Science.gov

Sample records for male fertility endpoints

  1. [Obesity and male fertility].

    PubMed

    Martini, Ana C; Molina, Rosa I; Ruiz, Rubén D; Fiol de Cuneo, Marta

    2012-01-01

    Obesity and male infertility have increased in the last decades; therefore, a possible association between these pathologies has been explored. Studies inform that obesity may affect fertility through different mechanisms, which alltogether could exert erectile dysfunction and/or sperm quality impairment. These include: 1) hypothalamic-pituitary-testicular (HPG) axis malfunction: obese hormonal profile is characterized by reduction of testosterone, gonadotrophins, SHBG and/or inhibin B concentrations (marker of Sertoli cells function) and hyperestrogenemy (consequence of aromatase overactivity ascribed to adipose tissue increase); 2) increased release of adipose-derived hormones: leptin increase could be responsible for some of the alterations on the HPG axis and could also exert direct deleterious effects on Leydig cells physiology, spermatogenesis and sperm function; 3) proinflammatory adipokines augmentation, higher scrotal temperature (due to fat accumulation in areas surrounding testes) and endocrine disruptors accumulation in adiposites, all of these responsible for the increase in testes oxidative stress and 4) sleep apnea, frequent in obese patients, suppresses the nocturnal testosterone rise needed for normal spermatogenesis. Finally, although controversial, all the above mentioned factors could comprise gametes quality; i.e. decrease sperm density and motility and increase DNA fragmentation, probably disturbing spermatogenesis and/or epididymal function. In summary, although obesity may impair male fertility by some/all of the described mechanisms, the fact is that only a small proportion of obese men are infertile, probably those genetically predisposed or morbidly obese. Nevertheless, it is likely that because the incidence of obesity is growing, the number of men with reduced fertility will increase as well.

  2. Fertility regulation in the male

    PubMed Central

    de Kretser, D. M.

    1978-01-01

    The current state of research into new methods of male contraception is reviewed, with special emphasis on the efforts of the WHO Special Programme of Research, Development and Research Training in Human Reproduction. The article concentrates mainly on the development of orally administered or injectable substances capable of either (a) interfering with the hormonal control of testicular function, (b) disrupting spermatogenesis by direct influence on testis function, or (c) interfering with the fertilizing ability of the sperm and their transport. It is concluded that, despite the numerous areas of research currently being pursued, the availability of a new male contraceptive remains several years away. PMID:308403

  3. Male Influences on Fertility: Needs for Research.

    ERIC Educational Resources Information Center

    Marciano, Teresa Donati

    1979-01-01

    A study comparing the processes of arriving at fertility decisions in marriage shows that the husband's preference for children or for childlessness controls more often than the wife's preference in either case. Using two childless samples and one sample with children, the strong effect of male preference was found. (Author)

  4. Properties of maximum likelihood male fertility estimation in plant populations.

    PubMed Central

    Morgan, M T

    1998-01-01

    Computer simulations are used to evaluate maximum likelihood methods for inferring male fertility in plant populations. The maximum likelihood method can provide substantial power to characterize male fertilities at the population level. Results emphasize, however, the importance of adequate experimental design and evaluation of fertility estimates, as well as limitations to inference (e.g., about the variance in male fertility or the correlation between fertility and phenotypic trait value) that can be reasonably drawn. PMID:9611217

  5. Zinc feeding and fertility of male rats.

    PubMed

    Samanta, K; Pal, B

    1986-01-01

    Supplementation of the diet of adult male rats with 4,000 ppm zinc as ZnSO4 for 30 to 32 days increased the zinc content in the testis and sperm by 25 and 18 per cent respectively, but did not change the same in accessory reproductive tissues, e.g. epididymis, seminal vesicle and prostate. The incidence of conception from mating between normal females and zinc fed males was lower as compared to mating between normal females and control males. This observation indicated reduced fertility of the males resulting from additional zinc ingestion. Motility of the sperm collected from the epididymis (tail) of the zinc treated rats was found to be inhibited. It has been suggested that excess zinc in the sperm was responsible for their poor motility and hence a reduced fertilising capacity.

  6. Sexually transmitted infections: impact on male fertility.

    PubMed

    Ochsendorf, F R

    2008-04-01

    The impact of sexually transmitted diseases (STD) on male fertility is strongly dependent on the local prevalence of the STDs. In Western countries STD-infections are of minor relevance. In other regions, i.e. Africa or South East Asia, the situation appears to be different. Acute urethritis could not be associated with male infertility. Chronic infections (gonorrhoea) can cause urethral strictures and epididymo-orchitis. Chlamydia trachomatis and Neisseria gonorrhoea can be transmitted to the female partner and cause pelvic inflammatory disease with tubal obstruction. Ureaplasma urealyticum may impair spermatozoa (motility, DNA condensation). Trichomonas vaginalis has, if any, only minor influence on male fertility. The relevance of viral infections (HPV, HSV) for male infertility is not resolved. Any STD increases the chances of transmission of the human immunodeficiency virus (HIV). The HIV infection is associated with infectious semen and the risk of virus transmission. Semen quality deteriorates with the progression of immunodeficiency. Special counselling of serodiscordant couples is needed. STDs should be treated early and adequately to prevent late sequelae for both men and women.

  7. Male fertility preservation before gonadotoxic therapies

    PubMed Central

    Wyns, C.

    2010-01-01

    Background: Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. Unfortunately, aggressive chemotherapy, radiotherapy and preparative regimens for bone marrow transplantation can severely affect male germ cells, including spermatogonial stem cells (SSCs), and lead to permanent loss of fertility. Different options for fertility preservation are dependent on the pubertal state of the patient. Methods: Relevant studies were identified by an extensive Medline search of English and French language articles. Results: Sperm cryopreservation prior to gonadotoxic treatment is a well established method after puberty. In case of ejaculation failure by masturbation, assisted ejaculation methods or testicular tissue sampling should be considered. Although no effective gonadoprotective drug is yet available for in vivo spermatogonial stem cell (SSC) protection in humans, current evidence supports the feasibility of immature testicular tissue (ITT) cryopreservation. The different cryopreservation protocols and available fertility restoration options from frozen tissue, i.e. cell suspension transplantation, tissue grafting and in vitro maturation, are presented. Results obtained in humans are discussed in the light of lessons learned from animal studies. Conclusion: Advances in reproductive technology have made fertility preservation a real possibility in young patients whose gonadal function is threatened by gonadotoxic therapies. The putative indications for such techniques, as well as their limitations according to disease, are outlined. PMID:25302103

  8. Proteomic Analysis of Male-Fertility Restoration in CMS Onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The production of hybrid-onion seed is dependent on cytoplasmic-genic male sterility (CMS) systems. For the most commonly used CMS, male-sterile (S) cytoplasm interacts with a dominant allele at one nuclear male-fertility restoration locus (Ms) to condition male fertility. We are using proteomics ...

  9. Proteomic analyses of male-fertility restoration in CMS onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The production of hybrid-onion seed is dependent on cytoplasmic-genic male sterility (CMS) systems. For the most commonly used CMS, male-sterile (S) cytoplasm interacts with a dominant allele at one nuclear male-fertility restoration locus (Ms) to condition male fertility. We are using a proteomics ...

  10. Development of male-fertility-regulating agents.

    PubMed

    Ray, S; Verma, P; Kumar, A

    1991-09-01

    Steroidal, nonsteroidal, plant-derived, gonadotropin-related and immunological agents investigated for control of male fertility are reviewed with brief descriptions of their effects, and illustrations of their structures. The physiology of the male reproductive system is presented as an introduction: an ideal male antifertility agent would inhibit spermatogenesis at the level of the Sertoli cells, without affecting endogenous androgen production by Leydig cells, needed for libido and potency. Androgens down-regulate their own production at physiological levels, but few long-acting orally active derivatives are available. Anti-androgens with mixed androgen and progestin activity, combined with a pure androgen are potentially useful. Androgen-progestin combinations are being tested by WHO as implants. Dozens of miscellaneous nonsteroidal compounds have been discovered serendipitously to have antifertility activity in men or male animals, including alkylating agents antimetabolites, antibiotics, sulfa derivatives, fungicides, trichomonocides, amebicides, alpha blockers, antimalarials, coumarins, and carbohydrate derivatives. Various plant alkaloids have been screened. Those of Hibiscus, Vitex and Plumbago species, as well as Tripterygium wilfordii glycosides, which are being evaluated in combination with gossypol, are mentioned here. Gossypol has been thoroughly tested in China, but rejected because of its side effects, particularly hypokalemic paralysis, its low therapeutic index, and uncertain recovery of fertility. Gonadotropin-releasing hormone (GnRH) agonists and antagonists are being researched in combination with androgens with some success. The GnRH antagonists to date have low activity , or cause histamine-related side effects at higher doses; the androgens require a new route such as a long-acting implant to overcome the need for daily injections. Immunological contraception for males has not progressed beyond the research stage.

  11. [Male fertility after chemotherapy during childhood].

    PubMed

    Aubier, F; Patte, C; de Vathaire, F; Tournade, M F; Oberlin, O; Sakiroglu, O; Lemerle, J

    1995-01-01

    Chemotherapy has considerably improved the prognosis of solid tumours in children, but may have very adverse effects, particularly on fertility. A study was conducted at the Gustave Roussy Institute to identify the toxic effect of chemotherapy on male fertility. At present, 205 patients, treated during childhood have entered the study. Basal FSH-LH have been assayed to assess possible germ cell damage although azoosperia can not be eliminated. Results were normal in 127 patients (62%) and increased basal FSH levels were found in 78 (38%). Endocrine function was not altered: all patients were either impubertal or intrapubertal at diagnosis and subsequently achieved normal puberty. Multivariate analysis revealed an obvious toxic effect of 2 alkylating drugs: cyclophosphamide and procarbazine. No toxic effect was observed for vincristine, dohorubicin or actinomycin D. Age and pubertal status at diagnosis were not correlated with toxic effects. At present, no conclusion for other drugs may be made but results high dose metotrexate are promising. For lomustine and cisplatin, less favourable, though nonsignificant, results have been obtained. Complete recovery is possible several years later.

  12. Tapetum and middle layer control male fertility in Actinidia deliciosa

    PubMed Central

    Falasca, Giuseppina; D'Angeli, Simone; Biasi, Rita; Fattorini, Laura; Matteucci, Maja; Canini, Antonella; Altamura, Maria Maddalena

    2013-01-01

    Background and Aims Dioecism characterizes many crop species of economic value, including kiwifruit (Actinidia deliciosa). Kiwifruit male sterility occurs at the microspore stage. The cell walls of the microspores and the pollen of the male-sterile and male-fertile flowers, respectively, differ in glucose and galactose levels. In numerous plants, pollen formation involves normal functioning and degeneration timing of the tapetum, with calcium and carbohydrates provided by the tapetum essential for male fertility. The aim of this study was to determine whether the anther wall controls male fertility in kiwifruit, providing calcium and carbohydrates to the microspores. Methods The events occurring in the anther wall and microspores of male-fertile and male-sterile anthers were investigated by analyses of light microscopy, epifluorescence, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL assay) and transmission electron microscopy coupled with electron spectroscopy. The possibility that male sterility was related to anther tissue malfunctioning with regard to calcium/glucose/galactose provision to the microspores was also investigated by in vitro anther culture. Key Results Both tapetum and the middle layer showed secretory activity and both degenerated by programmed cell death (PCD), but PCD was later in male-sterile than in male-fertile anthers. Calcium accumulated in cell walls of the middle layer and tapetum and in the exine of microspores and pollen, reaching higher levels in anther wall tissues and dead microspores of male-sterile anthers. A specific supply of glucose and calcium induced normal pollen formation in in vitro-cultured anthers of the male-sterile genotype. Conclusions The results show that male sterility in kiwifruit is induced by anther wall tissues through prolonged secretory activity caused by a delay in PCD, in the middle layer in particular. In vitro culture results support the sporophytic control of male fertility

  13. The insults of illicit drug use on male fertility.

    PubMed

    Fronczak, Carolyn M; Kim, Edward D; Barqawi, Al B

    2012-01-01

    One-third of infertile couples may have a male factor present. Illicit drug use can be an important cause of male factor infertility and includes use of anabolic-androgenic steroids, marijuana, opioid narcotics, cocaine, and methamphetamines. The use of these illicit drugs is common in the United States, with a yearly prevalence rate for any drug consistently higher in males compared with females. We aim to provide a review of recent literature on the prevalence and effects of illicit drug use on male fertility and to aid health professionals when counseling infertile men whose social history suggests illicit drug use. Anabolic-androgenic steroids, marijuana, cocaine, methamphetamines, and opioid narcotics all negatively impact male fertility, and adverse effects have been reported on the hypothalamic-pituitary-testicular axis, sperm function, and testicular structure. The use of illicit drugs is prevalent in our society and likely adversely impacting the fertility of men who abuse drugs.

  14. Citrus limon extract: possible inhibitory mechanisms affecting testicular functions and fertility in male mice.

    PubMed

    Singh, Nidhi; Singh, Shio Kumar

    2016-01-01

    The effect of oral administration of 50% ethanolic leaf extract of Citrus limon (500 and 1,000 mg/kg body weight/day) for 35 days on fertility and various male reproductive endpoints was evaluated in Parkes strain of mice. Testicular indices such as histology, 3β- and 17β-HSD enzymes activity, immunoblot expression of StAR and P450scc, and germ cell apoptosis by TUNEL and CASP- 3 expression were assessed. Motility, viability, and number of spermatozoa in the cauda epididymidis, level of serum testosterone, fertility indices, and toxicological parameters were also evaluated. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules. Treatment had adverse effects on steroidogenic markers in the testis and induced germ cell apoptosis. Significant reductions were noted in epididymal sperm parameters and serum level of testosterone in Citrus-treated mice compared to controls. Fertility of the extract-treated males was also suppressed, but libido remained unaffected. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels suggesting that Citrus treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Suppression of spermatogenesis may result from germ cell apoptosis because of decreased production of testosterone. The present work indicated that Citrus leaves can affect male reproduction.

  15. Experimental Methods to Preserve Male Fertility and Treat Male Infertility

    PubMed Central

    Gassei, Kathrin; Orwig, Kyle E.

    2016-01-01

    Infertility is a prevalent condition that has insidious impacts on the infertile individuals, their families and society that extend far beyond the inability to have a biological child. Lifestyle changes, fertility treatments and assisted reproductive technologies are available to help many infertile couples achieve their reproductive goals. All of these technologies require that the infertile individual is able to produce at least a small number of functional gametes (eggs or sperm). It is not possible for a person who does not produce gametes to have a biological child. This review focuses on the infertile man and describes several stem cell-based methods and gene therapy approaches that are in the research pipeline and may lead to new fertility treatment options for azoospermic men. PMID:26746133

  16. Sperm wars and the evolution of male fertility.

    PubMed

    Simmons, Leigh W; Fitzpatrick, John L

    2012-11-01

    Females frequently mate with several males, whose sperm then compete to fertilize available ova. Sperm competition represents a potent selective force that is expected to shape male expenditure on the ejaculate. Here, we review empirical data that illustrate the evolutionary consequences of sperm competition. Sperm competition favors the evolution of increased testes size and sperm production. In some species, males appear capable of adjusting the number of sperm ejaculated, depending on the perceived levels of sperm competition. Selection is also expected to act on sperm form and function, although the evidence for this remains equivocal. Comparative studies suggest that sperm length and swimming speed may increase in response to selection from sperm competition. However, the mechanisms driving this pattern remain unclear. Evidence that sperm length influences sperm swimming speed is mixed and fertilization trials performed across a broad range of species demonstrate inconsistent relationships between sperm form and function. This ambiguity may in part reflect the important role that seminal fluid proteins (sfps) play in affecting sperm function. There is good evidence that sfps are subject to selection from sperm competition, and recent work is pointing to an ability of males to adjust their seminal fluid chemistry in response to sperm competition from rival males. We argue that future research must consider sperm and seminal fluid components of the ejaculate as a functional unity. Research at the genomic level will identify the genes that ultimately control male fertility.

  17. Regulation of male fertility by X-linked genes.

    PubMed

    Zheng, Ke; Yang, Fang; Wang, Peijing Jeremy

    2010-01-01

    Infertility is a worldwide reproductive health problem, affecting men and women about equally. Mouse genetic studies demonstrate that more than 200 genes specifically or predominantly regulate fertility. However, few genetic causes of infertility in humans have been identified. Here, we focus on the regulation of male fertility by X-linked, germ cell-specific genes. Previous genomic studies reveal that the mammalian X chromosome is enriched for genes expressed in early spermatogenesis. Recent genetic studies in mice show that X-linked, germ cell-specific genes, such as A-kinase anchor protein 4 (Akap4), nuclear RNA export factor 2 (Nxf2), TBP-associated factor 7l (Taf7l), and testis-expressed gene 11 (Tex11), indeed play important roles in the regulation of male fertility. Moreover, we find that the Taf7l Tex11 double-mutant males exhibit much more severe defects in meiosis than either single mutant, suggesting that these 2 X-linked genes regulate male meiosis synergistically. The X-linked, germ cell-specific genes are particularly attractive in the study of male infertility in humans. Because males are hemizygous for X-linked genes, loss-of-function mutations in the single-copy X-linked genes, unlike in autosomal genes, would not be masked by a normal allele. The genetic studies of X-linked, germ cell-specific genes in mice have laid a foundation for mutational analysis of their human orthologues in infertile men.

  18. DEFINING THE SPERMATOZOA RNA FINGERPRINT FOR THE NORMAL FERTILE MALE

    EPA Science Inventory

    Defining the spermatozoa RNA fingerprint for the normal fertile male
    G. Charles Ostermeier1, David Dix2, David Miller3, and Stephen A. Krawetz1

    1Departments of Ob/Gyn, CMMG & ISC, Wayne State University, USA.
    2Reproductive Toxicology Division, U.S. Environmental Pr...

  19. [Therapy of male fertility disorders with kallikrein].

    PubMed

    Schill, W B

    1976-11-26

    An overview of the use of kallikrein to treat male sterility is presented. Kallikrein was shown to increase sperm motility in both in vivo and in vitro studies. The vitality and longevity of the sperm are also enhanced. These effects are due to the stimulation of the intracellular concentration of cyclical adenosonemonophosphates in the sperm. Quinine receptors on the sperm surface are assumed to be the mechanism responsible for the kallikrein effect. Kallikrein stimulates spermal penetration of cervical mucus by about 80% and causes a significant increase in total sperm output 3 months from the beginning of treatment. After 2 months of use, kallikrein leads to an increase in the number of normally formed spermatozoa in the ejaculate. Kallikrein is indicated in cases of asthenospermia and oligozoospermia, in some cases of teratozoospermia, in cases of the vegetative-functional congestion syndrome desecribed by Hoffmann, and is recommended in cases of testicular parenchyme damage involving tubulus function. Parenteral administration involves 40 KE (1KE=8mcg) thrice weekly, oral administration 300-600 KE daily. Kallikrein is added directly to the ejaculate in instrumental insemination in cases of therapy-resistant decrease in motility associated with asthenospermia or oligozoospermia. Concentrations of 5 KE per ml ejaculate are used in such cases. Chronic infection, especially in the genital area, and the incidence of dizziness during therapy are contraindications to kellikrein use.

  20. Sperm head phenotype and male fertility in ram semen.

    PubMed

    Maroto-Morales, A; Ramón, M; García-Álvarez, O; Montoro, V; Soler, A J; Fernández-Santos, M R; Roldan, E R S; Pérez-Guzmán, M D; Garde, J J

    2015-12-01

    Although there is ample evidence for the effects of sperm head shape on sperm function, its impact on fertility has not been explored in detail at the intraspecific level in mammals. Here, we assess the relationship between sperm head shape and male fertility in a large-scale study in Manchega sheep (Ovis aries), which have not undergone any selection for fertility. Semen was collected from 83 mature rams, and before insemination, head shapes were measured for five parameters: area, perimeter, length, width, and p2a (perimeter(2)/2×π×area) using a computer-assisted sperm morphometric analysis. In addition, a cluster analysis using sperm head length and p2a factor was performed to determine sperm subpopulations (SPs) structure. Our results show the existence of four sperm SPs, which present different sperm head phenotype: SP1 (large and round), SP2 (short and elongated), SP3 (shortest and round), and SP4 (large and the most elongated). No relationships were found between males' fertility rates and average values of sperm head dimensions. However, differences in fertility rates between rams were strongly associated to the proportion of spermatozoa in an ejaculate SP with short and elongated heads (P < 0.001). These findings show how the heterogeneity in sperm head shape of the ejaculate has an effect on reproductive success, and highlight the important role of modulation of the ejaculate at the intraspecific level.

  1. Sphingomyelin Synthase 1 Is Essential for Male Fertility in Mice

    PubMed Central

    Scherthan, Harry; Horsch, Marion; Beckers, Johannes; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Ford, Steven J.; Burton, Neal C.; Razansky, Daniel; Trümbach, Dietrich; Aichler, Michaela; Walch, Axel Karl; Calzada-Wack, Julia; Neff, Frauke; Wurst, Wolfgang; Hartmann, Tobias; Floss, Thomas

    2016-01-01

    Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes. Lipid profiling revealed a reduction in several long chain unsaturated phosphatidylcholins, lysophosphatidylcholins and sphingolipids in the testes of mutants. Multi-Spectral Optoacoustic Tomography indicated blood-testis barrier dysfunction. A supplementary diet of the essential omega-3 docosahexaenoic acid and eicosapentaenoic acid diminished germ cell sloughing from the seminiferous epithelium and restored spermatogenesis and fertility in 50% of previously infertile mutants. Our findings indicate that SMS1 has a wider than anticipated role in testis polyunsaturated fatty acid homeostasis and for male fertility. PMID:27788151

  2. Influence of hernioplastic implants on male fertility in rats.

    PubMed

    Kolbe, T; Lechner, W

    2007-05-01

    This study explored the vulnerability of the ductus deferens due to mesh induced inflammation and shrinkage after hernia repair in the rodent model. Two commonly used types of hernioplastic implants (Prolene and Vypro II) were surgically wrapped around the ductus deferentes on both sides in 20 juvenile and 20 adult Sprague-Dawley rats. Twenty male rats underwent sham surgeries as controls. After 3 months, each male was mated with 2-3 adult females, which were subsequently sacrificed and oocytes or embryos were flushed and counted. Histochemical investigations of the implants and the ductus recovered surgically 4 weeks after implantation (one side) and after the fertility test (second side) were conducted. All groups exhibited 1-3 males with decreased or restricted fertility but there was no difference between groups. Histochemical analysis of the implants and the ductus recovered 4 weeks and 4 months after implantation revealed some sperm granulomes due to lesions of the spermatic cord caused by the implant in the Prolene group. There was no inflammatory reaction in the mucosa or blockage of the spermatic cord visible. Both types of hernioplastic implants tested in this investigation do not give an indication of a negative influence on male fertility in juvenile or adult rats.

  3. Sam68: a new STAR in the male fertility firmament.

    PubMed

    Sette, Claudio; Messina, Valeria; Paronetto, Maria Paola

    2010-01-01

    Male infertility accounts for approximately 50% of the cases of sterile human couples, and in many instances the genetic or molecular defects involved remain unknown. Studies conducted in animal models have elucidated the key role played by RNA-binding proteins and by the posttranscriptional regulation of gene expression during spermatogenesis. Ablation of proteins involved in each of the steps required for the processing and the utilization of messenger RNAs impairs the production of fertile spermatozoa. Recent evidence indicates that the RNA-binding protein Sam68 is absolutely required for the correct progression of spermatogenesis and for male fertility in the mouse. Sam68 belongs to the evolutionary conserved signal transduction and activation of RNA (STAR) family of RNA-binding proteins. The members of this family have been demonstrated to play crucial roles in cell differentiation and development, including male and female gametogenesis. In this review we will summarize the observations gathered on the functions of STAR proteins in different organisms, with particular emphasis on the role of Sam68 in male fertility.

  4. Bisphenol-A Affects Male Fertility via Fertility-related Proteins in Spermatozoa

    PubMed Central

    Rahman, Md Saidur; Kwon, Woo-Sung; Lee, June-Sub; Yoon, Sung-Jae; Ryu, Buom-Yong; Pang, Myung-Geol

    2015-01-01

    The xenoestrogen bisphenol-A (BPA) is a widespread environmental contaminant that has been studied for its impact on male fertility in several species of animals and humans. Growing evidence suggests that xenoestrogens can bind to receptors on spermatozoa and thus alter sperm function. The objective of the study was to investigate the effects of varying concentrations of BPA (0.0001, 0.01, 1, and 100 μM for 6 h) on sperm function, fertilization, embryonic development, and on selected fertility-related proteins in spermatozoa. Our results showed that high concentrations of BPA inhibited sperm motility and motion kinematics by significantly decreasing ATP levels in spermatozoa. High BPA concentrations also increased the phosphorylation of tyrosine residues on sperm proteins involved in protein kinase A-dependent regulation and induced a precocious acrosome reaction, which resulted in poor fertilization and compromised embryonic development. In addition, BPA induced the down-regulation of β-actin and up-regulated peroxiredoxin-5, glutathione peroxidase 4, glyceraldehyde-3-phosphate dehydrogenase, and succinate dehydrogenase. Our results suggest that high concentrations of BPA alter sperm function, fertilization, and embryonic development via regulation and/or phosphorylation of fertility-related proteins in spermatozoa. We conclude that BPA-induced changes in fertility-related protein levels in spermatozoa may be provided a potential cue of BPA-mediated disease conditions. PMID:25772901

  5. Male fertility potential alteration in rheumatic diseases: a systematic review

    PubMed Central

    Tiseo, Bruno Camargo; Cocuzza, Marcello; Bonfá, Eloisa; Srougi, Miguel; Clovis, A

    2016-01-01

    ABSTRACT Background Improved targeted therapies for rheumatic diseases were developed recently resulting in a better prognosis for affected patients. Nowadays, patients are living longer and with improved quality of life, including fertility potential. These patients are affected by impaired reproductive function and the causes are often multifactorial related to particularities of each disease. This review highlights how rheumatic diseases and their management affect testicular function and male fertility. Materials and Methods A systematic review of literature of all published data after 1970 was conducted. Data was collected about fertility abnormalities in male patients with systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, ankylosing spondylitis, Behçet disease and gout. Two independent researchers carried out the search in online databases. Results A total of 19 articles were included addressing the following diseases: 7 systemic lupus erythematosus, 6 Behçet disease, 4 ankylosing spondylitis, 2 rheumatoid arthritis, 2 dermatomyositis and one gout. Systemic lupus erythematosus clearly affects gonadal function impairing spermatogenesis mainly due to antisperm antibodies and cyclophosphamide therapy. Behçet disease, gout and ankylosing spondylitis patients, including those under anti-TNF therapy in the latter disease, do not seem to have reduced fertility whereas in dermatomyositis, the fertility potential is hampered by disease activity and by alkylating agents. Data regarding rheumatoid arthritis is scarce, gonadal dysfunction observed as consequence of disease activity and antisperm antibodies. Conclusions Reduced fertility potential is not uncommon. Its frequency and severity vary among the different rheumatic diseases. Permanent infertility is rare and often associated with alkylating agent therapy. PMID:27120778

  6. Cholesterol and male fertility: what about orphans and adopted?

    PubMed

    Maqdasy, Salwan; Baptissart, Marine; Vega, Aurélie; Baron, Silvère; Lobaccaro, Jean-Marc A; Volle, David H

    2013-04-10

    The link between cholesterol homeostasis and male fertility has been clearly suggested in patients who suffer from hyperlipidemia and metabolic syndrome. This has been confirmed by the generation of several transgenic mouse models or in animals fed with high cholesterol diet. Next to the alteration of the endocrine signaling pathways through steroid receptors (androgen and estrogen receptors); "orphan" and "adopted" nuclear receptors, such as the Liver X Receptors (LXRs), the Proliferating Peroxisomal Activated Receptors (PPARs) or the Liver Receptor Homolog-1 (LRH-1), have been involved in this cross-talk. These transcription factors show distinct expression patterns in the male genital tract, explaining the large panel of phenotypes observed in transgenic male mice and highlighting the importance of lipid homesostasis and the complexity of the molecular pathways involved. Increasing our knowledge of the roles of these nuclear receptors in male germ cell differentiation could help in proposing new approaches to either treat infertile men or define new strategies for contraception.

