muscle and a 2.4-kb mRNA that is abundant in testis. Whereas the 1.8-kb mRNA encodes a distinct alpha-tubulin isotype, the 2.4-kb mRNA is defective in that the methionine residue required for translational initiation is missing. Patterns of developmental expression of the various alpha-tubulin isotypes are presented. Our data support the view that individual tubulin isotypes are capable of conferring functional specificity on different kinds of microtubules. Images PMID:3785200

  14. Sertoli cells in the testis of caecilians, Ichthyophis tricolor and Uraeotyphlus cf. narayani (Amphibia: Gymnophiona): light and electron microscopic perspective.

    PubMed

    Smita, Mathew; Oommen, Oommen V; George, Jancy M; Akbarsha, M A

    2003-12-01

    The caecilians have evolved a unique pattern of cystic spermatogenesis in which cysts representing different stages in spermatogenesis coexist in a testis lobule. We examined unsettled issues relating to the organization of the caecilian testis lobules, including the occurrence of a fatty matrix, the possibility of both peripheral and central Sertoli cells, the origin of Sertoli cells from follicular cells, and the disengagement of older Sertoli cells to become loose central Sertoli cells. We subjected the testis of Ichthyophis tricolor (Ichthyophiidae) and Uraeotyphlus cf. narayani (Uraeotyphliidae) from the Western Ghats of Kerala, India, to light and transmission electron microscopic studies. Irrespective of the functional state of the testis, whether active or regressed, Sertoli cells constitute a permanent feature of the lobules. The tall Sertoli cells adherent to the basal lamina with basally located pleomorphic nuclei extend deeper into the lobule to meet at the core. There they provide for association of germ cells at different stages of differentiation, an aspect that has earlier been misconceived as the fatty matrix. Germ cells up to the 4-cell stage remain in the intercalating region of the Sertoli cells and they are located at the apices of the Sertoli cells from the 8-cell stage onwards. The developing germ cells are intimately associated with the Sertoli cell adherent to the basal lamina until spermiation. There are ameboid cells in the core of the lobules that appear to interact with the germ cells at the face opposite to their attachment with the Sertoli cells. Adherence of the Sertoli cells to the basal lamina is a permanent feature of the caecilian testicular lobules. The ameboid cells in the core are neither Sertoli cells nor their degeneration products. PMID:14584033

  15. Morphological evidence for a permeability barrier in the testis and spermatic duct of Gymnotus carapo (Teleostei: Gymnotidae).

    PubMed

    Meneguelli De Souza, Lara C; Retamal, Claudio A; Rocha, Gustavo M; Lopez, Maria Luisa

    2015-09-01

    Cell-cell interactions play essential roles in the regulation of gametogenesis. The involvement of junctional complexes in permeability barriers, for example, provides structural and physiological support for male germ-cell development. This study describes morphological characteristics of the reproductive system of Gymnotus carapo, a neo-tropical freshwater fish widely distributed in South and Central America, focusing on the detection of permeability barriers using morphological and biochemical approaches. Ultrastructural analysis of testes treated with the lanthanum nitrate exclusion technique showed that the tracer penetrated the interstitial compartment of the testis, surrounding and appearing within cysts containing spermatogonia and spermatocytes in early stages of meiosis, but was not detected in the spermatid cysts or inside the lumen of spermatogenic tubules. These results suggest the presence of a permeability barrier that is stabilized after meiosis is completed and serves to protect the haploid cells from the vascular system. In the spermatic-duct region, the tracer was obstructed near the lumen of the duct. Junctional complexes and focal tight junctions between adjacent cells were observed in the testis and spermatic duct. Freeze-fracture methods indeed confirmed the presence of tight junctions, which were visualized as parallel rows of individual particles between adjacent cells. More evidence supporting the existence of a permeability barrier was gathered from differences observed in the electrophoretic protein profiles of testis and spermatic-duct fluids compared to blood plasma. Together, these observations demonstrate the existence of a permeability barrier formed by tight junctions in the testis and spermatic duct of G. carapo. PMID:26073744

  16. Germ cell differentiation and proliferation in the developing testis of the South American plains viscacha, Lagostomus maximus (Mammalia, Rodentia).

    PubMed

    Gonzalez, C R; Muscarsel Isla, M L; Fraunhoffer, N A; Leopardo, N P; Vitullo, A D

    2012-08-01

    Cell proliferation and cell death are essential processes in the physiology of the developing testis that strongly influence the normal adult spermatogenesis. We analysed in this study the morphometry, the expression of the proliferation cell nuclear antigen (PCNA), cell pluripotency marker OCT-4, germ cell marker VASA and apoptosis in the developing testes of Lagostomus maximus, a rodent in which female germ line develops through abolished apoptosis and unrestricted proliferation. Morphometry revealed an increment in the size of the seminiferous cords with increasing developmental age, arising from a significant increase of PCNA-positive germ cells and a stable proportion of PCNA-positive Sertoli cells. VASA showed a widespread cytoplasmic distribution in a great proportion of proliferating gonocytes that increased significantly at late development. In the somatic compartment, Leydig cells increased at mid-development, whereas peritubular cells showed a stable rate of proliferation. In contrast to other mammals, OCT-4 positive gonocytes increased throughout development reaching 90% of germ cells in late-developing testis, associated with a conspicuous increase in circulating FSH from mid- to late-gestation. TUNEL analysis was remarkable negative, and only a few positive cells were detected in the somatic compartment. These results show that the South American plains viscacha displays a distinctive pattern of testis development characterized by a sustained proliferation of germ cells throughout development, with no signs of apoptosis cell demise, in a peculiar endocrine in utero ambiance that seems to promote the increase of spermatogonial number as a primary direct effect of FSH.

  17. Postnatal development of the testis in the rat: morphologic study and correlation of morphology to neuroendocrine parameters.

    PubMed

    Picut, Catherine A; Remick, Amera K; de Rijk, Eveline P C T; Simons, Michelle L; Stump, Donald G; Parker, George A

    2015-04-01

    Histopathologic examination of the testis from juvenile rats is often necessary to characterize the safety of new drugs for pediatric use and is a required end point in male pubertal development and thyroid function assays. To aid in evaluation and interpretation of the immature testis, the characteristic histologic features of the developing rat testis throughout postnatal development are described and correlated with published neuroendocrine parameter changes. During the neonatal period (postnatal day [PND] 3-7), seminiferous tubules contained gonocytes and mitotically active immature Sertoli cells. Profound proliferation of spermatogonia and continued Sertoli cell proliferation occurred in the early infantile period (PND 8-14). The spermatogonia reached maximum density forming double-layered rosettes with Sertoli cells in the late infantile period (PND 15-20). Leptotene/zygotene spermatocytes appeared centrally as tubular lumina developed, and individual tubules segregated into stages. The juvenile period (PND 21-32) featured a dramatic increase in number and size of pachytene spermatocytes with the formation of round spermatids and loss of "infantile" rosette architecture. In the peri-pubertal period (PND 32-55), stage VII tubules containing step 19 spermatids were visible by PND 46. The presented baseline morphologic and endocrinologic information will help pathologists distinguish delayed development from xenobiotic effects, determine pathogenesis when confronted with nonspecific findings, and identify sensitive time points for targeted study design.

  18. Correlation of meiotic events in testis sections and microspreads of mouse spermatocytes relative to the mid-pachytene checkpoint.

    PubMed

    Ashley, Terry; Gaeth, Ann P; Creemers, Laura B; Hack, Adelle M; de Rooij, Dirk G

    2004-09-01

    In mouse, asynaptic meiotic mutants arrest at Testis Epithelial Stage IV. This arrest is 4.5 days after homologous chromosomes begin to synapse and approximately 2.5 days after synapsis is usually completed. To correlate cytological events with meiotic progression in testis and to determine which meiotic events are normally completed by Stage IV, we induced spermatogenic arrest by placing mice on a vitamin A deficient diet. Subsequent injection of retinoic acid and a return to a normal diet resulted in resumption of spermatogenesis with all spermatocytes proceeding through meiosis in a highly synchronous cohort. Between Days 11 and 16 post-injection we prepared one testis for immunocytological and the other for histological evaluation, then used antibodies to SCP3 and either RPA, or MLH1 to follow quantitative changes in synapsis and recombination. RPA was found at sites along the synaptonemal complex as soon as homologs synapsed, and most, but not all, RPA disappeared by Stage IV. MLH1 foci appeared between Stage II and IV and remained through Stage VII, the end point of the study. The data suggest that the earliest the mid-pachytene checkpoint can be activated is Epithelial Stage IV, but that activities monitored by the checkpoint may not be completed by this time.

  19. Isolation, identification and enrichment of type a spermatogonia from the testis of chinese cross-bred buffaloes (swamp × river).

    PubMed

    Ahmad, S; Xiao, Y; Han, L; Hua, H; Riaz, H; Liang, A; Yang, L-G

    2013-06-01

    The proportion of type A spermatogonia in the isolated testis cells is a prerequisite for conducting experiments and the manipulation of these germ cells. Thus, this study was designed to examine the wide range of strategies for the isolation, identification and enrichment of type A spermatogonia in pre-pubertal buffalo calves (3-6 months). Histological findings revealed the presence of maximum number of type A spermatogonia at 5 months, which was further confirmed by DBA immunohistochemistry. In a newly modified strategy for the isolation of testis tissues, mincing followed by trituration and two rounds of digestion with collagenase, hyaluronidase and DNase yielded more than 95% testis cell population. Differential plating with laminin, poly-l-lysine and gelatin significantly (p < 0.05) affected the purity of type A spermatogonia. Among these extracellular matrix (ECMs) molecules, laminin and gelatin performed well and reached at a purity of 39.38 ± 1.21% and 32.15 ± 1.60%, respectively. In addition, combination of laminin and gelatin followed by Percoll centrifugation performed the best and yielded >90% type A spermatogonial purity. Moreover, viability of the cells was not affected (p > 0.05) irrespective of different enrichment methods. In conclusion, type A spermatogonia isolation and enrichment system was developed using different ECM molecules in buffaloes, which will aid in solving wide range of problems especially fertility-related problems and transgenic animal production in buffaloes.

  20. Effects of Common Fig (Ficus carica) Leaf Extracts on Sperm Parameters and Testis of Mice Intoxicated with Formaldehyde.

    PubMed

    Naghdi, Majid; Maghbool, Maryam; Seifalah-Zade, Morteza; Mahaldashtian, Maryam; Makoolati, Zohreh; Kouhpayeh, Seyed Amin; Ghasemi, Afsaneh; Fereydouni, Narges

    2016-01-01

    Formaldehyde (FA) is the leading cause of cellular injury and oxidative damage in testis that is one of the main infertility causes. There has been an increasing evidence of herbal remedies use in male infertility treatment. This assay examines the role of Ficus carica (Fc) leaf extracts in sperm parameters and testis of mice intoxicated with FA. Twenty-five adult male mice were randomly divided into control; sham; FA-treated (10 mg/kg twice per day); Fc-treated (200 mg/kg); and FA + Fc-treated groups. Cauda epididymal spermatozoa were analyzed for viability, count, and motility. Testes were weighed and gonadosomatic index (GSI) was calculated. Also, histoarchitecture of seminiferous tubules was assessed in the Haematoxylin and Eosin stained paraffin sections. The findings showed that FA significantly decreased GSI and increased percentage of immotile sperm compared with control group. Disorganized and vacuolated seminiferous epithelium, spermatogenic arrest, and lumen filled with immature germ cells were also observed in the testes. However, Fc leaf extracts improved sperm count, nonprogressive motility of spermatozoa, and GSI in FA-treated testes. Moreover, seminiferous tubule with spermatogenic arrest was rarely seen, indicating that Fc has the positive effects on testis and epididymal sperm parameters exposed with FA. PMID:26904140

  1. TCTEX1D4 Interactome in Human Testis: Unraveling the Function of Dynein Light Chain in Spermatozoa

    PubMed Central

    Freitas, Maria João; Korrodi-Gregório, Luís; Morais-Santos, Filipa; da Cruz e Silva, Edgar

    2014-01-01

    Abstract Studies were designed to identify the TCTEX1D4 interactome in human testis, with the purpose of unraveling putative protein complexes essential to male reproduction and thus novel TCTEX1D4 functions. TCTEX1D4 is a dynein light chain that belongs to the DYNT1/TCTEX1 family. In spermatozoa, it appears to be important to sperm motility, intraflagellar transport, and acrosome reaction. To contribute to the knowledge on TCTEX1D4 function in testis and spermatozoa, a yeast two-hybrid assay was performed in testis, which allowed the identification of 40 novel TCTEX1D4 interactors. Curiously, another dynein light chain, TCTEX1D2, was identified and its existence demonstrated for the first time in human spermatozoa. Immunofluorescence studies proved that TCTEX1D2 is an intra-acrosomal protein also present in the midpiece, suggesting a role in cargo movement in human spermatozoa. Further, an in silico profile of TCTEX1D4 revealed that most TCTEX1D4 interacting proteins were not previously characterized and the ones described present a very broad nature. This reinforces TCTEX1D4 as a dynein light chain that is capable of interacting with a variety of functionally different proteins. These observations collectively contribute to a deeper molecular understanding of the human spermatozoa function. PMID:24606217

  2. The testis and ovary transcriptomes of the rock bream (Oplegnathus fasciatus): A bony fish with a unique neo Y chromosome.

    PubMed

    Xu, Dongdong; Shen, Kang-Ning; Fan, Zhaofei; Huang, Wei; You, Feng; Lou, Bao; Hsiao, Chung-Der

    2016-03-01

    The rock bream (Oplegnathus fasciatus) is considerably one of the most economically important marine fish in East Asia and has a unique neo-Y chromosome system that is a good model to study the sex determination and differentiation in fish. In the present study, we used Illumina sequencing technology (HiSeq2000) to sequence, assemble and annotate the transcriptome of the testis and ovary tissues of rock bream. A total of 40,004,378 (NCBI SRA database SRX1406649) and 53,108,992 (NCBI SRA database SRX1406648) high quality reads were obtained from testis and ovary RNA sequencing, respectively, and 60,421 contigs (with average length of 1301 bp) were obtained after de novo assembling with Trinity software. Digital gene expression analysis reveals 14,036 contigs that show gender-enriched expressional profile with either testis-enriched (237 contigs) or ovary-enriched (581 contigs) with RPKM > 100. There are 237 male- and 582 female-abundant expressed genes that show sex dimorphic expression. We hope that the gonad transcriptome and those gender-enriched transcripts of rock bream can provide some insight into the understanding of genome-wide transcriptome profile of teleost gonad tissue and give useful information in fish gonad development. PMID:26981410

  3. Effects of Common Fig (Ficus carica) Leaf Extracts on Sperm Parameters and Testis of Mice Intoxicated with Formaldehyde

    PubMed Central

    Naghdi, Majid; Maghbool, Maryam; Seifalah-Zade, Morteza; Mahaldashtian, Maryam; Makoolati, Zohreh; Kouhpayeh, Seyed Amin; Ghasemi, Afsaneh; Fereydouni, Narges

    2016-01-01

    Formaldehyde (FA) is the leading cause of cellular injury and oxidative damage in testis that is one of the main infertility causes. There has been an increasing evidence of herbal remedies use in male infertility treatment. This assay examines the role of Ficus carica (Fc) leaf extracts in sperm parameters and testis of mice intoxicated with FA. Twenty-five adult male mice were randomly divided into control; sham; FA-treated (10 mg/kg twice per day); Fc-treated (200 mg/kg); and FA + Fc-treated groups. Cauda epididymal spermatozoa were analyzed for viability, count, and motility. Testes were weighed and gonadosomatic index (GSI) was calculated. Also, histoarchitecture of seminiferous tubules was assessed in the Haematoxylin and Eosin stained paraffin sections. The findings showed that FA significantly decreased GSI and increased percentage of immotile sperm compared with control group. Disorganized and vacuolated seminiferous epithelium, spermatogenic arrest, and lumen filled with immature germ cells were also observed in the testes. However, Fc leaf extracts improved sperm count, nonprogressive motility of spermatozoa, and GSI in FA-treated testes. Moreover, seminiferous tubule with spermatogenic arrest was rarely seen, indicating that Fc has the positive effects on testis and epididymal sperm parameters exposed with FA. PMID:26904140

  4. Cancer/Testis OIP5 and TAF7L Genes are Up-Regulated in Breast Cancer.

    PubMed

    Mobasheri, Maryam Beigom; Shirkoohi, Reza; Modarressi, Mohammad Hossein

    2015-01-01

    Breast cancer still remains as the most frequent cancer with second mortality rate in women worldwide. There are no validated biomarkers for detection of the disease in early stages with effective power in diagnosis and therapeutic approaches. Cancer/testis antigens are recently promising tumor antigens and suitable candidates for targeted therapies and generating cancer vaccines. We conducted the present study to analyze transcript changes of two cancer/testis antigens, OIP5 and TAF7L, in breast tumors and cell lines in comparison with normal breast tissues by quantitative real time RT-PCR for the first time. Significant over-expression of OIP5 was observed in breast tumors and three out of six cell lines including MDA-MB-468, T47D and SKBR3. Not significant expression of TAF7L was evident in breast tumors but significant increase was noted in three out of six cell lines including MDA-MB-231, BT474 and T47D. OIP5 has ssignificant role in chromatin organization and cell cycle control during cell cycle exit and normal chromosome segregation during mitosis and TAF7L is a component of the transcription factor ??D, which is involved in transcription initiation of most protein coding genes. TAF7Lis located at X chromosome and belongs to the CT-X gene family of cancer/testis antigens which contains about 50% of CT antigens, including those which have been used in cancer immunotherapy.

  5. TCTEX1D4 interactome in human testis: unraveling the function of dynein light chain in spermatozoa.

    PubMed

    Freitas, Maria João; Korrodi-Gregório, Luís; Morais-Santos, Filipa; Cruz e Silva, Edgar da; Fardilha, Margarida

    2014-04-01

    Studies were designed to identify the TCTEX1D4 interactome in human testis, with the purpose of unraveling putative protein complexes essential to male reproduction and thus novel TCTEX1D4 functions. TCTEX1D4 is a dynein light chain that belongs to the DYNT1/TCTEX1 family. In spermatozoa, it appears to be important to sperm motility, intraflagellar transport, and acrosome reaction. To contribute to the knowledge on TCTEX1D4 function in testis and spermatozoa, a yeast two-hybrid assay was performed in testis, which allowed the identification of 40 novel TCTEX1D4 interactors. Curiously, another dynein light chain, TCTEX1D2, was identified and its existence demonstrated for the first time in human spermatozoa. Immunofluorescence studies proved that TCTEX1D2 is an intra-acrosomal protein also present in the midpiece, suggesting a role in cargo movement in human spermatozoa. Further, an in silico profile of TCTEX1D4 revealed that most TCTEX1D4 interacting proteins were not previously characterized and the ones described present a very broad nature. This reinforces TCTEX1D4 as a dynein light chain that is capable of interacting with a variety of functionally different proteins. These observations collectively contribute to a deeper molecular understanding of the human spermatozoa function.