  7. Male coercive mating in externally fertilizing species: male coercion, female reluctance and explanation for female acceptance

    PubMed Central

    Matsumoto, Yukio; Takegaki, Takeshi

    2016-01-01

    Male coercive mating exerts a strong evolutionary pressure on mating-related traits of both sexes. However, it is extremely rare in externally fertilizing species probably because the male mating behaviour is incomplete until females release their eggs. Here we showed that males of the externally fertilizing fish Rhabdoblennius nitidus coercively confine females to the nests until spawning, and investigated why females accept male coercive mating. The females entered the males’ nests following male courtship displays, but they usually tried to escape when there were no eggs because males tended to cannibalize all the eggs when there were few. Most males that used small, tight nests acquired new eggs but with experimentally enlarged nests, 90% of the males without eggs failed to confine the females. Spawning tended to occur during the early/late spawning period in nests with no eggs (i.e. male coercive mating). In the nests where the first eggs were deposited in the early period, subsequent matings with other females were more likely to occur, whereas in the late period, most parental care of the eggs failed without additional matings. The females that spawned in the late period may have been compelled to accept male coercive mating due to time constraints. PMID:27087584

  8. Fertility of a spontaneous hexaploid male Siberian sturgeon, Acipenser baerii

    PubMed Central

    2014-01-01

    Background Evolution of sturgeons and paddlefishes (order Acipenseriformes) is inherently connected with polyploidization events which resulted in differentiation of ploidy levels and chromosome numbers of present acipenseriform species. Moreover, allopolyploidization as well as autopolyploidization seems to be an ongoing process in these fishes and individuals with abnormal ploidy levels were occasionally observed within sturgeon populations. Here, we reported occurrence of Siberian sturgeon (Acipenser baerii) male with abnormal ploidy level for this species, accessed its ploidy level and chromosome number and investigate its potential sterility or fertility in comparison with normal individuals of sterlet (A. ruthenus), Russian sturgeon (A. gueldenstaedtii) and Siberian sturgeon (A. baerii). Results Acipenser ruthenus possessed 120 chromosomes, exhibiting recent diploidy (2n), A. gueldenstaedtii and A. baerii had ~245 chromosomes representing recent tetraploidy (4n), and A. baerii male with abnormal ploidy level had ~ 368 chromosomes, indicating recent hexaploidy (6n). Genealogy assessed from the mtDNA control region did not reveal genome markers of other sturgeon species and this individual was supposed to originate from spontaneous 1.5 fold increment in number of chromosome sets with respect to the number most frequently found in nature for this species. Following hormone stimulation, the spontaneous hexaploid male produced normal sperm with ability for fertilization. Fertilization of A. baerii and A. gueldenstaedtii ova from normal 4n level females with sperm of the hexaploid male produced viable, non-malformed pentaploid (5n) progeny with a ploidy level intermediate to those of the parents. Conclusion This study firstly described occurrence of hexaploid individual of A. baerii and confirmed its autopolyploid origin. In addition to that, the first detailed evidence about fertility of spontaneous hexaploid sturgeon was provided. If 1.5 fold increment in

  9. In vitro fertilization/intracytoplasmic sperm injection for male infertility

    PubMed Central

    Merchant, Rubina; Gandhi, Goral; Allahbadia, Gautam N.

    2011-01-01

    Progress in the field of assisted reproduction, and particularly micromanipulation, now heralds a new era in the management of severe male factor infertility, not amenable to medical or surgical correction. By overcoming natural barriers to conception, in vitro fertilization and embryo transfer (IVF-ET), subzonal sperm insemination, partial zona dissection, and intracytoplasmatic injection of sperm (ICSI) now offer couples considered irreversibly infertile, the option of parenting a genetically related child. However, unlike IVF, which necessitates an optimal sperm number and function to successfully complete the sequence of events leading to fertilization, micromanipulation techniques, such as ICSI, involving the direct injection of a spermatozoon into the oocyte, obviate all these requirements and may be used to alleviate severe male factor infertility due to the lack of sperm in the ejaculate due to severely impaired spermatogenesis (non-obstructive azoospermia) or non-reconstructable reproductive tract obstruction (obstructive azoospermia). ICSI may be performed with fresh or cryopreserved ejaculate sperm where available, microsurgically extracted epididymal or testicular sperm with satisfactory fertilization, clinical pregnancy, and ongoing pregnancy rates. However, despite a lack of consensus regarding the genetic implications of ICSI or the application and efficacy of preimplantation genetic diagnosis prior to assisted reproductive technology (ART), the widespread use of ICSI, increasing evidence of the involvement of genetic factors in male infertility and the potential risk of transmission of genetic disorders to the offspring, generate major concerns with regard to the safety of the technique, necessitating a thorough genetic evaluation of the couple, classification of infertility and adequate counseling of the implications and associated risks prior to embarking on the procedure. The objective of this review is to highlight the indications, advantages

  10. The hazardous effects of tobacco smoking on male fertility

    PubMed Central

    Dai, Jing-Bo; Wang, Zhao-Xia; Qiao, Zhong-Dong

    2015-01-01

    The substantial harmful effects of tobacco smoking on fertility and reproduction have become apparent but are not generally appreciated. Tobacco smoke contains more than 4000 kinds of constituents, including nicotine, tar, carbonic monoxide, polycyclic aromatic hydrocarbons, and heavy metals. Because of the complexity of tobacco smoke components, the toxicological mechanism is notably complicated. Most studies have reported reduced semen quality, reproductive hormone system dysfunction and impaired spermatogenesis, sperm maturation, and spermatozoa function in smokers compared with nonsmokers. Underlying these effects, elevated oxidative stress, DNA damage, and cell apoptosis may play important roles collaboratively in the overall effect of tobacco smoking on male fertility. In this review, we strive to focus on both the phenotype of and the molecular mechanism underlying these harmful effects, although current studies regarding the mechanism remain insufficient. PMID:25851659

  11. Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: ability to detect effects on thyroid endpoints.

    PubMed

    Stoker, T E; Ferrell, J M; Laws, S C; Cooper, R L; Buckalew, A

    2006-11-10

    The U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol was designed as a screen to detect endocrine-disrupting chemicals which may alter reproductive development or thyroid function. One purpose of this in vivo screening protocol is to detect thyrotoxicants via a number of different mechanisms of action, such as thyroid hormone synthesis or clearance. Here we evaluate the ability of this EDSP male pubertal protocol to detect the known thyrotoxicant ammonium perchlorate as an endocrine disruptor. Ammonium perchlorate is a primary ingredient in rocket fuel, fertilizers, paints, and lubricants. Over the past 50 years, potassium perchlorate has been used to treat hyperthyroidism in humans. Perchlorate alters thyroid hormone secretion by competitively inhibiting iodide uptake by the thyroid gland. In this study, ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male Wistar rats based on a pilot study of oral dosing. Doses of 125-500 mg/kg perchlorate decreased T4 in a dose-dependent manner. TSH was significantly increased in a dose-responsive manner at the same doses, while T3 was unchanged at any dose. Thyroid histology was significantly altered at all doses, even at the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase in follicular cell height. No effects on preputial separation, a marker of pubertal progression, or reproductive tract development were observed at any dose. These results demonstrate that the male pubertal protocol is useful for detecting thyrotoxicants which target the thyroid axis by this mechanism (altered uptake of iodide). This study also found that perchlorate exposure during this period did not alter any of the reproductive developmental endpoints.

  12. Adverse effects of common medications on male fertility.

    PubMed

    Samplaski, Mary K; Nangia, Ajay K

    2015-07-01

    An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility.

  13. High male fertility in males of a subdioecious shrub in hand-pollinated crosses

    PubMed Central

    Wang, Hui; Matsushita, Michinari; Tomaru, Nobuhiro; Nakagawa, Michiko

    2016-01-01

    Female reproductive success in females versus hermaphrodites has been well documented. However, documenting a potential advantage in male fertility of male versus hermaphrodite individuals in subdioecious species is also essential for understanding the evolutionary pathway toward dioecy from hermaphroditism via gynodioecy. Siring success in terms of fruit set, fruit mass, number of seeds and mean seed mass was compared by hand-pollinated crosses in the subdioecious shrub Eurya japonica. The pollen was from male and hermaphrodite individuals, and the pollen recipients were females and hermaphrodites. Seed quality was also evaluated in terms of seed germination rate, seed germination day and seedling survival. Overall, pollen from males sired more fruits of larger size and more seeds than did pollen from hermaphrodites. The male advantage was observed when pollen recipients were females, whereas no effect was found in hermaphrodite recipients. Pollen from males also produced better quality seeds with higher germination rate and sooner germination day. Although these results could also be explained by a higher pollen load for crosses with male pollen donors, we took care to saturate the stigma regardless of the pollen donor. Therefore, these results suggest that male individuals of E. japonica have advantages in male fertility in terms of both quantity and quality. Our previous studies indicated that females exhibit higher female reproductive success compared with hermaphrodites. Thus, both the female and male functions of hermaphrodites are outperformed by females and males, respectively, raising the possibility that the subdioecious E. japonica at this study site is entering the transitional phase to dioecy along the gynodioecy–dioecy pathway. PMID:27658818

  14. The effect of alkylating agents on male rat fertility

    PubMed Central

    Jackson, H.; Fox, B. W.; Craig, A. W.

    1959-01-01

    The effects of tumour inhibitory doses of tretamine (triethylenemelamine), busulphan, and melphalan on the fertility of male rats have been examined. The aromatic nitrogen mustard, melphalan, was inactive, but busulphan has a highly selective action on spermatogenesis which contrasts strikingly with that of tretamine. The main action of tretamine was exerted upon spermatocytes or spermatids, but, with increasing dose, the effects spread to involve a wide range of spermatogenic cells including mature sperm, so that infertility could be induced very rapidly. Busulphan, however, interfered with the development of spermatogonia for several weeks, although other germinal cells were unaffected and continued to develop into mature spermatozoa. This accounted for the continuation of normal fertility for 7 weeks after a dose, before sterility suddenly developed. The antifertility activity of tretamine could be simulated by a variety of other ethyleneimino compounds, potency being greatest in trifunctional and least in monofunctional compounds. The latter were, however, very destructive to the seminiferous epithelium with increasing dose. In the rat, there appeared to be no definite relationship between the ability of alkylating substances to interfere with the activity of normal and pathological proliferating tissues, as represented by the germinal epithelium, haematopoietic, and tumour tissue. Although carcinogenicity was a biological property of alkylating agents, other chemical types of carcinogen did not interfere with fertility. ImagesFIG. 2aFIG. 2bFIG. 2c PMID:13662565

  15. Y-chromosomal genes affecting male fertility: A review

    PubMed Central

    Dhanoa, Jasdeep Kaur; Mukhopadhyay, Chandra Sekhar; Arora, Jaspreet Singh

    2016-01-01

    The mammalian sex-chromosomes (X and Y) have evolved from autosomes and are involved in sex determination and reproductive traits. The Y-chromosome is the smallest chromosome that consists of 2-3% of the haploid genome and may contain between 70 and 200 genes. The Y-chromosome plays major role in male fertility and is suitable to study the evolutionary relics, speciation, and male infertility and/or subfertility due to its unique features such as long non-recombining region, abundance of repetitive sequences, and holandric inheritance pattern. During evolution, many holandric genes were deleted. The current review discusses the mammalian holandric genes and their functions. The commonly encountered infertility and/or subfertility problems due to point or gross mutation (deletion) of the Y-chromosomal genes have also been discussed. For example, loss or microdeletion of sex-determining region, Y-linked gene results in XY males that exhibit female characteristics, deletion of RNA binding motif, Y-encoded in azoospermic factor b region results in the arrest of spermatogenesis at meiosis. The holandric genes have been covered for associating the mutations with male factor infertility. PMID:27536043

  16. Marijuana, phytocannabinoids, the endocannabinoid system, and male fertility.

    PubMed

    du Plessis, Stefan S; Agarwal, Ashok; Syriac, Arun

    2015-11-01

    Marijuana has the highest consumption rate among all of the illicit drugs used in the USA, and its popularity as both a recreational and medicinal drug is increasing especially among men of reproductive age. Male factor infertility is on the increase, and the exposure to the cannabinoid compounds released by marijuana could be a contributing cause. The endocannabinoid system (ECS) is deeply involved in the complex regulation of male reproduction through the endogenous release of endocannabinoids and binding to cannabinoid receptors. Disturbing the delicate balance of the ECS due to marijuana use can negatively impact reproductive potential. Various in vivo and in vitro studies have reported on the empirical role that marijuana plays in disrupting the hypothalamus-pituitary-gonadal axis, spermatogenesis, and sperm function such as motility, capacitation, and the acrosome reaction. In this review, we highlight the latest evidence regarding the effect of marijuana use on male fertility and also provide a detailed insight into the ECS and its significance in the male reproductive system.

  17. Acute alcohol exposure markedly influences male fertility and fetal outcome in the male rat.

    PubMed

    Cicero, T J; Nock, B; O'Connor, L; Adams, M L; Sewing, B N; Meyer, E R

    1994-01-01

    Although it is recognized that drugs ingested by pregnant females produce marked cognitive and physiological deficits in their offspring, the possibility that paternal exposure to drugs prior to mating may have adverse effects on fertility and fetal outcome has not received much attention. The purpose of the present studies was to examine whether a single, acute exposure to alcohol influences the subsequent ability of adult male rats to mate and produce healthy and viable litters. Our results showed that a relatively large dose of alcohol 24 hours prior to breeding had little effect on the mating behavior of male rats, but there were markedly fewer pregnancies in females mated with alcohol-exposed male rats than in controls. Of equal importance, we found that, even when conception occurred and live births were produced, there were striking differences in fetal outcome. Alcohol-treated males sired many fewer pups than control males and there was a markedly enhanced mortality rate in their offspring. Collectively, these data suggest that acute paternal alcohol administration 24 hours prior to breeding does not affect mating behavior, but results in a greatly diminished fertility rate and fewer and less viable offspring. These studies suggest that paternal alcohol use may be as important as maternal alcohol abuse as a negative variable in pregnancy and fetal outcome.

  18. Endocrine regulation of male fertility by the skeleton

    PubMed Central

    Oury, Franck; Sumara, Grzegorz; Sumara, Olga; Ferron, Mathieu; Chang, Haixin; Smith, Charles E.; Hermo, Louis; Suarez, Susan; Roth, Bryan L.; Ducy, Patricia; Karsenty, Gerard

    2011-01-01

    Although the endocrine capacity of bone is widely recognized, interactions between bone and the reproductive system have until now focused on the gonads as a regulator of bone remodeling. We now show that in males, bone acts as a regulator of fertility. Using co-culture assays, we demonstrate that osteoblasts are able to induce testosterone production by the testes, while they fail to influence estrogen production by the ovaries. Analyses of cell-specific loss- and gain-of-function models reveal that the osteoblast-derived hormone osteocalcin performs this endocrine function. By binding to a G-protein coupled receptor expressed in the Leydig cells of the testes, osteocalcin regulates in a CREB-dependent manner the expression of enzymes required for testosterone synthesis, promoting germ cell survival. This study expands the physiological repertoire of osteocalcin, and provides the first evidence that the skeleton is an endocrine regulator of reproduction. PMID:21333348

  19. Body size correlates with fertilization success but not gonad size in grass goby territorial males.

    PubMed

    Pujolar, Jose Martin; Locatello, Lisa; Zane, Lorenzo; Mazzoldi, Carlotta

    2012-01-01

    In fish species with alternative male mating tactics, sperm competition typically occurs when small males that are unsuccessful in direct contests steal fertilization opportunities from large dominant males. In the grass goby Zosterisessor ophiocephalus, large territorial males defend and court females from nest sites, while small sneaker males obtain matings by sneaking into nests. Parentage assignment of 688 eggs from 8 different nests sampled in the 2003-2004 breeding season revealed a high level of sperm competition. Fertilization success of territorial males was very high but in all nests sneakers also contributed to the progeny. In territorial males, fertilization success correlated positively with male body size. Gonadal investment was explored in a sample of 126 grass gobies collected during the period 1995-1996 in the same area (61 territorial males and 65 sneakers). Correlation between body weight and testis weight was positive and significant for sneaker males, while correlation was virtually equal to zero in territorial males. That body size in territorial males is correlated with fertilization success but not gonad size suggests that males allocate much more energy into growth and relatively little into sperm production once the needed size to become territorial is attained. The increased paternity of larger territorial males might be due to a more effective defense of the nest in comparison with smaller territorial males.

  20. Male-male sexual behavior in Japanese quail: being "on top" reduces mating and fertilization with females.

    PubMed

    Adkins-Regan, Elizabeth

    2014-10-01

    Male Japanese quail (Coturnix japonica) engage in vigorous same-sex sexual interactions that have been interpreted as aggressive behavior reflecting dominance relationships. The consequences of this behavior for reproductive success, and whether it is a form of competition over mating and fertilization, are unclear. Three experiments were conducted to determine the effect of seeing or interacting with another male on a male's subsequent mating and fertilization success with females. A vigorous interaction with another male in which the subject performed more cloacal contact movements (movements to try to make contact with the other bird's cloacal opening) reduced subsequent mating and fertilization success with a female to a similar extent as a prior mating with a different female. Receiving one or more cloacal contacts from another male was less detrimental for subsequent success. The mere presence of another (stimulus) male delayed mating initiation in those male subjects that approached the stimulus first instead of the female. These results do not support the idea that the male "on top" in male-male sexual interactions is the dominant bird who goes on to achieve greater reproductive success. Instead, the results are consistent with male-male sexual behavior as an occasionally costly by-product of strong mating motivation.

  1. Variation in Male Fertilities and Pairwise Mating Probabilities in Picea glauca

    PubMed Central

    Schoen, D. J.; Stewart, S. C.

    1987-01-01

    Frequencies of multilocus male gametes in seeds collected from clones in several blocks of a white spruce seed orchard were analyzed as part of a 2-yr study of mating system variation in this species. Observed frequencies of male gamete types departed significantly from those expected assuming equal male fertilities among clones. Male gamete frequencies in seed crops were significantly heterogeneous among clones within blocks, and among blocks within clones. Clonal male fertilities were estimated from male gamete frequency data. These estimates were highly skewed, with a small proportion of the clones contributing male gametes to the majority of the seed. The estimates were significantly heterogeneous among clones within blocks, and among blocks within clones. Between-year variation in clonal male fertilities was also pronounced, with male fertilities of some clones changing by as much as three orders of magnitude. Clonal male fertility was significantly correlated with clonal male cone production in both years. These results are important with regard to assumptions made for the estimation of general combining ability, average genetic correlation among progeny from single parents, and expected response to selection in open-pollinated plant populations. PMID:17246377

  2. Female Choice for Males with Greater Fertilization Success in the Swedish Moor Frog, Rana arvalis

    PubMed Central

    Sherman, Craig D. H.; Sagvik, Jörgen; Olsson, Mats

    2010-01-01

    Background Studies of mate choice in anuran amphibians have shown female preference for a wide range of male traits despite females gaining no direct resources from males (i.e. non-resource based mating system). Nevertheless, theoretical and empirical studies have shown that females may still gain indirect genetic benefits from choosing males of higher genetic quality and thereby increase their reproductive success. Methodology/Principal Findings We investigated two components of sexual selection in the Moor frog (Rana arvalis), pre-copulatory female choice between two males of different size (‘large’ vs. ‘small’), and their fertilization success in sperm competition and in isolation. Females' showed no significant preference for male size (13 small and six large male preferences) but associated preferentially with the male that subsequently was the most successful at fertilizing her eggs in isolation. Siring success of males in competitive fertilizations was unrelated to genetic similarity with the female and we detected no effect of sperm viability on fertilization success. There was, however, a strong positive association between a male's innate fertilization ability with a female and his siring success in sperm competition. We also detected a strong negative effect of a male's thumb length on his competitive siring success. Conclusions/Significance Our results show that females show no preference for male size but are still able to choose males which have greater fertilization success. Genetic similarity and differences in the proportion of viable sperm within a males ejaculate do not appear to affect siring success. These results could be explained through pre- and/or postcopulatory choice for genetic benefits and suggest that females are able to perceive the genetic quality of males, possibly basing their choice on multiple phenotypic male traits. PMID:21049015

  3. Genomic and proteomic analyses of male-fertility restoration in onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Production of hybrid-onion seed is dependent on cytoplasmic-genic male sterility (CMS). The most commonly used CMS in onion requires the presence of male-sterile (S) cytoplasm and recessive alleles at one nuclear male-fertility restoration (Ms) locus. Molecular markers have been developed that dis...

  4. Short-term exposure to 17alpha-ethynylestradiol decreases the fertility of sexually maturing male rainbow trout (Oncorhynchus mykiss)

    SciTech Connect

    Schultz, Irv R.; Skillman, Ann D.; Nicolas, Jean-Marc; Cyr, Daniel G.; Nagler, James J.

    2003-06-01

    The synthetic estrogen 17alpha-ethynylestradiol (EE2) is a commonly used oral contraceptive that has been increasingly detected in sewage effluents. This study determined whether EE2 exposure adversely affected reproduction in sexually maturing male rainbow trout (Oncorhynchus mykiss). We exposed male trout to graded water concentrations of EE2 (10, 100, and 1,000 ng/ L) for 62 d leading up to the time of spawning. Semen and blood plasma samples were removed from each fish. Semen was used to fertilize groups of eggs from one nonexposed female. As a measure of fertility, eggs were incubated for 28 d after fertilization to determine the proportion that attained the eyed stage of embryonic development. Additional endpoints also measured included sperm motility, spermatocrit, gonadosomatic and hepatosomatic indices, testis histology, and circulating plasma levels of the sex steroids 17alpha, 20beta-dihydroxyprogesterone (17,20-DHP) and 11-ketotestosterone (11-KT). Exposure to 1,000 ng/L of EE2 caused complete mortality of the treatment group by day 57. Exposure to lower EE2 water concentrations (10 and 100 ng/L) caused an increase in sperm density, while a significant reduction in testis mass was observed only in the 100-ng/L exposure group. Most significantly, semen harvested from fish exposed to 10 and 100 ng/L EE2 caused an approximately 50% reduction in the number of eggs attaining the eyed stage of embryonic development. Plasma levels of 17,20-DHP in exposed fish were roughly twice the level of the controls, while levels of 11-KT were significantly reduced in fish exposed to 100 ng/L EE2. These results suggest that sexually maturing male rainbow trout are susceptible to detrimental reproductive effects of short-term exposures to environmentally relevant levels of EE2.

  5. Effects of lead on the male mouse as investigated by in vitro fertilization and blastocyst culture

    SciTech Connect

    Johansson, L.; Sjoeblom, P.; Wide, M.

    1987-02-01

    Long-term exposure of male mice to inorganic lead (lead chloride, 1 g/liter) in the drinking water reduces their fertility. The cause of this reduction, expressed as a decrease in the number of mated females showing inplantations, was investigated, using an in vivo fertilization method. It was found that spermatozoa from lead-exposed males had a significantly lower ability to fertilize mouse eggs than those from unexposed males. Preimplantation embryos, isolated from uterine horns of mice mated with lead-exposed males. Preimplantation embryos, isolated from uterine horns of mice mated with lead-exposed males, were examined. No morphologically abnormal embryos were found. However, when cultured in vitro over the implantation period, blastocysts of the group mated with lead-exposed males showed an increased frequency of delayed hatching from the zona pellucida or an inability to hatch. Among blastocysts from this group a decreased frequency of inner cell mass development was also found.

  6. The genetics of male fertility--from basic science to clinical evaluation.

    PubMed

    Pastuszak, Alexander W; Lamb, Dolores J

    2012-01-01

    Our understanding of male fertility has increased dramatically over the past several decades, in large part because of advances in technology and the ability to rapidly analyze large quantities of high-resolution genetic data. These research efforts have led to an understanding of some of the genes involved in male fertility and have enabled us to test for defects in these genes that result in infertility in men. However, our understanding of male fertility remains far from comprehensive, and many genes involved in male fertility likely remain to be identified and their mechanisms of action elucidated. This can only be accomplished through continued, persistent investigations using cutting-edge technologies. In this review, we discuss the history of genetic testing and how it applies to male fertility, from the identification of the sex chromosomes at the turn of the century to classification of single-nucleotide polymorphisms that may result in infertility and are the crux of modern genetic analysis. We discuss the genetic testing methodologies traditionally used for genetic assessment of infertile males, including karyotype analysis, sperm fluorescence in situ hybridization, and polymerase chain reaction-based testing for Y chromosomal evaluation, as well as cutting-edge genetic testing methodologies using microarrays and whole-genome sequencing, permitting analysis at a nucleotide-level resolution. Finally, we describe our vision of the future of genetic testing in the setting of male infertility, culminating in truly personalized medicine for each affected infertile male.

  7. Heterozygous alleles restore male fertility to cytoplasmic male-sterile radish (Raphanus sativus L.): a case of overdominance.

    PubMed

    Wang, Zhi Wei; De Wang, Chuan; Wang, Chuan; Gao, Lei; Mei, Shi Yong; Zhou, Yuan; Xiang, Chang Ping; Wang, Ting

    2013-04-01

    The practice of hybridization has greatly contributed to the increase in crop productivity. A major component that exploits heterosis in crops is the cytoplasmic male sterility (CMS)/nucleus-controlled fertility restoration (Rf) system. Through positional cloning, it is shown that heterozygous alleles (RsRf3-1/RsRf3-2) encoding pentatricopeptide repeat (PPR) proteins are responsible for restoring fertility to cytoplasmic male-sterile radish (Raphanus sativus L.). Furthermore, it was found that heterozygous alleles (RsRf3-1/RsRf3-2) show higher expression and RNA polymerase II occupancy in the CMS cytoplasmic background compared with their homozygous alleles (RsRf3-1/RsRf3-1 or RsRf3-2/RsRf3-2). These data provide new insights into the molecular mechanism of fertility restoration to cytoplasmic male-sterile plants and illustrate a case of overdominance.

  8. THE SAGA OF A MALE FERTILITY PROTEIN (SP22)

    EPA Science Inventory

    Toxicologic studies designed to identify chemical-induced alterations in the structure and function of the epididymis, particularly the acquisition of fertility by proximal cauda epididymal sperm, have lead to the discovery of a novel sperm protein (SP22) that is well correlated ...

  9. Differential protein expression in seminal plasma from fertile and infertile males

    PubMed Central

    Cadavid J, Angela P.; Alvarez, Angela; Markert, Udo R.; Maya, Walter Cardona

    2014-01-01

    AIM: The aim of this study was to analyze human seminal plasma proteins in association with male fertility status using the proteomic mass spectrometry technology Surface-Enhanced Laser Desorption Ionization Time-of-Flight (SELDI-TOF-MS). MATERIALS AND METHODS: Semen analysis was performed using conventional methods. Protein profiles of the seminal plasma were obtained by SELDI-TOF mass spectrometry over a strong anion exchanger, ProteinChip® Q10 array. RESULTS AND CONCLUSION: We found statistically significant differences in motility and sperm count between fertile and infertile men. In addition, we observed ten seminal proteins that are significantly up-regulated in the infertile group. In conclusion, comparison of seminal plasma proteome in fertile and infertile men provides new aspects in the physiology of male fertility and might help in identifying novel markers of male infertility. PMID:25395747

  10. Isolation and characterization of a male fertility gene (Ms4) in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Identifying a stable male-sterility system is crucial for the development of hybrid soybean. In soybean, eleven male-sterile, female-fertile mutants (ms1, ms2, ms3, ms4, ms5, ms6, ms7, ms8, ms9, msMOS, and msp) have been identified and some of which have been mapped to soybean chromosomes. The objec...

  11. Heterosis for viability, fecundity, and male fertility in Drosophila melanogaster: comparison of mutational and standing variation.

    PubMed

    Fry, J D; Heinsohn, S L; Mackay, T F

    1998-03-01

    If genetic variation for fitness traits in natural populations ("standing" variation) is maintained by recurrent mutation, then quantitative-genetic properties of standing variation should resemble those of newly arisen mutations. One well-known property of standing variation for fitness traits is inbreeding depression, with its converse of heterosis or hybrid vigor. We measured heterosis for three fitness traits, pre-adult viability, female fecundity, and male fertility, among a set of inbred Drosophilia melanogaster lines recently derived from the wild, and also among a set of lines that had been allowed to accumulate spontaneous mutations for over 200 generations. The inbred lines but not the mutation-accumulation (MA) lines showed heterosis for pre-adult viability. Both sets of lines showed heterosis for female fecundity, but heterosis for male fertility was weak or absent. Crosses among a subset of the MA lines showed that they were strongly differentiated for male fertility, with the differences inherited in autosomal fashion; the absence of heterosis for male fertility among the MA lines was therefore not caused by an absence of mutations affecting this trait. Crosses among the inbred lines also gave some, albeit equivocal, evidence for male fertility variation. The contrast between the results for female fecundity and those for male fertility suggests that mutations affecting different fitness traits may differ in their average dominance properties, and that such differences may be reflected in properties of standing variation. The strong differentiation among the MA lines in male fertility further suggests that mutations affecting this trait occur at a high rate.

  12. Male soy food intake was not associated with in vitro fertilization outcomes among their partners attending a fertility center

    PubMed Central

    Mínguez-Alarcón, Lidia; Afeiche, Myriam C; Chiu, Yu-Han; Vanegas, Jose C; Williams, Paige L; Tanrikut, Cigdem; Toth, Thomas L; Hauser, Russ; Chavarro, Jorge E

    2015-01-01

    Male factor etiology may be a contributing factor in up to 60% of infertility cases. Dietary intake of phytoestrogens has been related to abnormal semen quality and hormone levels. However, its effect on couple fecundity is still unclear. Intake of soy products was assessed in 184 men from couples undergoing infertility treatment with in vitro fertilization (IVF). Couples were recruited between February 2007 and May 2014 and prospectively followed to document treatment outcomes including fertilization, implantation, clinical pregnancy and live birth. Multivariate generalized linear mixed models with random intercepts, binomial distribution and logit link function were used to examine this relation while accounting for repeated treatment cycles and adjusting for potential confounders. Male partner’s intake of soy foods and soy isoflavones was unrelated to fertilization rates, the proportions of poor quality embryos, accelerated or slow embryo cleavage rate, and implantation, clinical pregnancy and live birth. The adjusted live birth rates per initiated cycle (95% CI) for partners of men in increasing categories of soy food intake were 0.36 (0.28 to 0.45), 0.42 (0.29 to 0.56), 0.36 (0.24 to 0.51), and 0.37 (0.24 to 0.52), respectively. Soy food intake in men was not related to clinical outcomes among couples presenting at an infertility clinic. Data on the relation between phytoestrogens and male reproductive potential remains scarce and additional research is needed to clarify its role in human reproduction. PMID:26097060

  13. Inbreeding depresses sperm competitiveness, but not fertilization or mating success in male Tribolium castaneum.

    PubMed

    Michalczyk, Lukasz; Martin, Oliver Y; Millard, Anna L; Emerson, Brent C; Gage, Matthew J G

    2010-11-22

    As populations decline to levels where reproduction among close genetic relatives becomes more probable, subsequent increases in homozygous recessive deleterious expression and/or loss of heterozygote advantage can lead to inbreeding depression. Here, we measure how inbreeding across replicate lines of the flour beetle Tribolium castaneum impacts on male reproductive fitness in the absence or presence of male-male competition. Effects on male evolution from mating pattern were removed by enforcing monogamous mating throughout. After inbreeding across eight generations, we found that male fertility in the absence of competition was unaffected. However, we found significant inbreeding depression of sperm competitiveness: non-inbred males won 57 per cent of fertilizations in competition, while inbred equivalents only sired 42 per cent. We also found that the P(2) 'offence' role in sperm competition was significantly more depressed under inbreeding than sperm 'defence' (P(1)). Mating behaviour did not explain these differences, and there was no difference in the viability of offspring sired by inbred or non-inbred males. Sperm length variation was significantly greater in the ejaculates of inbred males. Our results show that male ability to achieve normal fertilization success was not depressed under strong inbreeding, but that inbreeding depression in these traits occurred when conditions of sperm competition were generated.

  14. Atropine-induced inhibition of sperm and semen transport impairs fertility in male rats.

    PubMed

    Sato, Takahiro; Ban, Yoshiki; Uchida, Miki; Gondo, Eri; Yamamoto, Masakatsu; Sekiguchi, Yoshiko; Sakaue, Akiko; Kemi, Masayuki; Nakatsuka, Toshio

    2005-08-01

    Previous studies revealed that atropine reduced male fertility in rats without any effects on mating performance, sperm production and motility, and testicular morphology. The present study was conducted to investigate whether the impairment of male fertility induced by atropine was related to the inhibition of sperm and semen transports from the vas deferens and seminal vesicle to the urethra during the process of emission. Male rats were treated with atropine at 125 mg/kg/day for 10-17 days prior to mating with untreated females. After confirmation of mating, male rats were euthanized and sperm number in the vas deferens and weights of the seminal vesicle and copulatory plug were determined as indicators of inhibition of sperm and semen transports, respectively. Reproductive status of mated females was determined on gestation days 15-17. A low pregnancy rate associated with a decreased number of implants was observed in females that mated with the atropine-treated males. The average number of sperm in the vas deferens was increased in the atropine-treated males. The average seminal vesicle weight in the atropine-treated males was greater than that of controls. The copulatory plug weights were decreased in the atropine-treated males. These results suggest that inhibitions of sperm and semen transports from the vas deferens and seminal vesicle to the urethra during the process of emission result in reduced male fertility in rats.

  15. The role of oxidative stress and antioxidants in male fertility

    PubMed Central

    Walczak–Jedrzejowska, Renata; Wolski, Jan Karol

    2013-01-01

    Oxidative stress results from the imbalance between production of the reactive oxygen species (ROS) and the protective effect of the antioxidant system responsible for their neutralization and removal. An excess of ROS causes a pathological reaction resulting in damage to cells and tissues. Spermatozoa are particularly vulnerable to the harmful effects of ROS. Oxidative stress affects their activity, damages DNA structure, and accelerates apoptosis, all of which consequently decrease their numbers, hinders motility and development of normal morphology, and impairs function. This leads to disturbances in fertility or embryo development disorder. The main cellular source of ROS in the semen are immature sperm cells and white blood cells. The increase in the number of leukocytes may be due to infection and inflammation, but can also be secondary to harmful environmental factors, long sexual abstinence, or varicocele. The protective antioxidant system in the semen is composed of enzymes, as well as nonenzymatic substances, which closely interact with each other to ensure optimal protection against ROS. Non–enzymatic antioxidants include vitamins A, E, C, and B complex, glutathione, pantothenic acid, coenzyme Q10 and carnitine, and micronutrients such as zinc, selenium, and copper. It seems that a deficiency of any of them can cause a decrease in total antioxidant status. In vitro and in vivo that studies demonstrate many antioxidants possess a beneficial effect on fertility and, therefore, their use is recommended as supportive therapy for the treatment of infertility in men. PMID:24578993

  16. 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.

  17. Repeated carbon nanotube administrations in male mice cause reversible testis damage without affecting fertility

    PubMed Central

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

    2010-01-01

    Soluble carbon nanotubes are promising materials for in vivo delivery and imaging applications. Several reports have described the in vivo toxicity of carbon nanotubes, however, their effects on male reproduction have not been examined. Here we show that repeated intravenous injections of water-soluble multi-walled 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 after 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. PMID:20693989

  18. Inbreeding depresses sperm competitiveness, but not fertilization or mating success in male Tribolium castaneum

    PubMed Central

    Michalczyk, Łukasz; Martin, Oliver Y.; Millard, Anna L.; Emerson, Brent C.; Gage, Matthew J. G.

    2010-01-01

    As populations decline to levels where reproduction among close genetic relatives becomes more probable, subsequent increases in homozygous recessive deleterious expression and/or loss of heterozygote advantage can lead to inbreeding depression. Here, we measure how inbreeding across replicate lines of the flour beetle Tribolium castaneum impacts on male reproductive fitness in the absence or presence of male–male competition. Effects on male evolution from mating pattern were removed by enforcing monogamous mating throughout. After inbreeding across eight generations, we found that male fertility in the absence of competition was unaffected. However, we found significant inbreeding depression of sperm competitiveness: non-inbred males won 57 per cent of fertilizations in competition, while inbred equivalents only sired 42 per cent. We also found that the P2 ‘offence’ role in sperm competition was significantly more depressed under inbreeding than sperm ‘defence’ (P1). Mating behaviour did not explain these differences, and there was no difference in the viability of offspring sired by inbred or non-inbred males. Sperm length variation was significantly greater in the ejaculates of inbred males. Our results show that male ability to achieve normal fertilization success was not depressed under strong inbreeding, but that inbreeding depression in these traits occurred when conditions of sperm competition were generated. PMID:20554548

  19. Intact Cell MALDI-TOF MS on Sperm: A Molecular Test For Male Fertility Diagnosis.

    PubMed

    Soler, Laura; Labas, Valérie; Thélie, Aurore; Grasseau, Isabelle; Teixeira-Gomes, Ana-Paula; Blesbois, Elisabeth

    2016-06-01

    Currently, evaluation of sperm quality is primarily based on in vitro measures of sperm function such as motility, viability and/or acrosome reaction. However, results are often poorly correlated with fertility, and alternative diagnostic tools are therefore needed both in veterinary and human medicine. In a recent pilot study, we demonstrated that MS profiles from intact chicken sperm using MALDI-TOF profiles could detect significant differences between fertile/subfertile spermatozoa showing that such profiles could be useful for in vitro male fertility testing. In the present study, we performed larger standardized experimental procedures designed for the development of fertility- predictive mathematical models based on sperm cell MALDI-TOF MS profiles acquired through a fast, automated method. This intact cell MALDI-TOF MS-based method showed high diagnostic accuracy in identifying fertile/subfertile males in a large male population of known fertility from two distinct genetic lineages (meat and egg laying lines). We additionally identified 40% of the m/z peaks observed in sperm MS profiles through a top-down high-resolution protein identification analysis. This revealed that the MALDI-TOF MS spectra obtained from intact sperm cells contained a large proportion of protein degradation products, many implicated in important functional pathways in sperm such as energy metabolism, structure and movement. Proteins identified by our predictive model included diverse and important functional classes providing new insights into sperm function as it relates to fertility differences in this experimental system. Thus, in addition to the chicken model system developed here, with the use of appropriate models these methods should effectively translate to other animal taxa where similar tests for fertility are warranted.

  20. An intact Pms2 ATPase domain is not essential for male fertility

    PubMed Central

    Fischer, Jared M; Dudley, Sandra; Miller, Ashleigh J; Liskay, R Michael

    2016-01-01

    The DNA mismatch repair (MMR) machinery in mammals plays critical roles in both mutation avoidance and spermatogenesis. Meiotic analysis of knockout mice of two different MMR genes, Mlh1 and Mlh3, revealed both male and female infertility associated with a defect in meiotic crossing over. In contrast, another MMR gene knockout, Pms2 (Pms2ko/ko), which contained a deletion of a portion of the ATPase domain, produced animals that were male sterile but female fertile. However, the meiotic phenotype of Pms2ko/ko males was less clear-cut than for Mlh1- or Mlh3-deficient meiosis. More recently, we generated a different Pms2 mutant allele (Pms2cre), which results in deletion of the same portion of the ATPase domain. Surprisingly, Pms2cre/cre male mice were completely fertile, suggesting that the ATPase domain of Pms2 is not required for male fertility. To explore the difference in male fertility, we examined the Pms2 RNA and found that alternative splicing of the Pms2cre allele results in a predicted Pms2 containing the C-terminus, which contains the Mlh1-interaction domain, a possible candidate for stabilizing Mlh1 levels. To study further the basis of male fertility, we examined Mlh1 levels in testes and found that whereas Pms2 loss in Pms2ko/ko mice results in severely reduced levels of Mlh1 expression in the testes, Mlh1 levels in Pms2cre/cre testes were reduced to a lesser extent. Thus, we propose that a primary function of Pms2 during spermatogenesis is to stabilize Mlh1 levels prior to its critical crossing over function with Mlh3. PMID:26753533

  1. Toward a comprehensive genetic analysis of male fertility in Drosophila melanogaster.

    PubMed Central

    Wakimoto, Barbara T; Lindsley, Dan L; Herrera, Cheryl

    2004-01-01

    Drosophila melanogaster is a widely used model organism for genetic dissection of developmental processes. To exploit its full potential for studying the genetic basis of male fertility, we performed a large-scale screen for male-sterile (ms) mutations. From a collection of 12,326 strains carrying ethyl-methanesulfonate-treated, homozygous viable second or third chromosomes, 2216 ms lines were identified, constituting the largest collection of ms mutations described to date for any organism. Over 2000 lines were cytologically characterized and, of these, 81% failed during spermatogenesis while 19% manifested postspermatogenic processes. Of the phenotypic categories used to classify the mutants, the largest groups were those that showed visible defects in meiotic chromosome segregation or cytokinesis and those that failed in sperm individualization. We also identified 62 fertile or subfertile lines that showed high levels of chromosome loss due to abnormal mitotic or meiotic chromosome transmission in the male germ line or due to paternal chromosome loss in the early embryo. We argue that the majority of autosomal genes that function in male fertility in Drosophila are represented by one or more alleles in the ms collection. Given the conservation of molecular mechanisms underlying important cellular processes, analysis of these mutations should provide insight into the genetic networks that control male fertility in Drosophila and other organisms, including humans. PMID:15166148

  2. Environmental toxins: alarming impacts of pesticides on male fertility.

    PubMed

    Sengupta, Pallav; Banerjee, Rajdeb

    2014-10-01

    This review comprehensively summarizes the effects of more than 15 mostly used pesticides on male reproductive physiology, as recent experimental and epidemiological research have indicated their alarming impact on overall human health. Mechanisms have described that pesticide exposure damages spermatozoa, alter Sertoli or Leydig cell function, both in vitro and in vivo and thus affects semen quality. But, the literature suggests a need for more intricate research in those pesticides that are defined as mutagens or carcinogens and directly affect the hypothalamic-pituitary-gonadal axis. This literature review also proposes specific solutions to overcome these health effects.

  3. The role of cysteine-rich secretory proteins in male fertility.

    PubMed

    Koppers, Adam J; Reddy, Thulasimala; O'Bryan, Moira K

    2011-01-01

    The cysteine-rich secretory proteins (CRISPs) are a subgroup of the CRISP, antigen 5 and Pr-1 (CAP) protein superfamily, and are found only in vertebrates. They show a strong expression bias to the mammalian male reproductive tract and the venom of poisonous reptiles. Within the male reproductive tract CRISPs have been implicated in many aspects of male germ cell biology spanning haploid germ cell development, epididymal maturation, capacitation, motility and the actual processes of fertilization. At a structural level, CRISPs are composed of two domains, a CAP domain, which has been implicated in cell-cell adhesion, and a CRISP domain, which has been shown to regulate several classes of ion channels across multiple species. Herein, we will review the current literature on the role of CRISPs in male fertility, and by inference to related non-mammalian protein, infer potential biochemical functions.

  4. The role of cysteine-rich secretory proteins in male fertility

    PubMed Central

    Koppers, Adam J; Reddy, Thulasimala; O'Bryan, Moira K

    2011-01-01

    The cysteine-rich secretory proteins (CRISPs) are a subgroup of the CRISP, antigen 5 and Pr-1 (CAP) protein superfamily, and are found only in vertebrates. They show a strong expression bias to the mammalian male reproductive tract and the venom of poisonous reptiles. Within the male reproductive tract CRISPs have been implicated in many aspects of male germ cell biology spanning haploid germ cell development, epididymal maturation, capacitation, motility and the actual processes of fertilization. At a structural level, CRISPs are composed of two domains, a CAP domain, which has been implicated in cell–cell adhesion, and a CRISP domain, which has been shown to regulate several classes of ion channels across multiple species. Herein, we will review the current literature on the role of CRISPs in male fertility, and by inference to related non-mammalian protein, infer potential biochemical functions. PMID:20972450

  5. A study on the acceptability of male fertility regulating methods in Korea.

    PubMed

    Ahn K-c; Kim O-k

    1978-11-01

    In order to assess the acceptability of existing and potential male fertility regulating methods in Korea, a total of 353 male respondents were interviewed from 3 sampling areas: 99 cases from urban middle socioeconomic status, 104 cases from urban low socioeconomic status, and 150 cases from the rural area. Respondents from each area differed in terms of educational attainment and socioeconomic status. Respondents from each area have about the same level of knowledge of contraceptive methods, but their behaviors differ considerably. The rate of currently practicing contraception was highest among rural samples and lowest among urban low socioeconomic groups. The relative acceptability of 2 existing (condom and vasectomy) and 2 potential (daily pill and monthly injection) male fertility regulating methods was assessed using several measures of acceptability. Whatever measure used, the most consistent finding among sampling groups was that vasectomy is the least acceptable method. Vasectomy is least preferred among potential users, and this finding suggests that the current target system on vasectomy in the national family planning program should be reconsidered. For all measures of acceptability potential methods were more preferred than either condom or vasectomy for the rural and urban low socioeconomic status samples. With regard to the potential male methods, methods with longer duration of action are preferred to methods with a shorter duration. Urban-rural residence was found to be significantly related to the acceptability of condom and vasectomy; urban residents liked condom and vasectomy more than rural residents. Age of respondents was not significantly related to the attitudes toward using each male method but significantly related to the behavioral intention to use each male method. The education level is not significantly related to the acceptability of condom but related to the acceptability of other male fertility regulating methods. More than 1/2 of

  6. A novel male sterility-fertility restoration system in plants for hybrid seed production.

    PubMed

    Singh, Surendra Pratap; Singh, Sudhir P; Pandey, Tripti; Singh, Ram Rakshpal; Sawant, Samir V

    2015-06-15

    Hybrid seeds are used for stimulated crop production, as they harness heterosis. The achievement of complete male-sterility in the female-parent and the restored-fertility in F1-hybrids are the major bottlenecks in the commercial hybrid seed production. Here, we report a male sterility-fertility restoration system by engineering the in most nutritive anther wall layer tapetum of female and male parents. In the female parent, high-level, and stringent expression of Arabidopsis autophagy-related gene BECLIN1 was achieved in the tapetum, which altered the tapetal degeneration program, leading to male sterility. This works on our previously demonstrated expression cassette based on functional complementation of TATA-box mutant (TGTA) promoter and TATA-binding protein mutant3 (TBPm3), with modification by conjugating Long Hypocotyle in Far-Red1 fragment (HFR1(NT131)) with TBPm3 (HFR1(NT131)-TBPm3) to exercise regulatory control over it. In the male parent, tapetum-specific Constitutive photo-morphogenesis1 (COP1) was expressed. The F1 obtained by crossing these engineered parents showed decreased BECLIN1 expression, which was further completely abolished when COP1-mutant (COP1(L105A)) was used as a male parent, leading to normal tapetal development and restored fertility. The system works on COP1-HFR1 interaction and COP1-mediated degradation of TBPm3 pool (HFR1(NT131)-TBPm3). The system can be deployed for hybrid seed production in agricultural crops.

  7. Protein and carbohydrate intake influence sperm number and fertility in male cockroaches, but not sperm viability

    PubMed Central

    Bunning, Harriet; Rapkin, James; Belcher, Laurence; Archer, C. Ruth; Jensen, Kim; Hunt, John

    2015-01-01

    It is commonly assumed that because males produce many, tiny sperm, they are cheap to produce. Recent work, however, suggests that sperm production is not cost-free. If sperm are costly to produce, sperm number and/or viability should be influenced by diet, and this has been documented in numerous species. Yet few studies have examined the exact nutrients responsible for mediating these effects. Here, we quantify the effects of protein (P) and carbohydrate (C) intake on sperm number and viability in the cockroach Nauphoeta cinerea, as well as the consequences for male fertility. We found the intake of P and C influenced sperm number, being maximized at a high intake of diets with a P : C ratio of 1 : 2, but not sperm viability. The nutritional landscapes for male fertility and sperm number were closely aligned, suggesting that sperm number is the major determinant of male fertility in N. cinerea. Under dietary choice, males regulate nutrient intake at a P : C ratio of 1 : 4.95, which is midway between the ratios needed to maximize sperm production and pre-copulatory attractiveness in this species. This raises the possibility that males regulate nutrient intake to balance the trade-off between pre- and post-copulatory traits in this species. PMID:25608881

  8. Diversifying sunflower germplasm by integration and mapping of a novel male fertility restoration gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The combination of a single cytoplasmic male-sterile (CMS) PET-1, originating from wild Helianthus petiolaris subsp. petiolaris Nutt., and the corresponding fertility restoration gene Rf1, has been used for commercial sunflower hybrid seed production worldwide since the early 1970s. A new CMS line 5...

  9. TOWARDS USING STABLE SPERMATOZOAL RNAS FOR PROGNOSTIC ASSESSMENT OF MALE FACTOR FERTILITY

    EPA Science Inventory

    Objective: To establish the stability of spermatozoal RNAs as a means to validate their use as a male fertility marker. Design: Semen samples were randomly selected for 1 of 3 cryopreservation treatments. Setting: An academic research environment. Patient(s): Men aged...

  10. THE EFFECTS OF HYPERTHERMIA ON SPERMATOGENESIS, APOPTOSIS, GENE EXPRESSION AND FERTILITY IN ADULT MALE MICE

    EPA Science Inventory

    The effects of hyperthermia on spermatogenesis, apoptosis, gene expression and fertility in adult male mice
    John C. Rockett1, Faye L. Mapp1, J. Brian Garges1, J. Christopher Luft1, Chisato Mori2 and David J. Dix1.
    1Reproductive Toxicology Division, National Health and Envir...

  11. Preoperative duplex ultrasound parameters predicting male fertility after successful varicocelectomy

    PubMed Central

    Alshehri, Fahad M.; Akbar, Mahboob H.; Altwairgi, Adel K.; AlThaqufi, Omar J.

    2015-01-01

    Objectives: To assess duplex ultrasound (DUS) parameters, and predicti the outcome of varicocele ligation in male infertility. Methods: This retrospective and follow up study was conducted at Dr. Sulaiman Al Habib Hospital, AlQassim, Saudi Arabia between January 2011 and December 2012. Eighty-two patients were selected, who presented with clinical/subclinical varicocele and male infertility. All these patients had DUS of the scrotum and underwent for low ligation varicocelectomy. These patients were followed for a period of 12-24 months after surgery for the occurrence of paternity. We reviewed pre-operative scrotal DUS of these 82 patients for the testicular size and volume, pampiniform veins caliber and duration of reflux in the dilated veins at rest, and after valsalva maneuver. These DUS parameters were correlated with the postoperative paternity rate. Results: Postoperative paternity was achieved in 18 patients (31.6%) with normal-sized testes, and in 3 patients (12%) with small size testes. The positive paternity rate was higher (38.5%) in patients with clinically detected varicocele, compared with only 16.7% of patients with subclinical varicocele (detected by ultrasound only). In addition, postoperative paternity was significantly higher in patients with bilateral varicocele (70.6%), with shunt-type varicocele (71.4%), and patients with a permanent grade of venous reflux (62.5%). Conclusion: Selection of patients for the successful paternity after varicocele repair depends mainly on DUS parameters, which includes normal size testicles with shunt type of bilateral varicocele and continuous reflux. PMID:26620986

  12. QTL involved in the partial restoration of male fertility of C-type cytoplasmic male sterility in maize.

    PubMed

    Kohls, Susanne; Stamp, Peter; Knaak, Carsten; Messmer, Rainer

    2011-07-01

    Partial restoration of male fertility limits the use of C-type cytoplasmic male sterility (C-CMS) for the production of hybrid seeds in maize. Nevertheless, the genetic basis of the trait is still unknown. Therefore, the aim to this study was to identify genomic regions that govern partial restoration by means of a QTL analysis carried out in an F(2) population (n = 180). This population was derived from the Corn Belt inbred lines B37C and K55. F(2)BC(1) progenies were phenotyped at three locations in Switzerland. Male fertility was rated according to the quality and number of anthers as well as the anthesis-silking interval. A weak effect of environment on the expression of partial restoration was reflected by high heritabilities of all fertility-related traits. Partial restoration was inherited like an oligogenic trait. Three major QTL regions were found consistently across environments in the chromosomal bins 2.09, 3.06 and 7.03. Therefore, a marker-assisted counter-selection of partial restoration is promising. Minor QTL regions were found on chromosomes 3, 4, 5, 6 and 8. A combination of partial restorer alleles at different QTL can lead to full restoration of fertility. The maternal parent was clearly involved in the partial restoration, because the restorer alleles at QTL in bins 2.09, 6.04 and 7.03 originated from B37. The three major QTL regions collocated with other restorer genes of maize, a phenomenon, which seems to be typical for restorer genes. Therefore, a study of the clusters of restorer genes in maize could lead to a better understanding of their evolution and function. In this respect, the long arm of chromosome 2 is particularly interesting, because it harbors restorer genes for the three major CMS systems (C, T and S) of maize.

  13. Cul4A is essential for spermatogenesis and male fertility.

    PubMed

    Kopanja, Dragana; Roy, Nilotpal; Stoyanova, Tanya; Hess, Rex A; Bagchi, Srilata; Raychaudhuri, Pradip

    2011-04-15

    The mammalian Cul4 genes, Cul4A and Cul4B, encode the scaffold components of the cullin-based E3 ubiquitin ligases. The two Cul4 genes are functionally redundant. Recent study indicated that mice expressing a truncated CUL4A that fails to interact with its functional partner ROC1 exhibit no developmental phenotype. We generated a Cul4A-/- strain lacking exons 4-8 that does not express any detectable truncated protein. In this strain, the male mice are infertile and exhibit severe deficiencies in spermatogenesis. The primary spermatocytes are deficient in progression through late prophase I, a time point when expression of the X-linked Cul4B gene is silenced due to meiotic sex chromosome inactivation. Testes of the Cul4A-/- mice exhibit extensive apoptosis. Interestingly, the pachytene spermatocytes exhibit persistent double stranded breaks, suggesting a deficiency in homologous recombination. Also, we find that CUL4A localizes to the double stranded breaks generated in pre-pachytene spermatocytes. The observations identify a novel function of CUL4A in meiotic recombination and demonstrate an essential role of CUL4A in spermatogenesis.

  14. Genome-wide association study identifies candidate genes for male fertility traits in humans.

    PubMed

    Kosova, Gülüm; Scott, Nicole M; Niederberger, Craig; Prins, Gail S; Ober, Carole

    2012-06-08

    Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10(-4) for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values < 0.05 and seven with p values < 0.01 in the validation study. On the basis of 5,000 permutations of our data, the probabilities of observing this many or more small p values were 0.0014 and 5.6 × 10(-4), respectively. Among the nine associated loci, outstanding candidates for male fertility genes include USP8, an essential deubiquitinating enzyme that has a role in acrosome assembly; UBD and EPSTI1, which have potential roles in innate immunity; and LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population.

  15. Genome-wide Association Study Identifies Candidate Genes for Male Fertility Traits in Humans

    PubMed Central

    Kosova, Gülüm; Scott, Nicole M.; Niederberger, Craig; Prins, Gail S.; Ober, Carole

    2012-01-01

    Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10−4 for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values < 0.05 and seven with p values < 0.01 in the validation study. On the basis of 5,000 permutations of our data, the probabilities of observing this many or more small p values were 0.0014 and 5.6 × 10−4, respectively. Among the nine associated loci, outstanding candidates for male fertility genes include USP8, an essential deubiquitinating enzyme that has a role in acrosome assembly; UBD and EPSTI1, which have potential roles in innate immunity; and LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population. PMID:22633400

  16. Male fertility in natural populations of red deer is determined by sperm velocity and the proportion of normal spermatozoa.

    PubMed

    Malo, Aurelio F; Garde, J Julián; Soler, Ana J; García, Andrés J; Gomendio, Montserrat; Roldan, Eduardo R S

    2005-04-01

    Male reproductive success is determined by the ability of males to gain sexual access to females and by their ability to fertilize ova. Among polygynous mammals, males differ markedly in their reproductive success, and a great deal of effort has been made to understand how selective forces have shaped traits that enhance male competitiveness both before and after copulation (i.e., sperm competition). However, the possibility that males also may differ in their fertility has been ignored under the assumption that male infertility is rare in natural populations because selection against it is likely to be strong. In the present study, we examined which semen traits correlate with male fertility in natural populations of Iberian red deer (Cervus elaphus hispanicus). We found no trade-offs between semen traits. Our analyses revealed strong associations between sperm production and sperm swimming velocity, sperm motility and proportion of morphologically normal spermatozoa, and sperm viability and acrosome integrity. These last two variables had the lowest coefficients of variation, suggesting that these traits have stabilized at high values and are unlikely to be related to fitness. In a fertility trial, our results show a large degree of variation in male fertility, and differences in fertility were determined mainly by sperm swimming velocity and by the proportion of morphologically normal sperm. We conclude that male fertility varies substantially in natural populations of Iberian red deer and that, when sperm numbers are equal, it is determined mainly by sperm swimming velocity and sperm morphology.

  17. All males are not created equal: Fertility differences depend on gamete recognition polymorphisms in sea urchins

    PubMed Central

    Palumbi, Stephen R.

    1999-01-01

    Behaviors, morphologies, and genetic loci directly involved in reproduction have been increasingly shown to be polymorphic within populations. Explaining how such variants are maintained by selection is crucial to understanding the genetic basis of fertility differences, but direct tests of how alleles at reproductive loci affect fertility are rare. In the sea urchin genus Echinometra, the protein bindin mediates sperm attachment to eggs, evolves quickly, and is polymorphic within species. Eggs exposed to experimental sperm mixtures show strong discrimination on the basis of the males’ bindin genotype. Different females produce eggs that nonrandomly select sperm from different males, showing that variable egg–sperm interactions determine fertility. Eggs select sperm with a bindin genotype similar to their own, suggesting strong linkage between female choice and male trait loci. These experiments demonstrate that alleles at a single locus can have a strong effect on fertilization and that reproductive loci may retain functional polymorphisms through epistatic interactions between male and female traits. They also suggest that positive selection at gamete recognition loci like bindin involves strong selection within species on mate choice interactions. PMID:10535974

  18. Effects of prenatal hydrocortisone acetate exposure on fertility and sexual behavior in male rats.

    PubMed

    Pereira, Oduvaldo C M; Arena, Arielle C; Yasuhara, Fabiana; Kempinas, Wilma G

    2003-08-01

    The aim of the present study was to investigate the effects of hydrocortisone during the prenatal period and its later repercussions on the fertility and sexual behavior of male rats. Pregnant rats were treated (s.c.) with hydrocortisone acetate, at 1.5 mg/day on the 17th, 18th, and 19th days of gestation. Decreased body weight and no alteration in anogenital distance were observed in male offspring. Adulthood, presented reductions of body weight, plasma testosterone levels, and seminal-vesicle wet weight without secretion as well as no alteration in the wet weights of the testes, epididymis, and seminal vesicle with secretion in the treated group. Males exposed to hydrocortisone during the prenatal period were able to mate with normal females, which became pregnant but exhibited an increased number of post-implantation losses. In spite of this, these treated males exhibited decreased male sexual behavior and the appearance of female sexual behavior after these male rats were castrated and pretreated with exogenous estrogen. These results indicate that exposure to hydrocortisone in the later stages of pregnancy may have a long-term effect on the fertility and sexual behavior of male rats, suggesting an incomplete masculinization and defeminization of the central nervous system.

  19. Parentage testing implications of male fertility after allogeneic bone marrow transplantation.

    PubMed

    Lipton, J H; Marshall, W H; Waye, J S

    1999-01-01

    Fertility is expected to be reduced after the extensive chemotherapy and/or radiotherapy that is needed for conditioning prior to bone marrow transplantation. However, a male patient can be fertile, and in very rare situations such as reported here, this may confuse subsequent paternity testing. The patient, initially excluded as the biological father by red cell types but not by HLA, was subsequently included after the history of his previous marrow transplant was revealed, a review of the HLA results and further RFLP testing on buccal mucosal cells. This case points to the need for good history taking before performing paternity testing.