  6. Coordinate Regulation of Stem Cell Competition by Slit-Robo and JAK-STAT Signaling in the Drosophila Testis

    PubMed Central

    Stine, Rachel R.; Greenspan, Leah J.; Ramachandran, Kapil V.; Matunis, Erika L.

    2014-01-01

    Stem cells in tissues reside in and receive signals from local microenvironments called niches. Understanding how multiple signals within niches integrate to control stem cell function is challenging. The Drosophila testis stem cell niche consists of somatic hub cells that maintain both germline stem cells and somatic cyst stem cells (CySCs). Here, we show a role for the axon guidance pathway Slit-Roundabout (Robo) in the testis niche. The ligand Slit is expressed specifically in hub cells while its receptor, Roundabout 2 (Robo2), is required in CySCs in order for them to compete for occupancy in the niche. CySCs also require the Slit-Robo effector Abelson tyrosine kinase (Abl) to prevent over-adhesion of CySCs to the niche, and CySCs mutant for Abl outcompete wild type CySCs for niche occupancy. Both Robo2 and Abl phenotypes can be rescued through modulation of adherens junction components, suggesting that the two work together to balance CySC adhesion levels. Interestingly, expression of Robo2 requires JAK-STAT signaling, an important maintenance pathway for both germline and cyst stem cells in the testis. Our work indicates that Slit-Robo signaling affects stem cell function downstream of the JAK-STAT pathway by controlling the ability of stem cells to compete for occupancy in their niche. PMID:25375180

  7. Immunohistochemical detection of GnRH-like peptides in the neural ganglia and testis of Haliotis asinina.

    PubMed

    Nuurai, Parinyaporn; Primphon, Jeerawan; Seangcharoen, Tawanchay; Tinikul, Yotsawan; Wanichanon, Chaitip; Sobhon, Prasert

    2014-02-01

    Gonadotropin releasing hormone (GnRH) is a peptide that is conserved in both vertebrate and invertebrate species. In this study, we have demonstrated the distribution pattern of two isoforms of GnRH-like peptides in the neural ganglia and testis of reproductively mature male abalone, H. asinina, by immunohistochemistry and whole mount immunofluorescence. We found octopus (oct) GnRH and tunicate-I (t) GnRH-I immunoreactivities (ir) in type 1 neurosecretory cells (NS1) and they were expressed mostly within the ventral horn of the cerebral ganglion, whereas in pleuropedal ganglia they were localized primarily in the dorsal horn. Furthermore, tGnRH-I-ir were strongly detected in fibers at the caudal part of the cerebral ganglia and both ventral and dorsal horns of the pleuropedal ganglia. In the testis, only octGnRH-ir was found primarily in the granulated cell and central capillaries within the trabeculae. These results suggest that multiple GnRH-like peptides are present in the neural ganglia which could be the principal source of their production, whereas GnRH may also be synthesized locally in the testis and act as the paracrine control of testicular maturation.

  8. Expression patterns of taste receptor type 1 subunit 3 and α-gustducin in the mouse testis during development.

    PubMed

    Gong, Ting; Wei, Quanwei; Mao, Dagan; Shi, Fangxiong

    2016-01-01

    Taste receptor type 1 subunit 3 (T1R3) and its associated heterotrimeric G protein α-gustducin (Gα) are involved in sweet and umami sensing in taste cells. They are also strongly expressed in the testis and sperm, but their expression patterns and potential roles involved were previously unknown. In present study, we investigated the expression patterns of T1R3 and Gα in the mouse testis at critical stages of postnatal life, and throughout the spermatogenic cycle. Our results indicated that T1R3 and Gα exhibited a stage-dependent expression pattern during mouse development, and a cell-specific pattern during the spermatogenic cycle. Their expressions have been increased significantly from prepubertal to pubertal periods (P<005), and decreased significantly in aged mice (P<005). The changes were mainly attributed to the differential expression of T1R3 or Gα in elongated spermatids and Leydig cells at different stages of the spermatogenic cycle. In addition, the expression of T1R3 and Gα were first observed in residual bodies of spermatozoa and endothelial cells of blood vessels at post-pubertal mice, while Gα was located in apoptotic spermatogonia of postnatal mice. These novel expression patterns suggest a role of T1R3 and Gα in the onset of spermatogenesis, pace of spermatogenic cycle, and aging of the testis. PMID:26589384

  9. Identification, localization, and functional analysis of the homologues of mouse CABS1 protein in porcine testis.

    PubMed

    Shawki, Hossam H; Kigoshi, Takumi; Katoh, Yuki; Matsuda, Manabu; Ugboma, Chioma M; Takahashi, Satoru; Oishi, Hisashi; Kawashima, Akihiro

    2016-07-29

    Previously, we have identified a calcium-binding protein that is specifically expressed in spermatids and localized to the flagella of the mature sperm in mouse, so-called mCABS1. However, the physiological roles of CABS1 in the male reproductive system have not been fully elucidated yet. In the current study, we aimed to localize and clarify the role of CABS1 in porcine (pCABS1). We determined for the first time the full nucleotides sequence of pCABS1 mRNA. pCABS1 protein was detected on SDS-PAGE gel as two bands at 75 kDa and 70 kDa in adult porcine testis, whereas one band at 70 kDa in epididymal sperm. pCABS1 immunoreactivity in seminiferous tubules was detected in the elongated spermatids, and that in the epididymal sperm was found in the acrosome as well as flagellum. The immunoreactivity of pCABS1 in the acrosomai region disappeared during acrosome reaction. We also identified that pCABS1 has a transmembrane domain using computational prediction of the amino acids sequence. The treatment of porcine capacitated sperm with anti-pCABS1 antiserum significantly decreased acrosome reactions. These results suggest that pCABS1 plays an important role in controlling calcium ion signaling during the acrosome reaction. PMID:26960363

  10. Testis-Specific Bb8 Is Essential in the Development of Spermatid Mitochondria

    PubMed Central

    Vedelek, Viktor; Laurinyecz, Barbara; Kovács, Attila L.; Juhász, Gábor

    2016-01-01

    Mitochondria are essential organelles of developing spermatids in Drosophila, which undergo dramatic changes in size and shape after meiotic division, where mitochondria localized in the cytoplasm, migrate near the nucleus, aggregate, fuse and create the Nebenkern. During spermatid elongation the two similar mitochondrial derivatives of the Nebenkern start to elongate parallel to the axoneme. One of the elongated mitochondrial derivatives starts to lose volume and becomes the minor mitochondrial derivative, while the other one accumulates paracrystalline and becomes the major mitochondrial derivative. Proteins and intracellular environment that are responsible for cyst elongation and paracrystalline formation in the major mitochondrial derivative need to be identified. In this work we investigate the function of the testis specific big bubble 8 (bb8) gene during spermatogenesis. We show that a Minos element insertion in bb8 gene, a predicted glutamate dehydrogenase, causes recessive male sterility. We demonstrate bb8 mRNA enrichment in spermatids and the mitochondrial localisation of Bb8 protein during spermatogenesis. We report that megamitochondria develop in the homozygous mutant testes, in elongating spermatids. Ultrastructural analysis of the cross section of elongated spermatids shows enlarged mitochondria and the production of paracrystalline in both major and minor mitochondrial derivatives. Our results suggest that the Bb8 protein and presumably glutamate metabolism has a crucial role in the normal development and establishment of the identity of the mitochondrial derivatives during spermatid elongation. PMID:27529784

  11. Effects of estradiol and methoxychlor on Leydig cell regeneration in the adult rat testis.

    PubMed

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-05-06

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7-15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

  12. Effect of intratesticular administration of TRH or anti-TRH antiserum on function of rat testis.

    PubMed

    Gerendai, I; Sziebert, P; Görcs, T; Csaba, Z; Csernus, V

    2000-06-01

    The effect of intratesticular administration of thyrotropin-releasing hormone (TRH) and anti-TRH antiserum on steroidogenesis was studied in immature and adult rats. In 9-day-old animals local administration of the neuropeptide resulted in an increase in basal testosterone secretion in vitro. Similar treatment of 15-day-old rats suppressed hCG-stimulated testosterone secretion with no change in basal testosterone production. In both immature groups the treatment did not affect serum testosterone concentration. By contrast, in adults TRH decreased serum testosterone level, but did not influence basal and hCG-stimulated testosterone secretion. Both in immature and adult rats, the changes in steroidogenesis were evident 1 hour posttreatment. Five days after the administration of anti-TRH antiserum into the remaining testis of immature rats subjected to hemicastration just prior to the antiserum treatment, the alterations in steroidogenesis were opposite to those detected after treatment with TRH. In 9-day-old rats the antiserum suppressed steroidogenesis, while in 15-day-old animals it stimulated testosterone secretion. The results suggest that testicular TRH might exert a local action on testicular steroidogenesis, and the effect is age-dependent.

  13. The incidence and histological characteristics of intratubular germ cell neoplasia in postpubertal cryptorchid testis

    PubMed Central

    Ryang, Seung Hoon; Jung, Jae Hung; Eom, Minseob; Song, Jae Mann; Chung, Hyun Chul; Chae, Yunbyung; Lee, Chang Min

    2015-01-01

    Purpose It is well known that testicular germ cell tumors arise with increased frequency in patients with cryptorchidism. In addition, intratubular germ cell neoplasia (ITGCN) is a precursor lesion to testicular germ cell tumor. Approximately 50% of patients with ITGCN will develop an invasive of testicular germ cell tumors within 5 years. Therefore, we evaluated that the incidence of ITGCN in postpubertal cryptorchidism. Materials and Methods Between January 2002 and August 2012, orchiectomy specimens from 31 postpubertalpatients (aged 12 or over) with cryptorchid testis were reviewed. The specimens were evaluated for ITGCN using immunohistochemical stains of placental-like alkaline phosphatase and Oct 3/4 with routine hematoxylin-eosin stain. Additionally, the degree of spermatogenesis was assessed using the Johnsen score. Results Mean age was 34 years (range, 17 to 74 years) at surgery. All patients were diagnosed as unilateral cryptorchidism. One patient (3.2%) of 20-year-old had ITGCN in surgical specimen with all positive markers. Histological assessment of spermatogenesis showed that mean Johnsen score was 3.42 (range, 1 to 9). Majority of patients (27 of 31) presented impaired spermatogenesis with low Johnsen score lesser than 5. Conclusions Considering the risk of malignancy and low spermatogenesis, we should perform immunohistochemical stains and discuss preventative orchiectomy for the postpubertal cryptorchidism. PMID:26175870

  14. Cytokines produced by microwave-radiated Sertoli cells interfere with spermatogenesis in rat testis.

    PubMed

    Wu, H; Wang, D; Shu, Z; Zhou, H; Zuo, H; Wang, S; Li, Y; Xu, X; Li, N; Peng, R

    2012-05-01

    Microwave radiation resulted in degeneration, apoptosis or necrosis in germ cells at different stages. The molecular mechanisms by which microwaves induce spermatogenesis disorder have not been completely understood. Sertoli cells play crucial roles in mammalian spermatogenesis. Cytokines produced by Sertoli cells play pleiotropic roles in different conditions. At physiologically low concentration, TNFα, IL-1β and IL-6 behave as survival factors; while under pathological condition, these cytokines can induce apoptosis in testis. The effects of cytokines produced by microwave-radiated Sertoli cells on spermatogenesis are poorly understood. The purpose of this study was to determine the effect of cytokines produced by microwave-radiated Sertoli cells on the germ cells. We focused the effect of TNFα, IL-1β and IL-6 on the germ cells. The results showed that TNFα, IL-1β and IL-6 were increased in Sertoli cells after exposure to microwave radiation. These up-regulated cytokines can induce apoptosis and lipid peroxidation in the membrane of germ cells. In addition, germ cell apoptosis was associated with the up-regulation of Bax/Bcl-2 and caspase-3. These results suggest that cytokines produced by microwave-radiated Sertoli cells may disrupt spermatogenesis. Our data provided novel insight into the injury mechanism of germ cells induced by microwave radiation.

  15. Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

    PubMed Central

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-01-01

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms. PMID:24806340

  16. A survey of ovary-, testis-, and soma-biased gene expression in Drosophila melanogaster adults

    PubMed Central

    Parisi, Michael; Nuttall, Rachel; Edwards, Pamela; Minor, James; Naiman, Daniel; Lü, Jining; Doctolero, Michael; Vainer, Marina; Chan, Cathy; Malley, James; Eastman, Scott; Oliver, Brian

    2004-01-01

    Background Sexual dimorphism results in the formation of two types of individuals with specialized reproductive roles and is most evident in the germ cells and gonads. Results We have undertaken a global analysis of transcription between the sexes using a 31,464 element FlyGEM microarray to determine what fraction of the genome shows sex-biased expression, what tissues express these genes, the predicted functions of these genes, and where these genes map onto the genome. Females and males (both with and without gonads), dissected testis and ovary, females and males with genetically ablated germlines, and sex-transformed flies were sampled. Conclusions Using any of a number of criteria, we find extensive sex-biased expression in adults. The majority of cases of sex differential gene expression are attributable to the germ cells. There is also a large class of genes with soma-biased expression. There is little germline-biased expression indicating that nearly all genes with germline expression also show sex-bias. Monte Carlo simulations show that some genes with sex-biased expression are non-randomly distributed in the genome. PMID:15186491

  17. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model.

    PubMed

    van den Driesche, Sander; Macdonald, Joni; Anderson, Richard A; Johnston, Zoe C; Chetty, Tarini; Smith, Lee B; McKinnell, Chris; Dean, Afshan; Homer, Natalie Z; Jorgensen, Anne; Camacho-Moll, Maria E; Sharpe, Richard M; Mitchell, Rod T

    2015-05-20

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45% reduction; P = 0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; P = 0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after the final dose) in exposed host mice were substantially below those reported in humans after a therapeutic oral dose. Subsequent in utero exposure studies in rats indicated that the acetaminophen-induced reduction in testosterone likely results from reduced expression of key steroidogenic enzymes (Cyp11a1, Cyp17a1). Our results suggest that protracted use of acetaminophen (1 week) may suppress fetal testosterone production, which could have adverse consequences. Further studies are required to establish the dose-response and treatment-duration relationships to delineate the maximum dose and treatment period without this adverse effect.

  18. Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications

    PubMed Central

    Czerewaty, Michał; Deskur, Anna; Safranow, Krzysztof; Urasińska, Elżbieta; Starzyńska, Teresa

    2016-01-01

    Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly (p < 0.05) overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells. PMID:27635108

  19. Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate toxicity in rat testis.

    PubMed

    Sawada, Stefanie; Oberemm, Axel; Buhrke, Thorsten; Meckert, Christine; Rozycki, Christel; Braeuning, Albert; Lampen, Alfonso

    2015-09-01

    Thermal treatment of foodstuff containing fats and salt promotes the formation of 3-chloropropane-1,2-diol (3-MCPD) and its fatty acid esters. 3-MCPD-exposed rats develop testicular lesions and Leydig cell tumors. 3-MCPD and 3-MCPD ester toxicity is thought to be caused by 3-MCPD and its metabolites, since 3-MCPD esters are hydrolyzed in the gut. Inhibition of glycolysis is one of the few known molecular mechanisms of 3-MCPD toxicity. To obtain deeper insight into this process, a comparative proteomic approach was chosen, based on a 28-days repeated-dose feeding study with male Wistar rats. Animals received equimolar doses of 3-MCPD or 3-MCPD dipalmitate. A lower dose of 3-MCPD dipalmitate was also administered. Absence of histopathological changes supported an analysis of early cellular disturbance. Testes were analyzed by two-dimensional gel electrophoresis followed by mass-spectrometric protein identification. Data provide a comprehensive overview of proteomic changes induced by 3-MCPD and 3-MCPD dipalmitate in rat testis in an early phase of organ impairment. Results are compatible with known 3-MCPD effects on reproductive function, substantially extend our knowledge about cellular responses to 3-MCPD and support the hypothesis that toxicity of 3-MCPD and 3-MCPD esters is mediated via common effectors. DJ-1 was identified as a candidate marker for 3-MCPD exposure.

  20. Changes of sperm quality and hormone receptors in the rat testis after exposure to methamphetamine.

    PubMed

    Nudmamud-Thanoi, Sutisa; Sueudom, Wanvipa; Tangsrisakda, Nareelak; Thanoi, Samur

    2016-10-01

    Methamphetamine (METH) is known to damage neurons and induce psychosis. It can also induce apoptosis in seminiferous tubules and affect sperm quality. The present study was carried out to investigate the effect of a rat model of METH addiction on sperm quality and expression of progesterone receptors (PR) and estrogen receptors (ER) in the testis. Sperm quality parameters including sperm motility, sperm morphology and sperm concentration were examined. Protein and gene expressions PR, ERα and ERβ were studied using immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively. The percentages of normal sperm motility and normal sperm morphology were significantly decreased in animals receiving METH, especially in escalating dose (ED METH) and escalating dose-binge (ED-binge METH) groups when compared with control. In addition, sperm concentrations in ED METH and ED-binge METH groups were numerically decreased. PR, ERα and ERβ immunoreactive cells were significantly decreased in spermatogonia, spermatogenic cells and especially in Sertoli cells in all METH-treated groups. Furthermore, messenger RNA expression of PR, ERα and ERβ were also significantly decreased in all METH-treated animals. These results indicate that METH can induce abnormal sperm quality. These changes of sperm quality may relate to the reduction of PR, ERα and ERβ expressions in male germ cells and Sertoli cells which are essential for spermatogenesis and development of sperm. PMID:26864947

  1. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

    NASA Astrophysics Data System (ADS)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-01

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  2. Premeiotic germ cell defect in seminiferous tubules of Atm-null testis

    SciTech Connect

    Takubo, Keiyo . E-mail: keiyot@gmail.com; Hirao, Atsushi; Ohmura, Masako; Azuma, Masaki; Arai, Fumio; Nagamatsu, Go; Suda, Toshio . E-mail: sudato@sc.itc.keio.ac.jp

    2006-12-29

    Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16{sup Ink4a} activation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16{sup Ink4a}-mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16{sup Ink4a}-mediated senescence.