  20. Male fertility: Is spermiogenesis the critical step for answering biomedical issues?

    PubMed Central

    Baptissart, Marine; Vega, Aurélie; Martinot, Emmanuelle; Volle, David H.

    2013-01-01

    Regarding male fertility, biomedical issues have opposite goals to treat infertility or develop contraceptive drugs. Recently, the identification of the molecular mechanisms involved in germ cell differentiation suggest that spermiogenesis has to be put at the crossroad to reach these goals. Concerning fertility issues, citizens in our modern world are schizophrenic. On one side, couples have the possibility to control conception; and on the other side, more and more couples suffer from the misfortune of being infertile. These two societal problems lead to intensive research and conflicting government policies. However, these opposing goals rely on a better understanding of germ cell differentiation. PMID:23885302

  1. Association of body mass index with some fertility markers among male partners of infertile couples

    PubMed Central

    Hajshafiha, Masoumeh; Ghareaghaji, Rasul; Salemi, Sedigheh; Sadegh-Asadi, Nahid; Sadeghi-Bazargani, Homayoun

    2013-01-01

    Background The available evidence on the role of obesity and body mass index (BMI) on male infertility has been controversial or inconclusive to some extent. Objectives The aim of this study was to investigate the role of BMI on some male-fertility laboratory indicators both among infertile and fertile men in an Iranian population. Methods and materials A total of 159 male patients who had lived as a partner in an infertile couple for at least 1 year, after regular reproductive activity in their married life, and who sought infertility consultation, were investigated. BMI was assessed, and a morning blood sample was taken assessing serum levels of testosterone, sex hormone-binding globulin, prolactin, luteinizing hormone (LH), follicle-stimulating hormone, and estradiol. Semen-analysis parameters were also measured. Results In this study, it was found that the likelihood of oligospermia was increased at higher BMI values. Obese men were found to be 3.5 times more likely to have oligospermia than those with normal BMI. BMI was not found to be associated with mean numeric values of the semen-analysis parameters, including sperm count, sperm morphology, and sperm motility. BMI was not significantly correlated with some hormone levels, such as LH, prolactin, and LH/follicle-stimulating hormone ratio. However, a statistically significant association was observed between BMI and estradiol (P < 0.01), sex hormone-binding globulin (P < 0.001), and also the testosterone/estradiol ratio (P < 0.001). A different pattern of associations in this study was observed when the associations between BMI and sexual hormone levels were compared between fertile and subfertile/infertile men. Conclusion The association explored between BMI and some sexual hormones and semen characteristics, as well as different patterns of this association between fertile and subfertile/infertile men, will be of help to broaden our understanding of the effect of obesity on some male reproductive

  2. Impact of boric acid exposure at different concentrations on testicular DNA and male rats fertility.

    PubMed

    El-Dakdoky, Mai H; Abd El-Wahab, Hanan M F

    2013-06-01

    The aim of this study was to investigate the consequences of exposure to three levels of boric acid (BA) on male rats reproduction, fertility and progeny outcome, with emphasis on testicular DNA level and quality. Adult male rats (12 weeks old) were treated orally with 125, 250 and 500 mg/kg bwt/d of BA for 60 d. The results indicated that BA administration at 125 mg/kg bwt had no adverse effects on fertility, sperm characteristics or prenatal development of the impregnated females. However, at dose 250 mg, BA treatment significantly increased serum nitric oxide, testosterone, estradiol levels and testicular boron and calcium levels and also significantly reduced serum arginase activity, sperm quality and testicular DNA content with minor DNA fragmentation. The impact of BA exposure at dose 250 mg on male rats fertility was translated into increases in pre-implantation loss with a resulting decrease in the number of live fetuses/litter. In addition to the significant alteration of biochemical measurements, observed at dose 250 mg, administration of BA at 500 mg caused testicular atrophy, severe damage of spermatogenesis, spermiation failure and significant reduction of Mg and Zn testicular levels. None of the male rats, treated with 500 mg/kg bwt, could impregnate untreated females, suggesting the occurrence of definitive loss of fertility. In conclusion, BA impaired fertility, in a dose-dependant manner, by targeting the highly proliferative cells, the germ cells, through decreasing DNA synthetic rate rather than the induction of DNA damage.

  3. Sensory properties and instrumental texture analysis of chevon patties from intact male Boer and Kiko goats harvested at four endpoints.

    PubMed

    Leick, C M; Behrends, J M; Solaiman, S G; Broadway, P R; Min, B R; Mikel, W B; Williams, J B; Schilling, M W

    2012-07-01

    Intact male Boer and Kiko goats (n=48) were harvested after 0, 4, 8, or 12 weeks on a 16% crude protein concentrate diet. Boneless goat carcass left sides were ground and formed into patties to evaluate cook loss, texture profile analysis, and descriptive sensory characteristics. Increasing feeding duration increased percent fat and decreased moisture in raw ground meat (P<0.05). Boer ground meat had more fat and less moisture than Kiko meat (P<0.05). Breed and feeding duration did not affect cook loss (P>0.05). Increased feeding duration increased aroma intensity and goaty, bloody, musty, and liver/organy aromas; salty, bitter, umami, grassy, goaty, fat, liver/organy, metallic, earthy, and chemical flavors; and juiciness and oiliness, while decreasing chewiness and crumbliness (P<0.05). Boer and Kiko patties had similar sensory properties after 0 and 4weeks on feed, but breeds were more distinguishable after 8 or 12 weeks on feed.

  4. Male mice produced by in vitro culture have reduced fertility and transmit organomegaly and glucose intolerance to their male offspring.

    PubMed

    Calle, Alexandra; Miranda, Alberto; Fernandez-Gonzalez, Raul; Pericuesta, Eva; Laguna, Ricardo; Gutierrez-Adan, Alfonso

    2012-08-01

    It has been reported that suboptimal in vitro culture (IVC) of mouse embryos can affect the postnatal expression of epigenetically sensitive alleles, resulting in altered postnatal growth, organ dimensions, health, and behavior in the offspring. Although these detrimental impacts on the offspring are well described, the relative contribution of the IVC-produced fathers is unclear. In this work, we have analyzed if suboptimal IVC (achieved by altering the culture medium by the addition of FCS) can affect male fertility and if organ size and glucose clearance, two of the adverse effects produced by suboptimal IVC conditions, were transmitted to the next two generations. IVC-produced males had lower sperm concentrations (5.8 × 10(6) spermatozoa in IVC vs. 14.5 × 10(6) spermatozoa in control), and these sperm exhibited decreased overall motility (49.6% vs. 72.8% in control) and progressive motility (22.6% vs. 32.2% in control). Fertility tests demonstrated that the percentage of pregnancies was reduced for IVC males (35% for IVC-produced males vs. 86% for in vivo controls). These features were related to a modified gene expression pattern in adult male testes, showing an altered gene expression in genes involved in DNA repair and apoptosis that was confirmed by TUNEL assay. Regarding the IVC related adverse phenotype transmitted to offspring, male glucose intolerance was shown only in F1 and F2 male but not female offspring. The same occurred with male abnormalities in the organ size of the liver, which were transmitted to F1 and F2 males but not to F1 females; moreover, analysis of the F0, F1, and F2 males revealed greater coefficients of variance in body weight and glucose intolerance than the control group. Finally, we analyzed, through gene silencing, the effect of IVC on the mRNA expression at the blastocyst stage for 11 known gene expression modifiers of epigenetic reprogramming. Suboptimal IVC reduced the expression of Kap1, Sox2, Hdac1, Dnmt1, and Dnmt3a

  5. Interaction of genotype × artificial insemination conditions for male effect on fertility and prolificacy.

    PubMed

    Tusell, L; García-Tomás, M; Baselga, M; Rekaya, R; Rafel, O; Ramon, J; López-Bejar, M; Piles, M

    2010-11-01

    Failures in fertilization or embryogenesis have been shown to be partly the result of poor semen quality. When AI is practiced, fertilization rate depends on the number and quality of spermatozoa in the insemination dose around the time of application. Individual variation in the male effect on fertility (success or failure to conceive; Fert) and prolificacy (total number of kids born per litter; TB) could also depend on these factors, and it could be better observed under limited conditions of AI, such as decreased sperm concentration, small or null preselection of ejaculates for any semen quality trait, or a long storage period of the AI doses. The aim of this research was to determine if an interaction existed between male genotype and the AI conditions for male effects on Fert and TB after AI was performed under different conditions. Fertility and TB were assumed to be different traits and were analyzed in 2 sets of independent analyses. In the first step, the different conditions were determined uniquely by the sperm dosage. Artificial insemination was performed at 10 and 40 × 10(6) spermatozoa/mL. In the second step, the different conditions were determined by all the factors involved in the AI process as a whole (conditions and duration of the storage period of the dose, genetic type of the female, and environmental conditions on the farm). Data from AI from the former experiment were analyzed with data from AI performed under different conditions. Threshold and linear 2-trait models were assumed for Fert and TB, respectively. The sperm dosage had a clear effect on Fert and TB, which favored the greater dosage (+0.13% and +1.25 kids born, respectively). Prolificacy was more sensitive to sperm reduction than was fertility. Male heritabilities for Fert were 0.09 for both sperm dosages, and were 0.08 and 0.06 for male TB with a smaller and larger sperm dosage, respectively. No genotype × sperm dosage interaction was found. Therefore, the same response to

  6. Modelling the maintenance of male-fertile cytoplasm in a gynodioecious population.

    PubMed

    Dufaÿ, M; Touzet, P; Maurice, S; Cuguen, J

    2007-09-01

    Gynodioecy is the co-occurrence of females and hermaphrodites in populations. It is usually due to the combined action of cytoplasmic male sterility (CMS) genes and nuclear genes that restore male fertility. According to previous theoretical studies, it is very difficult to explain the maintenance of gynodioecy with CMS and male-fertile cytotypes, although it has been observed in some species. However, only very specific situations have been investigated so far. We present a model to investigate the conditions that promote the maintenance of this breeding system in the case of an outcrossed species when CMS and male-fertile (non-CMS) cytotypes are present in an infinite panmictic population. We show that the type of cost of restoration strongly affects the conditions for stable maintenance of gynodioecy. Stable nuclear-cytoplasmic gynodioecy requires a female advantage, which is a classical condition for gynodioecy, but also a cost of CMS for female fitness, which had been rarely investigated. A cost of restoration is also needed, which could affect either pollen or seeds. Finally, we found that gynodioecy was attainable for a large set of parameter values, including low differences in fitness among genotypes and phenotypes. Our theoretical predictions are compared with previous theoretical work and with results of empirical studies on various gynodioecious species.

  7. Can Male Fertility Be Improved Prior to Assisted Reproduction through The Control of Uncommonly Considered Factors?

    PubMed Central

    Campagne, Daniel M.

    2013-01-01

    Male factor infertility or subfertility is responsible for up to 50% of infertility cases. A considerable body of recent studies indicates that lifestyle as well as environmental and psychological factors can negatively affect male fertility, more than previously thought. These negative effects have been shown in many cases to be reversible. This review aims to provide a rationale for early clinical attention to these factors and presents a non-exhaustive evidence-based collection of primary relevant conditions and recommendations, specifically with a view to making first line diagnostics and recommendations. The presently available evidence suggests that considering the high cost, success rates, and possible side effects of assisted reproduction techniques (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), early efforts to improve male fertility appear to be an attainable and worthwhile primary goal. A series of searches was conducted of Medline, Cochrane and related databases from November 14th, 2010 to January 26th, 2012 with the following keywords: male, fertility, infertility, sperm defects, IVF, ICSI, healthy habits, and lifestyle. Subsequent follow-up searches were performed for upcoming links. The total number of studies contemplated were 1265; of these, 296 studies were reviewed with criteria of relevance; the date of study or review; study sample size and study type; and publishing journal impact status. Data were abstracted based upon probable general clinical relevancy and use. Only a selection of the references has been reflected here because of space limitations. The main results obtained were evidence-supported indications as to the other causes of male infertility, their early detection, and treatment. PMID:24520443

  8. Male fertility and obesity: are ghrelin, leptin and glucagon-like peptide-1 pharmacologically relevant?

    PubMed

    Alves, Marco G; Jesus, Tito T; Sousa, Mário; Goldberg, Erwin; Silva, Branca M; Oliveira, Pedro F

    2016-01-01

    Obesity is rising to unprecedented numbers, affecting a growing number of children, adolescents and young adult men. These individuals face innumerous health problems, including subfertility or even infertility. Overweight and obese men present severe alterations in their body composition and hormonal profile, particularly in ghrelin, leptin and glucagon-like peptide-1 (GLP-1) levels. It is well known that male reproductive health is under the control of the individual's nutritional status and also of a tight network of regulatory signals, particularly hormonal signaling. However, few studies have been focused on the effects of ghrelin, leptin and GLP-1 in male reproduction and how energy homeostasis and male reproductive function are linked. These hormones regulate body glucose homeostasis and several studies suggest that they can serve as targets for anti-obesity drugs. In recent years, our understanding of the mechanisms of action of these hormones has grown significantly. Curiously, their effect on male reproductive potential, that is highly dependent of the metabolic cooperation established between testicular cells, remains a matter of debate. Herein, we review general concepts of male fertility and obesity, with a special focus on the effects of ghrelin, leptin and GLP-1 on male reproductive health. We also discuss the possible pharmacological relevance of these hormones to counteract the fertility problems that overweight and obese men face.

  9. Consequences of Nosema apis infection for male honey bees and their fertility.

    PubMed

    Peng, Yan; Baer-Imhoof, Barbara; Millar, A Harvey; Baer, Boris

    2015-06-30

    The queens of eusocial bees, ants and wasps mate only during a very short period early in life and males therefore produce ejaculates consisting of large numbers of high quality sperm. Such extreme selection for high fecundity resulted in males investing minimally into their somatic survival, including their immune system. However, if susceptible males are unable to protect their reproductive tissue from infections, they compromise queen fitness if they transfer pathogens during mating. We used the honey bee Apis mellifera and investigated the course of infection of the sexually transmitted pathogen Nosema apis. We predicted that honey bee males are susceptible but protect their reproductive tissues from infections. We investigated the effects of N. apis infections on the midgut, the accessory glands and the accessory testes and quantified the consequences of infection on male survival and fecundity. We found that N. apis is able to infect males, and as infections progressed, it significantly impacted fertility and survival in older males. Even though we confirm males to be able to minimize N. apis infections of their reproductive tissues, the parasite is present in ejaculates of older males. Consequently N. apis evolved alternative routes to successfully infect ejaculates and get sexually transmitted.

  10. Consequences of Nosema apis infection for male honey bees and their fertility

    PubMed Central

    Peng, Yan; Baer-Imhoof, Barbara; Harvey Millar, A.; Baer, Boris

    2015-01-01

    The queens of eusocial bees, ants and wasps mate only during a very short period early in life and males therefore produce ejaculates consisting of large numbers of high quality sperm. Such extreme selection for high fecundity resulted in males investing minimally into their somatic survival, including their immune system. However, if susceptible males are unable to protect their reproductive tissue from infections, they compromise queen fitness if they transfer pathogens during mating. We used the honey bee Apis mellifera and investigated the course of infection of the sexually transmitted pathogen Nosema apis. We predicted that honey bee males are susceptible but protect their reproductive tissues from infections. We investigated the effects of N. apis infections on the midgut, the accessory glands and the accessory testes and quantified the consequences of infection on male survival and fecundity. We found that N. apis is able to infect males, and as infections progressed, it significantly impacted fertility and survival in older males. Even though we confirm males to be able to minimize N. apis infections of their reproductive tissues, the parasite is present in ejaculates of older males. Consequently N. apis evolved alternative routes to successfully infect ejaculates and get sexually transmitted. PMID:26123530

  11. A novel male sterility-fertility restoration system in plants for hybrid seed production

    PubMed Central

    Singh, Surendra Pratap; Singh, Sudhir P.; Pandey, Tripti; Singh, Ram Rakshpal; Sawant, Samir V.

    2015-01-01

    Hybrid seeds are used for stimulated crop production, as they harness heterosis. The achievement of complete male-sterility in the female-parent and the restored-fertility in F1-hybrids are the major bottlenecks in the commercial hybrid seed production. Here, we report a male sterility–fertility restoration system by engineering the inmost nutritive anther wall layer tapetum of female and male parents. In the female parent, high–level, and stringent expression of Arabidopsis autophagy–related gene BECLIN1 was achieved in the tapetum, which altered the tapetal degeneration program, leading to male sterility. This works on our previously demonstrated expression cassette based on functional complementation of TATA-box mutant (TGTA) promoter and TATA-binding protein mutant3 (TBPm3), with modification by conjugating Long Hypocotyle in Far-Red1 fragment (HFR1NT131) with TBPm3 (HFR1NT131-TBPm3) to exercise regulatory control over it. In the male parent, tapetum–specific Constitutive photo-morphogenesis1 (COP1) was expressed. The F1 obtained by crossing these engineered parents showed decreased BECLIN1 expression, which was further completely abolished when COP1-mutant (COP1L105A) was used as a male parent, leading to normal tapetal development and restored fertility. The system works on COP1-HFR1 interaction and COP1–mediated degradation of TBPm3 pool (HFR1NT131-TBPm3). The system can be deployed for hybrid seed production in agricultural crops. PMID:26073981

  12. Female house mice avoid fertilization by t haplotype incompatible males in a mate choice experiment

    PubMed Central

    Manser, A; König, B; Lindholm, A K

    2015-01-01

    The t haplotype in house mice is a well-known selfish genetic element with detrimental, nonadditive fitness consequences to its carriers: recessive lethal mutations cause t/t homozygotes to perish in utero. Given the severe genetic incompatibility imposed by the t haplotype, we predict females to avoid fertilization by t haplotype incompatible males. Indeed, some of the strongest evidence for compatibility mate choice is related to the t haplotype in house mice. However, all previous evidence for compatibility mate choice in this system is based on olfactory preference. It is so far unknown how general these preferences are and whether they are relevant in an actual mating context. Here, we assess female compatibility mate choice related to t haplotypes in a setting that – for the first time – allowed females to directly interact and mate with males. This approach enabled us to analyse female behaviour during the testing period, and the resulting paternity success and fitness consequences of a given choice. We show that genetic incompatibilities arising from the t haplotype had severe indirect fitness consequences and t females avoided fertilization by t incompatible males. The results are inconclusive whether this avoidance of t fertilization by t females was caused by pre- or post-copulatory processes. PMID:25494878

  13. Reduction of germ cells in the Odysseus null mutant causes male fertility defect in Drosophila melanogaster.

    PubMed

    Cheng, Ya-Jen; Fang, Shu; Tsaur, Shun-Chern; Chen, Yi-Ling; Fu, Hua-Wen; Patel, Nipam H; Ting, Chau-Ti

    2012-01-01

    Odysseus (OdsH) has been identified as a hybrid male sterility gene between Drosophila mauritiana and D. simulans with accelerated evolutionary rate in both expression and DNA sequence. Loss of a testis-specific expression of OdsH causes male fertility defect in D. melanogaster. Yet, the underlying mechanisms at the cellular level are unknown. In an attempt to identify the possible mechanisms and functional roles of OdsH in spermatogenesis, the cell numbers at different developmental stages during spermatogenesis between the OdsH null mutant and wild-type flies were compared. The results showed that the early developing germ cells, including spermatogonia and spermatocytes, were reduced in the OdsH mutant males. In addition, the number of germline stem cells in aged males was also reduced, presumably due to the disruption of germline stem cell maintenance, which resulted in more severe fertility defect. These results suggest that the function of the enhancement of sperm production by OdsH acted across males of all ages.

  14. IUSSP activities. Committee on Anthropological Demography. Report: Seminar on Fertility and the Male Life Cycle in the Era of Fertility Decline, Zacatecas, Mexico, 13-16 November 1995.

    PubMed

    Infesta Dominquez, G

    1996-05-01

    This article gives an overview of a conference on Fertility and the Male Life Cycle held in Mexico on November 13-16, 1995. The seminars, organized by anthropological demographers, were based on the view that differences in men's life course events affect how many children are produced, when children are produced, and the kind of support given to children. Little research has focused on male fertility. Two overview papers addressed the issues of men's changing sexual and reproductive intentions as a response to economic changes (Jane Guyer) and theories of male fertility trends in industrialized countries (David Coleman). Other papers were presented on the following topics: changes in male fertility, sexuality and the male life cycle, polygyny and fertility, men's notions of sexuality and reproductive health, masculinity and reproduction, and future research directions. Laurent Toulemon and Evelyne Lapierre-Adamcyk and Katarina Pohl presented papers on gender differences in fertility. Philip Setel presented an analysis of the social construction of parenthood among Coastal Boiken in Papua New Guinea. Paul Miret discussed men's role in the sharp decline in Spanish fertility. Nosa Orobaton contrasted African men's changing roles over the life course. Differences in fertility among polygynous populations in Africa and in China were analyzed by Ann Blanc and Anastasia Gage, and James Lee and Wang Feng. Other papers were prepared by Juan Gillermo Figueroa Perea, John Anarfi and Clara Korkor, Frances L. Goldscheider et al., Benno de Keijzer, and Mario Humberto Ruz, Ondina Fachel Leal and Jandyra M.G. Fachel, and Kamran Asdar Ali. Seminar papers were expected to be published in several collections.

  15. Male Fertility Is Reduced by Chronic Intermittent Hypoxia Mimicking Sleep Apnea in Mice

    PubMed Central

    Torres, Marta; Laguna-Barraza, Ricardo; Dalmases, Mireia; Calle, Alexandra; Pericuesta, Eva; Montserrat, Josep M.; Navajas, Daniel; Gutierrez-Adan, Alfonso; Farré, Ramon

    2014-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia and oxidative stress. However, it is unknown whether intermittent hypoxia mimicking OSA modifies male fertility. We tested the hypothesis that male fertility is reduced by chronic intermittent hypoxia mimicking OSA in a mouse model. Design: Case-control comparison in a murine model. Setting: University research laboratory. Participants: Eighteen F1 (C57BL/6xCBA) male mice. Interventions: Mice were subjected to a pattern of periodic hypoxia (20 sec at 5% O2 followed by 40 sec of room air) 6 h/day for 60 days or normoxia. After this period, mice performed a mating trial to determine effective fertility by assessing the number of pregnant females and fetuses. Measurements and Results: After euthanasia, oxidative stress in testes was assessed by measuring the expression of glutathione peroxidase 1 (Gpx1) and superoxide dismutase-1 (Sod1) by reverse-transcription polymerase chain reaction. Sperm motility was determined by Integrated Semen Analysis System (ISAS). Intermittent hypoxia significantly increased testicular oxidative stress, showing a reduction in the expression of Gpx1 and Sod1 by 38.9% and 34.4%, respectively, as compared with normoxia (P < 0.05). Progressive sperm motility was significantly reduced from 27.0 ± 6.4% in normoxia to 12.8 ± 1.8% in the intermittent hypoxia group (P = 0.04). The proportion of pregnant females and number of fetuses per mating was significantly lower in the intermittent hypoxia group (0.33 ± 0.10 and 2.45 ± 0.73, respectively) than in normoxic controls (0.72 ± 0.16 and 5.80 ± 1.24, respectively). Conclusions: These results suggest that the intermittent hypoxia associated with obstructive sleep apnea (OSA) could induce fertility reduction in male patients with this sleep breathing disorder. Citation: Torres M, Laguna-Barraza R, Dalmases M, Calle A, Pericuesta E, Montserrat JM, Navajas D, Gutierrez-Adan A, Farré R. Male fertility is

  16. Comparative Transcriptome Analysis of Recessive Male Sterility (RGMS) in Sterile and Fertile Brassica napus Lines

    PubMed Central

    Zhao, Huiyan; Liu, Chuan; Li, Jiana; Tang, Zhanglin; Xu, Xinfu; Qiu, Xiao; Wang, Rui; Lu, Kun

    2015-01-01

    The recessive genetic male sterility (RGMS) system plays a key role in the production of hybrid varieties in self-pollinating B. napus plants, and prevents negative cytoplasmic effects. However, the complete molecular mechanism of the male sterility during male-gametogenesis in RGMS remains to be determined. To identify transcriptomic changes that occur during the transition to male sterility in RGMS, we examined the male sterile line WSLA and male fertile line WSLB, which are near-isogenic lines (NILs) differing only in the fertility trait. We evaluated the phenotypic features and sterility stage using anatomical analysis. Comparative RNA sequencing analysis revealed that 3,199 genes were differentially expressed between WSLA and WSLB. Many of these genes are mainly involved in biological processes related to flowering, including pollen tube development and growth, pollen wall assembly and modification, and pollen exine formation and pollination. The transcript profiles of 93 genes associated with pollen wall and anther development were determined by quantitative RT-PCR in different flower parts, and classified into the following three major clades: 1) up-regulated in WSLA plants; 2) down-regulated in WSLA plants; and 3) down-regulated in buds, but have a higher expression in stigmas of WSLA than in WSLB. A subset of genes associated with sporopollenin accumulation were all up-regulated in WSLA. An excess of sporopollenin results in defective pollen wall formation, which leads to male sterility in WSLA. Some of the genes identified in this study are candidates for future research, as they could provide important insight into the molecular mechanisms underlying RGMS in WSLA. PMID:26656530

  17. Male Investments in High Quality Sperm Improve Fertilization Success, but May Have Negative Impact on Offspring Fitness in Whitefish

    PubMed Central

    Kekäläinen, Jukka; Soler, Carles; Veentaus, Sami; Huuskonen, Hannu

    2015-01-01

    Many ejaculate traits show remarkable variation in relation to male social status. Males in disfavoured (subordinate) mating positions often invest heavily on sperm motility but may have less available resources on traits (e.g., secondary sexual ornaments) that improve the probability of gaining matings. Although higher investments in sperm motility can increase the relative fertilization success of subordinate males, it is unclear whether status-dependent differences in sperm traits could have any consequences for offspring fitness. We tested this possibility in whitefish (Coregonus lavaretus L.) by experimentally fertilizing the eggs of 24 females with the sperm of either highly-ornamented (large breeding tubercles, dominant) or less-ornamented (small tubercles, subordinate) males (split-clutch breeding design). In comparison to highly-ornamented individuals, less-ornamented males had higher sperm motility, which fertilized the eggs more efficiently, but produced embryos with impaired hatching success. Also offspring size and body condition were lower among less-ornamented males. Furthermore, sperm motility was positively associated with the fertilization success and offspring size, but only in highly-ornamented males. Together our results indicate that male investments on highly motile (fertile) sperm is not necessarily advantageous during later offspring ontogeny and that male status-dependent differences in sperm phenotype may have important effects on offspring fitness in different life-history stages. PMID:26389594

  18. Male Investments in High Quality Sperm Improve Fertilization Success, but May Have Negative Impact on Offspring Fitness in Whitefish.

    PubMed

    Kekäläinen, Jukka; Soler, Carles; Veentaus, Sami; Huuskonen, Hannu

    2015-01-01

    Many ejaculate traits show remarkable variation in relation to male social status. Males in disfavoured (subordinate) mating positions often invest heavily on sperm motility but may have less available resources on traits (e.g., secondary sexual ornaments) that improve the probability of gaining matings. Although higher investments in sperm motility can increase the relative fertilization success of subordinate males, it is unclear whether status-dependent differences in sperm traits could have any consequences for offspring fitness. We tested this possibility in whitefish (Coregonus lavaretus L.) by experimentally fertilizing the eggs of 24 females with the sperm of either highly-ornamented (large breeding tubercles, dominant) or less-ornamented (small tubercles, subordinate) males (split-clutch breeding design). In comparison to highly-ornamented individuals, less-ornamented males had higher sperm motility, which fertilized the eggs more efficiently, but produced embryos with impaired hatching success. Also offspring size and body condition were lower among less-ornamented males. Furthermore, sperm motility was positively associated with the fertilization success and offspring size, but only in highly-ornamented males. Together our results indicate that male investments on highly motile (fertile) sperm is not necessarily advantageous during later offspring ontogeny and that male status-dependent differences in sperm phenotype may have important effects on offspring fitness in different life-history stages.

  19. Female sperm use and storage between fertilization events drive sperm competition and male ejaculate allocation.

    PubMed

    Requena, Gustavo S; Alonzo, Suzanne H

    2014-12-01

    Sperm competition theory has traditionally focused on how male allocation responds to female promiscuity, when males compete to fertilize a single clutch of eggs. Here, we develop a model to ask how female sperm use and storage across consecutive reproductive events affect male ejaculate allocation and patterns of mating and paternity. In our model, sperm use (a single parameter under female control) is the main determinant of sperm competition, which alters the effect of female promiscuity on male success and, ultimately, male reproductive allocation. Our theory reproduces the general pattern predicted by existing theory that increased sperm competition favors increased allocation to ejaculates. However, our model predicts a negative correlation between male ejaculate allocation and female promiscuity, challenging the generality of a prevailing expectation of sperm competition theory. Early models assumed that the energetic costs of precopulatory competition and the level of sperm competition are both determined by female promiscuity, which leads to an assumed covariation between these two processes. By modeling precopulatory costs and sperm competition independently, our theoretical framework allows us to examine how male allocation should respond independently to variation in sperm competition and energetic trade-offs in mating systems that have been overlooked in the past.