  3. A testis cytoplasmic RNA-binding protein that has the properties of a translational repressor.

    PubMed Central

    Lee, K; Fajardo, M A; Braun, R E

    1996-01-01

    Translation of the mouse protamine 1 (Prm-1) mRNA is repressed for several days during male germ cell differentiation. With the hope of cloning genes that regulate the translational repression of Prm-1, we screened male germ cell cDNA expression libraries with the 3' untranslated region of the Prm-1 RNA. From this screen we obtained two independent clones that encode Prbp, a Prm-1 RNA-binding protein. Prbp contains two copies of a double-stranded-RNA-binding domain. In vitro, the protein binds to a portion of the Prm-1 3' untranslated region previously shown to be sufficient for translational repression in transgenic mice, as well as to poly(I). poly(C). Prbp protein is present in multiple forms in cytoplasmic extracts prepared from wild-type mouse testes and is absent from testes of germ cell-deficient mouse mutants, suggesting that Prbp is restricted to the germ cells of the testis. Immunocytochemical localization confirmed that Prbp is present in the cytoplasmic compartment of late-stage meiotic cells and haploid round spermatids. Recombinant Prbp protein inhibits the translation of multiple mRNAs in a wheat germ lysate, suggesting that Prbp acts to repress translation in round spermatids. While this protein lacks complete specificity for Prm-1-containing RNAs in vitro, the properties of Prbp are consistent with it acting as a general repressor of translation. PMID:8649414

  4. [Inhibin B immunocytochemistry for the prognosis assessment of undescended testis damage in children].

    PubMed

    Nicòtina, P A; Arena, F; Romeo, C; Ferlazzo, G; Arena, S; Basile, G; Romeo, G

    2001-01-01

    Inhibin B immunocytochemistry of both the alpha- and beta-subunits was studied in testicular biopsies from 18 prepubertal and postpubertal patients, with unilateral or bilateral cryptorchism. The present investigation was carried out to seek any prognostic significance for the expected fertility of such subjects in adulthood. All samples were also evaluated by histological and morphometric assessments, according a 1-6 grading sy-stem. In this way, the individual testicular changes were scored by quantitating tubular and germ cell hypoplasia, Sertoli cell hyperplasia, and peritubular fibrosis, where present. The results showed that in bilateral maldescended testes an unexpected expression often occurred of inhibin B beta-subunit in Sertoli cells, while inhibin B alpha-subunit there did not, denoting an early developmental arrest of the testis. It co-related with the high grade testicular damages, as a poor predictor of spermatogenesis. Unlike, unilateral retained testes mainly expressed inhibin B alpha-subunit, irrespective of tubular changes. In the latter instance, different pathogenetic factors of imbalanced testicular regulation can be perspected, other than the Inhibin-Activin system.

  5. An experimental study on effects of pyrrolidine dithiocarbamate on ischemia-reperfusion injury in testis

    PubMed Central

    Kemahli, Eray; Yildiz, Mevlüt; Firat, Tülin; Özyalvaçli, Mehmet Emin; Üyetürk, Uğur; Yilmaz, Burak; Gücük, Adnan

    2016-01-01

    Introduction: The aim of this experimental study was to investigate the histopathological and biochemical effects of pyrrolidine dithiocarbamate, an antioxidant and inhibitor of NF-kβ, on ischemiareperfusion injury in rats. Methods: A total of 21 male Wistar-Albino rats were randomly distributed into three groups as sham group (Group 1), ischemia-reperfusion (I/R) group (Group 2) and I/R with pyrrolidine dithiocarbamate (PDTC) group (Group 3). Left testicles of rats in Groups 2 and 3 underwent testicular torsion of 720° for four hours and 100 mg/kg of PDTC was administered intraperitoneally prior to detorsion in Group 3. An hour after detorsion process, left orchiectomies were performed and 5 ml of intracardiac blood samples were drawn from rats in all three groups. Histopathological examination of testis tissues performed and measurement of superoxide dismutase (SOD) and malondialdehyde (MDA) levels in blood samples were taken. Results: Elevated levels of MDA and decreased SOD activity, together with decreased Johnson tubular biopsy scores consistent with I/R injury were observed in Group 2 (p<0.05). Group 1 and Group 3 were similar in terms of MDA levels, SOD activity, and Johnson scores (p>0.05). Conclusions: Our results indicated that PDTC may have beneficial effects for alleviation of I/R injury in testicular tissue in rats. Understanding the underlying mechanisms and exploration of its diagnostic and therapeutic potential requires further randomized, controlled trials on a larger scale. PMID:27330576

  6. [Funcion sparing surgery in uro-oncology: germ cell tumors of the testis].

    PubMed

    Catanzaro, Mario; Piva, Luigi; Torelli, Tullio; Biasoni, Davide; Stagni, Silvia; Milani, Angelo; Necchi, Andrea; Giannatempo, Patrizia; Nicolai, A; Salvioni, Roberto

    2012-01-01

    Surgery in germ cell tumors of the testis (TGT) may result in andrological disorders, both after orchiectomy and after retroperitoneal lymphadenectomy (RPLND). Bilateral orchiectomy suppresses both testicular functions: exocrine and endocrine. In selected cases with bilateral TGT (metachronous/synchronous), or in the case of TGT in monorchid patients, partial orchiectomy (enucleation of the tumor) can preserve both functions with a low risk of relapse in residual testicular parenchyma, in the absence of intraepithelial neoplasia (TIN). In cases of TIN and normal testosterone levels (80%), the fertility is maintained in 50% of patients. In these cases the use of radiotherapy on the residual testicular parenchyma can prevent the future development of invasive cancer, though compromising the hormonal function. The RPLND (open or laparoscopic) can produce major side effects, such as retrograde ejaculation. Knowledge of the adrenergic fiber retroperitoneal neuroanatomy enables to implement a "nerve sparing" surgery with an almost total reduction of this serious side effect, but that option is only available in few centers of excellence. Semen cryopreservation has become a common practice performed before any treatment that might impact on the andrological function of patients. PMID:23371266

  7. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

    PubMed Central

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-01-01

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered. PMID:27585557

  8. Testis-Specific Bb8 Is Essential in the Development of Spermatid Mitochondria.

    PubMed

    Vedelek, Viktor; Laurinyecz, Barbara; Kovács, Attila L; Juhász, Gábor; Sinka, Rita

    2016-01-01

    Mitochondria are essential organelles of developing spermatids in Drosophila, which undergo dramatic changes in size and shape after meiotic division, where mitochondria localized in the cytoplasm, migrate near the nucleus, aggregate, fuse and create the Nebenkern. During spermatid elongation the two similar mitochondrial derivatives of the Nebenkern start to elongate parallel to the axoneme. One of the elongated mitochondrial derivatives starts to lose volume and becomes the minor mitochondrial derivative, while the other one accumulates paracrystalline and becomes the major mitochondrial derivative. Proteins and intracellular environment that are responsible for cyst elongation and paracrystalline formation in the major mitochondrial derivative need to be identified. In this work we investigate the function of the testis specific big bubble 8 (bb8) gene during spermatogenesis. We show that a Minos element insertion in bb8 gene, a predicted glutamate dehydrogenase, causes recessive male sterility. We demonstrate bb8 mRNA enrichment in spermatids and the mitochondrial localisation of Bb8 protein during spermatogenesis. We report that megamitochondria develop in the homozygous mutant testes, in elongating spermatids. Ultrastructural analysis of the cross section of elongated spermatids shows enlarged mitochondria and the production of paracrystalline in both major and minor mitochondrial derivatives. Our results suggest that the Bb8 protein and presumably glutamate metabolism has a crucial role in the normal development and establishment of the identity of the mitochondrial derivatives during spermatid elongation. PMID:27529784

  9. Biochemical and histopathological evaluations of ghrelin effects following cadmium toxicity in the rat testis.

    PubMed

    Kheradmand, A; Alirezaei, M; Dezfoulian, O

    2015-08-01

    Numerous reports demonstrate that cadmium (Cd) induces oxidative stress by increasing lipid peroxidation and altering antioxidative enzymes status. Thirty male rats were subdivided into control-saline, Cd-saline and Cd-ghrelin groups. A single dose of Cd was injected to induce testicular injury and also ghrelin for 10 consecutive days to group 3. SOD activity decreased and lipid peroxidation increased by Cd administration. The mean activities of GPx and CAT as well as GSH content were lower in the Cd-saline rats; however, they did not statistically differ compared with the controls. Exposure to Cd resulted in complete degeneration of seminiferous tubules with severe depletion of germ cells and arrest in spermatogenesis. Notably, ghrelin treatment not only prevented reduction in SOD, GPx, CAT and GSH level, but also increased enzyme activities form their normal values. Moreover, TBARS concentration was significantly reduced by ghrelin administration. Furthermore, ghrelin pre-treatment resulted in partial but not significant prevention in testicular histopathological features damaged by Cd. In conclusion, the obtained results indicate for the first time the novel evidences of ghrelin ability in promotion of antioxidant enzyme activities and reduction of lipid peroxidation following Cd-induced oxidative stress in the rat testis. These observations also demonstrate that ghrelin may be considered as promising antioxidant agent in prevention and attenuation of testicular injury upon Cd toxicity. PMID:25059551

  10. Rictor Regulates Spermatogenesis by Controlling Sertoli Cell Cytoskeletal Organization and Cell Polarity in the Mouse Testis.

    PubMed

    Dong, Heling; Chen, Zhenguo; Wang, Caixia; Xiong, Zhi; Zhao, Wanlu; Jia, Chunhong; Lin, Jun; Lin, Yan; Yuan, Weiping; Zhao, Allan Z; Bai, Xiaochun

    2015-11-01

    Maintenance of cell polarity is essential for Sertoli cell and blood-testis barrier (BTB) function and spermatogenesis; however, the signaling mechanisms that regulate the integrity of the cytoskeleton and polarity of Sertoli cells are not fully understood. Here, we demonstrate that rapamycin-insensitive component of target of rapamycin (TOR) (Rictor), a core component of mechanistic TOR complex 2 (mTORC2), was expressed in the seminiferous epithelium during testicular development, and was down-regulated in a cadmium chloride-induced BTB damage model. We then conditionally deleted the Rictor gene in Sertoli cells and mutant mice exhibited azoospermia and were sterile as early as 3 months old. Further study revealed that Rictor may regulate actin organization via both mTORC2-dependent and mTORC2-independent mechanisms, in which the small GTPase, ras-related C3 botulinum toxin substrate 1, and phosphorylation of the actin filament regulatory protein, Paxillin, are involved, respectively. Loss of Rictor in Sertoli cells perturbed actin dynamics and caused microtubule disarrangement, both of which accumulatively disrupted Sertoli cell polarity and BTB integrity, accompanied by testicular developmental defects, spermiogenic arrest and excessive germ cell loss in mutant mice. Together, these findings establish the importance of Rictor/mTORC2 signaling in Sertoli cell function and spermatogenesis through the maintenance of Sertoli cell cytoskeletal dynamics, BTB integrity, and cell polarity. PMID:26360620

  11. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.

    PubMed

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-02

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  12. Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications.

    PubMed

    Tarnowski, Maciej; Czerewaty, Michał; Deskur, Anna; Safranow, Krzysztof; Marlicz, Wojciech; Urasińska, Elżbieta; Ratajczak, Mariusz Z; Starzyńska, Teresa

    2016-01-01

    Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly (p < 0.05) overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells. PMID:27635108

  13. Identification, localization, and functional analysis of the homologues of mouse CABS1 protein in porcine testis

    PubMed Central

    Shawki, Hossam H.; Kigoshi, Takumi; Katoh, Yuki; Matsuda, Manabu; Ugboma, Chioma M.; Takahashi, Satoru; Oishi, Hisashi; Kawashima, Akihiro

    2016-01-01

    Previously, we have identified a calcium-binding protein that is specifically expressed in spermatids and localized to the flagella of the mature sperm in mouse, so-called mCABS1. However, the physiological roles of CABS1 in the male reproductive system have not been fully elucidated yet. In the current study, we aimed to localize and clarify the role of CABS1 in porcine (pCABS1). We determined for the first time the full nucleotides sequence of pCABS1 mRNA. pCABS1 protein was detected on SDS-PAGE gel as two bands at 75 kDa and 70 kDa in adult porcine testis, whereas one band at 70 kDa in epididymal sperm. pCABS1 immunoreactivity in seminiferous tubules was detected in the elongated spermatids, and that in the epididymal sperm was found in the acrosome as well as flagellum. The immunoreactivity of pCABS1 in the acrosomai region disappeared during acrosome reaction. We also identified that pCABS1 has a transmembrane domain using computational prediction of the amino acids sequence. The treatment of porcine capacitated sperm with anti-pCABS1 antiserum significantly decreased acrosome reactions. These results suggest that pCABS1 plays an important role in controlling calcium ion signaling during the acrosome reaction. PMID:26960363

  14. Inutero exposure to diisononyl phthalate caused testicular dysgenesis of rat fetal testis.

    PubMed

    Li, Linxi; Bu, Tiao; Su, Huina; Chen, Zhichuan; Liang, Yuyuan; Zhang, Gaolong; Zhu, Danyan; Shan, Yuanyuan; Xu, Renai; Hu, Yuanyuan; Li, Junwei; Hu, Guoxin; Lian, Qingquan; Ge, Ren-Shan

    2015-01-22

    Diisononyl phthalate (DINP) is a synthetic material that has been widely used as a substitute for other plasticizers prohibited due to reproductive toxicity in consumer products. Some phthalates have been associated with testicular dysgenesis syndrome in male fetus when female pregnant dams were exposed to them. The present study investigated effects of DINP on fetal Leydig cell function and testis development. Female pregnant Sprague Dawley rats received control vehicle (corn oil) or DINP (10, 100, 500, and 1000 mg/kg) by oral gavage from gestational day (GD) 12 to 21. At GD 21.5, testicular testosterone production, fetal Leydig cell numbers and distribution, testicular gene and protein expression levels were examined. DINP showed dose-dependent increase of fetal Leydig cell aggregation with the low observed adverse-effect level (LOAEL) of 10 mg/kg and multinucleated gonocyte with LOAEL of 100 mg/kg. At 10 mg/kg, DINP also significantly increased fetal Leydig cell size, but inhibited insulin-like 3 and 3β-hydroxysteroid dehydrogenase gene expression and protein levels. DINP inhibited testicular testosterone levels at 1000 mg/kg. The results indicate that in utero exposure to DINP affects the expression levels of some fetal Leydig cell steroidogenic genes, gonocyte multinucleation and Leydig cell aggregation. PMID:25445723

  15. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.

    PubMed

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-01-01

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered. PMID:27585557

  16. The effect of R-(-)-deprenyl administration on antioxidant enzymes in rat testis.

    PubMed

    Horváthová, Františka; Danielisová, Viera; Domoráková, Iveta; Solár, Peter; Rybárová, Silvia; Hodorová, Ingrid; Mihalik, Jozef

    2016-10-01

    The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the activity and localization of superoxide dismutases (SODs) and catalase (CAT) in rat testis. After 30 days of intraperitoneal administration of either saline (control) or R-(-)-deprenyl dissolved in saline at concentrations of 0.0025mg/kg (low dose of deprenyl, LDD) or 0.25mg/kg (high dose of deprenyl, HDD), males were killed by thiopental, and their testes were collected. We found that deprenyl administration significantly increased the activity of antioxidant enzymes, and this effect varied by dosage. LDD caused significant elevation of all monitored enzymes, but HDD did not increase the activity of SOD2. Employing immunohistochemistry, we detected enzymes predominantly in Leydig cells (SOD1, SOD2, CAT), in late spermatids and residual bodies (SOD1, SOD2), and in primary spermatocytes (SOD2). Histopathological examination did not reveal testicular damage in experimental groups compared to control. Deprenyl proved to be a potent stimulator of antioxidant enzymes in rat testes; therefore, it could be used in the therapy of male infertility. On the other hand, it is crucial to choose a proper dose, since lower dose was more competent compared to a dosage that was one hundred times higher. PMID:27292162

  17. Alleviative effect of quercetin on rat testis against arsenic: a histological and biochemical study.

    PubMed

    Jahan, Sarwat; Iftikhar, Natasha; Ullah, Hizb; Rukh, Gul; Hussain, Ishtiaq

    2015-04-01

    The preventive effect of quercetin on arsenic stimulated reproductive ailments in male Sprague Dawely (SD) rats was investigated. Twenty rats were divided into four groups. The first group served as a control and was provided tap water. The second group of rats was treated with sodium arsenite at the dose of 50 ppm in drinking water. The third group served as a positive control and received an oral dose of quercetin (50 mg/kg). In the fourth group, quercetin (50 mg/kg) was co-administered orally with arsenic (50 ppm in drinking water). All the treatments were carried out for 49 days. Arsenic treatment resulted in adverse morphological and histopathological changes in testis of rats including reduced epithelial height and tubular diameter, and increased luminal diameter. In contrast, these adverse effects of arsenic were eliminated by co-administration of quercetin. Additionally arsenic treatment significantly increased testicular thiobarbituric acid reactive substance (TBARS) levels while catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and glutathione reductase (GSR) activities, and plasma and intra-testicular testosterone concentrations, were decreased significantly. Lipid peroxidation (LPO) was significantly suppressed and depleted antioxidant defense mechanism was restored by the quercetin co-treatment. Also quercetin treatment resulted in a marked increase in plasma and testicular testosterone concentrations. On the basis of these findings, it was concluded that quercetin may be used as a potential therapeutic drug against arsenic induced reproductive toxicity. PMID:25539033

  18. Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications

    PubMed Central

    Czerewaty, Michał; Deskur, Anna; Safranow, Krzysztof; Urasińska, Elżbieta; Starzyńska, Teresa

    2016-01-01

    Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly (p < 0.05) overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells.

  19. Induction of cancer testis antigen expression in circulating acute myeloid leukemia blasts following hypomethylating agent monotherapy

    PubMed Central

    Srivastava, Pragya; Paluch, Benjamin E.; Matsuzaki, Junko; James, Smitha R.; Collamat-Lai, Golda; Blagitko-Dorfs, Nadja; Ford, Laurie Ann; Naqash, Rafeh; Lübbert, Michael; Karpf, Adam R.; Nemeth, Michael J.; Griffiths, Elizabeth A.

    2016-01-01

    Cancer testis antigens (CTAs) are promising cancer associated antigens in solid tumors, but in acute myeloid leukemia, dense promoter methylation silences their expression. Leukemia cell lines exposed to HMAs induce expression of CTAs. We hypothesized that AML patients treated with standard of care decitabine (20mg/m2 per day for 10 days) would demonstrate induced expression of CTAs. Peripheral blood blasts serially isolated from AML patients treated with decitabine were evaluated for CTA gene expression and demethylation. Induction of NY-ESO-1 and MAGEA3/A6, were observed following decitabine. Re-expression of NY-ESO-1 and MAGEA3/A6 was associated with both promoter specific and global (LINE-1) hypomethylation. NY-ESO-1 and MAGEA3/A6 mRNA levels were increased irrespective of clinical response, suggesting that these antigens might be applicable even in patients who are not responsive to HMA therapy. Circulating blasts harvested after decitabine demonstrate induced NY-ESO-1 expression sufficient to activate NY-ESO-1 specific CD8+ T-cells. Induction of CTA expression sufficient for recognition by T-cells occurs in AML patients receiving decitabine. Vaccination against NY-ESO-1 in this patient population is feasible. PMID:26883197

  20. Alleviative effect of quercetin on rat testis against arsenic: a histological and biochemical study.

    PubMed

    Jahan, Sarwat; Iftikhar, Natasha; Ullah, Hizb; Rukh, Gul; Hussain, Ishtiaq

    2015-04-01

    The preventive effect of quercetin on arsenic stimulated reproductive ailments in male Sprague Dawely (SD) rats was investigated. Twenty rats were divided into four groups. The first group served as a control and was provided tap water. The second group of rats was treated with sodium arsenite at the dose of 50 ppm in drinking water. The third group served as a positive control and received an oral dose of quercetin (50 mg/kg). In the fourth group, quercetin (50 mg/kg) was co-administered orally with arsenic (50 ppm in drinking water). All the treatments were carried out for 49 days. Arsenic treatment resulted in adverse morphological and histopathological changes in testis of rats including reduced epithelial height and tubular diameter, and increased luminal diameter. In contrast, these adverse effects of arsenic were eliminated by co-administration of quercetin. Additionally arsenic treatment significantly increased testicular thiobarbituric acid reactive substance (TBARS) levels while catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and glutathione reductase (GSR) activities, and plasma and intra-testicular testosterone concentrations, were decreased significantly. Lipid peroxidation (LPO) was significantly suppressed and depleted antioxidant defense mechanism was restored by the quercetin co-treatment. Also quercetin treatment resulted in a marked increase in plasma and testicular testosterone concentrations. On the basis of these findings, it was concluded that quercetin may be used as a potential therapeutic drug against arsenic induced reproductive toxicity.

  1. [Diffuse large B-cell lymphoma of the testis relapsed 16 years after achieving complete response].

    PubMed

    Nagasaka, Isao; Mitsui, Takeki; Ishizaki, Takuma; Koiso, Hiromi; Yokohama, Akihiko; Saitoh, Takayuki; Hirato, Junko; Igarashi, Tadahiko; Kojima, Masaru; Tsukamoto, Norifumi; Nojima, Yoshihisa; Murakami, Hirokazu; Handa, Hiroshi

    2015-12-01

    Testicular lymphoma is a rare disease, accounting for 1-2% of non-Hodgkin lymphoma and 5-9% of all testicular tumors, and has a high relapse rate with a poor prognosis. We report a patient with testicular diffuse large B-cell lymphoma (DLBCL) who relapsed after being in remission for 16 years. He had undergone orchiectomy of the right testis and was diagnosed as having DLBCL (stage IAE) at 49 years of age. After 3 cycles of CHOP, he achieved a complete remission. Orchiectomy was performed because of a left testicular tumor, and he was again diagnosed with DLBCL at the age of 65. VH3-21 was detected in lymphoma cells at the times of both the first diagnosis and the relapse based on analysis of the variable region of the immunoglobulin heavy chain. Accordingly, the lymphoma cells at relapse were confirmed to be the same clone as that which had been documented at the first diagnosis. PMID:26725353

  2. Single scrotal-incision orchidopexy for palpable undescended testis in children

    PubMed Central

    Zouari, Mohamed; Dhaou, Mahdi Ben; Jallouli, Mohamed; Mhiri, Riadh

    2014-01-01

    Objective To evaluate the single scrotal-incision orchidopexy (SSIO) technique in patients with an undescended testis palpable in the inguinal canal or below the external inguinal ring. Patients and methods Between January 2011 and December 2013 we performed 100 SSIOs in 89 patients. The mean (range) follow-up was 9 (3–36) months. Results In 88 testes the SSIO was performed with no difficulties. In four patients an additional dissection by opening the external ring and canal was necessary; none of these patients developed an inguinal hernia after surgery. In eight patients conversion to an inguinal approach was necessary because of difficulty in controlling the hernial sacs and inadequate mobilisation. At the follow-up assessment, of the 89 patients, none developed testicular atrophy, one (1%) had wound dehiscence and four (5%) had a scrotal haematoma. There was no statistically significant difference between the testicular size at baseline and that during the follow-up. At 3 months after surgery the overall cosmetic result was excellent. Conclusion The SSIO is minimal-access surgery allowing less dissection, less discomfort for the patient, rapid healing, excellent cosmetic results and a good success rate. This technique is safe and effective for undescended testes palpable in the inguinal canal or below the external inguinal ring. PMID:26413331

  3. Disruption of blood-testis barrier dynamics in ether-lipid-deficient mice.

    PubMed

    Komljenovic, Dorde; Sandhoff, Roger; Teigler, Andre; Heid, Hans; Just, Wilhelm W; Gorgas, Karin

    2009-08-01

    One of the major roles of Sertoli cells is to establish the blood-testis (Sertoli cell) barrier (BTB), which is permanently assembled and disassembled to accommodate the translocation of leptotene spermatocytes from the basal into the adluminal compartment of the seminiferous epithelium and to guarantee completion of meiosis and spermiogenesis. Recently, we have demonstrated spermatogenesis to be arrested before spermatid elongation in Gnpat-null mice with selective deficiency of ether lipids (ELs) whose functions are poorly understood. In this study, we have focused on the spatio-temporal expression of several BTB tight-junctional proteins in the first wave of spermatogenesis to obtain insights into the physiological role of ELs during BTB establishment and dynamics. Our data confirm the transient existence of Russell's intermediate or translocation compartment delineated by two separate claudin-3-positive luminal and basal tight junctions and reveal that EL deficiency blocks BTB remodeling. This block is associated with (1) downregulation and mistargeting of claudin-3 and (2) impaired BTB disassembly resulting in deficient sealing of the intermediate compartment as shown by increased BTB permeability to biotin. These results suggest that ELs are essential for cyclic BTB dynamics ensuring the sluice mechanism for leptotene translocation into the adluminal compartment. PMID:19495798

  4. Isolation and characterization of testis-specific DMRT1 in the tropical abalone (Haliotis asinina).

    PubMed

    Klinbunga, Sirawut; Amparyup, Piti; Khamnamtong, Bavornlak; Hirono, Ikuo; Aoki, Takashi; Jarayabhand, Padermsak

    2009-02-01

    The Doublesex Male abnormal-3 Related Transcription factor-1 (DMRT1) gene encodes a protein containing the DNA-binding motif called the DM domain, involved in the sexual development of various species. To gain insight into its implications for gonadal differentiation in the tropical abalone (Haliotis asinina), a DMRT1 homolog was identified and characterized. The full length cDNA of HADMRT1 (1,740 bp with an ORF of 732 bp corresponding to a putative polypeptide of 243 amino acids) and its DM domain-less variant (HADMRT1-like, 1,430 bp with an ORF of 312 bp, 103 amino acids) were successfully isolated and reported for the first time in molluscs. HADMRT1 was specifically expressed in the testes of adult H. asinina (N = 16) but not in whole juveniles (2, 3, 5 months old, N = 6 for each group) and ovaries (N = 16), and pooled hemocytes (from 50 individuals) of adults. Tissue distribution analysis further revealed testis-specific expression of HADMRT1. Semiquantitative RT-PCR illustrated that the relative expression level of HADMRT1 in developed testes (stages II, III, and IV) was significantly greater than that in undeveloped testes (stage I) of abalone broodstock (P < 0.05).

  5. Mechanisms involved in the blood-testis barrier increased permeability induced by EMP.

    PubMed

    Wang, Xiao-Wu; Ding, Gui-Rong; Shi, Chang-Hong; Zeng, Li-Hua; Liu, Jun-Ye; Li, Jing; Zhao, Tao; Chen, Yong-Bin; Guo, Guo-Zhen

    2010-09-30

    The blood-testis barrier (BTB) plays an important role in male reproductive system. Lots of environmental stimulations can increase the permeability of BTB and then result in antisperm antibody (AsAb) generation, which is a key step in male immune infertility. Here we reported the results of male mice exposed to electromagnetic pulse (EMP) by measuring the expression of tight-junction-associated proteins (ZO-1 and Occludin), vimentin microfilaments, and transforming growth factor-beta (TGF-beta3) as well as AsAb level in serum. Male BALB/c mice were sham exposed or exposed to EMP at two different intensities (200kV/m and 400kV/m) for 200 pulses. The testes were collected at different time points after EMP exposure. Immunofluorescence histocytochemistry, western blotting, laser confocal microscopy and RT-PCR were used in this study. Compared with sham group, the expression of ZO-1 and TGF-beta3 significantly decreased accompanied with unevenly stained vimentin microfilaments and increased serum AsAb levels in EMP-exposed mice. These results suggest a potential BTB injury and immune infertility in male mice exposed to a certain intensity of EMP.

  6. The growing teratoma syndrome: an unusual manifestation of treated, nonseminomatous germ cell tumors of the testis.

    PubMed

    Lorigan, J G; Eftekhari, F; David, C L; Shirkhoda, A

    1988-08-01

    Residual masses are a common finding after chemotherapy for retroperitoneal and other metastases from nonseminomatous germ cell tumors of the testis. These may contain mature teratoma, fibrotic tissue, or tumor. Mature teratoma, which is unresponsive to chemotherapy, may result from evolution of a malignant lesion during treatment, or it may represent a metastasis from a focus of mature teratoma in the primary testicular tumor. An enlarging retroperitoneal mass during the course of chemotherapy is usually due to treatment failure but rarely may be due to an enlarging mature teratoma, the so-called growing teratoma syndrome. This report concerns five patients with nonseminomatous germ cell tumors metastatic to the retroperitoneum in whom mature teratomas were found at surgery. These tumors had grown despite the administration of combination systemic chemotherapy, and the cystic component had increased in size. Three patients had evidence of urinary tract compression, three had vascular compression or displacement, and one had gastrointestinal compression. The retroperitoneal mass was excised in each patient, and all are alive 4-27 months after surgery without evidence of recurrence. Growing mature teratoma is unresponsive to chemotherapy but is cured by surgical excision. The possibility of the growing teratoma syndrome should be considered so that these lesions can be treated appropriately.

  7. T3 fails to restore mitochondrial thiol redox status altered by experimental hypothyroidism in rat testis.

    PubMed

    Chattopadhyay, Sutapa; Choudhury, Supragyanshree; Roy, Anita; Chainy, Gagan B N; Samanta, Luna

    2010-10-01

    Oxidative stress impaired sperm function might lead to infertility. The objective of this study was to evaluate the effects of altered thyroid hormone levels on regulation of mitochondrial glutathione redox status and its dependent antioxidant defense system in adult rat testis and their correlation with testicular function. Adult male Wistar rats were rendered hypothyroid by administration of 6-n-propyl-2-thiouracil in drinking water for six weeks. At the end of the treatment period, a subset of the hypothyroid rats was treated with T(3) (20 μg/100g body weight/day for 3 days). Mitochondria were isolated from euthyroid, hypothyroid and hypothyroid+T(3)-treated rat testes, and sub-fractionated into sub-mitochondrial particles and matrix fractions. Mitochondrial respiration, oxidative stress indices and antioxidant defenses were assayed. The results were correlated with daily testicular sperm production and epididymal sperm viability. Increased pro-oxidant level and reduced antioxidant capacity rendered the hypothyroid mitochondria susceptible to oxidative injury. The extent of damage was more evident in the membrane fraction. This was reflected in higher degree of oxidative damages inflicted upon membrane lipids and proteins. While membrane proteins were more susceptible to carbonylation, thiol residue damage was evident in matrix fraction. Reduced levels of glutathione and ascorbate further weakened the antioxidant defenses and impaired testicular function. Hypothyroid condition disturbed intra-mitochondrial thiol redox status leading to testicular dysfunction. Hypothyroidism-induced oxidative stress condition could not be reversed with T(3) treatment.

  8. Evolutionary origin and human-specific expansion of a cancer/testis antigen gene family.

    PubMed

    Zhang, Qu; Su, Bing

    2014-09-01

    Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here, we presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multiexon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats. Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution.

  9. Pharmacological regulation of the cholesterol transport machinery in steroidogenic cells of the testis.

    PubMed

    Aghazadeh, Yasaman; Zirkin, Barry R; Papadopoulos, Vassilios

    2015-01-01

    Reduced serum testosterone (T), or hypogonadism, is estimated to affect about 5 million American men, including both aging and young men. Low serum T has been linked to mood changes, worsening cognition, fatigue, depression, decreased lean body mass and bone mineral density, increased visceral fat, metabolic syndrome, decreased libido, and sexual dysfunction. Administering exogenous T, known as T-replacement therapy (TRT), reverses many of the symptoms of low T levels. However, this treatment can result in luteinizing hormone suppression which, in turn, can lead to reduced sperm numbers and infertility, making TRT inappropriate for men who wish to father children. Additionally, TRT may result in supraphysiologic T levels, skin irritation, and T transfer to others upon contact; and there may be increased risk of prostate cancer and cardiovascular disease, particularly in aging men. Therefore, the development of alternate therapies for treating hypogonadism would be highly desirable. To do so requires greater understanding of the series of steps leading to T formation and how they are regulated, and the identification of key steps that are amenable to pharmacological modulation so as to induce T production. We review herein our current understanding of mechanisms underlying the pharmacological induction of T formation in hypogonadal testis.

  10. The let-7-Imp axis regulates ageing of the Drosophila testis stem-cell niche.

    PubMed

    Toledano, Hila; D'Alterio, Cecilia; Czech, Benjamin; Levine, Erel; Jones, D Leanne

    2012-05-31

    Adult stem cells support tissue homeostasis and repair throughout the life of an individual. During ageing, numerous intrinsic and extrinsic changes occur that result in altered stem-cell behaviour and reduced tissue maintenance and regeneration. In the Drosophila testis, ageing results in a marked decrease in the self-renewal factor Unpaired (Upd), leading to a concomitant loss of germline stem cells. Here we demonstrate that IGF-II messenger RNA binding protein (Imp) counteracts endogenous small interfering RNAs to stabilize upd (also known as os) RNA. However, similar to upd, Imp expression decreases in the hub cells of older males, which is due to the targeting of Imp by the heterochronic microRNA let-7. In the absence of Imp, upd mRNA therefore becomes unprotected and susceptible to degradation. Understanding the mechanistic basis for ageing-related changes in stem-cell behaviour will lead to the development of strategies to treat age-onset diseases and facilitate stem-cell-based therapies in older individuals.

  11. Cancer-testis antigens and immunotherapy in the light of cancer complexity.

    PubMed

    Grizzi, F; Mirandola, L; Qehajaj, D; Cobos, E; Figueroa, J A; Chiriva-Internati, M

    2015-03-01

    The ability of immunotherapy to evoke successful antitumor immune responses has been well documented over the past decade. Despite abundant preclinical data, it is only with the recent approval by the Food and Drug Administration (FDA) of the drugs such as sipuleucel-T and ipilimumab that immunotherapy is finally being recognized as a viable alternative to traditional therapies for treatment of various cancers. Despite the ability of immunotherapy to elicit successful antitumor immune responses, its efficacy is hindered by several factors. Among these are the paucity of tumor-associated antigens (TAA) that can be used as effective targets and the systemic toxicities that often lead to treatment interruption. Indeed, such adverse effects, which can be immunological and/or parenchymal, can be particularly severe and even fatal to some patients. A family of TAA called cancer-testis antigens (CTA) has been identified and their encoding genes have been extensively investigated. CTA expression has been demonstrated in a variety of human cancer tissues, and at least 19 CTA have been found to elicit humoral and/or cellular immune responses in cancer patients. Here we discuss how CTA and immunotherapy will most likely play a major role in the cure of cancer in the light of cancer complexity.

  12. Effects of in utero exposure to nonsteroidal estrogens on mouse testis.

    PubMed Central

    Pérez-Martínez, C; Ferreras-Estrada, M C; García-Iglesias, M J; Bravo-Moral, A M; Espinosa-Alvarez, J; Escudero-Diez, A

    1997-01-01

    Male mice exposed in utero to alpha-zearalanol (zeranol) or diethylstilbestrol (DES) were analyzed postnatally to evaluate the possible changes on their testicular morphology as part of an examination of the effects of transplacental exposure to non-steroidal estrogens on sensitive tissues. Pregnant NMRI mice were injected subcutaneously with ethyl oleate (0.1 mL) alone (negative control) or with 150 micrograms/kg of body weight of zeranol or DES (positive control) on days 9 and 10 of gestation. Experimental and control male offspring were euthanized at days 45 (n = 47), 90 (n = 44), 180 (n = 40) and 365 (n = 26) after birth and their gonads were examined by light and electron microscopy. The results suggested that prenatal zeranol or DES exposure induced more severe and earlier (at 45 d) testicular abnormalities than in negative control (at 6 mo). These age-related alterations were characterized by regressive changes in the germinal epithelium and Sertoli's cells as well as foci of Leydig's cells around atrophied seminiferous tubules and dysplasia of the rete testis epithelium. On the contrary, the presence of Leydig's cells with immature morphology and their arrangement in sheet could be attributable exclusively to estrogen treatment. The presence of no neoplasm was confirmed. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. PMID:9114959

  13. Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens

    PubMed Central

    Casalà, Carla; Briansó, Ferran; Castrejón, Nerea; Rodríguez, Eva; Suñol, Mariona; Carcaboso, Angel M.; Lavarino, Cinzia; Mora, Jaume; de Torres, Carmen

    2016-01-01

    The calcium–sensing receptor is a G protein-coupled receptor that exerts cell-type specific functions in numerous tissues and some cancers. We have previously reported that this receptor exhibits tumor suppressor properties in neuroblastoma. We have now assessed cinacalcet, an allosteric activator of the CaSR approved for clinical use, as targeted therapy for this developmental tumor using neuroblastoma cell lines and patient-derived xenografts (PDX) with different MYCN and TP53 status. In vitro, acute exposure to cinacalcet induced endoplasmic reticulum stress coupled to apoptosis via ATF4-CHOP-TRB3 in CaSR-positive, MYCN-amplified cells. Both phenotypes were partially abrogated by phospholipase C inhibitor U73122. Prolonged in vitro treatment also promoted dose- and time-dependent apoptosis in CaSR-positive, MYCN-amplified cells and, irrespective of MYCN status, differentiation in surviving cells. Cinacalcet significantly inhibited tumor growth in MYCN-amplified xenografts and reduced that of MYCN-non amplified PDX. Morphology assessment showed fibrosis in MYCN-amplified xenografts exposed to the drug. Microarrays analyses revealed up-regulation of cancer-testis antigens (CTAs) in cinacalcet-treated MYCN-amplified tumors. These were predominantly CTAs encoded by genes mapping on chromosome X, which are the most immunogenic. Other modulated genes upon prolonged exposure to cinacalcet were involved in differentiation, cell cycle exit, microenvironment remodeling and calcium signaling pathways. CTAs were up-regulated in PDX and in vitro models as well. Moreover, progressive increase of CaSR expression upon cinacalcet treatment was seen both in vitro and in vivo. In summary, cinacalcet reduces neuroblastoma tumor growth and up-regulates CTAs. This effect represents a therapeutic opportunity and provides surrogate circulating markers of neuroblastoma response to this treatment. PMID:26893368

  14. Methoxychlor induces apoptosis via mitochondria- and FasL-mediated pathways in adult rat testis.

    PubMed

    Vaithinathan, S; Saradha, B; Mathur, P P

    2010-04-29

    In the past few years, there has been much concern about the adverse health effects of environmental contaminants in general and organochlorine in particular. Studies have shown the repro-toxic effects of long-term exposure to methoxychlor, a member of the organochlorine family. However, the insight into the mechanisms of gonadal toxicity induced by methoxychlor is not well known. In the present study we sought to elucidate the mechanism(s) underpinning the gonadal effects within hours of exposure to methoxychlor. Experimental rats were divided into six groups of four each. Animals were orally administered with a single dose of methoxychlor (50mg/kg body weight) and killed at 0, 3, 6, 12, 24, and 72h post-treatment. The levels and time-course of induction of apoptosis-related proteins like cytochorome C, caspase 3 and procaspase 9, Fas-FasL and NF-kappaB were determined to assess sequential induction of apoptosis in the rat testis. DNA damage was assessed by TUNEL assay and flowcytometry. Administration of methoxychlor resulted in a significant increase in the levels of cytosolic cytochrome c and procaspase 9 as early as 6h following exposure. Time-dependent elevations in the levels of Fas, FasL, pro- and cleaved caspase 3 were observed. The DNA damage was measured and showed time-dependent increase in the TUNEL positive cells, and also by flowcytometry of testicular cells. The study demonstrates induction of testicular apoptosis in adult rats following exposure to a single dose of methoxychlor.