  20. Fruitless RNAi knockdown in the desert locust, Schistocerca gregaria, influences male fertility.

    PubMed

    Boerjan, Bart; Tobback, Julie; Vandersmissen, Hans Peter; Huybrechts, Roger; Schoofs, Liliane

    2012-02-01

    In Drosophila melanogaster, the male-specific splice isoform of the fruitless gene (Fru(M)) encodes a set of transcription factors that are involved in the regulation of male courtship and copulation. Recent insights from non-drosophilid insects suggest a conserved evolutionary role for the transcription factor Fruitless. In the desert locust, Schistocerca gregaria and the German cockroach, Blatella germanica, both orthopteran insects, a conserved functional role for fruitless has been proposed. Fru specific RNAi knockdown in the third nymphal stage of male Schistocera gregaria delays copulation initiation and results in reduced progeny. In order to identify the origin of the observed phenotypic effects following a fruitless RNAi treatment in the male, we show that the fru knockdown has no detectable effect on spermio- or spermatogenesis and on the transfer of spermatozoa during copulation. Nevertheless, it is clear that the male seminal vesicles contain significantly less spermatozoa after fru RNAi as compared to gfp RNAi controls. We conclude that a lowered male fertility, caused by the fru knockdown in male desert locusts may be the direct cause for the reduction of the progeny numbers in their naïve female copulation partners.

  1. [Calcium distribution in fertile and sterile anthers of a genic male sterile Chinese cabbage].

    PubMed

    Xie, Chao-Tian; Yang, Yan-Hong; Qiu, Yi-Lan; Ge, Li-Li; Tian, Hui-Qiao

    2005-12-01

    Potassium antimonite was used to locate calcium in the fertile and sterile anthers of a genic male sterile Chinese cabbage (Brassica campestris L. ssp. chinensis Makino) to probe the relation between Ca(2+) and fertility and sterility of anthers of the cabbage. During fertile anther development, calcium granules increase in number in anther wall cells after meiosis, and then appeared also in locule, suggesting a calcium influx into locule from anther wall cells (Plate I-4). Then the number of calcium granules in microspore cytoplasm also increased at early stage (Plate II-1), accumulated mainly on the membrane of small vacuoles which were fusing to form big ones to make a polarity in the cell and to prepare asymmetric division of microspore (Plate II-3,4). After microspore division and the big vacuole decomposition, many calcium granules accumulated again on the membrane of the vacuoles (Plate III-1,2), displaying calcium regulates vacuole formation and decomposition during pollen development. In sterile anthers, abnormal distribution of calcium granules first appeared in callus wall of microspore mother cell (Plate IV-1). However, only a few calcium granules appeared in early microspores, which then could not form small vacuoles and finally a big vacuole (Plate IV-2,3). The aborting microspores degenerate by cytoplasm shrinking (Plate IV-5,6). The difference pattern of distribution of calcium granules between the fertile and sterile anthers indicates that anomalies in the distribution of calcium accumulation are correlated with the failure of pollen development and pollen abortion.

  2. Chronic exposures and male fertility: the impacts of environment, diet, and drug use on spermatogenesis.

    PubMed

    Gabrielsen, J S; Tanrikut, C

    2016-07-01

    Several recent studies have suggested that sperm concentrations and semen quality have been decreasing over the past several decades in many areas of the world. The etiology of these decreases is currently unknown. Acute events can have significant impacts on spermatogenesis and are often readily identified during the male fertility evaluation. The majority of male factor infertility, however, is idiopathic. Chronic, low-dose exposures to chemicals and nutrients are more difficult to identify, but are extremely prevalent. These exposures have been shown to have dramatic effects on both individual and community health and interest in the cumulative and synergistic impacts of such agents on spermatogenesis has been increasing. While our understanding of these potential hazards is evolving, it is clear that they may significantly influence male reproductive potential. This review explores the literature related to effects of chronic exposures from drug use, dietary intake, and the environment on spermatogenesis in humans and animals.

  3. Phosphoglycerate Kinase 2 (PGK2) Is Essential for Sperm Function and Male Fertility in Mice1

    PubMed Central

    Danshina, Polina V.; Geyer, Christopher B.; Dai, Qunsheng; Goulding, Eugenia H.; Willis, William D.; Kitto, G. Barrie; McCarrey, John R.; Eddy, E.M.; O'Brien, Deborah A.

    2010-01-01

    Phosphoglycerate kinase 2 (PGK2), an isozyme that catalyzes the first ATP-generating step in the glycolytic pathway, is encoded by an autosomal retrogene that is expressed only during spermatogenesis. It replaces the ubiquitously expressed phosphoglycerate kinase 1 (PGK1) isozyme following repression of Pgk1 transcription by meiotic sex chromosome inactivation during meiotic prophase and by postmeiotic sex chromatin during spermiogenesis. The targeted disruption of Pgk2 by homologous recombination eliminates PGK activity in sperm and severely impairs male fertility, but does not block spermatogenesis. Mating behavior, reproductive organ weights (testis, excurrent ducts, and seminal vesicles), testis histology, sperm counts, and sperm ultrastructure were indistinguishable between Pgk2−/− and wild-type mice. However, sperm motility and ATP levels were markedly reduced in males lacking PGK2. These defects in sperm function were slightly less severe than observed in males lacking glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS), the isozyme that catalyzes the step preceding PGK2 in the sperm glycolytic pathway. Unlike Gapdhs−/− males, the Pgk2−/− males also sired occasional pups. Alternative pathways that bypass the PGK step of glycolysis exist. We determined that one of these bypass enzymes, acylphosphatase, is active in mouse sperm, perhaps contributing to phenotypic differences between mice lacking GAPDHS or PGK2. This study determined that PGK2 is not required for the completion of spermatogenesis, but is essential for sperm motility and male fertility. In addition to confirming the importance of the glycolytic pathway for sperm function, distinctive phenotypic characteristics of Pgk2−/− mice may provide further insights into the regulation of sperm metabolism. PMID:19759366

  4. Phosphoglycerate kinase 2 (PGK2) is essential for sperm function and male fertility in mice.

    PubMed

    Danshina, Polina V; Geyer, Christopher B; Dai, Qunsheng; Goulding, Eugenia H; Willis, William D; Kitto, G Barrie; McCarrey, John R; Eddy, E M; O'Brien, Deborah A

    2010-01-01

    Phosphoglycerate kinase 2 (PGK2), an isozyme that catalyzes the first ATP-generating step in the glycolytic pathway, is encoded by an autosomal retrogene that is expressed only during spermatogenesis. It replaces the ubiquitously expressed phosphoglycerate kinase 1 (PGK1) isozyme following repression of Pgk1 transcription by meiotic sex chromosome inactivation during meiotic prophase and by postmeiotic sex chromatin during spermiogenesis. The targeted disruption of Pgk2 by homologous recombination eliminates PGK activity in sperm and severely impairs male fertility, but does not block spermatogenesis. Mating behavior, reproductive organ weights (testis, excurrent ducts, and seminal vesicles), testis histology, sperm counts, and sperm ultrastructure were indistinguishable between Pgk2(-/-) and wild-type mice. However, sperm motility and ATP levels were markedly reduced in males lacking PGK2. These defects in sperm function were slightly less severe than observed in males lacking glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS), the isozyme that catalyzes the step preceding PGK2 in the sperm glycolytic pathway. Unlike Gapdhs(-/-) males, the Pgk2(-/-) males also sired occasional pups. Alternative pathways that bypass the PGK step of glycolysis exist. We determined that one of these bypass enzymes, acylphosphatase, is active in mouse sperm, perhaps contributing to phenotypic differences between mice lacking GAPDHS or PGK2. This study determined that PGK2 is not required for the completion of spermatogenesis, but is essential for sperm motility and male fertility. In addition to confirming the importance of the glycolytic pathway for sperm function, distinctive phenotypic characteristics of Pgk2(-/-) mice may provide further insights into the regulation of sperm metabolism.

  5. Sequencing and annotation of the chloroplast DNAs and identification of polymorphisms distinguishing normal male-fertile and male-sterile cytoplasms of onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Due the biennial generation time of onion, classical crossing takes at least four years to classify cytoplasms as normal (N) male-fertile or male-sterile (S). Molecular markers in the organellar DNAs that distinguish N and S cytoplasms are useful to reduce the time required to classify onion cytopla...

  6. Feeding broiler breeder males. 1. Effect of feeding program and dietary crude protein during rearing on body weight and fertility of broiler breeder males.

    PubMed

    Romero-Sanchez, H; Plumstead, P W; Brake, J

    2007-01-01

    A 2 x 2 factorial experiment was conducted to compare the effects of 2 male broiler breeder feed allocation programs (Concave or Sigmoid) during the rearing period to 26 wk of age and the interaction with dietary CP (12 or 17%) on BW and fertility. From 0 to 2 wk, all birds received a starter diet, after which, pens were randomly assigned to the 4 treatment combinations that ended at 26 wk of age. All males were weighed individually at 4, 8, 12, 16, 22, 26, 28, 32, 36, 40, 48, 52, 56, and 64 wk of age, and fertility was determined weekly from 27 to 32 wk of age and then every 2 wk to 64 wk of age. At 49 wk of age, the male feed allocation for all treatments was increased by 5 g/d. Even when fed the same as Sigmoid program males during the production period, males reared on the Concave feeding program lost BW from 32 to 40 wk of age and exhibited lower BW from 40 to 48 wk of age, which corresponded to a more rapid decrease in fertility. The 17% CP diet increased BW from 8 to 32 wk of age, but no significant differences were subsequently observed. The 12% CP rearing diet improved both weekly and cumulative fertility. A significant interaction between rearing feeding program and dietary CP during the third quartile period showed that the Concave program-17% CP diet combination was most negatively affected. The increase in male feed allocation at 49 wk restored fertility and caused differences among treatments to diminish. These data suggested that BW during the early rearing period did not affect fertility, but an increased BW due to either providing fast feed increments toward the end of the rearing period (Concave) or feeding a 17% CP diet produced males that were unable to sustain fertility after 40 wk of age without an appropriate allocation of feed.

  7. Fertility of male and female broiler breeders following exposure to elevated ambient temperatures.

    PubMed

    McDaniel, C D; Bramwell, R K; Wilson, J L; Howarth, B

    1995-06-01

    Because elevated ambient temperatures decrease fertility, this study was designed to segregate the male and female contribution to heat stress infertility in broiler breeders. Eighty hens and 16 roosters at 21 wk of age were divided equally among two heat stress (S) and two control (C) temperature chambers. For a 10-wk pretreatment period, all birds were maintained at an ambient temperature of 21.1 C and 40% relative humidity. Following the pretreatment period, birds in the S chambers were acclimated for 1 wk at a constant temperature of 29.4 C after which the temperature in the S chambers was increased to 32.2 C for 8 wk. The temperature in the two C chambers was maintained at 21.1 C. Hens in each chamber were artificially inseminated on a weekly basis with 5 x 10(7) sperm per 50 microL from either C or S males. Egg production, semen volume, spermatocrit, and percentage dead sperm were similar during the acclimation period, even though body temperature was significantly elevated in S birds (41.8 vs 41.3 C). Sperm penetration of the perivitelline layer overlying the germinal disc (GD) was decreased in eggs from hens inseminated with semen from S males compared to eggs from hens inseminated with semen from C males (9.5 vs 23.4 sperm per GD). Following the acclimation period, body temperature remained elevated in the S birds compared to the C birds (42.2 vs 41.3 C). Also, egg production was depressed in the S vs C hens (55.8 vs 82.9%). Semen volume, spermatocrit, and percentage dead sperm were not affected by S treatment. However, when hens were inseminated with semen from S males, sperm penetration of the perivitelline layer overlying the GD and egg fertility were decreased compared to hens inseminated with semen from C males (5.4 vs 14.9 sperm per GD, 45.5 vs 73.8% fertility). In conclusion, the male bird appears to contribute more to heat stress infertility than the female.

  8. A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster

    PubMed Central

    Patel, Maulik R; Miriyala, Ganesh K; Littleton, Aimee J; Yang, Heiko; Trinh, Kien; Young, Janet M; Kennedy, Scott R; Yamashita, Yukiko M; Pallanck, Leo J; Malik, Harmit S

    2016-01-01

    Due to their strict maternal inheritance in most animals and plants, mitochondrial genomes are predicted to accumulate mutations that are beneficial or neutral in females but harmful in males. Although a few male-harming mtDNA mutations have been identified, consistent with this ‘Mother’s Curse’, their effect on females has been largely unexplored. Here, we identify COIIG177S, a mtDNA hypomorph of cytochrome oxidase II, which specifically impairs male fertility due to defects in sperm development and function without impairing other male or female functions. COIIG177S represents one of the clearest examples of a ‘male-harming’ mtDNA mutation in animals and suggest that the hypomorphic mtDNA mutations like COIIG177S might specifically impair male gametogenesis. Intriguingly, some D. melanogaster nuclear genetic backgrounds can fully rescue COIIG177S -associated sterility, consistent with previously proposed models that nuclear genomes can regulate the phenotypic manifestation of mtDNA mutations. DOI: http://dx.doi.org/10.7554/eLife.16923.001 PMID:27481326

  9. Comparative study on the effect of Eurycoma longifolia and Smilax myosotiflora on male rats fertility

    NASA Astrophysics Data System (ADS)

    Mahmoud, Amal Salem Farag; Noor, Mahanem Mat

    2013-11-01

    The effects of Eurycoma longifolia Jack and Smilax myosotiflora were studied on sperm quality include sperm count, motility, viability and histology of the testis and pregnancy rate after mating with fertile proved females, as well as litter size on Sprague-Dawley (S-D) adult male rats. After dosing them with distilled water group A, group B 150 mg/kg body weight of aqueous extract of E. longifolia roots, group C 150 mg/kg body weight aqueous extract of S. myosotiflora leaf and group D 150 mg/kg body weight of E. longifolia combined with 150 mg/kg S. myosotiflora body weight daily for 14 days of stage (a) and 28 days for stage (b) of treatments. Results exhibited no significant variation (P>0.05) of stage (a),while results showed that E. longifolia Jack increase (P<0.05) the sperm count, motility, viability and histology of the testis and gender (male) of the litter size respectively of stage (b). This study provides evidence that E. longifolia Jack is a potent stimulator of fertility in male rat.

  10. Reproductive toxicity of 2,4-toluenediamine in the rat. 1. Effect on male fertility

    SciTech Connect

    Thysen, B.; Varma, S.K.; Bloch, E.

    1985-01-01

    Effects of 2,4-toluenediamine (TDA) on reproduction in adult male Sprague-Dawley rats were evaluated. Diets containing 0, 0.01 and 0.03% TDA were fed ad libitum to experimental animals for 10 wk. No signs of toxicity were found. Exposure to the high dose resulted in decreased mating frequency and an increase in infertile matings. Light-microscopic examination of the testes revealed reduced numbers of sperm in the seminiferous tubules and cauda epididymides. These results indicate that TDA is capable of reducing fertility and of exerting an inhibitory or toxic effect on spermatogenesis in the rat.

  11. Genetic parameters for male fertility and its relationship to skatole and androstenone in Danish Landrace boars.

    PubMed

    Strathe, A B; Velander, I H; Mark, T; Ostersen, T; Hansen, C; Kadarmideen, H N

    2013-10-01

    Concerns have been raised regarding selection against the boar taint compounds, androstenone and skatole, due to potential unfavorable genetic correlations with important male fertility traits (i.e., selection of boars with low levels of these boar taint compounds might also reduce male fertility). Hence, the objective of this investigation was to study the genetic association between direct measures of male fertility and the boar taint compounds in Danish Landrace pigs. Concentrations of skatole and androstenone in the back fat were available for approximately 6,000 and 1,000 Landrace boars, respectively. The litter size traits, such as total number born, live piglets at d 5, and piglet survival until d 5 on relatives of the slaughter boars, were extracted from the Danish Landrace breeding program, yielding 35,715 records. Semen volume, sperm concentration, subjective sperm quality score, and total number of sperm were available from 95,267 ejaculates. These ejaculates were collected between 2005 and 2012 and originated from 3,145 Landrace boars from 12 AI stations in Denmark. The traits were analyzed using single and multitrait animal models including univariate random regression models. Skatole and androstenone concentrations were moderate to highly heritable (i.e., 0.33 and 0.59, respectively). The genetic correlation between the two compounds was moderate (0.40). Genetic variance of sperm production per ejaculate increased during the productive life of the boar, resulting in heritability estimates increasing from 0.18 to 0.31. Genetic correlations between sperm production per ejaculate at different ages were high and generally larger than 0.8, indicating that later genetic merit can be predicted from records at an early age. The heritability (based on service-sire genetic component) of both total number of piglets born and survival to d 5 were 0.02, and the correlation between these effects and the additive genetic effect on boar taint ranged from 0.05 to -0

  12. Predator odour and its impact on male fertility and reproduction in Phodopus campbelli hamsters

    NASA Astrophysics Data System (ADS)

    Vasilieva, N. Y.; Cherepanova, E. V.; von Holst, D.; Apfelbach, R.

    This study investigated the influence of cat urine odour in suppressing development and fertility in Campbell's hamster males. Exposure to this odour from postnatal day 11 until day 45 (sexual maturation) resulted in reduced sex organ weights, reduced testosterone levels and in an increase in abnormalities of the synaptonemal complex in both sex chromosomes and autosomes. Subsequent breeding experiments revealed a significant decrease in litter size. All these data indicate a severe effect of predator odour on the breeding success of potential prey species. It is assumed that these effects are caused by the sulphurous compounds in the urine; however, the underlying mechanisms are not yet known.

  13. Recent progress in plant reproduction research: the story of the male gametophyte through to successful fertilization.

    PubMed

    Suzuki, Go

    2009-11-01

    Sexual reproduction is an important biological event not only for evolution but also for breeding in plants. It is a well known fact that Charles Darwin (1809-1882) was interested in the reproduction system of plants as part of his concept of 'species' and 'evolution.' His keen observation and speculation is timeless even in the current post-genome era. In the Darwin anniversary year of 2009, I have summarized recent molecular genetic studies of plant reproduction, focusing especially on male gametophyte development, pollination and fertilization. We are just beginning to understand the molecular mechanisms of the elaborate reproduction system in flowering plants, which have been a mystery for >100 years.

  14. Effects of Saikokaryukotsuboreito on Spermatogenesis and Fertility in Aging Male Mice

    PubMed Central

    Zang, Zhi-Jun; Ji, Su-Yun; Zhang, Ya-Nan; Gao, Yong; Zhang, Bin

    2016-01-01

    Background: Aspermia caused by exogenous testosterone limit its usage in late-onset hypogonadism (LOH) patients desiring fertility. Saikokaryukotsuboreito (SKRBT) is reported to improve serum testosterone and relieve LOH-related symptoms. However, it is unclear whether SKRBT affects fertility. We aimed to examine the effects of SKRBT on spermatogenesis and fertility in aging male mice. Methods: Thirty aging male mice were randomly assigned to three groups. Mice were orally administered with phosphate-buffer solution or SKRBT (300 mg/kg, daily) or received testosterone by subcutaneous injections (10 mg/kg, every 3 days). Thirty days later, each male mouse was mated with two female mice. All animals were sacrificed at the end of 90 days. Intratesticular testosterone (ITT) levels, quality of sperm, expression of synaptonemal complex protein 3 (SYCP3), and fertility were assayed. Results: In the SKRBT-treated group, ITT, quality of sperm, and expression of SYCP3 were all improved compared with the control group (ITT: 85.50 ± 12.31 ng/g vs. 74.10 ± 11.45 ng/g, P = 0.027; sperm number: [14.94 ± 4.63] × 106 cells/ml vs. [8.79 ± 4.38] × 106 cells/ml, P = 0.002; sperm motility: 43.16 ± 9.93% vs. 33.51 ± 6.98%, P = 0.015; the number of SYCP3-positive cells/tubule: 77.50 ± 11.01 ng/ml vs. 49.30 ± 8.73 ng/ml, P < 0.001; the expression of SYCP3 protein: 1.23 ± 0.09 vs. 0.84 ± 0.10, P < 0.001), but fertility was not significantly changed (P > 0.05, respectively). In the testosterone-treated group, ITT, quality of sperm, and expression of SYCP3 were markedly lower than the control group (ITT: 59.00 ± 8.67, P = 0.005; sperm number: [4.34 ± 2.45] × 106 cells/ml, P = 0.018; sperm motility: 19.53 ± 7.69%, P = 0.001; the number of SYCP3-positive cells/tubule: 30.00 ± 11.28, P < 0.001; the percentage of SYCP3-positive tubules/section 71.98 ± 8.88%, P = 0.001; the expression of SYCP3 protein: 0.71 ± 0.09, P < 0.001), and fertility was also suppressed (P < 0

  15. Fertility suppression in male albino rats by administration of methanolic extract of Opuntia dillenii.

    PubMed

    Bajaj, V K; Gupta, R S

    2012-05-01

    To control growing world population, there is a need for male contraceptive methods that are comparable to female contraceptives, but due to lack of knowledge or investigation, no sufficient safe and effective contraceptives were developed till now. In the present investigation, the effect of 100% methanol extract of Opuntia dillenii phylloclade on reproduction in male rats was studied. A first group (I) received vehicle alone to serve as control. The second group (II) was further divided into treated and recovery groups, and the plant extract at 50 mg kg body weight(-1) was administered orally for 30 days. Biochemical, haematological and histopathological analyses were carried out to reveal the effects on reproductive organs in the male rats. The weights of reproductive organs were recorded. It was found that the number of fertile males, number of inseminated females, number of litters delivered and testosterone levels were reduced significantly. Epididymal sperm count and motility were also significantly decreased. Biochemical parameters support the antifertility activity of O. dillenii i.e. decreases in protein, glycogen content and elevation in cholesterol level. Testes and sperm morphology were altered significantly. Haematological parameters have not shown any significant changes. It is concluded that 100% methanol extract of O. dillenii possesses antifertility effects on male reproduction without change in general physiology.

  16. Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility.

    PubMed

    Esther, C R; Howard, T E; Marino, E M; Goddard, J M; Capecchi, M R; Bernstein, K E

    1996-05-01

    Mammals produce two isozymes of angiotensin-converting enzyme (ACE). Somatic ACE plays an important role in the control of blood pressure. The function of testis ACE, produced by male and germ cells, is not known. To examine the roles of these isozymes, we used targeted homologous recombination to introduce a modified ACE allele into a mouse line. Mice homozygous for this mutant allele lack both ACE isozymes and have markedly reduced blood pressures. Contrary to a previous report, we found heterozygous male mice to have normal blood pressures. Homozygous mutant mice also have severe renal disease. The renal papilla is markedly reduced, and the intrarenal arteries exhibit vascular hyperplasia associated with a perivascular inflammatory infiltrate. These animals cannot effectively concentrate urine. They also have an abnormally low urinary sodium to potassium ratio despite reduced levels of aldosterone. Homozygous mutant male mice sire significantly smaller litters than wild-type male mice; however, no defect in sperm number, morphology, or motility was detected. ACE-deficient animals demonstrate the role of this enzyme in systemic blood pressure, renal development and function, and male fertility.

  17. Using the product threshold model for estimating separately the effect of temperature on male and female fertility.

    PubMed

    Tusell, L; David, I; Bodin, L; Legarra, A; Rafel, O; López-Bejar, M; Piles, M

    2011-12-01

    Animals under environmental thermal stress conditions have reduced fertility due to impairment of some mechanisms involved in their reproductive performance that are different in males and females. As a consequence, the most sensitive periods of time and the magnitude of effect of temperature on fertility can differ between sexes. The objective of this study was to estimate separately the effect of temperature in different periods around the insemination time on male and on female fertility by using the product threshold model. This model assumes that an observed reproduction outcome is the result of the product of 2 unobserved variables corresponding to the unobserved fertilities of the 2 individuals involved in the mating. A total of 7,625 AI records from rabbits belonging to a line selected for growth rate and indoor daily temperature records were used. The average maximum daily temperature and the proportion of days in which the maximum temperature was greater than 25°C were used as temperature descriptors. These descriptors were calculated for several periods around the day of AI. In the case of males, 4 periods of time covered different stages of the spermatogenesis, the transit through the epididymus of the sperm, and the day of AI. For females, 5 periods of time covered the phases of preovulatory follicular maturation including day of AI and ovulation, fertilization and peri-implantational stage of the embryos, embryonic and early fetal periods of gestation, and finally, late gestation until birth. The effect of the different temperature descriptors was estimated in the corresponding male and female liabilities in a set of threshold product models. The temperature of the day of AI seems to be the most relevant temperature descriptor affecting male fertility because greater temperature records on the day of AI caused a decrease in male fertility (-6% in male fertility rate with respect to thermoneutrality). Departures from the thermal zone in temperature

  18. Male meiosis in Crustacea: synapsis, recombination, epigenetics and fertility in Daphnia magna.

    PubMed

    Gómez, Rocío; Van Damme, Kay; Gosálvez, Jaime; Morán, Eugenio Sánchez; Colbourne, John K

    2016-09-01

    We present the first detailed cytological study of male meiosis in Daphnia (Crustacea: Branchiopoda: Cladocera)-an aquatic microcrustacean with a cyclical parthenogenetic life cycle. Using immunostaining of the testes in Daphnia magna for baseline knowledge, we characterized the different stages of meiotic division and spermiogenesis in relation to the distribution of proteins involved in synapsis, early recombination events and sister chromatid cohesion. We also studied post-translational histone modifications in male spermatocytes, in relation to the dynamic chromatin progression of meiosis. Finally, we applied a DNA fragmentation test to measure sperm quality of D. magna, with respect to levels of inbreeding. As a proxy for fertility, this technique may be used to assess the reproductive health of a sentinel species of aquatic ecosystems. Daphnia proves to be a model species for comparative studies of meiosis that is poised to improve our understanding of the cytological basis of sexual and asexual reproduction.

  19. The enhancing effects of alcoholic extract of Nigella sativa seed on fertility potential, plasma gonadotropins and testosterone in male rats

    PubMed Central

    Parandin, Rahmatollah; Yousofvand, Namdar; Ghorbani, Rostam

    2012-01-01

    Background: The task force on plants for fertility regulation in men continued with its program to identify novel prototypes in plants alleged to have fertility regulating properties. Nigella Sativa seeds are frequently used in folk medicine in the Middle East and some Asian countries for the promotion of good health and treatment of many ailments. Objective: To evaluated the role of alcoholic extract of Nigella sativa on fertility potential, Pituitary-testicular axis hormones and Testosterone in male rats. Materials and Methods: 24 male rats were randomly divided into 3 groups; control, group A and group B, each group comprising of 8 rats. Animals in control group received 1 ml of normal saline and treatment groups (A and B) received (gavage) graded doses of 200 and 400 mg/kg body weight of alcoholic extract of Nigella sativa seeds on a daily basis for 60 days. At the end of treatment period, fertility parameters such as body and reproductive organs weight, sperm motility, viability and count, epididymal sperm reserve (ESR), daily sperm production (DSP), blood testosterone concentration, Gonadotropins levels and fertility index were measured. Results: There was a significant difference in testes and epididymidis weight, sperm count, ESR, DSP, blood testosterone concentration, LH and fertility index in both the lower dose group and the higher group as compared to the control group. Conclusion: The results of this study showed that alcoholic extract of Nigella sativa seed especially in higher doses could increase fertility potential, LH and testosterone concentration in male rats. PMID:25246898

  20. An EAR-Dependent Regulatory Module Promotes Male Germ Cell Division and Sperm Fertility in Arabidopsis.

    PubMed

    Borg, Michael; Rutley, Nicholas; Kagale, Sateesh; Hamamura, Yuki; Gherghinoiu, Mihai; Kumar, Sanjeev; Sari, Ugur; Esparza-Franco, Manuel A; Sakamoto, Wataru; Rozwadowski, Kevin; Higashiyama, Tetsuya; Twell, David

    2014-05-01

    The production of the sperm cells in angiosperms requires coordination of cell division and cell differentiation. In Arabidopsis thaliana, the germline-specific MYB protein DUO1 integrates these processes, but the regulatory hierarchy in which DUO1 functions is unknown. Here, we identify an essential role for two germline-specific DUO1 target genes, DAZ1 and DAZ2, which encode EAR motif-containing C2H2-type zinc finger proteins. We show that DAZ1/DAZ2 are required for germ cell division and for the proper accumulation of mitotic cyclins. Importantly, DAZ1/DAZ2 are sufficient to promote G2- to M-phase transition and germ cell division in the absence of DUO1. DAZ1/DAZ2 are also required for DUO1-dependent cell differentiation and are essential for gamete fusion at fertilization. We demonstrate that the two EAR motifs in DAZ1/DAZ2 mediate their function in the male germline and are required for transcriptional repression and for physical interaction with the corepressor TOPLESS. Our findings uncover an essential module in a regulatory hierarchy that drives mitotic transition in male germ cells and implicates gene repression pathways in sperm cell formation and fertility.