  15. Structure-Function Relationships in Human Testis-determining Factor SRY

    PubMed Central

    Racca, Joseph D.; Chen, Yen-Shan; Maloy, James D.; Wickramasinghe, Nalinda; Phillips, Nelson B.; Weiss, Michael A.

    2014-01-01

    Human testis determination is initiated by SRY, a Y-encoded architectural transcription factor. Mutations in SRY cause 46 XY gonadal dysgenesis with female somatic phenotype (Swyer syndrome) and confer a high risk of malignancy (gonadoblastoma). Such mutations cluster in the SRY high mobility group (HMG) box, a conserved motif of specific DNA binding and bending. To explore structure-function relationships, we constructed all possible substitutions at a site of clinical mutation (W70L). Our studies thus focused on a core aromatic residue (position 15 of the consensus HMG box) that is invariant among SRY-related HMG box transcription factors (the SOX family) and conserved as aromatic (Phe or Tyr) among other sequence-specific boxes. In a yeast one-hybrid system sensitive to specific SRY-DNA binding, the variant domains exhibited reduced (Phe and Tyr) or absent activity (the remaining 17 substitutions). Representative nonpolar variants with partial or absent activity (Tyr, Phe, Leu, and Ala in order of decreasing side-chain volume) were chosen for study in vitro and in mammalian cell culture. The clinical mutation (Leu) was found to markedly impair multiple biochemical and cellular activities as respectively probed through the following: (i) in vitro assays of specific DNA binding and protein stability, and (ii) cell culture-based assays of proteosomal degradation, nuclear import, enhancer DNA occupancy, and SRY-dependent transcriptional activation. Surprisingly, however, DNA bending is robust to this or the related Ala substitution that profoundly impairs box stability. Together, our findings demonstrate that the folding, trafficking, and gene-regulatory function of SRY requires an invariant aromatic “buttress” beneath its specific DNA-bending surface. PMID:25258310

  16. The prion-related protein (testis-specific) gene (PRNT) is highly polymorphic in Portuguese sheep.

    PubMed

    Mesquita, P; Garcia, V; Marques, M R; Santos Silva, F; Oliveira Sousa, M C; Carolino, I; Pimenta, J; Fontes, C M G A; Horta, A E M; Prates, J A M; Pereira, R M

    2016-02-01

    The objective of this study was to search for polymorphisms in the ovine prion-related protein (testis-specific) gene (PRNT). Sampling included 567 sheep from eight Portuguese breeds. The PRNT gene-coding region was analyzed by single-strand conformation polymorphism and sequencing, allowing the identification of the first ovine PRNT polymorphisms, in codons 6, 38, 43 and 48: c.17C>T (p.Ser6Phe, which disrupts a consensus arginine-X-X-serine/threonine motif); c.112G>C (p.Gly38>Arg); c.129T>C and c.144A>G (synonymous) respectively. Polymorphisms in codons 6, 38 and 48 occur simultaneously in 50.6% of the animals, 38.8% presenting as heterozygous. To study the distribution of the polymorphism in codon 43, a restriction fragment length polymorphism analysis was performed. Polymorphic variant c.129C, identified in 89.8% of the animals with 32.8% presented as heterozygous, was considered the wild genotype in Portuguese sheep. Eight different haplotypes which have comparable distribution in all breeds were identified for the PRNT gene. In conclusion, the PRNT coding region is highly polymorphic in sheep, unlike the prion protein 2 dublet gene (PRND), in which we previously found only one synonymous substitution (c.78G>A), in codon 26. The absence or reduced number of PRND heterozygotes (c.78G>A) was significantly associated with three PRNT haplotypes (17C-112G-129T-144A,17CT-112GC-129CT-144AG and 17T-112C-129C-144G), and the only three animals found homozygous at c.78A had the 17C-112G-129C-144A PRNT haplotype. These results constitute evidence of an association between polymorphic variation in PRND and PRNT genes, as has already been observed for PRND and prion protein gene (PRNP).

  17. Oxidant and Antioxidant Status in Experimental Rat Testis after Testicular Torsion/Detorsion

    PubMed Central

    Cvetkovic, Tatjana; Stankovic, Jablan; Najman, Stevo; Pavlovic, Dusica; Stokanovic, Dragana; Vlajkovic, Slobodan; Dakovic-Bjelakovic, Marija; Cukuranovic, Jovana; Zivkovic, Vladimir; Stefanovic, Vladisav

    2015-01-01

    Background The aim of this study was to determine oxidative stress (OS) parameters after testicular torsion/detorsion in adult rats. Materials and Methods In this experimental study, male adult Wistar rats were divided into four groups, each consisting of seven animals: group I-one hour right testicular torsion with subsequent orchiectomy, group II-one hour right testicular torsion followed by detorsion, group III-unilateral right-sided orchiectomy without previous torsion and group IV-control. After 30 days, bilateral orchiectomies were performed in rats with both testes and unilateral orchiectomies in rats with single testicles. Parameters of OS were determined in testicular tissue and in plasma. Results Plasma concentrations of advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS) were higher (p<0.05 and p<0.01, respectively), whilst the plasma concentration of the total sulfhydryl (T-SH)-groups was lower (p<0.05) in group I compared to the control group. Group II had higher plasma concentrations of AOPP compared to group IV (p<0.05), as well as significantly increased TBARS and decreased T-SH-group levels compared to groups III (p<0.05 and p<0.01, respectively) and IV (p<0.01, for both parameters). There were significant differences in OS markers between the ipsilateral and contralateral testis, as well as significant correlations among levels of both plasma and tissue markers of OS. Conclusion The increase in TBARS levels seen throughout the experimental period indicated that OS development was caused by ischemia/reperfusion in the testicular tissue. The oxidant-antioxidant system of the testicular tissue was altered during torsion as well as detorsion. PMID:25918600

  18. Evaluation of endocrine profile, hypothalamic-pituitary-testis axis and semen quality in multiple sclerosis.

    PubMed

    Safarinejad, M R

    2008-12-01

    Several endocrine and sexual disturbances have been demonstrated in multiple sclerosis (MS) patients of both sexes. The endocrine profile, hypothalamic-pituitary-testis (HPT) axis and semen quality were evaluated in male patients with MS. A total of 68 male MS patients aged 18 years or older were recruited. Forty-eight age-matched healthy male volunteers served as controls. All subjects underwent complete physical examination and routine semen analysis. Two blood samples were drawn from each participant at 15-min intervals for the determination of the resting levels of: luteinising-hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone, oestradiol and sex hormone binding globulin. The HPT axis was assessed using gonadotrophin-releasing hormone (GnRH) and human chorionic gonadotrophin tests. The mean basal serum levels for LH, FSH and testosterone in MS patients were significantly lower than the mean for normal controls (P = 0.01). The injection of GnRH analogue did not yield a significant increase in FSH and LH levels in the MS patients compared to normal controls (P = 0.001). Total sperm count, sperm motility and percent normal sperm morphology were lower in MS patients compared to controls. MS subjects with progressive disease had higher and more severe HPT axis abnormalities than that for patients with relapsing remitting MS. Most subjects with MS have hypogonadotrophic hypogonadism state and fertility impairment. It appears that the damage to HPT axis is both in pituitary and testicular levels. Further studies are needed to better elucidate the underlying pathophysiology of HPT axis dysregulation.

  19. A histological study of testis development and ultrastructural features of spermatogenesis in cultured Acrossocheilus fasciatus.

    PubMed

    Fu, Su-Yan; Jiang, Jian-Hu; Yang, Wan-Xi; Zhu, Jun-Quan

    2016-02-01

    Testis development and ultrastructural features of spermatogenesis in Acrossocheilus fasciatus (Cypriniformes, Barbinae), a commercial stream fish, were studied using light and electron microscopy. The reproduction cycle in A. fasciatus testes is classified into six successive stages from Stage I to Stage VI. Based on an analysis of previous results, May to July can be confirmed as the best breeding season for A. fasciatus males. During this time, the A. fasciatus testes are in Stage V and the sperm in males is most abundant. In the first reproductive cycle, sexually mature male testes return to Stage III in October, subsequently overwintering at this stage. In the lobular-type testes of A. fasciatus, cystic type spermatogenesis occurs with restricted spermatogonia. All spermatogenic cells at different stages are distributed along the seminiferous lobules, which contain spermatogonia, spermatocytes, spermatids and spermatozoa. At the end of spermatogenesis, spermatogenic cysts open to release spermatozoa into the lobule lumen. Ultrastructural observation of A. fasciatus spermiogenesis reveals that electron-dense substances appear at the different stages of germ cells, from primary spermatogonia to secondary spermatocytes. We have termed these dense substances as "nuage" when free in the cytoplasm or adjacent to the nuclear envelope, while those close to the mitochondria are called inter-mitochondrial cement. The spermatozoa in A. fasciatus can be classified as type I due to the presence of nuclear rotation. Although the nuclear chromatin in the head of sperm was highly condensed, no acrosome was formed. The cytoplasmic canal, a common ultrastructural feature of Teleostei spermatozoa, was also present in the midpiece. In addition, numerous fused mitochondria were observed. The distal centriole and proximal centriole constituting the centriolar complex were oriented incompletely perpendicular to each other. The flagellum showed a typical 9+2 arrangement pattern

  20. The prion-related protein (testis-specific) gene (PRNT) is highly polymorphic in Portuguese sheep.

    PubMed

    Mesquita, P; Garcia, V; Marques, M R; Santos Silva, F; Oliveira Sousa, M C; Carolino, I; Pimenta, J; Fontes, C M G A; Horta, A E M; Prates, J A M; Pereira, R M

    2016-02-01

    The objective of this study was to search for polymorphisms in the ovine prion-related protein (testis-specific) gene (PRNT). Sampling included 567 sheep from eight Portuguese breeds. The PRNT gene-coding region was analyzed by single-strand conformation polymorphism and sequencing, allowing the identification of the first ovine PRNT polymorphisms, in codons 6, 38, 43 and 48: c.17C>T (p.Ser6Phe, which disrupts a consensus arginine-X-X-serine/threonine motif); c.112G>C (p.Gly38>Arg); c.129T>C and c.144A>G (synonymous) respectively. Polymorphisms in codons 6, 38 and 48 occur simultaneously in 50.6% of the animals, 38.8% presenting as heterozygous. To study the distribution of the polymorphism in codon 43, a restriction fragment length polymorphism analysis was performed. Polymorphic variant c.129C, identified in 89.8% of the animals with 32.8% presented as heterozygous, was considered the wild genotype in Portuguese sheep. Eight different haplotypes which have comparable distribution in all breeds were identified for the PRNT gene. In conclusion, the PRNT coding region is highly polymorphic in sheep, unlike the prion protein 2 dublet gene (PRND), in which we previously found only one synonymous substitution (c.78G>A), in codon 26. The absence or reduced number of PRND heterozygotes (c.78G>A) was significantly associated with three PRNT haplotypes (17C-112G-129T-144A,17CT-112GC-129CT-144AG and 17T-112C-129C-144G), and the only three animals found homozygous at c.78A had the 17C-112G-129C-144A PRNT haplotype. These results constitute evidence of an association between polymorphic variation in PRND and PRNT genes, as has already been observed for PRND and prion protein gene (PRNP). PMID:26538093

  1. Discovery of ZIP transporters that participate in cadmium damage to testis and kidney

    PubMed Central

    He, Lei; Wang, Bin; Hay, Everett B.; Nebert, Daniel W.

    2009-01-01

    It has been known for decades that cadmium (Cd) must enter the cell to cause damage, but there was no mechanism to explain genetic differences in response to Cd toxicity until 2005. Starting with the mouse Cdm locus associated with differences in Cd-induced testicular necrosis between inbred strains, a 24.6-centiMorgan region on chromosome 3 was reduced ultimately to 880 kb; in this segment is the Slc39a8 gene encoding the ZIP8 Zn2+/HCO3− symporter. In endothelial cells of the testis vasculature, Cd-sensitive mice exhibit high ZIP8 expression, Cd-resistant mice exhibit very low expression. A 168.7-kb bacterial artificial chromosome (BAC) from a 129S6 (Cd-sensitive) BAC library containing the Slc39a8 gene was inserted into the Cd-resistant C57BL/6J genome: Cd treatment produced testicular necrosis in BAC-transgenic BTZIP8-3 mice but not in non-transgenic littermates, thereby proving that the Slc39a8 gene is indeed the Cdm locus. Cd-induced renal failure also occurred in these BTZIP8-3 mice. Immunohistochemistry showed highly expressed ZIP8 protein in the renal proximal tubular epithelial apical surface, suggesting that ZIP8 participates in Cd-induced renal failure. Slc39a14, most closely evolutionarily related to Slc39a8, encodes differentially-spliced products ZIP14A and ZIP14B that display properties similar to ZIP8. ZIP8 in alveolar cells brings environmental Cd into the organism and ZIP14 in intestinal enterocytes carries Cd into the organism and into the hepatocyte. We believe these two transporters function endogenously as Zn2+/HCO3− symporters important in combating inflammation and carrying out other physiological functions; Cd is able to displace the endogenous cation, enter the cell, and produce tissue damage and disease. PMID:19265717

  2. GATA4 Regulates Blood-Testis Barrier Function and Lactate Metabolism in Mouse Sertoli Cells.

    PubMed

    Schrade, Anja; Kyrönlahti, Antti; Akinrinade, Oyediran; Pihlajoki, Marjut; Fischer, Simon; Rodriguez, Verena Martinez; Otte, Kerstin; Velagapudi, Vidya; Toppari, Jorma; Wilson, David B; Heikinheimo, Markku

    2016-06-01

    Conditional deletion of Gata4 in Sertoli cells (SCs) of adult mice has been shown to increase permeability of the blood-testis barrier (BTB) and disrupt spermatogenesis. To gain insight into the molecular underpinnings of these phenotypic abnormalities, we assessed the impact of Gata4 gene silencing in cell culture models. Microarray hybridization identified genes dysregulated by siRNA-mediated inhibition of Gata4 in TM4 cells, an immortalized mouse SC line. Differentially expressed genes were validated by quantitative RT-PCR analysis of primary cultures of Gata4(flox/flox) mouse SCs that had been subjected to cre-mediated recombination in vitro. Depletion of GATA4 in TM4 cells and primary SCs was associated with altered expression of genes involved in key facets of BTB maintenance, including tight/adherens junction formation (Tjp1, Cldn12, Vcl, Tnc, Csk) and extracellular matrix reorganization (Lamc1, Col4a1, Col4a5, Mmp10, Mmp23, Timp2). Western blotting and immunocytochemistry demonstrated reduced levels of tight junction protein-1, a prototypical tight junction protein, in GATA4-depleted cells. These changes were accompanied by a loss of morphologically recognizable junctional complexes and a decline in epithelial membrane resistance. Furthermore, Gata4 gene silencing was associated with altered expression of Hk1, Gpi1, Pfkp, Pgam1, Gls2, Pdk3, Pkd4, and Ldhb, genes regulating the production of lactate, a key nutrient that SCs provide to developing germ cells. Comprehensive metabolomic profiling demonstrated impaired lactate production in GATA4-deficient SCs. We conclude that GATA4 plays a pivotal role in the regulation of BTB function and lactate metabolism in mouse SCs. PMID:26974005

  3. Laparoscopy in the Surgical Management of the Non-Palpable Testis

    PubMed Central

    Castillo-Ortiz, Javier; Muñiz-Colon, Luis; Escudero, Karina; Perez-Brayfield, Marcos

    2014-01-01

    Introduction: To demonstrate that laparoscopic intervention should be considered as the initial surgical approach in the management of the non-palpable testis (NPT). Methods: From 2007 to 2011, 100 testicular units underwent same surgeon laparoscopic management for NPT. Diagnostic laparoscopy was performed in all NPT and intra-abdominal testes (IAT) were managed by laparoscopic orchiopexy if low, laparoscopic Fowler-Stephens technique if high, and laparoscopic orchiectomy if atrophic. Percutaneous access to the abdomen was performed in most cases and laparoscopic management was performed with three 5 mm ports. We compared patient’s age, race, pre/post-operative exam, pre-operative work up, and IAT location upon laparoscopic intervention with surgical outcome. Fisher’s exact test for two independent proportions was used for statistical analysis and reported our results. Results: One hundred testicular units underwent diagnostic laparoscopy for NPT. All patients were from Puerto Rican descent. 55.0% were found to be intra-abdominal and were subdivided into groups according to surgical intervention. Mean post-operative follow-up was 24 months. Patients 24 months of age or younger undergoing diagnostic laparoscopy for NPT had a statistically significant probability of resulting in successful laparoscopic orchiopexy as opposed to laparoscopic orchiectomy due to an atrophied IAT (n = 55 testicular units, p < 0.05). No laparoscopic related complications were reported. Conclusion: Our findings support the use of an initial laparoscopic approach in the NPT as the majority of these patients will have IAT, avoiding unnecessary inguinal and scrotal explorations. We also recommend that patients with IAT should undergo laparoscopic orchiopexy prior to 2 years of age to increase probability of successful management. Further studies focusing in patients with NPT are needed in the future to confirm our findings. PMID:24783184

  4. Discovery of ZIP transporters that participate in cadmium damage to testis and kidney.

    PubMed

    He, Lei; Wang, Bin; Hay, Everett B; Nebert, Daniel W

    2009-08-01

    It has been known for decades that cadmium (Cd) must enter the cell to cause damage, but there was no mechanism to explain genetic differences in response to Cd toxicity until 2005. Starting with the mouse Cdm locus associated with differences in Cd-induced testicular necrosis between inbred strains, a 24.6-centiMorgan region on chromosome 3 was reduced ultimately to 880 kb; in this segment is the Slc39a8 gene encoding the ZIP8 Zn(2+)/HCO(3)(-) symporter. In endothelial cells of the testis vasculature, Cd-sensitive mice exhibit high ZIP8 expression, Cd-resistant mice exhibit very low expression. A 168.7-kb bacterial artificial chromosome (BAC) from a 129S6 (Cd-sensitive) BAC library containing the Slc39a8 gene was inserted into the Cd-resistant C57BL/6J genome: Cd treatment produced testicular necrosis in BAC-transgenic BTZIP8-3 mice but not in non-transgenic littermates, thereby proving that the Slc39a8 gene is indeed the Cdm locus. Cd-induced renal failure also occurred in these BTZIP8-3 mice. Immunohistochemistry showed highly expressed ZIP8 protein in the renal proximal tubular epithelial apical surface, suggesting that ZIP8 participates in Cd-induced renal failure. Slc39a14, most closely evolutionarily related to Slc39a8, encodes differentially-spliced products ZIP14A and ZIP14B that display properties similar to ZIP8. ZIP8 in alveolar cells brings environmental Cd into the organism and ZIP14 in intestinal enterocytes carries Cd into the organism and into the hepatocyte. We believe these two transporters function endogenously as Zn(2+)/HCO(3)(-) symporters important in combating inflammation and carrying out other physiological functions; Cd is able to displace the endogenous cation, enter the cell, and produce tissue damage and disease. PMID:19265717

  5. Characterization of spermatogonial markers in the mature testis of the dogfish (Scyliorhinus canicula L.).

    PubMed

    Bosseboeuf, Adrien; Gautier, Aude; Auvray, Pierrick; Mazan, Sylvie; Sourdaine, Pascal

    2014-01-01

    In dogfish, spermatogenesis progresses from a restricted germinative zone, which lines the dorsal testicular vessel. Single spermatogonia (A(s)), including the spermatogonial stem cells (SSCs), produce successively paired (A(p)), undifferentiated (A(u4) to A(u512)), and differentiated (A(d1) to A(d8)) spermatogonia and preleptotene (PL) spermatocytes through 13 mitoses. Dogfish spermatogonial subpopulations present classical morphological characteristics but cannot be distinguished on the basis of molecular markers. This characterization has been initiated in mammals despite the difficulty to separate each spermatogonial subpopulation. For instance, both glial cell-derived neurotrophic factor family receptor alpha 1 (GFRα1) and promyelocytic leukemia zinc finger protein (PLZF) are markers of undifferentiated spermatogonia, whereas receptor tyrosine kinase C-kit is a marker of differentiated spermatogonia. The aim of this study is to characterize spermatogonial markers and to differentiate several spermatogonial subpopulations. Dogfish cDNA sequences have been identified and validated by phylogenetic analyses for gfrα1, plzf, pou2, as well as for high-mobility group box proteins 2 and 3 (hmgb2 and 3) and for mini-chromosome maintenance protein 6 (mcm6). We have used the anatomical advantage of the polarized dogfish testis to analyze the expression of those markers by RT-PCR and in situ hybridization. gfrα1, pou2, and plzf have been detected in the testicular germinative zone, suggesting that spermatogonial markers are relatively well conserved among vertebrates but with a less restricted expression for plzf. Moreover, hmgb3 and mcm6 have been identified as new markers of differentiated spermatogonia. Finally, this first molecular characterization of spermatogonial subpopulations in a chondrichthyan model will be useful for further studies on the SSC niche evolution. PMID:24123129

  6. Aquaporins in the human testis and spermatozoa - identification, involvement in sperm volume regulation and clinical relevance.

    PubMed

    Yeung, C H; Callies, C; Tüttelmann, F; Kliesch, S; Cooper, T G

    2010-08-01

    Despite the high water-permeability of human spermatozoa, little is known about the identity and the role of aquaporins (AQP) in them or germ cells. Using ejaculates from donors, sperm AQPs were identified by western blotting followed by the analysis of mRNA with RT-PCR. Protein expression in the testis and spermatozoa was localized by immunocytochemistry. Inhibitors were used to investigate the involvement of aquaporins in water transport when ejaculated spermatozoa were swollen in medium mimicking uterine hypo-osmolality by quinine that blocks volume regulation. Sperm AQP7 and AQP8 in 39 infertile patients and 11 healthy donors were quantified by flow cytometry. AQP1 was absent from spermatozoa. Sperm and testicular AQP7-9 had nucleotide sequences identical to those of somatic cells but AQP8 mRNA also showed shorter variants. AQP7 was expressed abundantly by round and elongated spermatids and ejaculated spermatozoa, AQP8 by all germ cells and spermatozoa, and AQP9 rarely by spermatocytes or Sertoli cells. Protein bands showed specificity by western blotting for AQP7 and AQP8 but not AQP9. The absence of sperm AQP9 was further suggested by the ineffectiveness of its inhibitor phloretin in blocking quinine-induced swelling, but HgCl(2,) which inhibits AQP8, was effective. Sperm AQP7 expression was correlated with progressive motility and was lower in patients than in donors. Sperm AQP8 expression was inversely correlated with the extent of sperm coiling, which is a swelling phenomenon, but showed no difference between patients and donors. In conclusion, AQP7 and AQP8 were identified in human spermatozoa and could play a role in glycerol metabolism and water transport respectively.

  7. Differential proteome and gene expression for testis of mice exposed to carbon ion radiation

    NASA Astrophysics Data System (ADS)

    Zhang, Hong; Li, Hongyan

    Objective To investigate the effect and mechanism of high linear energy transfer (LET) carbon ion irradiation (CIR) on reproduction in the testis of male Swiss Webster mice, and assess the risk associated with space environment. Methods Male mice underwent whole-body irradiation with CIR (0.5, 1 and 4Gy), and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF) analysis was used to determine the alteration in protein expression in 2-DE (two-dimensional gel electrophoresis) gels of testes caused by irradiation after 7, 14 days. Results 15 differentially expressed proteins, such as glucose-regulated protein(GRP78), aconitate hydratase-mitochondrial precursor (ACO), pyruvate kinase isozymes M1/M2 (PKM1/M2), glutathione-S-transferaseA3 (GSTA3), glutathione S-transferase Pi 1 (GSTP1), Cu/Zn super-oxide dismutase (SOD1), Peptidyl-prolyl cis-trans isomerase (Pin1) and Heat shock 70 kDa protein 4L (HSPa4L), were identified and these proteins were mainly involved in energy supply, the endoplasmic reticulum, cell proliferation, cell cycle, antioxidant capacity and mitochondrial respiration, which play important roles in the inhibition of testicular function in response to CIR. Furthermore, we confirmed the relationship between transcription of mRNA and the abundance of proteins. Conclusion The findings of the present study demonstrated that these proteins may lead to new insights into the molecular mechanism of CIR toxicity, and suggested that the gene expression response to CIR involves diverse regulatory mechanisms from transcription of mRNA to the formation of functional proteins. These data also may provide a scientific basis for protecting astronauts and space traveler’s health and safety.

  8. Discovery of ZIP transporters that participate in cadmium damage to testis and kidney

    SciTech Connect

    He Lei; Wang Bin; Hay, Everett B.; Nebert, Daniel W.

    2009-08-01

    It has been known for decades that cadmium (Cd) must enter the cell to cause damage, but there was no mechanism to explain genetic differences in response to Cd toxicity until 2005. Starting with the mouse Cdm locus associated with differences in Cd-induced testicular necrosis between inbred strains, a 24.6-centiMorgan region on chromosome 3 was reduced ultimately to 880 kb; in this segment is the Slc39a8 gene encoding the ZIP8 Zn{sup 2+}/HCO{sub 3}{sup -} symporter. In endothelial cells of the testis vasculature, Cd-sensitive mice exhibit high ZIP8 expression, Cd-resistant mice exhibit very low expression. A 168.7-kb bacterial artificial chromosome (BAC) from a 129S6 (Cd-sensitive) BAC library containing the Slc39a8 gene was inserted into the Cd-resistant C57BL/6J genome: Cd treatment produced testicular necrosis in BAC-transgenic BTZIP8-3 mice but not in non-transgenic littermates, thereby proving that the Slc39a8 gene is indeed the Cdm locus. Cd-induced renal failure also occurred in these BTZIP8-3 mice. Immunohistochemistry showed highly expressed ZIP8 protein in the renal proximal tubular epithelial apical surface, suggesting that ZIP8 participates in Cd-induced renal failure. Slc39a14, most closely evolutionarily related to Slc39a8, encodes differentially-spliced products ZIP14A and ZIP14B that display properties similar to ZIP8. ZIP8 in alveolar cells brings environmental Cd into the organism and ZIP14 in intestinal enterocytes carries Cd into the organism and into the hepatocyte. We believe these two transporters function endogenously as Zn{sup 2+}/HCO{sub 3}{sup -} symporters important in combating inflammation and carrying out other physiological functions; Cd is able to displace the endogenous cation, enter the cell, and produce tissue damage and disease.

  9. Expression and immunotherapeutic targeting of the SSX family of cancer-testis antigens in prostate cancer.

    PubMed

    Smith, Heath A; Cronk, Robert J; Lang, Joshua M; McNeel, Douglas G

    2011-11-01

    Recent U.S. Food and Drug Administration approval of the first immunotherapy for prostate cancer encourages efforts to improve immune targeting of this disease. The synovial sarcoma X chromosome breakpoint (SSX) proteins comprise a set of cancer-testis antigens that are upregulated in MHC class I-deficient germline cells and in various types of advanced cancers with a poor prognosis. Humoral and cell-mediated immune responses to the SSX family member SSX2 can arise spontaneously in prostate cancer patients. Thus, SSX2 and other proteins of the SSX family may offer useful targets for tumor immunotherapy. In this study, we evaluated the expression of SSX family members in prostate cancer cell lines and tumor biopsies to identify which members might be most appropriate for immune targeting. We found that SSX2 was expressed most frequently in prostate cell lines, but that SSX1 and SSX5 were also expressed after treatment with the DNA demethylating agent 5-aza-2'-deoxycytidine. Immunohistochemical analysis of microarrayed tissue biopsies confirmed a differential level of SSX protein expression in human prostate cancers. Notably, SSX expression in patient tumor samples was restricted to metastatic lesions (5/22; 23%) and no expression was detected in primary prostate tumors examined (0/73; P < 0.001). We determined that cross-reactive immune responses to a dominant HLA-A2-specific SSX epitope (p103-111) could be elicited by immunization of A2/DR1 transgenic mice with SSX vaccines. Our findings suggest that multiple SSX family members are expressed in metastatic prostate cancers which are amenable to simultaneous targeting. PMID:21880588

  10. Cytoreductive surgery in disseminated non-seminomatous germ cell tumours of testis.

    PubMed

    Kulkarni, R P; Reynolds, K W; Newlands, E S; Dawson, P M; Makey, A R; Theodorou, N A; Bradley, J; Begent, R H; Rustin, G J; Bagshawe, K D

    1991-02-01

    Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49.6 months (range 2-121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories.

  11. Neuregulins are essential for spermatogonial proliferation and meiotic initiation in neonatal mouse testis.

    PubMed

    Zhang, JiDong; Eto, Ko; Honmyou, Asuka; Nakao, Kazuki; Kiyonari, Hiroshi; Abé, Shin-ichi

    2011-08-01

    The transition from mitosis to meiosis is unique to germ cells. In murine embryonic ovaries and juvenile testes, retinoic acid (RA) induces meiosis via the stimulated by retinoic acid gene 8 (Stra8), but its molecular pathway requires elucidation. We present genetic evidence in vivo and in vitro that neuregulins (NRGs) are essential for the proliferation of spermatogonia and the initiation of meiosis. Tamoxifen (TAM) was injected into 14-day post-partum (dpp) Sertoli cell-specific conditional Nrg1(Ser-/-) mutant mice. TAM induced testis degeneration, suppressed BrdU incorporation into spermatogonia and pre-leptotene primary spermatocytes, and decreased and increased the number of STRA8-positive and TUNEL-positive cells, respectively. In testicular organ cultures from 5-6 dpp wild-type mice and cultures of their re-aggregated spermatogonia and Sertoli cells, FSH, RA [all-trans-retinoic acid (ATRA), AM580, 9-cis-RA] and NRG1 promoted spermatogonial proliferation and meiotic initiation. However, TAM treatment of testicular organ cultures from the Nrg1(Ser-/-) mutants suppressed spermatogonial proliferation and meiotic initiation that was promoted by FSH or AM580. In re-aggregated cultures of purified spermatogonia, NRG1, NRG3, ATRA and 9-cis-RA promoted their proliferation and meiotic initiation, but neither AM580 nor FSH did. In addition, FSH, RAs and NRG1 promoted Nrg1 and Nrg3 mRNA expression in Sertoli cells. These results indicate that in juvenile testes RA and FSH induced meiosis indirectly through Sertoli cells when NRG1 and NRG3 were upregulated, as NRG1 amplified itself and NRG3. The amplified NRG1 and NRG3 directly induced meiosis in spermatogonia. In addition, ATRA and 9-cis-RA activated spermatogonia directly and promoted their proliferation and eventually meiotic initiation.

  12. [Chemotherapy of carcinoma of the prostate and testis: experimental study in vivo and in vitro].

    PubMed

    Okada, K; Kanamaru, H; Yoshiki, T; Hashimura, T; Nishimura, K; Hida, S; Nishio, Y; Oishi, K; Yoshida, O; Yamauchi, T

    1988-11-01

    Prostate cancer: Considering the stagnation in chemotherapy of prostate cancer in recent years, the following experiments were carried out to determine their clinical value. Surgical specimens from 6 patients, 2 permanent cell lines (EB 33 and PC 93) originated from human prostate cancer and a tumor line serially transplanted in nude mice (PC-NCC) were subjected to chemosensitivity tests such as human tumor cloning assay (HTCA) and/or in vivo tumor growth curve experiments using nude mice. The possible chemosensitive drugs screened by using surgical specimens and PC-NCC tumor were cisplatinum (CDDP), bleomycin (BLM), 5-FU, vincristine (VCR), adriamycin (ADM) and methotrexate (MTX). Most of these drugs were also judged as "effective" by HTCA using a permanent cell line. The minimal discrepancy among them may lead to the conclusion that an in vitro assay using a cell line can substitute for the assay using surgical specimens which can not be obtained frequently. Partly based on the data obtained a chemotherapy regimen, VPM-CisCF, consisting of VCR, peplomycin, MTX, CDDP, cytosine arabinoside (Ara-C) and 5-FU, was designed. The effectiveness of this regimen was demonstrated experimentally. Testis cancer: Two different lines of experiments were performed. A human testicular cancer serially transplanted in nude mice was repeatedly exposed to CDDP in vivo to obtain hyposensitivity to this drug. The synergistic effect of CDDP and VP-16 was demonstrated in the tumor thus obtained. One of its mechanisms has been suggested by partial accumulation of cancer cells in the G1-S and G2-M phase in which CDDP exerts its potential effect.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Cell context-specific expression of primary cilia in the human testis and ciliary coordination of Hedgehog signalling in mouse Leydig cells.

    PubMed

    Nygaard, Marie Berg; Almstrup, Kristian; Lindbæk, Louise; Christensen, Søren Tvorup; Svingen, Terje

    2015-01-01

    Primary cilia are sensory organelles that coordinate numerous cellular signalling pathways during development and adulthood. Defects in ciliary assembly or function lead to a series of developmental disorders and diseases commonly referred to as ciliopathies. Still, little is known about the formation and function of primary cilia in the mammalian testis. Here, we characterized primary cilia in adult human testis and report a constitutive expression of cilia in peritubular myoid cells and a dynamic expression of cilia in differentiating Leydig cells. Primary cilia are generally absent from cells of mature seminiferous epithelium, but present in Sertoli cell-only tubules in Klinefelter syndrome testis. Peritubular cells in atrophic testis produce overly long cilia. Furthermore cultures of growth-arrested immature mouse Leydig cells express primary cilia that are enriched in components of Hedgehog signalling, including Smoothened, Patched-1, and GLI2, which are involved in regulating Leydig cell differentiation. Stimulation of Hedgehog signalling increases the localization of Smoothened to the cilium, which is followed by transactivation of the Hedgehog target genes, Gli1 and Ptch1. Our findings provide new information on the spatiotemporal formation of primary cilia in the testis and show that primary cilia in immature Leydig cells mediate Hedgehog signalling. PMID:25992706

  14. Organizational and expressional uniqueness of a testis-specific mRNA transcript of protooncogene c-kit receptor in water buffalo Bubalus bubalis.

    PubMed

    Srivastava, Jyoti; Premi, Sanjay; Garg, Lalit C; Ali, Sher

    2006-09-01

    Protooncogene c-kit receptor is implicated with spermatogenesis, melanogenesis, and hematopoeisis, and undergoes tissue/stage specific alternate splicing. We have isolated 2973-bp full-length cDNA sequence (CDS) of this gene from testis and other tissues of water buffalo Bubalus bubalis. Upon comparison, the c-kit sequences showed tissue specific nucleotide changes resulting in novel truncated peptides. These peptides lacked intracellular and/or transmembrane domains in all the tissues except testis. Other alternately spliced tissue-specific transcripts were also detected, which are the integral parts of the open reading frame and have been reported in other mammals. Phylogenetic analysis of the sequences revealed unique tyrosine kinase domain in buffalo. Copy number calculation and expressional analysis of c-kit using real-time PCR established its single copy status and highest expression (137-177 folds) in testis compared to that (least) in liver. c-kit expression was detected in semen samples although 10 times lesser compared to that in testis. The highest expression of c-kit in testis and the presence of mRNA transcript in sperms substantiate its predominant role in spermatogenesis. This study establishes unequivocal involvement of an autosomal gene c-kit receptor in testicular function.

  15. Cell context-specific expression of primary cilia in the human testis and ciliary coordination of Hedgehog signalling in mouse Leydig cells.