  1. Influence of genetic abnormalities on semen quality and male fertility: A four-year prospective study

    PubMed Central

    Elfateh, Fadlalla; Wang, Ruixue; Zhang, Zhihong; Jiang, Yuting; Chen, Shuang; Liu, Ruizhi

    2014-01-01

    Background: Wide range of disorders ranging from genetic disorders to coital difficulties can influence male fertility. In this regard, genetic factors are highlighted as the most frequent, contributed to 10-15%, of male infertility causes. Objective: To investigate the influence of genetic abnormalities on semen quality and reproductive hormone levels of infertile men from Northeast China. Materials and Methods: 2034 infertile men including 691 patients with abnormal sperm parameters were investigated retrospectively. Semen analysis was performed according to the World Health Organization guidelines. Y chromosome micro deletions were detected by polymerase chain reaction assays. Chromosome analysis was performed using G-banding. Results: The incidence of abnormal chromosomal karyotype in the patients with abnormal sperm parameters was 12.01% (83/691). The most frequent cause was Klinefelter's syndrome 37.35% (31/83). As the same as chromosomal abnormalities group, the volumes of testes (p=0.000 and 0.000, respectively) and the levels of testosterone (T) (p=0.000), and testosterone/ luteinizing hormone (T/LH) (p=0.000) of patients with Y chromosome micro deletions were significantly lower than those of fertile group. In addition, the levels of follicle-stimulating hormone (FSH) (p=0.000), and luteinizing hormone (LH) (p=0.000) were significantly higher in patients with Y chromosome micro deletions than those in the fertile group. Translocation abnormalities displayed slight effect on sperm motility. Conclusion: Y chromosome micro deletions and sex chromosome disorders particularly Klinefelter’s (47, XXY), have severe adverse influence on normal hormone levels, testicular volume and sperm count, whereas translocation abnormalities may inversely correlate with sperm motility. PMID:24799866

  2. Withania somnifera Improves Semen Quality in Stress-Related Male Fertility.

    PubMed

    Mahdi, Abbas Ali; Shukla, Kamla Kant; Ahmad, Mohammad Kaleem; Rajender, Singh; Shankhwar, Satya Narain; Singh, Vishwajeet; Dalela, Deepansh

    2009-09-29

    Stress has been reported to be a causative factor for male infertility. Withania somnifera has been documented in Ayurveda and Unani medicine system for its stress-combating properties. However, limited scientific literature is available on this aspect of W. somnifera. We undertook the present study to understand the role of stress in male infertility, and to test the ability of W. somnifera to combat stress and treat male infertility. We selected normozoospermic but infertile individuals (N = 60), further categorized in three groups: normozoospermic heavy smokers (N = 20), normozoospermics under psychological stress (N = 20) and normozoospermics with infertility of unknown etiology (N = 20). Normozoospermic fertile men (N = 60) were recruited as controls. The subjects were given root powder of W. somnifera at a rate of 5 g/day for 3 months. Measuring various biochemical and stress parameters before and after treatment, suggested a definite role of stress in male infertility and the ability of W. somnifera to treat stress-related infertility. Treatment resulted in a decrease in stress, improved the level of anti-oxidants and improved overall semen quality in a significant number of individuals. The treatment resulted in pregnancy in the partners of 14% of the patients.

  3. Withania somnifera Improves Semen Quality in Stress-Related Male Fertility

    PubMed Central

    Mahdi, Abbas Ali; Shukla, Kamla Kant; Ahmad, Mohammad Kaleem; Rajender, Singh; Shankhwar, Satya Narain; Singh, Vishwajeet; Dalela, Deepansh

    2011-01-01

    Stress has been reported to be a causative factor for male infertility. Withania somnifera has been documented in Ayurveda and Unani medicine system for its stress-combating properties. However, limited scientific literature is available on this aspect of W. somnifera. We undertook the present study to understand the role of stress in male infertility, and to test the ability of W. somnifera to combat stress and treat male infertility. We selected normozoospermic but infertile individuals (N = 60), further categorized in three groups: normozoospermic heavy smokers (N = 20), normozoospermics under psychological stress (N = 20) and normozoospermics with infertility of unknown etiology (N = 20). Normozoospermic fertile men (N = 60) were recruited as controls. The subjects were given root powder of W. somnifera at a rate of 5 g/day for 3 months. Measuring various biochemical and stress parameters before and after treatment, suggested a definite role of stress in male infertility and the ability of W. somnifera to treat stress-related infertility. Treatment resulted in a decrease in stress, improved the level of anti-oxidants and improved overall semen quality in a significant number of individuals. The treatment resulted in pregnancy in the partners of 14% of the patients. PMID:19789214

  4. Methyltestosterone efficiently induces male development in the self-fertilizing hermaphrodite fish, Kryptolebias marmoratus.

    PubMed

    Kanamori, Akira; Yamamura, Aki; Koshiba, Satoshi; Lee, Jae-Seong; Orlando, Edward F; Hori, Hiroshi

    2006-10-01

    A hermaphrodite fish, Kryptolebias marmoratus, is the only known vertebrate that reproduces by self-fertilization. In nature, males have been rarely observed. Low-temperature treatment during late embryonic stages is known to induce males but its efficacy is variable. Here we report that 17alpha-methyltestosterone (MT) treatment of the embryos converted most of the fish to males. We examined a time course of this male induction with histological and marker gene expression analyses. Oogenesis started in the gonads of the control embryo at hatching; spermatogenesis did not start until two months after hatching. In the MT-treated fish, oogenesis started initially as in the control but stopped completely within one month after hatching. Instead, spermatogonial proliferation started earlier than in the control fish and progressed to full spermatogenesis. Expression profiles of the sex-specific marker genes corresponded well with histological observations. From one month after hatching, expression of an oocyte-specific marker, figalpha, and a testicular somatic cell marker, dmrt1, started to increase in the control and in the MT-treated fish, respectively.

  5. Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples.

    PubMed

    Bhongade, M B; Prasad, S; Jiloha, R C; Ray, P C; Mohapatra, S; Koner, B C

    2015-04-01

    The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases.

  6. Genetic correlation between growth and female and male contributions to fertility in rabbit.

    PubMed

    Piles, M; Tusell, L

    2012-08-01

    A Bayesian bivariate Linear-Threshold Animal Model was implemented to determine the genetic correlation between fertility (F), defined as success or failure to conceive, and average daily gain (ADG) in a rabbit line selected for ADG. A total of 27 234 records of F from 7895 females and 1293 males, and 114 135 records of ADG were used for the analysis. The pedigree included 114 485 animals. The model used for ADG included the systematic effects of year-season, parity order and number of kids born alive, the animal additive effect, the maternal and paternal permanent environmental effects, the common litter permanent environmental effect and the residual. The model for the liability of F included the systematic effects of year-season and physiological status of the female, the female and male additive genetic effects, the female and male permanent environmental effects and the residual, which was divided into a permanent environmental effect related to the common litter effect for ADG, and an independent term. The estimated heritabilities were 0.15 for ADG and 0.07 and 0.04 for the female and male contributions to F, respectively. Male and female contributions to F had a positive genetic correlation (0.34). The genetic correlation between ADG and the female component of F was low to moderate and negative (-0.31), whereas it was null for the male contribution to F. Thus, it is expected that only the female contribution to reproductive performance may be impaired by selection for ADG in rabbit lines.

  7. Differential Mitochondrial Electron Transport through the Cyanide-Sensitive and Cyanide-Insensitive Pathways in Isonuclear Lines of Cytoplasmic Male Sterile, Male Fertile, and Restored Petunia1

    PubMed Central

    Connett, Marie B.; Hanson, Maureen R.

    1990-01-01

    Three pairs of isonuclear lines of cytoplasmic male sterile (CMS) and fertile Petunia cells (Petunia hybrida [Hook] Vilm. and Petunia parodii L.S.M.) grown in suspension culture were examined for sensitivity to inhibitors of respiratory electron transport at time-points after transfer into fresh media. Cells from CMS lines differed from cells of fertile lines in their utilization of the cyanide-insensitive oxidase pathway. Under our culture regime, after approximately 3 days of culture cells from the CMS lines exhibited much lower cyanide-insensitive, salicylhydroxamic acid-sensitive respiration than cells from the fertile lines. This respiratory difference was shown to be specific to the mitochondrial alternative oxidase pathway by using other characteristic inhibitors of mitochondrial electron transport in experiments with isolated mitochondria. Immature anthers from CMS plants also showed lower alternative oxidase activity relative to anthers from male fertile plants, but no such difference was detected in leaf tissue, ovary or perianth tissue, or anthers collected just prior to anthesis. A cell line from a fertile plant carrying a nuclear fertility restorer gene and the CMS cytoplasm exhibited increased activity of the alternative pathway compared with the CMS lines. PMID:16667667

  8. Male fertility and apoptosis in normal spermatogenesis are regulated by vacuolar-ATPase isoform a2.

    PubMed

    Jaiswal, Mukesh K; Agrawal, Varkha; Katara, Gajendra K; Pamarthy, Sahithi; Kulshrestha, Arpita; Chaouat, Gerard; Gilman-Sachs, Alice; Beaman, Kenneth D

    2015-11-01

    The a2 isoform of vacuolar-ATPase (ATP6V0A2, referred to as a2V) is required for normal spermatogenesis and maturation of sperm. Treatment of male mice with anti-a2V disturbs the testicular cytokine/chemokine balance and leads to severe deficiencies of spermatogenesis. The aim of the present study was to investigate the role of a2V in male fertility and in the regulation of apoptotic pathways required for normal spermatogenesis in mice. To study the role of a2V single dose of anti-a2V monoclonal antibody or mouse IgG isotype (3μg/animal) was injected i.p. into males on alternate days for 10 days. The expression of sperm maturation-related molecules and pro-apoptotic molecules was measured by real-time PCR or immunohistochemistry in control and anti-a2V-treated testes. The caspase levels and their activity were measured by western blot and fluorometry. We found that the expression of the sperm maturation-related molecules SPAM1, ADAM1, and ADAM2 was significantly decreased in testes from anti-a2V-treated males. The expression of pro-apoptotic molecules (Bax, p53, and p21) and molecules involved in the intrinsic pathway of apoptosis (caspase-9, caspase-3, and PARP), which are crucial for normal spermatogenesis was significantly reduced in testes from anti-a2V-treated males compared with the control. The total ATP level was significantly lower in anti-a2V-treated testes. The data provide novel evidence showing that a2V can regulate the apoptotic pathways, an essential testicular feature, and is necessary for efficient spermatogenesis.

  9. Biobanking efforts and new advances in male fertility preservation for rare and endangered species

    PubMed Central

    Comizzoli, Pierre

    2015-01-01

    Understanding and sustaining biodiversity is a multi-disciplinary science that benefits highly from the creation of organized and accessible collections of biomaterials (Genome Resource Banks). Large cryo-collections are invaluable tools for understanding, cataloging, and protecting the genetic diversity of the world's unique animals and plants. Specifically, the systematic collection and preservation of semen from rare species has been developed significantly in recent decades with some biobanks now being actively used for endangered species management and propagation (including the introduction of species such as the black-footed ferret and the giant panda). Innovations emerging from the growing field of male fertility preservation for humans, livestock species, and laboratory animals are also becoming relevant to the protection and the propagation of valuable domestic and wild species. These new approaches extend beyond the “classical” methods associated with sperm freezing to include testicular tissue preservation combined with xenografting or in vitro culture, all of which have potential for rescuing vast amounts of unused germplasm. There also are other options under development that are predicted to have a high impact within the next decade (stem cell technologies, bio-stabilization of sperm cells at ambient temperatures, and the use of genomics tools). However, biobanking efforts and new fertility preservation strategies have to expand the way beyond mammalian species, which will offer knowledge and tools to better manage species that serve as valuable biomedical models or require assistance to reverse endangerment. PMID:25966625

  10. Biobanking efforts and new advances in male fertility preservation for rare and endangered species.

    PubMed

    Comizzoli, Pierre

    2015-01-01

    Understanding and sustaining biodiversity is a multi-disciplinary science that benefits highly from the creation of organized and accessible collections of biomaterials (Genome Resource Banks). Large cryo-collections are invaluable tools for understanding, cataloging, and protecting the genetic diversity of the world's unique animals and plants. Specifically, the systematic collection and preservation of semen from rare species has been developed significantly in recent decades with some biobanks now being actively used for endangered species management and propagation (including the introduction of species such as the black-footed ferret and the giant panda). Innovations emerging from the growing field of male fertility preservation for humans, livestock species, and laboratory animals are also becoming relevant to the protection and the propagation of valuable domestic and wild species. These new approaches extend beyond the "classical" methods associated with sperm freezing to include testicular tissue preservation combined with xenografting or in vitro culture, all of which have potential for rescuing vast amounts of unused germplasm. There also are other options under development that are predicted to have a high impact within the next decade (stem cell technologies, bio-stabilization of sperm cells at ambient temperatures, and the use of genomics tools). However, biobanking efforts and new fertility preservation strategies have to expand the way beyond mammalian species, which will offer knowledge and tools to better manage species that serve as valuable biomedical models or require assistance to reverse endangerment.

  11. Deleterious effects of obesity upon the hormonal and molecular mechanisms controlling spermatogenesis and male fertility.

    PubMed

    Davidson, Lien M; Millar, Kate; Jones, Celine; Fatum, Muhammad; Coward, Kevin

    2015-09-01

    Worldwide obesity rates have nearly doubled since 1980 and currently over 10% of the population is obese. In 2008, over 1.4 billion adults aged 20 years and older had a body mass index or BMI above a healthy weight and of these, over 200 million men and nearly 300 million women were obese. While obesity can have many ramifications upon adult life, one growing area of concern is that of reproductive capacity. Obesity affects male infertility by influencing the hypothalamic-pituitary-gonadal axis, thus causing detrimental effects upon spermatogenesis and subsequent fertility. In particular, evidence indicates that excess adipose tissue can alter the relative ratio of testosterone and oestrogen. Additional effects involve the homeostatic disruption of insulin, sex-hormone-binding-globulin, leptin and inhibin B, leading to diminished testosterone production and impairment to spermatogenesis. Aberrant spermatogenesis arising from obesity is associated with downstream changes in key semen parameters, defective sperm capacitation and binding, and deleterious effects on sperm chromatin structure. More recent investigations into trans-generational epigenetic inheritance further suggest that molecular changes in sperm that arise from obesity-related impaired spermatogenesis, such as modified sperm RNA levels, DNA methylation, protamination and histone acetylation, can impact upon the development of offspring. Here, we summarise our current understanding of how obesity exerts influence over spermatogenesis and subsequent fertility status, and make recommendations for future investigative research.

  12. Protective effect of honey against cigarette smoke induced-impaired sexual behavior and fertility of male rats.

    PubMed

    Mohamed, Mahaneem; Sulaiman, Siti Amrah; Sirajudeen, Kuttulebbai Nainamohamed Salam

    2013-04-01

    Cigarette smoking is associated with sexual dysfunction and impaired fertility in males. The aim of this study was to determine the potential protective effect of honey against the toxic effect of cigarette smoke (CS) on sexual behavior and fertility of male rats. Thirty-two adult Sprague-Dawley rats were randomly divided into four groups (8 rats/group) as control, honey (H), CS and H plus CS (H + CS) groups. Rats in control and CS groups received oral administration of distilled water daily while rats in H and H + CS groups received honey (1.2 g/kg body weight/day) by oral gavage. Rats in CS and H + CS groups were also exposed to CS for 8 min 3 times/day. From 10 to 13 weeks of treatment, each male rat was cohabited with 3 untreated female rats for sexual behavioral and reproductive performance studies. Honey significantly increased the percentages of rats achieving intromission and ejaculation as well as increased mating and fertility indexes of male rats exposed to CS. Thus, honey has a protective effect against CS-induced impaired sexual behavior and fertility in male rats.

  13. Proteasome activators, PA28γ and PA200, play indispensable roles in male fertility.

    PubMed

    Huang, Lin; Haratake, Kousuke; Miyahara, Hatsumi; Chiba, Tomoki

    2016-03-22

    Protein degradation mediated by the proteasome is important for the protein homeostasis. Various proteasome activators, such as PA28 and PA200, regulate the proteasome function. Here we show double knockout (dKO) mice of Psme3 and Psme4 (genes for PA28γ and PA200), but not each single knockout mice, are completely infertile in male. The dKO sperms exhibited remarkable defects in motility, although most of them showed normal appearance in morphology. The proteasome activity of the mutant sperms decreased notably, and the sperms were strongly positive with ubiquitin staining. Quantitative analyses of proteins expressed in dKO sperms revealed up-regulation of several proteins involved in oxidative stress response. Furthermore, increased 8-OHdG staining was observed in dKO sperms head, suggesting defective response to oxidative damage. This report verified PA28γ and PA200 play indispensable roles in male fertility, and provides a novel insight into the role of proteasome activators in antioxidant response.

  14. Update on the impact of Chlamydia trachomatis infection on male fertility.

    PubMed

    Gonzales, G F; Muñoz, G; Sánchez, R; Henkel, R; Gallegos-Avila, G; Díaz-Gutierrez, O; Vigil, P; Vásquez, F; Kortebani, G; Mazzolli, A; Bustos-Obregón, E

    2004-02-01

    With approximately 90 million cases annually, infection with Chlamydia trachomatis is the most prevalent sexually transmitted bacterial disease in the world. Considering that these infections are often asymptomatic and cause major complications like acute pelvic inflammatory disease, ectopic pregnancy, infertility or infant pneumonia, the estimated costs for diagnosis and treatment in the USA amounts to 2.2 million US dollars for each 500 cases. Therefore, there is a high need for correct, quick and cost-effective diagnosis and treatment of this urogenital tract infection. New innovative therapies provide good results with regard to efficacy and patients' compliance. The success rates of treatments are at least 95%. However, the occurrence of antibiotic resistance should not be ignored and new treatment schemes must be developed. The state-of-the-art of diagnosis and treatment of chlamydial infections as well as the pathophysiology is discussed in this review. In conclusion, infections with C. trachomatis is an important public health problem, especially in third world and developing countries, and more socio-economic studies linking secondary prevention of chlamydial infections, infertility and adverse pregnancy outcome are needed to understand more of its aetiology. In addition, diagnosis and treatment should be improved. Data in men revealed that past infections but not present infections are more related to male infertility. There is still controversial results. In future studies, function of the seminal vesicles and evaluation of the antioxidant capacity should be taken into account when role of C. trachomatis infection on male fertility is assessed.

  15. A new and unified nomenclature for male fertility restorer (RF) proteins in higher plants.

    PubMed

    Kotchoni, Simeon O; Jimenez-Lopez, Jose C; Gachomo, Emma W; Seufferheld, Manfredo J

    2010-12-28

    The male fertility restorer (RF) proteins belong to extended protein families associated with the cytoplasmic male sterility in higher plants. Up till now, there is no devised nomenclature for naming the RF proteins. The systematic sequencing of new plant species in recent years has uncovered the existence of several novel RF genes and their encoded proteins. Their naming has been simply arbitrary and could not be adequately handled in the context of comparative functional genomics. We propose in this study a unified nomenclature for the RF extended protein families across all plant species. This new and unified nomenclature relies upon previously developed nomenclature for the first ever characterized RF gene, RF2A/ALDH2B2, a member of ALDH gene superfamily, and adheres to the guidelines issued by the ALDH Genome Nomenclature Committees. The proposed nomenclature reveals that RF gene superfamily encodes currently members of 51 families. This unified nomenclature accommodates functional RF genes and pseudogenes, and offers the flexibility needed to incorporate additional RFs as they become available in future. In addition, we provide a phylogenetic relationship between the RF extended families and use computational protein modeling to demonstrate the high divergence of RF functional specializations through specific structural features of selected members of RF superfamily.

  16. Singular features of fertilization and their impact on the male reproductive system in eutherian mammals.

    PubMed

    Bedford, J Michael

    2014-02-01

    Therian (marsupial and eutherian) mammals have evolved a suite of novel reproductive features - seen variously in their gametes, the steps of fertilization and the male reproductive tract - whose adaptive significance remains unclear. Present evidence for the better-understood eutherian mammals suggests that the 'prime mover' in their evolution has been the character of the egg coat, with other such features being adaptations to the consequences of this. Its elastic thickness allows the zona pellucida to stretch to a variable degree and yet remain around the blastocyst during much or all of its expansion before implantation, but its character represents an unusual challenge for spermatozoa. Novel aspects of the acrosome related to this challenge enable it to maintain a relatively prolonged binding after the onset of the acrosome reaction, and the structure, shape and behaviour of the sperm head point to physical thrust as a major element of zona penetration - with the unique configuration of gamete fusion as a sequela of this strategy. In the male, such adaptations are reflected in sperm head formation in the testis and in sperm maturation in the epididymis involving at least the sperm head's structure, plasmalemma and acrosome. This complexity allied to a slow epididymal sperm transport, a relatively modest sperm production and the brief life span of mature spermatozoa kept above the cauda epididymidis could account for the evolution of the sperm storage function - a development seemingly linked, in turn, to the need for sperm capacitation and scrotal evolution.

  17. The Anti-fertility Effects of Acacia nilotica in Male Wistar Rats

    PubMed Central

    Lampiao, Fanuel

    2013-01-01

    Background A bulk of contraceptives on the market is women-oriented today. The aim of this study was to investigate the effect of a medicinal herb, Acacia nilotica on various parameters of male fertility using a rat model. Methods Male Wistar rats (n = 40) were randomly divided in to two groups. One group received Acacia nilotica, while the other acted as controls. Ten animals from each group were sacrificed after 16 weeks. Treatment was withdrawn for the remaining animals for 8 weeks. Blood was collected for hormonal analysis. The testis was removed for histological examination, while epididymal spermatozoa were retrieved for motility and morphological analysis. The data were analyzed using ANOVA and Bonferroni post hoc test. A value of p<0.05 was considered statistically significant. Results Sperm motility, progressive motility and sperm concentration significantly decreased in treated animals compared to the controls (p<0.05). Withdrawing the treatment did not restore these parameters (p<0.05). Abnormal sperm morphology significantly increased in both the treated and treatment withdrawn groups when compared to the controls (p<0.05). Testosterone concentrations were significantly lower in the treated group when compared to the controls (p<0.05) and no significant differences were observed between the controls and the treated animals when treatment was withdrawn. Histological observations showed that Acacia nilotica treatment disrupted semeniferous tubule architechture and consequently the spermatogenesis process. Conclusion These results show that Acacia nilotica severely affects sperm morphology, progressive motility and sperm concentration irreversibly in Wistar rats. PMID:23926560

  18. Proteasome activators, PA28γ and PA200, play indispensable roles in male fertility

    PubMed Central

    Huang, Lin; Haratake, Kousuke; Miyahara, Hatsumi; Chiba, Tomoki

    2016-01-01

    Protein degradation mediated by the proteasome is important for the protein homeostasis. Various proteasome activators, such as PA28 and PA200, regulate the proteasome function. Here we show double knockout (dKO) mice of Psme3 and Psme4 (genes for PA28γ and PA200), but not each single knockout mice, are completely infertile in male. The dKO sperms exhibited remarkable defects in motility, although most of them showed normal appearance in morphology. The proteasome activity of the mutant sperms decreased notably, and the sperms were strongly positive with ubiquitin staining. Quantitative analyses of proteins expressed in dKO sperms revealed up-regulation of several proteins involved in oxidative stress response. Furthermore, increased 8-OHdG staining was observed in dKO sperms head, suggesting defective response to oxidative damage. This report verified PA28γ and PA200 play indispensable roles in male fertility, and provides a novel insight into the role of proteasome activators in antioxidant response. PMID:27003159

  19. Altered helper Tcell-mediated immune responses in male mice conceived through in vitro fertilization.

    PubMed

    Karimi, Hiwa; Mahdavi, Pooya; Fakhari, Shohreh; Faryabi, Mohammad Reza; Esmaeili, Parisa; Banafshi, Omid; Mohammadi, Ebrahim; Fathi, Fardin; Mokarizadeh, Aram

    2017-03-08

    A study using a mouse IVF model was conducted to examine the hypothesis that in vitro fertilization (IVF) treatment may lead to immune alteration in the offspring. Phagocytic activity and lymphocyte proliferative responses to mitogen, alloantigen, and purified protein derivative (PPD) of Mycobacterium bovis were investigated in the splenocytes of BCG-treated male mice conceived by IVF or natural conception. Intracellular expression of T-bet and GATA3 in helper T-cell population were examined in both groups. Moreover, the serum levels of IFN-γ and IL-4 along with BCG-specific levels of IgG1 and IgG2a were assessed by ELISA. In comparison with naturally-conceived mice, PPD-specific proliferative response and T-bet/GATA3 ratio were significantly decreased in IVF-conceived mice. Moreover, IVF-conceived mice exhibited marked decreases in IFN-γ/IL-4 and IgG2a/IgG1 ratios. Results indicate that in comparison with male mice conceived by natural conception, IVF counterparts exhibit less efficient immune responses against BCG through further promotion of Th2 responses.

  20. Performance of non-motile male gametes in the sea: analysis of paternity and fertilization success in a natural population of a red seaweed, Gracilaria gracilis

    PubMed Central

    Engel, C. R.; Wattier, R.; Destombe, C.; Valero, M.

    1999-01-01

    In haploid–diploid red seaweeds, the dispersal of male gametes is presumed limited due to their lack of flagella. It has been suggested that this group suffers from sperm limitation and, consequently, that fertilization is relatively inefficient. Fertilization in most floridean rhodophytes results in the formation a cystocarp, a swelling on the haploid female thallus housing the diploid zygote and its thousands of diploid daughter spores. To study the performance of non-motile male gametes in the sea, we evaluated both female and male fertilization success in a natural population of the red marine alga Gracilaria gracilis. Female fertilization success, estimated by cystocarp yield per unit female thallus, was evaluated with respect to the availability of male gametes. Male fertilization success, estimated by the individual contribution of different males to zygotes, was assessed by paternity analyses on 350 cystocarps produced in one reproductive season using two microsatellite loci. The results show that cystocarp yield is not sperm limited and that the large variation in male fertilization success cannot be solely explained by the distance travelled by the male gamete to find a mate. Taken together, the results suggest that, not only is fertilization efficient, but that male–male competition and/or female choice may play a role in shaping population mating patterns.

  1. Intraflagellar transport protein IFT20 is essential for male fertility and spermiogenesis in mice

    PubMed Central

    Zhang, Zhengang; Li, Wei; Zhang, Yong; Zhang, Ling; Teves, Maria E.; Liu, Hong; Strauss, Jerome F.; Pazour, Gregory J.; Foster, James A.; Hess, Rex A.; Zhang, Zhibing

    2016-01-01

    Intraflagellar transport (IFT) is a conserved mechanism believed to be essential for the assembly and maintenance of cilia and flagella. However, little is known about its role in mammalian sperm flagella formation. To fill this gap, we disrupted the Ift20 gene in male germ cells. Homozygous mutant mice were infertile, with significantly reduced sperm counts and motility. In addition, abnormally shaped, elongating spermatid heads and bulbous, round spermatids were found in the lumen of the seminiferous tubules. Electron microscopy revealed increased cytoplasmic vesicles, fiber-like structures, abnormal accumulation of mitochondria, and a decrease in mature lysosomes. The few developed sperm had disrupted axonemes, and some retained cytoplasmic lobe components on the flagella. ODF2 and SPAG16L, two sperm flagella proteins, failed to be incorporated into sperm tails of the mutant mice, and in the germ cells, both were assembled into complexes with lighter density in the absence of IFT20. Disrupting IFT20 did not significantly change expression levels of IFT88, a component of the IFT-B complex, and IFT140, a component of the IFT-A complex. Even though the expression level of an autophagy core protein that associates with IFT20, ATG16, was reduced in the testis of the Ift20 mutant mice, expression levels of other major autophagy markers, including LC3 and ubiquitin, were not changed. Our studies suggest that IFT20 is essential for male fertility and spermiogenesis in mice, and its major function is to transport cargo proteins for sperm flagella formation. It also appears to be involved in removing excess cytoplasmic components. PMID:27682589

  2. Dose-dependent adverse effects of salinomycin on male reproductive organs and fertility in mice.

    PubMed

    Ojo, Olajumoke Omolara; Bhadauria, Smrati; Rath, Srikanta Kumar

    2013-01-01

    Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis

  3. Dose-Dependent Adverse Effects of Salinomycin on Male Reproductive Organs and Fertility in Mice

    PubMed Central

    Ojo, Olajumoke Omolara; Bhadauria, Smrati; Rath, Srikanta Kumar

    2013-01-01

    Salinomycin is used as an antibiotic in animal husbandry. Its implication in cancer therapy has recently been proposed. Present study evaluated the toxic effects of Salinomycin on male reproductive system of mice. Doses of 1, 3 or 5 mg/kg of Salinomycin were administered daily for 28 days. Half of the mice were sacrificed after 24 h of the last treatment and other half were sacrificed 28 days after withdrawal of treatment. Effects of SAL on body and reproductive organ weights were studied. Histoarchitecture of testis and epididymis was evaluated along with ultrastructural changes in Leydig cells. Serum and testicular testosterone and luteinizing hormones were estimated. Superoxide dismutase, reduced glutathione, lipid peroxidation, catalase and lactate dehydrogenase activities were measured. Spermatozoa count, morphology, motility and fertility were evaluated. Expression patterns of steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage proteins (CYP11A1) were assessed by Western blotting. Salinomycin treatment was lethal to few mice and retarded body growth in others with decreased weight of testes and seminal vesicles in a dose dependent manner. Seminiferous tubules in testes were disrupted and the epithelium of epididymis showed frequent occurrence of vacuolization and necrosis. Leydig cells showed hypertrophied cytoplasm with shrunken nuclei, condensed mitochondria, proliferated endoplasmic reticulum and increased number of lipid droplets. Salinomycin decreased motility and spermatozoa count with increased number of abnormal spermatozoa leading to infertility. The testosterone and luteinizing hormone levels were decreased in testis but increased in serum at higher doses. Depletion of superoxide dismutase and reduced glutathione with increased lipid peroxidation in both testis and epididymis indicated generation of oxidative stress. Suppressed expression of StAR and CYP11A1 proteins indicates inhibition of steroidogenesis

  4. Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility.