    PubMed

    Nygaard, Marie Berg; Almstrup, Kristian; Lindbæk, Louise; Christensen, Søren Tvorup; Svingen, Terje

    2015-01-01

    Primary cilia are sensory organelles that coordinate numerous cellular signalling pathways during development and adulthood. Defects in ciliary assembly or function lead to a series of developmental disorders and diseases commonly referred to as ciliopathies. Still, little is known about the formation and function of primary cilia in the mammalian testis. Here, we characterized primary cilia in adult human testis and report a constitutive expression of cilia in peritubular myoid cells and a dynamic expression of cilia in differentiating Leydig cells. Primary cilia are generally absent from cells of mature seminiferous epithelium, but present in Sertoli cell-only tubules in Klinefelter syndrome testis. Peritubular cells in atrophic testis produce overly long cilia. Furthermore cultures of growth-arrested immature mouse Leydig cells express primary cilia that are enriched in components of Hedgehog signalling, including Smoothened, Patched-1, and GLI2, which are involved in regulating Leydig cell differentiation. Stimulation of Hedgehog signalling increases the localization of Smoothened to the cilium, which is followed by transactivation of the Hedgehog target genes, Gli1 and Ptch1. Our findings provide new information on the spatiotemporal formation of primary cilia in the testis and show that primary cilia in immature Leydig cells mediate Hedgehog signalling.

  16. Coexpression of Nuclear Receptors and Histone Methylation Modifying Genes in the Testis: Implications for Endocrine Disruptor Modes of Action

    PubMed Central

    Anderson, Alison M.; Carter, Kim W.; Anderson, Denise; Wise, Michael J.

    2012-01-01

    Background Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. Methodology/Principal Findings The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. Conclusions/Significance This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods. PMID:22496781

  17. CD90 and CD105 expression in the mouse ovary and testis at different stages of postnatal development.

    PubMed

    Tepekoy, Filiz; Ozturk, Saffet; Sozen, Berna; Ozay, Recep S; Akkoyunlu, Gokhan; Demir, Necdet

    2015-12-01

    CD90 (i.e., THY1) and CD105 (i.e., endoglin) are glycoproteins known as mesenchymal stem cell markers that are expressed in various cell types including male and female gonadal cells. We aimed to determine ovarian and testicular expression of CD90 and CD105 in various cell types during postnatal development in mice. The present study was carried out on male (C57BL/6) and female (Balb/C) mice during critical stages of gonadal development. Immunohistochemical localization of CD90 and CD105 was determined in the ovaries obtained at postnatal days (PND) -1, -7, -21 and -60 and in the testes obtained at PND6, -8, -16, -20, -29, -32 and -88. The relative expression of CD90 and CD105 was evaluated by ImageJ software and data were analyzed by analysis of variance. The relative expression of CD90 and CD105 varied during postnatal development and increased significantly in the adult ovary (PND60) and testis (PND88) compared to the early postnatal gonads. In the ovaries, the expression of CD90 was significantly higher in somatic cells in comparison to germ cell compartments. In the testis, CD90 expression was greater in germ cells and Sertoli cells compared to other cell types. Expression of CD105 was higher in germ cells than somatic cells of both the ovary and testis. In addition to different expression of CD90 and CD105 during various developmental stages, also their altered expression in particular cell types suggests specific roles of these glycoproteins in physiological processes of mouse gonads.

  18. Maternal obesity disturbs the postnatal development of gonocytes in the rat without impairment of testis structure at prepubertal age.

    PubMed

    Christante, Caroline Maria; Taboga, Sebastião Roberto; Pinto-Fochi, Maria Etelvina; Góes, Rejane Maira

    2013-12-01

    In this study, we evaluated whether maternal obesity (MO) affects testis development and gonocyte differentiation in the rat from 0.5 to 14.5 postnatal days. Male Wistar rats were used at 0.5, 4.5, 7.5, and 14.5 days post partum (dpp). These rats were born from obese mothers, previously fed with a high-fat diet (20% saturated fat), for 15 weeks, or normal mothers that had received a balanced murine diet (4% lipids). MO did not affect testis weight or histology at birth but changed the migratory behavior of gonocytes. The density of relocated cells was higher in MO pups at 0.5 dpp, decreased at 4.5 dpp, and differed from those of control pups, where density increased exponentially from 0.5 to 7.5 dpp. The numerical density of gonocytes within seminiferous cords did not vary in MO, in relation to control neonates, for any age considered, but the testis weight was 50% lower at 4.5 dpp. A wide variation in plasmatic testosterone and estrogen levels was observed among the groups during the first week of age and MO pups exhibited higher steroid concentrations at 4.5 dpp, in comparison with controls. At this age, higher estrogen levels of MO pups impaired the gonocyte proliferation. At 7.5 dpp, the testicular size and other parameters of gonocyte development are retrieved. In conclusion, MO and saturated lipid diets disturb gonocyte development and sexual steroid levels during the first days of life, with recovery at prepubertal age.

  19. Prepubertal mouse testis growth and maturation and androgen production are acutely sensitive to di-n-butyl phthalate.

    PubMed

    Moody, Sarah; Goh, Hoey; Bielanowicz, Amanda; Rippon, Paul; Loveland, Kate L; Itman, Catherine

    2013-09-01

    Phthalates are plasticizers with widespread industrial, domestic, and medical applications. Epidemiological data indicating increased incidence of testicular dysgenesis in boys exposed to phthalates in utero are reinforced by studies demonstrating that phthalates impair fetal rodent testis development. Because humans are exposed to phthalates continuously from gestation through adulthood, it is imperative to understand what threat phthalates pose at other life stages. To determine the impact during prepuberty, we assessed the consequences of oral administration of 1 to 500 mg di-n-butyl phthalate (DBP)/kg/d in corn oil to wild-type (C57BL/6J) male mice from 4 to 14 days of age. Dose-dependent effects on testis growth correlated with reduced Sertoli cell proliferation. Histological and immunohistochemical analyses identified delayed spermatogenesis and impaired Sertoli cell maturation after exposure to 10 to 500 mg DBP/kg/d. Interference with the hypothalamic-pituitary-gonadal axis was indicated in mice fed 500 mg DBP/kg/d, which had elevated circulating inhibin but no change in serum FSH. Increased immunohistochemical staining for inhibin-α was apparent at doses of 10 to 500 mg DBP/kg/d. Serum testosterone and testicular androgen activity were lower in the 500 mg DBP/kg/d group; however, reduced anogenital distance in all DBP-treated mice suggested impaired androgen action at earlier time points. Long-term effects were evident, with smaller anogenital distance and indications of disrupted spermatogenesis in adult mice exposed prepubertally to doses from 1 mg DBP/kg/d. These data demonstrate the acute sensitivity of the prepubertal mouse testis to DBP at doses 50- to 500-fold lower than those used in rat and identify the upregulation of inhibin as a potential mechanism of DBP action.

  20. The SPANX gene family of cancer/testis-specific antigens: rapid evolution and amplification in African great apes and hominids.

    PubMed

    Kouprina, Natalay; Mullokandov, Michael; Rogozin, Igor B; Collins, N Keith; Solomon, Greg; Otstot, John; Risinger, John I; Koonin, Eugene V; Barrett, J Carl; Larionov, Vladimir

    2004-03-01

    Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes comprise a gene family with five known members (SPANX-A1, -A2, -B, -C, and -D), encoding cancer/testis-specific antigens that are potential targets for cancer immunotherapy. These highly similar paralogous genes cluster on the X chromosome at Xq27. We isolated and sequenced primate genomic clones homologous to human SPANX. Analysis of these clones and search of the human genome sequence revealed an uncharacterized group of genes, SPANX-N, which are present in all primates as well as in mouse and rat. In humans, four SPANX-N genes comprise a series of tandem duplicates at Xq27; a fifth member of this subfamily is located at Xp11. Similarly to SPANX-A/D, human SPANX-N genes are expressed in normal testis and some melanoma cell lines; testis-specific expression of SPANX is also conserved in mouse. Analysis of the taxonomic distribution of the long and short forms of the intron indicates that SPANX-N is the ancestral form, from which the SPANX-A/D subfamily evolved in the common ancestor of the hominoid lineage. Strikingly, the coding sequences of the SPANX genes evolved much faster than the intron and the 5' untranslated region. There is a strong correlation between the rates of evolution of synonymous and nonsynonymous codon positions, both of which are accelerated 2-fold or more compared to the noncoding sequences. Thus, evolution of the SPANX family appears to have involved positive selection that affected not only the protein sequence but also the synonymous sites in the coding sequence.

  1. The role of CAPE in PI3K/AKT/mTOR activation and oxidative stress on testis torsion.

    PubMed

    Dilber, Yagmur; Inan, Sevinc; Ercan, Gulinnaz Alper; Sencan, Aydin

    2016-01-01

    Ischemia reperfusion injury arises from testicular torsion resulting in a loss of spermatogenesis and significant germ cell apoptosis. This study evaluates the prooxidant/antioxidant effects of caffeic acid phenethyl ester (CAPE) through PI3K/AKT/mTOR signal pathways on testis torsion. A total of (28) male Wistar rats were divided randomly into 4 groups (n=7 for each group):group A (sham) group,group B torsion/detorsion group, group C (saturation group, during four days of CAPE, one dose (10 μmol/kg, i.p)) and group D (a single dose of CAPE 2h after torsion and before detorsion). At the end of the study, unilateral orchiectomies were performed for measurements of MDA and 8OHdG levels, histopathologic and immunohistochemical and TUNEL apoptotic cell examination. Testicular torsion-detorsion led to a significant decrease in the mean values of the Johnsen's scores and a significant increase in the apoptotic cell values of group B. There were no significant differences between group D and group A. In addition, the MDA and 8OHdG levels increased significantly in group B. The MDA and 8OHdG values were lower in group D. However, the 8OHdG levels were higher in group C than the groups A and D. On the other hand, CAPE suppresses mTOR activation and reduces the apoptosis on ischemia/reperfusion damage in rat testis. These results demonstrate that CAPE suppresses mTOR activation and reduces the apoptosis on ischemia/reperfusion damage in rat testis. PMID:26651953

  2. Secretion of Unconjugated Androgens and Estrogens by the Normal and Abnormal Human Testis before and after Human Chorionic Gonadotropin

    PubMed Central

    Weinstein, R. L.; Kelch, R. P.; Jenner, M. R.; Kaplan, S. L.; Grumbach, M. M.

    1974-01-01

    The secretion of androgens and estrogens by normal and abnormal testes was compared by determining the concentrations of dehydroepiandrosterone (DHEA), androstenedione (Δ4A), testosterone (T), estrone (E1), and 17β-estradiol (E2) in peripheral and spermatic venous plasma samples from 14 normal men and 5 men with unilateral testicular atrophy. Four normal men and one patient with unilateral atrophy of the testis were given human chorionic gonadotropin (HCG) before surgery. Plasma estrogens were determined by radioimmunoassay; plasma androgens were measured by the double-isotope dilution derivative technique. Peripheral concentrations of these steroids before and after HCG were similar in both the normal men and the patients with unilateral testicular atrophy. In normal men, the mean ±SE spermatic venous concentrations were DHEA, 73.1±11.7 ng/ml; Δ4A, 30.7±7.9 ng/ml; T, 751±114 ng/ml; E1, 306±55 pg/ml; and E2, 1298±216 pg/ml. Three of four subjects with unilateral testicular atrophy had greatly diminished spermatic venous levels of androgens and estrogens. HCG treatment increased the testicular secretion of DHEA and T fivefold, Δ4A threefold, E1 sixfold, and E2 eightfold in normal men. In the single subject with an atrophic testis who received HCG, the spermatic venous concentrations of androgens and estrogens were much less than in normal men similarly treated. We conclude that: (a) E1 is secreted by the human testis, but testicular secretion of E1 accounts for less than 5% of E1 production in normal men; (b) HCG stimulation produces increases in spermatic venous estrogens equal to or greater than the changes in androgens, including testosterone; and (c) strikingly decreased secretion of androgen and estrogen by unilateral atrophic human tests cannot be appreciated by analyses of peripheral steroid concentrations. PMID:4271572

  3. Wt1 dictates the fate of fetal and adult Leydig cells during development in the mouse testis.

    PubMed

    Wen, Qing; Zheng, Qiao-Song; Li, Xi-Xia; Hu, Zhao-Yuan; Gao, Fei; Cheng, C Yan; Liu, Yi-Xun

    2014-12-15

    Wilms' tumor 1 (Wt1) is a tumor suppressor gene encoding ∼24 zinc finger transcription factors. In the mammalian testis, Wt1 is expressed mostly by Sertoli cells (SCs) involved in testis development, spermatogenesis, and adult Leydig cell (ALC) steroidogenesis. Global knockout (KO) of Wt1 is lethal in mice due to defects in embryogenesis. Herein, we showed that Wt1 is involved in regulating fetal Leydig cell (FLC) degeneration and ALC differentiation during testicular development. Using Wt1(-/flox);Amh-Cre mice that specifically deleted Wt1 in the SC vs. age-matched wild-type (WT) controls, FLC-like-clusters were found in Wt1-deficient testes that remained mitotically active from postnatal day 1 (P1) to P56, and no ALC was detected at these ages. Leydig cells in mutant adult testes displayed morphological features of FLC. Also, FLC-like cells in adult mutant testes had reduced expression in ALC-associated genes Ptgds, Sult1e1, Vcam1, Hsd11b1, Hsd3b6, and Hsd17b3 but high expression of FLC-associated genes Thbs2 and Hsd3b1. Whereas serum LH and testosterone level in mutant mice were not different from controls, intratesticular testosterone level was significantly reduced. Deletion of Wt1 gene also perturbed the expression of steroidogenic enzymes Star, P450c17, Hsd3b6, Hsd3b1, Hsd17b1, and Hsd17b3. FLCs in adult mutant testes failed to convert androstenedione to testosterone due to a lack of Hsd17b3, and this defect was rescued by coculturing with fetal SCs. In summary, FLC-like cells in mutant testes are putative FLCs that remain mitotically active in adult mice, illustrating that Wt1 dictates the fate of FLC and ALC during postnatal testis development.

  4. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice

    PubMed Central

    Miyata, Haruhiko; Castaneda, Julio M.; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R.; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L.; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M.; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M.

    2016-01-01

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201–12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract–enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the “gold standard” to determine whether a gene’s function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  5. Alternative splicing, promoter methylation, and functional SNPs of sperm flagella 2 gene in testis and mature spermatozoa of Holstein bulls.

    PubMed

    Guo, F; Yang, B; Ju, Z H; Wang, X G; Qi, C; Zhang, Y; Wang, C F; Liu, H D; Feng, M Y; Chen, Y; Xu, Y X; Zhong, J F; Huang, J M

    2014-02-01

    The sperm flagella 2 (SPEF2) gene is essential for development of normal sperm tail and male fertility. In this study, we characterized first the splice variants, promoter and its methylation, and functional single-nucleotide polymorphisms (SNPs) of the SPEF2 gene in newborn and adult Holstein bulls. Four splice variants were identified in the testes, epididymis, sperm, heart, spleen, lungs, kidneys, and liver tissues through RT-PCR, clone sequencing, and western blot analysis. Immunohistochemistry revealed that the SPEF2 was specifically expressed in the primary spermatocytes, elongated spermatids, and round spermatids in the testes and epididymis. SPEF2-SV1 was differentially expressed in the sperms of high-performance and low-performance adult bulls; SPEF2-SV2 presents the highest expression in testis and epididymis; SPEF2-SV3 was only detected in testis and epididymis. An SNP (c.2851G>T) in exon 20 of SPEF2, located within a putative exonic splice enhancer, potentially produced SPEF2-SV3 and was involved in semen deformity rate and post-thaw cryopreserved sperm motility. The luciferase reporter and bisulfite sequencing analysis suggested that the methylation pattern of the core promoter did not significantly differ between the full-sib bulls that presented hypomethylation in the ejaculated semen and testis. This finding indicates that sperm quality is unrelated to SPEF2 methylation pattern. Our data suggest that alternative splicing, rather than methylation, is involved in the regulation of SPEF2 expression in the testes and sperm and is one of the determinants of sperm motility during bull spermatogenesis. The exonic SNP (c.2851G>T) produces aberrant splice variants, which can be used as a candidate marker for semen traits selection breeding of Holstein bulls.

  6. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice.

    PubMed

    Miyata, Haruhiko; Castaneda, Julio M; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M

    2016-07-12

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201-12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract-enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the "gold standard" to determine whether a gene's function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  7. Ameliorative effects of N-acetylcysteine on fluoride-induced oxidative stress and DNA damage in male rats' testis.

    PubMed

    Feng, Demin; Huang, Hui; Yang, Yang; Yan, Ting; Jin, Yuefei; Cheng, Xuemin; Cui, Liuxin

    2015-10-01

    This study was to elucidate DNA damage in rats treated with sodium fluoride (NaF) by performing 8-Hydroxy-2-deoxyguanosine (8-OHdG) immunohistochemical staining assays on seminiferous tubules of rats' testis, and also to evaluate the protective effects of N-acetylcysteine (NAC) on spermatogenesis. Male Sprague Dawley (SD) rats were exposed to a single dose of NaF (25mg/kg/day) with or without NAC (150mg/kg/day) for 7 weeks (7W) by gastric gavage. Testicular fluorine content was detected by fluorine ion selective electrode method. Oxidative damage to DNA was evaluated by measuring the increase in 8-OHdG formation in testicular tissue through immunohistochemical staining assays and also the effects of NAC pretreatment. The biochemical indicators about oxidative stress were detected by colorimetric assays, sperm parameters and the morphological changes of testis were studied. NaF significantly increased serum levels of oxidative stress, markedly elevated testicular fluorine and 8-OHdG expression levels as well as the rate of sperm aberration compared to saline group. Testosterone in serum, sperm counts and the mobility of sperm were lower than those of the rats in control group. The pathological morphological changes in testicular seminiferous tubule were also obvious in the rats with NaF treatment. Pretreatment with NAC did not reduce the contents of fluoride content in testis, but significantly reduced 8-OHdG formation and lipid peroxidation. This study suggests that NAC may have certain antagonism on the reproductive damage induced by NaF.