    PubMed

    Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Buck Louis, Germaine M; Toppari, Jorma; Andersson, Anna-Maria; Eisenberg, Michael L; Jensen, Tina Kold; Jørgensen, Niels; Swan, Shanna H; Sapra, Katherine J; Ziebe, Søren; Priskorn, Lærke; Juul, Anders

    2016-01-01

    It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography.

  5. Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility

    PubMed Central

    Skakkebaek, Niels E.; Rajpert-De Meyts, Ewa; Buck Louis, Germaine M.; Toppari, Jorma; Andersson, Anna-Maria; Eisenberg, Michael L.; Jensen, Tina Kold; Jørgensen, Niels; Swan, Shanna H.; Sapra, Katherine J.; Ziebe, Søren; Priskorn, Lærke; Juul, Anders

    2015-01-01

    It is predicted that Japan and European Union will soon experience appreciable decreases in their populations due to persistently low total fertility rates (TFR) below replacement level (2.1 child per woman). In the United States, where TFR has also declined, there are ethnic differences. Caucasians have rates below replacement, while TFRs among African-Americans and Hispanics are higher. We review possible links between TFR and trends in a range of male reproductive problems, including testicular cancer, disorders of sex development, cryptorchidism, hypospadias, low testosterone levels, poor semen quality, childlessness, changed sex ratio, and increasing demand for assisted reproductive techniques. We present evidence that several adult male reproductive problems arise in utero and are signs of testicular dysgenesis syndrome (TDS). Although TDS might result from genetic mutations, recent evidence suggests that it most often is related to environmental exposures of the fetal testis. However, environmental factors can also affect the adult endocrine system. Based on our review of genetic and environmental factors, we conclude that environmental exposures arising from modern lifestyle, rather than genetics, are the most important factors in the observed trends. These environmental factors might act either directly or via epigenetic mechanisms. In the latter case, the effects of exposures might have an impact for several generations post-exposure. In conclusion, there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. We highlight a number of topics that need attention by researchers in human physiology, pathophysiology, environmental health sciences, and demography. PMID:26582516

  6. Transcription of gypsy elements in a Y-chromosome male fertility gene of Drosophila hydei

    SciTech Connect

    Hochstenbach, R.; Harhangi, H.; Hennig, W.

    1996-02-01

    We have found that defective gypsy retrotransposons are a major constituent of the lampbrush loop pair Nooses in the short arm of Y chromosome of Drosophila hydei. The loop pair is formed by male fertility gene Q during the primary spermatocyte stage of spermatogenesis, each loop being a single transcription unit with an estimated length of 260 kb. Using fluorescent in situ hybridization, we show that throughout the loop transcripts gypsy elements are interspersed with blocks of a tandemly repetitive Y-specific DNA sequence, ayl. Nooses transcripts containing both sequence types show a wide size range on Northern blots, do not migrate to the cytoplasm, and are degraded just before the first meiotic division. Only one strand of ayl and only the coding strand of gypsy can be detected in the loop transcripts. However, as cloned genomic DNA fragments also display opposite orientations of ayl and gypsy, such DNA sections cannot be part of the Nooses. Hence, they are most likely derived from the flanking heterochromatin. The direction of transcription of ayl and gypsy thus appears to be of a functional significance. 76 refs., 5 figs.

  7. Fertility considerations, counseling, and semen cryopreservation for males prior to the initiation of cancer therapy.

    PubMed

    Leonard, Marcia; Hammelef, Karen; Smith, Gary D

    2004-04-01

    An innovative program jointly sponsored by members of the departments of obstetrics and urology and the Comprehensive Cancer Center at the University of Michigan began in 2002. The Fertility Counseling and Gamete Cryopreservation Program (FCGCP) was created to provide counseling and education about therapy-induced infertility to newly diagnosed patients with cancer as well as facilitating the semen cryopreservation process. Unlike most sperm banking facilities in this country, this program is coordinated by an oncology nurse practitioner whose understanding of cancer and cancer treatments provides patients and staff with a unique perspective. Oncology staff misconceptions about sperm banking were addressed through intensive staff education programs. Patient education materials covering all aspects of infertility and sperm banking were developed and made available in patient care areas and on the Internet. Material aimed at young adolescents and their parents is prominent. Developmentally appropriate discussions are held with adolescent patients and their parents, both individually and together. Communication among patients and their families, the oncology team, and the sperm bank is maintained, permitting efficient and timely service. FCGCP provides an important service by affording all males with cancer the potential to father a child in the future.

  8. Analyzing the "correct" endpoint.

    PubMed

    Atherton, Pamela J; Novotny, Paul J; Tan, Angelina D

    2006-01-01

    The choice of QOL endpoints for a study should be based on which score will most likely change if the treatment is favorable. How the QOL change is calculated should be based on the expected amount of missing data, how many time points data will be collected, and whether extreme outliers in the scores impact results. The study should have sufficient power to detect a meaningful difference between arms (typically 10 points on a 0-100 point scale) in the chosen QOL endpoint. At the conclusion of a study, several secondary endpoints can be analyzed which can provide additional information and confirm primary endpoint results.

  9. An epididymis-specific carboxyl esterase CES5A is required for sperm capacitation and male fertility in the rat

    PubMed Central

    Ru, Yan-Fei; Xue, Hai-Min; Ni, Zi-Mei; Xia, Dong; Zhou, Yu-Chuan; Zhang, Yong-Lian

    2015-01-01

    Despite the fact that the phenomenon of capacitation was discovered over half century ago and much progress has been made in identifying sperm events involved in capacitation, few specific molecules of epididymal origin have been identified as being directly involved in this process in vivo. Previously, our group cloned and characterized a carboxyl esterase gene Ces5a in the rat epididymis. The CES5A protein is mainly expressed in the corpus and cauda epididymidis and secreted into the corresponding lumens. Here, we report the function of CES5A in sperm maturation. By local injection of Lentivirus-mediated siRNA in the CES5A-expressing region of the rat epididymis, Ces5a-knockdown animal models were created. These animals exhibited an inhibited sperm capacitation and a reduction in male fertility. These results suggest that CES5A plays an important role in sperm maturation and male fertility. PMID:25475668

  10. Significance of microRNA targeted estrogen receptor in male fertility

    PubMed Central

    Abhari, Alireza; Zarghami, Nosratollah; Shahnazi, Vahideh; Barzegar, Abolfazl; Farzadi, Laya; Karami, Hadi; Zununi Vahed, Sepideh; Nouri, Mohammad

    2014-01-01

    Objective(s): Estrogen receptor-alpha (ERα) mediates estrogen action in regulation of different levels of the hypothalamic-pituitary-testis axis. It has a key role in spermatogenesis. Estrogen receptor alpha knock-out (ER koα) male mice were infertile and severe impairment in spermatogenesis and seminiferous tubules was observed. Recently, it has been reported that microRNA (miRNA) mir-100 and let-7b were predicted to target ERα gene. MiRNA are small, endogenous, single stranded RNA molecules that regulate gene expression and have been implicated in various disease states. It has been proved that some miRNAs expression is tissue- and disease-specific, giving potential for identifying miRNAs as a diagnostic tool. Materials and Methods: In this study, the change in the expression levels of mir-100, let-7b and ERα expression levels were evaluated in oligospermic infertile patients (n=43) compared to control fertile subjects (n=43). After washing and separating sperms, total RNA was isolated and then cDNA was synthesized. The expression levels of mir-100 and let-7b and ERα were evaluated by real time PCR. Results: Mir-100, let-7b levels were significantly higher than those in control group (P=0.008 and P=0.009, respectively). We have found that, ERα level was significantly decreased in comparison with normal group (P< 0.0001). Conclusion: Changes in mir-100, let-7b and ERα expression levels in oligospermic patients may be associated with the susceptibility and progression of infertility. The results of this study indicate that miRNA can have a key role in spermatogenesis and might have a diagnostic and prognostic value in men infertility. PMID:24711889

  11. Influence of 50 Hz magnetic field on sex hormones and other fertility parameters of adult male rats.

    PubMed

    Al-Akhras, Moh'd-Ali; Darmani, Homa; Elbetieha, Ahmed

    2006-02-01

    The effects of an extremely low frequency (ELF) magnetic field on the sex hormones and other fertility parameters of adult male Sprague-Dawley rats were investigated. Adult male rats were exposed to a 50 Hz sinusoidal magnetic field at approximately 25 microT (rms) for 18 consecutive weeks. There were no significant effects on the absolute body weight and the weight of the testes of the exposed rats. However, the weights of seminal vesicles and preputial glands were significantly reduced in the exposed male rats. Similarly, a significant reduction in sperm count was observed in the exposed group. Furthermore, there were no significant effects on the serum levels of male follicle stimulating hormone (FSH) during the 18 weeks of exposure period. On the other hand, there was a significant increase in the serum levels of male luteinizing hormone (LH) after 18 weeks of exposure (P < .005), while testosterone levels were significantly decreased only after 6 and 12 weeks of the exposure period. These results suggest that long term exposure to ELF could have adverse effects on mammalian fertility and reproduction.

  12. Heterosis Increases Fertility, Fecundity, and Survival of Laboratory-Produced F1 Hybrid Males of the Malaria Mosquito Anopheles coluzzii.

    PubMed

    Ekechukwu, Nkiru E; Baeshen, Rowida; Traorè, Sékou F; Coulibaly, Mamadou; Diabate, Abdoulaye; Catteruccia, Flaminia; Tripet, Frédéric

    2015-10-23

    The success of vector control strategies aiming to decrease disease transmission via the release of sterile or genetically-modified male mosquitoes critically depends on mating between laboratory-reared males and wild females. Unfortunately, mosquito colonization, laboratory rearing, and genetic manipulations can all negatively affect male competitiveness. Heterosis is commonly used to produce domestic animals with enhanced vigor and homogenous genetic background and could therefore potentially improve the mating performance of mass-reared male mosquitoes. Here, we produced enhanced hybrid males of the malaria mosquito Anopheles coluzzii by crossing two strains colonized >35 and 8 years ago. We compared the amount of sperm and mating plug proteins they transferred to females, as well as their insemination rate, reproductive success and longevity under various experimental conditions. Across experiments, widespread adaptations to laboratory mating were detected in the older strain. In large-group mating experiments, no overall hybrid advantage in insemination rates and the amount of sperm and accessory gland proteins transferred to females was detected. Despite higher sperm activity, hybrid males did not appear more fecund. However, individual-male mating and laboratory-swarm experiments revealed that hybrid males, while inseminating fewer females than older inbred males, were significantly more fertile, producing larger mating plugs and drastically increasing female fecundity. Heterotic males also showed increased longevity. These results validate the use of heterosis for creating hybrid males with improved fitness from long-established inbred laboratory strains. Therefore, this simple approach could facilitate disease control strategies based on male mosquito releases with important ultimate benefits to human health.

  13. Heterosis Increases Fertility, Fecundity, and Survival of Laboratory-Produced F1 Hybrid Males of the Malaria Mosquito Anopheles coluzzii

    PubMed Central

    Ekechukwu, Nkiru E.; Baeshen, Rowida; Traorè, Sékou F.; Coulibaly, Mamadou; Diabate, Abdoulaye; Catteruccia, Flaminia; Tripet, Frédéric

    2015-01-01

    The success of vector control strategies aiming to decrease disease transmission via the release of sterile or genetically-modified male mosquitoes critically depends on mating between laboratory-reared males and wild females. Unfortunately, mosquito colonization, laboratory rearing, and genetic manipulations can all negatively affect male competitiveness. Heterosis is commonly used to produce domestic animals with enhanced vigor and homogenous genetic background and could therefore potentially improve the mating performance of mass-reared male mosquitoes. Here, we produced enhanced hybrid males of the malaria mosquito Anopheles coluzzii by crossing two strains colonized >35 and 8 years ago. We compared the amount of sperm and mating plug proteins they transferred to females, as well as their insemination rate, reproductive success and longevity under various experimental conditions. Across experiments, widespread adaptations to laboratory mating were detected in the older strain. In large-group mating experiments, no overall hybrid advantage in insemination rates and the amount of sperm and accessory gland proteins transferred to females was detected. Despite higher sperm activity, hybrid males did not appear more fecund. However, individual-male mating and laboratory-swarm experiments revealed that hybrid males, while inseminating fewer females than older inbred males, were significantly more fertile, producing larger mating plugs and drastically increasing female fecundity. Heterotic males also showed increased longevity. These results validate the use of heterosis for creating hybrid males with improved fitness from long-established inbred laboratory strains. Therefore, this simple approach could facilitate disease control strategies based on male mosquito releases with important ultimate benefits to human health. PMID:26497140

  14. Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity.

    PubMed

    Ghanayem, Burhan I; Bai, Re; Kissling, Grace E; Travlos, Greg; Hoffler, Undi

    2010-01-01

    The prevalence of human obesity and related chronic disorders such as diabetes, cardiovascular diseases, and cancer is rapidly increasing. Human studies have shown a direct relationship between obesity and infertility. The objective of the current work was to examine the effect of diet-induced obesity on male fertility and the effect of obesity on susceptibility to chemical-induced reproductive toxicity. From 5 to 30 wk of age, genetically intact male C57Bl/6J mice were fed a normal diet or one in which 60% of the kilocalories were from lard. Obese mice exhibited significant differences in the mRNA of several genes within the testes in comparison to lean males. Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. The fertility of male mice was compared through mating with control females. Acrylamide (AA)-induced reproductive toxicity was assessed in obese or lean males treated with water or 25 mg AA kg(-1) day(-1) via gavage for 5 days and then mated to control females. Percent body fat and weight were significantly increased in mice fed a high-fat vs. a normal diet. Obesity resulted in significant reduction in plugs and pregnancies of control females partnered with obese vs. lean males. Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. Sperm from obese males exhibited decreased motility and reduced hyperactivated progression vs. lean mice. Treatment with AA exacerbated male infertility of obese and lean mice; however, this effect was more pronounced in obese mice. Further, females partnered with AA-treated obese mice exhibited a further decrease in the percentage of live fetuses, whereas the percentage of resorptions increased. This work demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity.

  15. Transporters involved in pH and K+ homeostasis affect pollen wall formation, male fertility, and embryo development

    DOE PAGES

    Padmanaban, Senthilkumar; Czerny, Daniel D.; Levin, Kara A.; ...

    2017-02-23

    Flowering plant genomes encode multiple cation/H+ exchangers (CHXs) whose functions are largely unknown. AtCHX17, AtCHX18, and AtCHX19 are membrane transporters that modulate K+ and pH homeostasis and are localized in the dynamic endomembrane system. Loss of function reduced seed set, but the particular phase(s) of reproduction affected was not determined. Pollen tube growth and ovule targeting of chx17chx18chx19 mutant pollen appeared normal, but reciprocal cross experiments indicate a largely male defect. Although triple mutant pollen tubes reach ovules of a wild-type pistil and a synergid cell degenerated, half of those ovules were unfertilized or showed fertilization of the egg ormore » central cell, but not both female gametes. Fertility could be partially compromised by impaired pollen tube and/or sperm function as CHX19 and CHX18 are expressed in the pollen tube and sperm cell, respectively. When fertilization was successful in self-pollinated mutants, early embryo formation was retarded compared with embryos from wild-type ovules receiving mutant pollen. Thus CHX17 and CHX18 proteins may promote embryo development possibly through the endosperm where these genes are expressed. The reticulate pattern of the pollen wall was disorganized in triple mutants, indicating perturbation of wall formation during male gametophyte development. Lastly, as pH and cation homeostasis mediated by AtCHX17 affect membrane trafficking and cargo delivery, these results suggest that male fertility, sperm function, and embryo development are dependent on proper cargo sorting and secretion that remodel cell walls, plasma membranes, and extracellular factors.« less

  16. EVALUATION OF AMMONIUM PERCHLORATE IN THE ENDOCRINE DISRUPTOR SCREENING AND TESTING PROGRAM'S MALE PUBERTAL PROTOCOL: ABILITY TO DETECT EFFECTS OF THYROID ENDPOINTS.

    EPA Science Inventory

    The U.S EPA Endocrine Disruptor Screening Program Tier 1 male pubertal protocol was designed to detect reproductive development and thyroid function. One purpose of this in vivo protocol is to detect thyrotoxicants via a number of different mechanisms of action. Here we evaluate ...

  17. Molecular mapping of three male-sterile, female-fertile mutants and generation of a comprehensive map of all known male sterility genes in soybean.

    PubMed

    Yang, Yang; Speth, Benjamin D; Boonyoo, Napatsakorn; Baumert, Eric; Atkinson, Taylor R; Palmer, Reid G; Sandhu, Devinder

    2014-03-01

    In soybean, an environmentally stable male sterility system is vital for making hybrid seed production commercially viable. Eleven male-sterile, female-fertile mutants (ms1, ms2, ms3, ms4, ms5, ms6, ms7, ms8, ms9, msMOS, and msp) have been identified in soybean. Of these, eight (ms2, ms3, ms5, ms7, ms8, ms9, msMOS, and msp) have been mapped to soybean chromosomes. The objectives of this study were to (i) locate the ms1, ms4, and ms6 genes to soybean chromosomes; (ii) generate genetic linkage maps of the regions containing these genes; and (iii) develop a comprehensive map of all known male-sterile, female-fertile genes in soybean. The bulked segregant analysis technique was used to locate genes to soybean chromosomes. Microsatellite markers from the corresponding chromosomes were used on F2 populations to generate genetic linkage maps. The ms1 and ms6 genes were located on chromosome 13 (molecular linkage group F) and ms4 was present on chromosome 2 (molecular linkage group D1b). Molecular analyses revealed markers Satt516, BARCSOYSSR_02_1539, and AW186493 were located closest to ms1, ms4, and ms6, respectively. The ms1 and ms6 genes, although present on the same chromosome, were independently assorting with a genetic distance of 73.7 cM. Using information from this study and compiled information from previously published male sterility genes in soybean, a comprehensive genetic linkage map was generated. Eleven male sterility genes were present on seven soybean chromosomes. Four genes were present in two regions on chromosome 2 (molecular linkage group D1b) and two genes were present on chromosome 13 (molecular linkage group F).

  18. The goddard and saturn genes are essential for Drosophila male fertility and may have arisen de novo.

    PubMed

    Gubala, Anna M; Schmitz, Jonathan F; Kearns, Michael J; Vinh, Tery T; Bornberg-Bauer, Erich; Wolfner, Mariana F; Findlay, Geoffrey D

    2017-01-19

    New genes arise through a variety of mechanisms, including the duplication of existing genes and the de novo birth of genes from non-coding DNA sequences. While there are numerous examples of duplicated genes with important functional roles, the functions of de novo genes remain largely unexplored. Many newly evolved genes are expressed in the male reproductive tract, suggesting that these evolutionary innovations may provide advantages to males experiencing sexual selection. Using testis-specific RNA interference, we screened 11 putative de novo genes in Drosophila melanogaster for effects on male fertility and identified two, goddard and saturn, that are essential for spermatogenesis and sperm function. Goddard knockdown males fail to produce mature sperm, while saturn knockdown males produce fewer sperm that function inefficiently once transferred to females. Consistent with a de novo origin, both genes are identifiable only in Drosophila and are predicted to encode proteins with no sequence similarity to any annotated protein. However, since high levels of divergence prevented the unambiguous identification of the non-coding sequences from which each gene arose, we consider goddard and saturn to be putative de novo genes. Within Drosophila, both genes have been lost in certain lineages, but show conserved, male-specific patterns of expression in the species in which they are found. Goddard is consistently found in single-copy and evolves under purifying selection. In contrast, saturn has diversified through gene duplication and positive selection. These data suggest that de novo genes can evolve essential roles in male reproduction.

  19. Ameliorating effect of olive oil on fertility of male rats fed on genetically modified soya bean

    PubMed Central

    El-Kholy, Thanaa A. F.; Al-Abbadi, Hatim A.; Qahwaji, Dina; Al-Ghamdi, Ahmed K.; Shelat, Vishal G.; Sobhy, Hanan M.; Hilal, Mohammad Abu

    2015-01-01

    Background Genetically modified soya bean (GMSB) is a commercialized food. It has been shown to have adverse effects on fertility in animal trials. Extra virgin olive oil (EVOO) has many beneficial effects including anti-oxidant properties. The aim of this study is to elucidate if addition of EVOO ameliorates the adverse effects on reproductive organs of rats fed on GMSB containing diet. Methods Forty adult male albino rats (150–180 g) of Sprague Dawley strain were separated into four groups of 10 rats each: Group 1 – control group fed on basal ration, Group 2 – fed on basal ration mixed with EVOO (30%), Group 3 – fed on basal ration mixed with GMSB (15%), and Group 4 – fed on basal ration mixed with GMSB (15%) and EVOO (30%). This feeding regimen was administered for 65 days. Blood samples were collected to analyze serum zinc, vitamin E, and testosterone levels. Histopathological and weight changes in sex organs were evaluated. Results GMSB diet reduced weight of testis (0.66±0.06 vs. 1.7±0.06, p<0.001), epididymis (0.489±0.03 vs. 0.7±0.03, p<0.001), prostate (0.04±0.009 vs. 0.68±0.04, p<0.001), and seminal vesicles (0.057±0.01 vs. 0.8±0.04, p<0.001). GMSB diet adversely affected sperm count (406±7.1 vs. 610±7.8, p<0.001), motility (p<0.001), and abnormality (p<0.001). GMSB diet also reduced serum zinc (p<0.05), vitamin E (p<0.05), and testosterone (p<0.05) concentrations. EVOO diet had no detrimental effect. Addition of EVOO to GMSB diet increased the serum zinc (p<0.05), vitamin E (p<0.05), and testosterone (p<0.05) levels and also restored the weights of testis (1.35±0.16 vs. 0.66±0.06, p<0.01), epididymis (0.614±0.13 vs. 0.489±0.03, p<0.001), prostate (0.291±0.09 vs. 0.04±0.009, p<0.001), seminal vesicle (0.516±0.18 vs. 0.057±0.01, p<0.001) along with sperm count (516±3.1 vs. 406±7.1, p<0.01), motility (p<0.01), and abnormality (p<0.05). Conclusion EVOO ameliorates the adverse effects of GMSB on reproductive organs in adult male

  20. [Reproductive and developmental toxicity study of gadobenate dimeglumine formulation (E7155) (1)--Fertility study in male rats by intravenous administration].

    PubMed

    Okada, F; Sagami, F; Tirone, P; Morisetti, A; Bussi, S; Baguley, J K

    1999-11-01

    The influence of gadobenate dimeglumine formulation (E7155) on general reproductive performance and fertility in male rats of the Sprague-Dawley strain was assessed in this study. E7155 was administered by intravenous injection at a dosage of 0.3, 1.0, or 2.0 mmol/kg/day to groups of 22 male rats for 13 weeks. Control animals received 0.9% sterile physiological saline throughout the same period. After four weeks of treatment, each male was paired with an untreated female of the same strain. Each male was paired again after 10 weeks of treatment with another untreated female of the same strain. All females were killed on Day 14 of gestation for examination of pregnancy status. No significant toxicological signs associated with systemic exposure to E7155 were observed. There were no effects of treatment with E7155 on body weight gain, food consumption, macroscopic findings, reproductive organ weights and sperm count or sperm motility in male rats. Mating performance after pairing at Weeks 4 and 10 of treatment as well as litter size and number of survival embryos on Day 14 of gestation were not affected by paternal treatment with E7155. From these results, the No Observed Adverse Effect Level (NOAEL) of E7155 was 2.0 mmol/kg/day for general and reproductive toxicity parameters in male rats treated with E7155 and for development in their embryos.

  1. 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.

  2. A critical role of solute carrier 22a14 in sperm motility and male fertility in mice

    PubMed Central

    Maruyama, Shin-ya; Ito, Momoe; Ikami, Yuusuke; Okitsu, Yu; Ito, Chizuru; Toshimori, Kiyotaka; Fujii, Wataru; Yogo, Keiichiro

    2016-01-01

    We previously identified solute carrier 22a14 (Slc22a14) as a spermatogenesis-associated transmembrane protein in mice. Although Slc22a14 is a member of the organic anion/cation transporter family, its expression profile and physiological role have not been elucidated. Here, we show that Slc22a14 is crucial for sperm motility and male fertility in mice. Slc22a14 is expressed specifically in male germ cells, and mice lacking the Slc22a14 gene show severe male infertility. Although the overall differentiation of sperm was normal, Slc22a14−/− cauda epididymal spermatozoa showed reduced motility with abnormal flagellar bending. Further, the ability to migrate into the female reproductive tract and fertilise the oocyte were also impaired in Slc22a14−/− spermatozoa. The abnormal flagellar bending was thought to be partly caused by osmotic cell swelling since osmotic challenge or membrane permeabilisation treatment alleviated the tail abnormality. In addition, we found structural abnormalities in Slc22a14−/− sperm cells: the annulus, a ring-like structure at the mid-piece–principal piece junction, was disorganised, and expression and localisation of septin 4, an annulus component protein that is essential for the annulus formation, was also impaired. Taken together, our results demonstrated that Slc22a14 plays a pivotal role in normal flagellar structure, motility and fertility in mouse spermatozoa. PMID:27811987

  3. Polygyny, mate-guarding, and posthumous fertilization as alternative male mating strategies

    PubMed Central

    Zamudio, Kelly R.; Sinervo, Barry

    2000-01-01

    Alternative male mating strategies within populations are thought to be evolutionarily stable because different behaviors allow each male type to successfully gain access to females. Although alternative male strategies are widespread among animals, quantitative evidence for the success of discrete male strategies is available for only a few systems. We use nuclear microsatellites to estimate the paternity rates of three male lizard strategies previously modeled as a rock-paper-scissors game. Each strategy has strengths that allow it to outcompete one morph, and weaknesses that leave it vulnerable to the strategy of another. Blue-throated males mate-guard their females and avoid cuckoldry by yellow-throated “sneaker” males, but mate-guarding is ineffective against aggressive orange-throated neighbors. The ultradominant orange-throated males are highly polygynous and maintain large territories; they overpower blue-throated neighbors and cosire offspring with their females, but are often cuckolded by yellow-throated males. Finally, yellow-throated sneaker males sire offspring via secretive copulations and often share paternity of offspring within a female's clutch. Sneaker males sire more offspring posthumously, indicating that sperm competition may be an important component of their strategy. PMID:11106369

  4. The potential of sanrego (Lunasia amara) in enhancing fertility and anti-hyperglycemic effect in diabetic induced male rats

    NASA Astrophysics Data System (ADS)

    Nor Raidah, R.; Mahanem M., N.; Mohd Shazrul Fazry, S.

    2014-09-01

    Study on the effects of Lunasia amara (LA) aqueous extract on male fertility and its anti-hyperglycemic activity was carried out. Twelve adult male Sprague-Dawley rats were divided into two groups for fertility test; control given orally distilled water (n=6) and treatment (n=6) given 60 mg/kg aqueous extract of LA for 42 days. On day 43, all rats were sacrificed and cauda epididymis was isolated for sperm quality analysis that includes parameter of sperm count, motility and viability. Anti-hyperglycemic study was done on five groups of male rats; I-normal control, II-Diabetic control and three other groups induced diabetic given 500 mg/kg metformin, 60 mg/kg LA and 120 mg/kg LA respectively. Diabetes was induced in the male rats by intravenous injection of 55 mg/kg streptozotocin. On day 7, the fasting blood glucose level was measured from blood drawn by tail snip. Results showed that aqueous extract of LA increased significantly (p < 0.05) sperm count (39.88 ± 2.33) × 106, viability 82.46 ± 1.91 % and progressive motility 76.00 ± 1.51and of sperm data in treated group compared to control group. LA aqueous extract at dose 120 mg/kg was significantly reduced the fasting blood glucose in the diabetic rats by 49.53 %. In conclusion, the aqueous extract of LA effective in increasing sperm quality of male rats and suggest that LA may possess anti-hyperglycemic property.

  5. 46 XX karyotype during male fertility evaluation; case series and literature review

    PubMed Central

    Majzoub, Ahmad; Arafa, Mohamed; Starks, Christopher; Elbardisi, Haitham; Al Said, Sami; Sabanegh, Edmund

    2017-01-01

    Forty-six XX disorder of sex development is an uncommon medical condition observed at times during the evaluation of a man's fertility. The following is a case series and literature review of phenotypically normal men diagnosed with this karyotype. Our goal is to comprehend the patients’ clinical presentation as well as their laboratory results aiming to explore options available for their management. A formal literature review through PubMed and MEDLINE databases was performed using “46 XX man” as a word search. A total of 55 patients, including those conveyed in this article were diagnosed with a 46 XX karyotype during their fertility evaluation. The patients’ mean age ± s.d. was 34 ± 10 years and their mean height ± s.d. was 166 ± 6.5 cm. Overall, they presented with hypergonadotropic hypogonadism. Sexual dysfunction, reduced hair distribution, and gynecomastia were reported in 20% (4/20), 25.8% (8/31), and 42% (13/31) of the patients, respectively. The SRY gene was detected in 36 (83.7%) and was absent in the remaining seven (16.3%) patients. We found that a multidisciplinary approach to management is preferred in 46 XX patients. Screening for remnants of the mullerian ducts and for malignant transformation in dysgenetic gonads is imperative. Hypogonadism should be addressed, while fertility options are in vitro fertilization with donor sperm or adoption. PMID:27297128

  6. Isolation of RNA striped bass Monrone saxatilis spermatozoa: Implications for teleost male fertility and beyond?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vertebrate sperm has been shown to provide more than paternal genomic material to the oocyte. For example, specific transcripts have been identified in bull sperm associated with fertility and with motility in boar sperm. Very little is currently known about functional, residual RNA in spermatozoa a...