  8. Comparative Transcriptome Analysis of the Accessory Sex Gland and Testis from the Chinese Mitten Crab (Eriocheir sinensis)

    PubMed Central

    He, Lin; Jiang, Hui; Cao, Dandan; Liu, Lihua; Hu, Songnian; Wang, Qun

    2013-01-01

    The accessory sex gland (ASG) is an important component of the male reproductive system, which functions to enhance the fertility of spermatozoa during male reproduction. Certain proteins secreted by the ASG are known to bind to the spermatozoa membrane and affect its function. The ASG gene expression profile in Chinese mitten crab (Eriocheir sinensis) has not been extensively studied, and limited genetic research has been conducted on this species. The advent of high-throughput sequencing technologies enables the generation of genomic resources within a short period of time and at minimal cost. In the present study, we performed de novo transcriptome sequencing to produce a comprehensive transcript dataset for the ASG of E. sinensis using Illumina sequencing technology. This analysis yielded a total of 33,221,284 sequencing reads, including 2.6 Gb of total nucleotides. Reads were assembled into 85,913 contigs (average 218 bp), or 58,567 scaffold sequences (average 292 bp), that identified 37,955 unigenes (average 385 bp). We assembled all unigenes and compared them with the published testis transcriptome from E. sinensis. In order to identify which genes may be involved in ASG function, as it pertains to modification of spermatozoa, we compared the ASG and testis transcriptome of E. sinensis. Our analysis identified specific genes with both higher and lower tissue expression levels in the two tissues, and the functions of these genes were analyzed to elucidate their potential roles during maturation of spermatozoa. Availability of detailed transcriptome data from ASG and testis in E. sinensis can assist our understanding of the molecular mechanisms involved with spermatozoa conservation, transport, maturation and capacitation and potentially acrosome activation. PMID:23342039

  9. Influence of season on seminal characteristics, testis size and serum testosterone in the western spotted skunk (Spilogale gracilis).

    PubMed

    Kaplan, J B; Mead, R A

    1993-07-01

    The western spotted skunk is a seasonally breeding mammal: most copulations occur in late September and early October. This study was performed to characterize the seasonal changes in concentrations of testosterone and in ejaculate quality. Captive males (n = 22) were maintained on a natural photoperiod for 15 months. Semen samples were collected by electroejaculation; testis size was measured; and blood samples were collected. Of 110 electroejaculation attempts, 104 (95%) resulted in successful fluid collection and 101 (97%) samples contained spermatozoa. Significant increases (P < 0.05) in serum testosterone concentration, testis size and ejaculate volume were observed from August to November. Mean concentration of testosterone in serum ranged from 0.15 +/- 0.05 ng ml-1 in mid-January to 6.42 +/- 1.79 ng ml-1 in early October. Mean testis size ranged from 1.22 +/- 0.25 cm2 in February to 2.68 +/- 0.08 cm2 in October. Mean ejaculate volume ranged from 11 +/- 3 microliters in March to 129 +/- 22 microliters in October. Seasonal changes in the number of spermatozoa per ejaculate or motility of spermatozoa were not observed. Mean number of spermatozoa per ejaculate was 8.14 +/- 0.85 x 10(6) spermatozoa (n = 97); motility was 56 +/- 2.4% (n = 93); semen pH was 7.76 +/- 0.20 (n = 6); osmolarity was 394 +/- 13 mmol kg-1 (n = 10); and 70.3 +/- 1.5% of the spermatozoa were morphologically normal (n = 47).(ABSTRACT TRUNCATED AT 250 WORDS)

  10. The Drosophila BCL6 homolog ken and barbie promotes somatic stem cell self-renewal in the testis niche

    PubMed Central

    Issigonis, Melanie; Matunis, Erika

    2012-01-01

    Stem cells sustain tissue regeneration by their remarkable ability to replenish the stem cell pool and to generate differentiating progeny. Signals from local microenvironments, or niches, control stem cell behavior. In the Drosophila testis, a group of somatic support cells called the hub creates a stem cell niche by locally activating the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway in two adjacent types of stem cells: germline stem cells (GSCs) and somatic cyst stem cells (CySCs). Here, we find that ken and barbie (ken) is autonomously required for the self-renewal of CySCs but not GSCs. Furthermore, Ken misexpression in the CySC lineage induces the cell-autonomous self-renewal of somatic cells as well as the nonautonomous self-renewal of germ cells outside the niche. Thus, Ken, like Stat92E and its targets ZFH1 (Leatherman and Dinardo, 2008) and Chinmo (Flaherty et al., 2010), is necessary and sufficient for CySC renewal. However, ken is not a JAK-STAT target in the testis, but instead acts in parallel to Stat92E to ensure CySC self-renewal. Ken represses a subset of Stat92E targets in the embryo (Arbouzova et al., 2006) suggesting that Ken maintains CySCs by repressing differentiation factors. In support of this hypothesis, we find that the global JAKSTAT inhibitor Protein tyrosine phosphatase 61F (Ptp61F) is a JAK-STAT target in the testis that is repressed by Ken. Together, our work demonstrates that Ken has an important role in the in the inhibition of CySC differentiation. Studies of ken may inform our understanding of its vertebrate orthologue B-Cell Lymphoma 6 (BCL6) and how misregulation of this oncogene leads to human lymphomas. PMID:22580161

  11. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

    PubMed

    Li, Nan; Mruk, Dolores D; Mok, Ka-Wai; Li, Michelle W M; Wong, Chris K C; Lee, Will M; Han, Daishu; Silvestrini, Bruno; Cheng, C Yan

    2016-04-01

    Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to

  12. Ubiquitin ligase gene neurl3 plays a role in spermatogenesis of half-smooth tongue sole (Cynoglossus semilaevis) by regulating testis protein ubiquitination.

    PubMed

    Xu, Wenteng; Li, Hailong; Dong, Zhongdian; Cui, Zhongkai; Zhang, Ning; Meng, Liang; Zhu, Ying; Liu, Yang; Li, Yangzhen; Guo, Hua; Ma, Jialu; Wei, Zhanfei; Zhang, Nianwei; Yang, Yingming; Chen, Songlin

    2016-10-30

    E3 ubiquitin ligases are a large gene family that plays a diversity of roles in spermatogenesis. In this study, the functional characterization of a neuralized E3 ubiquitin protein ligase 3 (neurl3) revealed its potential participation in spermatogenesis. Firstly, we found that neurl3 exhibited male-biased transcription and that its translation was predominant in testis germ cells. The knockdown of neurl3 by RNA interference caused increased transcription of spermatogenesis-related genes. These results corroborate previous studies indicating a role for neurl3 in spermatogenesis. Moreover, the levels of neurl3 transcription and testis protein ubiquitination were closely correlated. Based on these findings, we speculate that neurl3 modulates testis protein ubiquitination in a dosage-dependent manner and that this influences spermatogenesis. PMID:27480167

  13. Molecular characterization and expression of dipeptidase 3, a testis-specific membrane-bound dipeptidase: complex formation with TEX101, a germ-cell-specific antigen in the mouse testis.

    PubMed

    Yoshitake, Hiroshi; Yanagida, Mitsuaki; Maruyama, Mayuko; Takamori, Kenji; Hasegawa, Akiko; Araki, Yoshihiko

    2011-08-01

    We previously established an anti-sperm head auto-monoclonal antibody designated Ts4. The immunoreactivity of this antibody was also observed in other reproduction-related cells, such as testicular germ cells and early embryos, suggesting that the Ts4-recognized molecules might play a role in the reproductive process. However, the molecular characteristics and functions of the antigens warrant further clarification. In this study, we primarily attempted identification of the mAb-recognized molecules within the mouse testis. An immunoprecipitation method, together with liquid chromatography-tandem mass spectrometry, revealed that the testicular immunoprecipitants with Ts4 contained dipeptidase 3 (DPEP3), a member of the membrane-bound dipeptidase family. A Western blot analysis using an anti-DPEP3 polyclonal antibody established in this study showed that this molecule was glycosylated and formed a disulfide-linked homodimer within the testis. Expression of DPEP3 protein was observed in the testicular germ cells, but not in the Sertoli or interstitial cells, or in any other major organs. Although Western blot analysis of testicular proteins separated by two-dimensional SDS-PAGE failed to demonstrate binding of Ts4 to DPEP3, we found that DPEP3 forms complexes with Ts4-immunoreactive molecules, such as TEX101, on the surfaces of spermatocytes, spermatids, and testicular spermatozoa. Based on data showing in the present study, further studies concerning DPEP3 on the testicular germ cells may help to clarify the molecular mechanisms of testicular germ-cell development.

  14. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

    SciTech Connect

    Lacorte, Livia M.; Rinaldi, Jaqueline C.; Justulin, Luis A.; Delella, Flávia K.; Moroz, Andrei; Felisbino, Sérgio L.

    2015-02-20

    Matrix metalloproteinases (MMPs) are zinc (Zn{sup 2+}) and calcium (Ca{sup 2+}) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd{sup 2+}) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd{sup 2+} intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl{sub 2} diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 μM or 2 mM cadmium chloride (CdCl{sub 2}) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl{sub 2} intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd{sup 2+} treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 μM and 2 mM of CdCl{sub 2}, respectively, even in the presence of 10 mM of CaCl{sub 2} within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its

  15. Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis.

    PubMed

    Amoyel, Marc; Anderson, Jason; Suisse, Annabelle; Glasner, Johanna; Bach, Erika A

    2016-01-01

    The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs), which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs), which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK) signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior. PMID:26807580

  16. Socs36E Controls Niche Competition by Repressing MAPK Signaling in the Drosophila Testis

    PubMed Central

    Amoyel, Marc; Anderson, Jason; Suisse, Annabelle; Glasner, Johanna; Bach, Erika A.

    2016-01-01

    The Drosophila testis is a well-established system for studying stem cell self-renewal and competition. In this tissue, the niche supports two stem cell populations, germ line stem cells (GSCs), which give rise to sperm, and somatic stem cells called cyst stem cells (CySCs), which support GSCs and their descendants. It has been established that CySCs compete with each other and with GSCs for niche access, and mutations have been identified that confer increased competitiveness to CySCs, resulting in the mutant stem cell and its descendants outcompeting wild type resident stem cells. Socs36E, which encodes a negative feedback inhibitor of the JAK/STAT pathway, was the first identified regulator of niche competition. The competitive behavior of Socs36E mutant CySCs was attributed to increased JAK/STAT signaling. Here we show that competitive behavior of Socs36E mutant CySCs is due in large part to unbridled Mitogen-Activated Protein Kinase (MAPK) signaling. In Socs36E mutant clones, MAPK activity is elevated. Furthermore, we find that clonal upregulation of MAPK in CySCs leads to their outcompetition of wild type CySCs and of GSCs, recapitulating the Socs36E mutant phenotype. Indeed, when MAPK activity is removed from Socs36E mutant clones, they lose their competitiveness but maintain self-renewal, presumably due to increased JAK/STAT signaling in these cells. Consistently, loss of JAK/STAT activity in Socs36E mutant clones severely impairs their self-renewal. Thus, our results enable the genetic separation of two essential processes that occur in stem cells. While some niche signals specify the intrinsic property of self-renewal, which is absolutely required in all stem cells for niche residence, additional signals control the ability of stem cells to compete with their neighbors. Socs36E is node through which these processes are linked, demonstrating that negative feedback inhibition integrates multiple aspects of stem cell behavior. PMID:26807580

  17. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis.

    PubMed

    Lacorte, Livia M; Rinaldi, Jaqueline C; Justulin, Luis A; Delella, Flávia K; Moroz, Andrei; Felisbino, Sérgio L

    2015-02-20

    Matrix metalloproteinases (MMPs) are zinc (Zn(2+)) and calcium (Ca(2+)) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd(2+)) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd(2+) intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl2 diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 μM or 2 mM cadmium chloride (CdCl2) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl2 intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd(2+) treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 μM and 2 mM of CdCl2, respectively, even in the presence of 10 mM of CaCl2 within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its exposure. PMID:25600809

  18. Primary carcinoid tumors of the testis: a clinicopathologic study of 29 cases.

    PubMed

    Wang, Wenle P; Guo, Charles; Berney, Daniel M; Ulbright, Thomas M; Ubright, Thomas M; Hansel, Donna E; Shen, Rulong; Ali, Tehmina; Epstein, Jonathan I

    2010-04-01

    Testicular carcinoid tumors are rare with only limited studies. We identified 29 primary testicular carcinoid cases from 7 academic institutions. Patients ranged in age from 12 to 65 years old (mean 36). The most common presenting symptom was the sole finding of either a testicular mass or swelling seen in 15/24 cases with available information. The next most common mode of presentation was as an incidental finding seen in 6 cases. Two patients had carcinoid syndrome including diarrhea, hot flashes, and palpitations. Nineteen were pure carcinoid tumors, 3 were associated with cystic teratoma, 2 with cysts lacking epithelial lining, 4 with epidermoid cyst, and 1 with dermoid cyst. The mean size was 2.5 cm. All 29 primary carcinoids lacked associated intratubular germ cell neoplasia, unclassified type. Mitotic figures were rare in primary carcinoid tumors with only 3 cases showing more than 2 per 10 HPF; necrosis was found in only 1 case. Random scattered mild to moderate nuclear atypia was seen in 12/29 cases. Of the 28 cases found premortem, treatment included focal excision in 3 patients and radical orchiectomy in 25 patients. Follow-up, available in 24 cases, ranged from 1 to 228 months (mean 52.7 mo); of the 20 patients with testicular typical carcinoid tumors found premortem, all were alive at last follow-up without recurrences or metastases. Of the 4 patients with a primary atypical carcinoid tumor, 1 at the time of diagnosis had retroperitoneal and lung metastases who after chemotherapy underwent resection of the retroperitoneal tumor showing metastatic yolk sac tumor and embryonal carcinoma. After resection, serum AFP levels remained elevated and the patient is scheduled for salvage chemotherapy and bone marrow transplant. The other 2 patients with atypical carcinoid and follow-up had no evidence of disease at 68 and 114 months. Most primary carcinoid tumors of the testis have a benign clinical course even if associated with epidermoid/dermoid cysts, or

  19. The role of tumor necrosis factor-alpha and interleukin-1 in the mammalian testis and their involvement in testicular torsion and autoimmune orchitis

    PubMed Central

    Lysiak, Jeffrey J

    2004-01-01

    This review will focus the roles of TNF-alpha, IL-1 alpha, and IL-1 beta in the mammalian testis and in two testicular pathologies, testicular torsion and orchitis. TNF alpha in the testis is produced by round spermatids, pachytene spermatocytes, and testicular macrophages. The type 1 TNF receptor has been found on Sertoli and Leydig cells and numerous studies suggest a paracrine mode of action for TNF alpha in the normal testis. IL-1 alpha has been reported to be produced by Sertoli cells, testicular macrophages, and possibly postmeiotic germ cells. IL-1 receptors have been reported on Sertoli cells, Leydig cells, testicular macrophages, and germ cells suggesting both autocrine and paracrine functions. While these proinflammatory cytokines have important roles in normal testicular homeostasis, an elevation of their expression can lead to testicular dysfunctions. Testicular torsion is a clinical pathology with results in testicular ischemia and surgical intervention is often required for reperfusion. A pivotal role for IL-1beta in the pathology of testicular torsion has been recently described whereby an increase in IL-1beta production after reperfusion of the testis is correlated with the activation of the stress-related kinase, c-jun N-terminal kinase, and ultimately resulting in neutrophil recruitment to the testis and germ cell apoptosis. In autoimmune orchitis, on the other hand, TNF alpha produced by T-lymphocytes and macrophages of the testis has been implicated in the development and progression of the disease. Thus, both proinflammatory cytokines, TNF alpha and IL-1, have significant roles in normal testicular functions as well as in certain testicular pathologies. PMID:15012831

  20. Morphometric studies on the testis of Korean ring-necked pheasant (Phasianus colchicus karpowi) during the breeding and non-breeding seasons.

    PubMed

    Tae, H J; Jang, B G; Ahn, D C; Choi, E Y; Kang, H S; Kim, N S; Lee, J H; Park, S Y; Yang, H H; Kim, I S

    2005-10-01

    The purpose of this study was to obtain detailed quantitative information on all cell types in the testis interstitium of Korean ring-necked pheasants and to combine these data with changes in the steroidogenic function of the testis during the breeding and non-breeding seasons. For animals collected during the breeding season, their testis weights, sperm production, serum testosterone levels and leuteinizing hormone (LH)-stimulated testosterone secretion were significantly (p < 0.01) increased compared to the non-breeding season. Testes of the pheasants during the non-breeding season displayed a 98% reduction in testis volume that was associated with a decrease in the absolute volume of seminiferous tubules (98% reduction), tubular lumen (100%), interstitium (90%), blood vessels (84%), lymphatic spaces (97%), Leydig cells (79%), mesenchymal cells (51%) and myoid cells (61%) compared to the breeding season. The numbers of Leydig cells, mesenchymal cells and myoid cells per testis in the breeding season were much higher than in the non-breeding season. Although the mean volume of a Leydig cell was 74% lower in the non-breeding season, the mean volumes of myoid and mesenchymal cells remained unchanged. These results demonstrate that there are striking differences in the testicular structure of the Korean ring-necked pheasant during the breeding and non-breeding seasons. Every structural parameter of the Leydig cell was positively correlated with both testosterone serum levels and LH-stimulated testosterone secretion. The correlation of changes in hormonal status with the morphometric alterations of Leydig cells suggests that the Korean-ring necked pheasant may be used as a model to study structure-function relationships in the avian testis.

  1. Injury to the blood-testis barrier after low-dose-rate chronic radiation exposure in mice.

    PubMed

    Son, Y; Heo, K; Bae, M J; Lee, C G; Cho, W S; Kim, S D; Yang, K; Shin, I S; Lee, M Y; Kim, J S

    2015-11-01

    Exposure to ionising radiation induces male infertility, accompanied by increasing permeability of the blood-testis barrier. However, the effect on male fertility by low-dose-rate chronic radiation has not been investigated. In this study, the effects of low-dose-rate chronic radiation on male mice were investigated by measuring the levels of tight-junction-associated proteins (ZO-1 and occludin-1), Niemann-Pick disease type 2 protein (NPC-2) and antisperm antibody (AsAb) in serum. BALB/c mice were exposed to low-dose-rate radiation (3.49 mGy h(-1)) for total exposures of 0.02 (6 h), 0.17 (2 d) and 1.7 Gy (21 d). Based on histological examination, the diameter and epithelial depth of seminiferous tubules were significantly decreased in 1.7-Gy-irradiated mice. Compared with those of the non-irradiated group, 1.7-Gy-irradiated mice showed significantly decreased ZO-1, occludin-1 and NPC-2 protein levels, accompanied with increased serum AsAb levels. These results suggest potential blood-testis barrier injury and immune infertility in male mice exposed to low-dose-rate chronic radiation.

  2. Identification of an isoform of colony-stimulating factor 1 receptor mRNA in the rat testis.

    PubMed

    Su, Hong; Wang, Yibiao; Söder, Olle; Hou, Mi

    2014-06-01

    Because alternative RNA splicing regulation in the testis is prevalent, we explored testes of Sprague-Dawley rats for existence of alternatively spliced colony-stimulating factor 1 receptor (CSF-1R) mRNA. Using RT-PCR and sequencing, we identified a variant of CSF-1R mRNA that was 284 bp shorter than the full-length