  7. Isolation of RNA from striped bass (Morone saxatilis) spermatozoa: implications for teleost male fertility and beyond?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vertebrate sperm has been shown to provide more than paternal genomic material to the oocyte. For example, specific transcripts have been identified in bull sperm associated with fertility and with motility in boar sperm. Very little is currently known about functional, residual RNA in spermatozoa a...

  8. Male reproductive traits, semen cryopreservation, and heterologous in vitro fertilization in the bobcat (Lynx rufus).

    PubMed

    Gañán, N; González, R; Sestelo, A; Garde, J J; Sánchez, I; Aguilar, J M; Gomendio, M; Roldan, E R S

    2009-08-01

    There is limited information on bobcat ejaculate traits and sperm cryopreservation and fertilizing ability. Bobcats were electroejaculated under general anesthesia in November (autumn) and April (spring), and endocrine and sperm traits were characterized. Testosterone (mean+/-SEM: 0.90+/-0.15 ng/mL) was not different between sampling times, but cortisol (average: 13.95+/-1.73 microg/dL) was significantly higher in April. Average number of spermatozoa was 10.0+/-3.4 x 10(6) sperm/ejaculate, with values being significantly higher in April. Sperm motility (average 55.7+/-5.8% motile sperm) was not different between sampling times. The proportion of normal spermatozoa in the ejaculate (average: 14.7+/-2.1%) was significantly higher in April, but the percentage of spermatozoa with intact acrosomes (average: 43.7+/-3.8%) was significantly higher in autumn. Spermatozoa were cryopreserved in a Tes-Tris-based diluent (TEST) or Biladyl, both containing 20% egg yolk and 4% glycerol. Diluted sperm were loaded into straws, refrigerated using a programmable thermoblock with a dry chamber, frozen in nitrogen vapors, thawed, and incubated in F-10 medium with 5% fetal bovine serum for up to 3h. After cryopreservation in TEST, there were about 50% motile sperm upon thawing, and survival was high during incubation post-thaw. Cryopreservation in Biladyl led to similar results, but motility decreased substantially during incubation post-thaw. Bobcat spermatozoa fertilized domestic cat oocytes matured in vitro. Fertilization rates were higher for sperm collected in April and cryopreserved in TEST (46%) than for those cryopreserved using Biladyl (<3%). Fertilized oocytes cleaved in culture, and some (27%) reached the morula stage. This study has allowed us to gain further baseline information on bobcat reproduction, explore sperm cryopreservation conditions, and show that fertilizing capacity can be tested using in vitro-matured cat oocytes. These results will be important for future

  9. Males are here to stay: fertilization enhances viable egg production by clonal queens of the little fire ant ( Wasmannia auropunctata)

    NASA Astrophysics Data System (ADS)

    Miyakawa, Misato O.; Mikheyev, Alexander S.

    2015-04-01

    Evolution of reproduction strategies is affected by both phylogenetic and physiological constraints. Although clonality may benefit females, it may not be selected if a male contribution is necessary to start egg laying and embryo development. In little fire ant, Wasmannia auropunctata, sexual populations employ a typical Hymenopteran system of reproduction. In clonal populations, however, queens and males are produced with only maternal and paternal genomes, respectively, whereas sterile workers are produced sexually. Although this system requires both sexes for worker production, previous work has shown that workers may also be produced clonally by the queens. If so, why are males maintained in this species? Our data suggest that fertilization is necessary to increase the hatching rate of eggs. Although clonal queens can indeed produce both workers and queens without mating, the hatching rate is far below the level necessary to maintain functional colonies. On the other hand, virgin queens from populations exhibiting the original Hymenopteran reproduction system also show low hatching rates, but produce only haploid male eggs. Reasons for the existence of W. auropunctata males have been disputed. However, our data suggest that physiological constraints, such as the requirement for insemination, must be considered in regard to evolution of reproduction systems, in addition to ecological data and theoretical considerations of fitness.

  10. Reduced Fertility of Drosophila melanogaster Hybrid male rescue (Hmr) Mutant Females Is Partially Complemented by Hmr Orthologs From Sibling Species

    PubMed Central

    Aruna, S.; Flores, Heather A.; Barbash, Daniel A.

    2009-01-01

    The gene Hybrid male rescue (Hmr) causes lethality in interspecific hybrids between Drosophila melanogaster and its sibling species. Hmr has functionally diverged for this interspecific phenotype because lethality is caused specifically by D. melanogaster Hmr but not by D. simulans or D. mauritiana Hmr. Hmr was identified by the D. melanogaster partial loss-of-function allele Hmr1, which suppresses hybrid lethality but has no apparent phenotype within pure-species D. melanogaster. Here we have investigated the possible function of Hmr in D. melanogaster females using stronger mutant alleles. Females homozygous for Hmr mutants have reduced viability posteclosion and significantly reduced fertility. We find that reduced fertility of Hmr mutants is caused by a reduction in the number of eggs laid as well as reduced zygotic viability. Cytological analysis reveals that ovarioles from Hmr mutant females express markers that distinguish various stages of wild-type oogenesis, but that developing egg chambers fail to migrate posteriorly. D. simulans and D. mauritiana Hmr+ partially complement the reduced fertility of a D. melanogaster Hmr mutation. This partial complementation contrasts with the complete functional divergence previously observed for the interspecific hybrid lethality phenotype. We also investigate here the molecular basis of hybrid rescue associated with a second D. melanogaster hybrid rescue allele, In(1)AB. We show that In(1)AB is mutant for Hmr function, likely due to a missense mutation in an evolutionarily conserved amino acid. Two independently discovered hybrid rescue mutations are therefore allelic. PMID:19153254

  11. Single nucleotide polymorphisms in linkage disequilibrium with the male-fertility restoration (Ms) locus in open-pollinated and inbred populations of onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintainer lines are used to seed propagate male-sterile lines for the development of hybrid-onion cultivars. The identification of maintainer lines would be more efficient with molecular markers distinguishing genotypes at the nuclear male-fertility restoration (Ms) locus. Ms has been mapped to chr...

  12. Birth Order and Sibling Sex Ratio in a Population with High Fertility: Are Turkish Male to Female Transsexuals Different?

    PubMed

    Bozkurt, Ali; Bozkurt, Ozlem Hekim; Sonmez, Ipek

    2015-07-01

    Western studies have consistently found that androphilic (sexually attracted to men) male-to-female transsexuals have a later birth order and a relative excess of brothers compared with appropriate control participants. However, non-Western studies on birth order and sibling sex ratio in androphilic males (transsexual or non-transsexual) are rare. The objective of the study was to test the hypothesis that androphilic male-to-female transsexuals have a late birth order and a relative excess of brothers in a non-Western culture with a higher fertility rate. The participants were 60 androphilic male-to-female transsexuals and 61 male heterosexual controls. The transsexual participants had significantly more older brothers than the control participants, but the groups did not differ in their numbers of older sisters, younger brothers, or younger sisters. The foregoing pattern is usually referred to as the "fraternal birth order effect." Slater's and Berglin's Indexes both showed that the mean birth order of the control participants was very close to that expected from a random sample drawn from a demographically stable population whereas the mean birth order of the transsexual participants was later. A measure of sibship composition, brothers/all siblings, showed that the transsexual group had a higher proportion of male siblings compared with the control group. In conclusion, the present study found that Turkish androphilic male-to-female transsexuals show the same high fraternal birth order that has been found in comparable androphilic samples in Western Europe, North America, and the South Pacific, which suggests a common underlying biological causal mechanism.

  13. Fertility Risk Assessment and Preservation in Male and Female Prepubertal and Adolescent Cancer Patients

    PubMed Central

    Zavras, Nikolaos; Siristatidis, Charalampos; Siatelis, Argyris; Koumarianou, Anna

    2016-01-01

    Cancer represents the second cause of death in prepubertal children and adolescents, although it is currently associated with an overall survival rate of 80%–85%. The annual incidence rate is 186.6 per 1 million children and adolescents aged up to 19 years. Both disease and treatment options are associated with life-altering, long-term effects that require monitoring. Infertility is a common issue, and as such, fertility preservation represents an essential part in the management of young patients with cancer who are at risk of premature gonadal failure. This review deals with the up-to-date available data on fertility risk assessment and preservation strategies that should be addressed prior to antineoplastic therapy in this vulnerable subgroup of cancer patients. PMID:27398041

  14. NMR-based plasma metabolomic discrimination for male fertility assessment of rats treated with Eurycoma longifolia extracts.

    PubMed

    Ebrahimi, Forough; Ibrahim, Baharudin; Teh, Chin-Hoe; Murugaiyah, Vikneswaran; Chan, Kit-Lam

    2017-03-17

    Male infertility is one of the leading causes of infertility which affects many couples worldwide. Semen analysis is a routine examination of male fertility status which is usually performed on semen samples obtained through masturbation that may be inconvenient to patients. Eurycoma longifolia (Tongkat Ali, TA), native to Malaysia, has been traditionally used as a remedy to boost male fertility. In our recent studies in rats, upon the administration of high-quassinoid content extracts of TA including TA water (TAW), quassinoid-rich TA (TAQR) extracts, and a low-quassinoid content extract including quassinoid-poor TA (TAQP) extract, sperm count (SC) increased in TAW- and TAQR-treated rats when compared to the TAQP-treated and control groups. Consequently, the rats were divided into normal- (control and TAQP-treated) and high- (TAW- and TAQR-treated) SC groups [Ebrahimi et al. 2016]. Post-treatment rat plasma was collected. An optimized plasma sample preparation method was developed with respect to the internal standards sodium 3- (trimethylsilyl) propionate- 2,2,3,3- d4 (TSP) and deuterated 4-dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA). Carr-Purcell-Meibum-Gill (CPMG) experiments combined with orthogonal partial least squares discriminant analysis (OPLS-DA) was employed to evaluate plasma metabolomic changes in normal- and high-SC rats. The potential biomarkers associated with SC increase were investigated to assess fertility by capturing the metabolomic profile of plasma. DSA was selected as the optimized internal standard for plasma analysis due to its significantly smaller half-height line width (W h/2) compared to that of TSP. The validated OPLS-DA model clearly discriminated the CPMG profiles in regard to the SC level. Plasma profiles of the high-SC group contained higher levels of alanine, lactate, and histidine, while ethanol concentration was significantly higher in the normal-SC group. This approach might be a new alternative applicable to the

  15. Male-female crosstalk during pollen germination, tube growth and guidance, and double fertilization.

    PubMed

    Dresselhaus, Thomas; Franklin-Tong, Noni

    2013-07-01

    Sperm cells of flowering plants are non-motile and thus require transportation to the egg apparatus via the pollen tube to execute double fertilization. During its journey, the pollen tube interacts with various sporophytic cell types that support its growth and guide it towards the surface of the ovule. The final steps of tube guidance and sperm delivery are controlled by the cells of the female gametophyte. During fertilization, cell-cell communication events take place to achieve and maximize reproductive success. Additional layers of crosstalk exist, including self-recognition and specialized processes to prevent self-fertilization and consequent inbreeding. In this review, we focus on intercellular communication between the pollen grain/pollen tube including the sperm cells with the various sporophytic maternal tissues and the cells of the female gametophyte. Polymorphic-secreted peptides and small proteins, especially those belonging to various subclasses of small cysteine-rich proteins (CRPs), reactive oxygen species (ROS)/NO signaling, and the second messenger Ca(2+), play center stage in most of these processes.

  16. Fertility preservation in males with cancer: 16-year monocentric experience of sperm banking and post-thaw reproductive outcomes

    PubMed Central

    Depalo, Raffaella; Falagario, Doriana; Masciandaro, Paola; Nardelli, Claudia; Vacca, Margherita Patrizia; Capuano, Pasquale; Specchia, Giorgina; Battaglia, Michele

    2016-01-01

    Background: Anticancer treatments can impair male fertility. Cryopreservation of semen is an efficient procedure for fertility preservation. The aim of this study was to evaluate pre-freeze semen parameters among the various types of cancer, post-thaw sperm viability and reproductive outcome of samples used for assisted reproductive treatment (ART). Methods: This study included 721 men with cancer that had their semen cryopreserved in our bank in 1999–2015. Semen analysis and cryopreservation were performed before the start of antineoplastic treatment, according to the World Health Organization recommendations, European Commission and Italian law. Results: Among the 721 patient, 196 had seminoma of the testis, 173 Hodgkin’s lymphoma, 108 mixed testicular tumors, 89 germ cell tumors, 67 other tumors, 46 hematological tumors, and 42 non-Hodgkin’s lymphoma. The mean age of patients was significantly lower in Hodgkin’s lymphoma compared to other tumors. Statistically significant lower volume, sperm count and number of straws stored were observed respectively in Hodgkin’s lymphoma, mixed testicular tumor and hematological tumors. Nineteen patients used their frozen semen for 20 ART cycles. After thawing a significant reduction of motility and vitality was recorded. A lower fertilization rate was observed in patients affected by testicular tumor and lymphoma (35.42% and 50%) compared with other cancers (71.43%). No significant differences were observed in terms of cleavage and implantation rates. A total of five pregnancies and seven healthy newborns were achieved. Conclusions: Fertility preservation before gonadotoxic therapy is of great importance to patients with cancer and must be indicate before the start of treatment. PMID:27800030

  17. The effect of ethanol on spermatogenesis and fertility in male Sprague-Dawley rats pretreated with acetylsalicylic acid.

    PubMed

    Dare, W N; Noronha, C C; Kusemiju, O T; Okanlawon, O A

    2002-12-01

    Prenatal alcohol is associated with a variety of developmental abnormalies, including neuroanatomical, physical and behavioural features. This study was designed to determine the effects of administration of alcohol, exemplified mostly by ethanol (15 ml/kg, 25%, v/v) and acetylsalicylic acid (ASA, 15 mg/kg) as a representative of nonsteroidal anti-inflammatory drugs, individually and their combination (ethanol 15 ml/kg, 25%, v/v ASA 15 mg/kg) on semen quality and fertility after paternal intraperitoneal administration in Sprague-Dawley rats. In the combination study, the rats received ASA about 1 hour before ethanol administration. The combination experiments were conducted to determine if the effects of ethanol can be prevented by pre-treatment with acetyl salicylic acid (ASA) which has been reported to antagonise the rate-depressant effects of ethanol. All animals received this treatment for ten weeks. Semen parameters were determined and compared with controls. The result showed that when given alone, ethanol significantly reduced the sperm density and percentage of motile spermatozoa relative to controls. Pre-treatment with ASA failed to stop the decrease in sperm density and percentage motility caused by ethanol. Moreover none of the experimental male rats was able to fertilize the females exposed to them despite successful mating demonstrated by the presence of sperm plug. The present study demonstrates that chronic consumption of ethanol or ingestion of ASA has toxic effect on spermatozoa and impairs fertility in male Sprague-Dawley rats. Moreover, pre-treatment with ASA has no effect on the deleterious effects caused by ethanol.

  18. An integrated approach to male-factor subfertility: bridging the gap between fertility specialists trained in urology and gynaecology.

    PubMed

    Hughes, Edward G; Grantmyre, John; Zini, Armand

    2015-03-01

    Subfertile men and women are usually cared for by different clinicians, namely urologists and gynaecologists. While these doctors share each other's goals, they may not always appreciate the content or implications of their opposite number's clinical decisions; to some degree they may practice in "silos." We address this problem by reviewing the effectiveness of medical treatments for male factor subfertility in the context of female factors. The effectiveness of treatments for couples with male factor subfertility, other than IVF with ICSI, appears modest. However, data from randomized controlled trials suggest benefits from some treatments: clomiphene and tamoxifen for the male (common odds ratio for pregnancy [COR] 2.42; 95% CI 1.47 to 3.94), antioxidants (COR 4.18; 95% CI 2.65 to 6.59) and surgical management of a clinical varicocele (COR 2.39; 95% CI 1.56 to 3.66). Nevertheless, close attention to female age and the duration of subfertility help to avoid lost opportunity through delays in treatment when IVF with ICSI is indicated. Making treatment decisions squarely in the context of the couple's overall prognosis is key for optimal outcomes. Future trials of male fertility treatments should focus on pregnancy as the primary outcome, rather than less important surrogates such as sperm quality.

  19. DISTINGUISHING BETWEEN FERTILIZATION FAILURE AND EARLY PREGNANCY LOSS WHEN IDENTIFYING MALE-MEDIATED ADVERSE PREGNANCY OUTCOMES

    EPA Science Inventory

    Successful reproduction depends upon the precise orchestration of many physiological processes. With respect to male reproductive performance, normal copulatory behavior and ejaculatory function are required to insure that semen is deposited in the female tract. Then, a suffici...

  20. Identification of Genes Potentially Associated with the Fertility Instability of S-Type Cytoplasmic Male Sterility in Maize via Bulked Segregant RNA-Seq

    PubMed Central

    Xing, Jinfeng; Zhao, Yanxin; Zhang, Ruyang; Li, Chunhui; Duan, Minxiao; Luo, Meijie; Shi, Zi; Zhao, Jiuran

    2016-01-01

    S-type cytoplasmic male sterility (CMS-S) is the largest group among the three major types of CMS in maize. CMS-S exhibits fertility instability as a partial fertility restoration in a specific nuclear genetic background, which impedes its commercial application in hybrid breeding programs. The fertility instability phenomenon of CMS-S is controlled by several minor quantitative trait locus (QTLs), but not the major nuclear fertility restorer (Rf3). However, the gene mapping of these minor QTLs and the molecular mechanism of the genetic modifications are still unclear. Using completely sterile and partially rescued plants of fertility instable line (FIL)-B, we performed bulk segregant RNA-Seq and identified six potential associated genes in minor effect QTLs contributing to fertility instability. Analyses demonstrate that these potential associated genes may be involved in biological processes, such as floral organ differentiation and development regulation, energy metabolism and carbohydrates biosynthesis, which results in a partial anther exsertion and pollen fertility restoration in the partially rescued plants. The single nucleotide polymorphisms (SNPs) identified in two potential associated genes were validated to be related to the fertility restoration phenotype by KASP marker assays. This novel knowledge contributes to the understanding of the molecular mechanism of the partial fertility restoration of CMS-S in maize and thus helps to guide the breeding programs. PMID:27669430

  1. Evidence that meiotic sex chromosome inactivation is essential for male fertility.

    PubMed

    Royo, Hélène; Polikiewicz, Grzegorz; Mahadevaiah, Shantha K; Prosser, Haydn; Mitchell, Mike; Bradley, Allan; de Rooij, Dirk G; Burgoyne, Paul S; Turner, James M A

    2010-12-07

    The mammalian X and Y chromosomes share little homology and are largely unsynapsed during normal meiosis. This asynapsis triggers inactivation of X- and Y-linked genes, or meiotic sex chromosome inactivation (MSCI). Whether MSCI is essential for male meiosis is unclear. Pachytene arrest and apoptosis is observed in mouse mutants in which MSCI fails, e.g., Brca1(-/-), H2afx(-/-), Sycp1(-/-), and Msh5(-/-). However, these also harbor defects in synapsis and/or recombination and as such may activate a putative pachytene checkpoint. Here we present evidence that MSCI failure is sufficient to cause pachytene arrest. XYY males exhibit Y-Y synapsis and Y chromosomal escape from MSCI without accompanying synapsis/recombination defects. We find that XYY males, like synapsis/recombination mutants, display pachytene arrest and that this can be circumvented by preventing Y-Y synapsis and associated Y gene expression. Pachytene expression of individual Y genes inserted as transgenes on autosomes shows that expression of the Zfy 1/2 paralogs in XY males is sufficient to phenocopy the pachytene arrest phenotype; insertion of Zfy 1/2 on the X chromosome where they are subject to MSCI prevents this response. Our findings show that MSCI is essential for male meiosis and, as such, provide insight into the differential severity of meiotic mutations' effects on male and female meiosis.

  2. Transcriptomic Analysis of Differentially Expressed Genes during Flower Organ Development in Genetic Male Sterile and Male Fertile Tagetes erecta by Digital Gene-Expression Profiling.

    PubMed

    Ai, Ye; Zhang, Qinghua; Wang, Weining; Zhang, Chunling; Cao, Zhe; Bao, Manzhu; He, Yanhong

    2016-01-01

    Tagetes erecta is an important commercial plant of Asteraceae family. The male sterile (MS) and male fertile (MF) two-type lines of T. erecta have been utilized in F1 hybrid production for many years, but no report has been made to identify the genes that specify its male sterility that is caused by homeotic conversion of floral organs. In this study, transcriptome assembly and digital gene expression profiling were performed to generate expression profiles of MS and MF plants. A cDNA library was generated from an equal mixture of RNA isolated from MS and MF flower buds (1 mm and 4 mm in diameter). Totally, 87,473,431 clean tags were obtained and assembled into 128,937 transcripts among which 65,857 unigenes were identified with an average length of 1,188 bp. About 52% of unigenes (34,176) were annotated in Nr, Nt, Pfam, KOG/COG, Swiss-Prot, KO (KEGG Ortholog database) and/or GO. Taking the above transcriptome as reference, 125 differentially expressed genes were detected in both developmental stages of MS and MF flower buds. MADS-box genes were presumed to be highly related to male sterility in T. erecta based on histological and cytological observations. Twelve MADS-box genes showed significantly different expression levels in flower buds 4 mm in diameter, whereas only one gene expressed significantly different in flower buds 1 mm in diameter between MS and MF plants. This is the first transcriptome analysis in T. erecta and will provide a valuable resource for future genomic studies, especially in flower organ development and/or differentiation.

  3. Transcriptomic Analysis of Differentially Expressed Genes during Flower Organ Development in Genetic Male Sterile and Male Fertile Tagetes erecta by Digital Gene-Expression Profiling

    PubMed Central

    Ai, Ye; Zhang, Qinghua; Wang, Weining; Zhang, Chunling; Cao, Zhe; Bao, Manzhu; He, Yanhong

    2016-01-01

    Tagetes erecta is an important commercial plant of Asteraceae family. The male sterile (MS) and male fertile (MF) two-type lines of T. erecta have been utilized in F1 hybrid production for many years, but no report has been made to identify the genes that specify its male sterility that is caused by homeotic conversion of floral organs. In this study, transcriptome assembly and digital gene expression profiling were performed to generate expression profiles of MS and MF plants. A cDNA library was generated from an equal mixture of RNA isolated from MS and MF flower buds (1 mm and 4 mm in diameter). Totally, 87,473,431 clean tags were obtained and assembled into 128,937 transcripts among which 65,857 unigenes were identified with an average length of 1,188 bp. About 52% of unigenes (34,176) were annotated in Nr, Nt, Pfam, KOG/COG, Swiss-Prot, KO (KEGG Ortholog database) and/or GO. Taking the above transcriptome as reference, 125 differentially expressed genes were detected in both developmental stages of MS and MF flower buds. MADS-box genes were presumed to be highly related to male sterility in T. erecta based on histological and cytological observations. Twelve MADS-box genes showed significantly different expression levels in flower buds 4 mm in diameter, whereas only one gene expressed significantly different in flower buds 1 mm in diameter between MS and MF plants. This is the first transcriptome analysis in T. erecta and will provide a valuable resource for future genomic studies, especially in flower organ development and/or differentiation. PMID:26939127

  4. Do males time their mate-guarding effort with the fertile phase in order to secure fertilisation in Cayo Santiago rhesus macaques?

    PubMed

    Dubuc, Constance; Muniz, Laura; Heistermann, Michael; Widdig, Anja; Engelhardt, Antje

    2012-05-01

    In contrast to most mammalian species, female sexual activity is not limited to the fertile phase of the ovarian cycle in anthropoid primates, which has long been proposed to conceal the timing of ovulation to males. It is now generally believed that females are still most attractive during the fertile phase, leading to high-ranking males successfully mate-guarding them specifically during this period. While studies conducted in species exhibiting exaggerated sexual swellings (probabilistic signal of the fertile phase) have generally supported this hypothesis, mixed support comes from others. Here, we investigated whether high-ranking males timed mate-guarding effort towards female fertile phases in rhesus macaques (Macaca mulatta). In this species, adult females do not exhibit sexual swellings, but undergo facial skin colour variation, an alternative oestrogen-dependent graded-signal of female reproductive status. We collected behavioural, hormonal and genetic paternity data during two mating seasons for one group of the free-ranging population of Cayo Santiago. Our results show that mate-guarding by top-ranking males did not completely cover the entire female fertile phase and that this tactic accounted for only 30-40% of all fertilisations observed. Males tended to prolong mate-guarding into the luteal phase (null probability of fertilisation), which mirrors the pattern of male attraction to female facial colour reported in an earlier study. These findings suggest that males may have limited knowledge regarding the exact timing of females' fertile phase in rhesus macaques, which presumably allows females to gain more control over reproduction relative to other anthropoid primate species.

  5. Mutagenic effect of Bisphenol A on adult rat male germ cells and their fertility.

    PubMed

    Tiwari, Dinesh; Vanage, Geeta

    2013-09-01

    The present study investigates the effects of Bisphenol A on the induction of dominant lethal mutation and male reproductive functions. The male rats were gavaged with BPA (10 μg, and 5.0 mg/kg/bw) over a period of six days and control group with vehicle. Each male was cohabited with untreated females sequentially over the period of eight weeks. The mated females were sacrificed on 15th day of gestation. The results revealed a significant increase in dominant lethal mutation rate during fourth and sixth week of mating intervals at 5.0mg/kgbw dose of BPA. These findings demonstrate that mid-spermatids and spermatocytes are more sensitive to BPA exposure. The male rats sacrificed at the end of mating study showed an increase in the sperm DNA damage, and decrease in motility at higher dose. However, significant reductions in sperm production effects were observed at both lower and higher doses of BPA. These preliminary results indicate that BPA may be a weak male germ cell mutagen.

  6. The control of male fertility by spermatid-specific factors: searching for contraceptive targets from spermatozoon's head to tail

    PubMed Central

    Chen, Su-Ren; Batool, Aalia; Wang, Yu-Qian; Hao, Xiao-Xia; Chang, Chawn-Shang; Cheng, C Yan; Liu, Yi-Xun

    2016-01-01

    Male infertility due to abnormal spermatozoa has been reported in both animals and humans, but its pathogenic causes, including genetic abnormalities, remain largely unknown. On the other hand, contraceptive options for men are limited, and a specific, reversible and safe method of male contraception has been a long-standing quest in medicine. Some progress has recently been made in exploring the effects of spermatid-specifical genetic factors in controlling male fertility. A comprehensive search of PubMed for articles and reviews published in English before July 2016 was carried out using the search terms ‘spermiogenesis failure', ‘globozoospermia', ‘spermatid-specific', ‘acrosome', ‘infertile', ‘manchette', ‘sperm connecting piece', ‘sperm annulus', ‘sperm ADAMs', ‘flagellar abnormalities', ‘sperm motility loss', ‘sperm ion exchanger' and ‘contraceptive targets'. Importantly, we have opted to focus on articles regarding spermatid-specific factors. Genetic studies to define the structure and physiology of sperm have shown that spermatozoa appear to be one of the most promising contraceptive targets. Here we summarize how these spermatid-specific factors regulate spermiogenesis and categorize them according to their localization and function from spermatid head to tail (e.g., acrosome, manchette, head-tail conjunction, annulus, principal piece of tail). In addition, we emphatically introduce small-molecule contraceptives, such as BRDT and PPP3CC/PPP3R2, which are currently being developed to target spermatogenic-specific proteins. We suggest that blocking the differentiation of haploid germ cells, which rarely affects early spermatogenic cell types and the testicular microenvironment, is a better choice than spermatogenic-specific proteins. The studies described here provide valuable information regarding the genetic and molecular defects causing male mouse infertility to improve our understanding of the importance of spermatid

  7. The Trojan Female Technique for pest control: a candidate mitochondrial mutation confers low male fertility across diverse nuclear backgrounds in Drosophila melanogaster

    PubMed Central

    Dowling, Damian K; Tompkins, Daniel M; Gemmell, Neil J

    2015-01-01

    Pest species represent a major ongoing threat to global biodiversity. Effective management approaches are required that regulate pest numbers, while minimizing collateral damage to nontarget species. The Trojan Female Technique (TFT) was recently proposed as a prospective approach to biological pest control. The TFT draws on the evolutionary hypothesis that maternally inherited mitochondrial genomes are prone to the accumulation of male, but not female, harming mutations. These mutations could be harnessed to provide trans-generational fertility-based control of pest species. A candidate TFT mutation was recently described in the fruit fly, Drosophila melanogaster, which confers male-only sterility in the specific isogenic nuclear background in which it is maintained. However, applicability of the TFT relies on mitochondrial mutations whose male-sterilizing effects are general across nuclear genomic contexts. We test this assumption, expressing the candidate TFT-mutation bearing haplotype alongside a range of nuclear backgrounds and comparing its fertility in males, relative to that of control haplotypes. We document consistently lower fertility for males harbouring the TFT mutation, in both competitive and noncompetitive mating contexts, across all nuclear backgrounds screened. This indicates that TFT mutations conferring reduced male fertility can segregate within populations and could be harnessed to facilitate this novel form of pest control. PMID:26495040

  8. The Trojan Female Technique for pest control: a candidate mitochondrial mutation confers low male fertility across diverse nuclear backgrounds in Drosophila melanogaster.

    PubMed

    Dowling, Damian K; Tompkins, Daniel M; Gemmell, Neil J

    2015-10-01

    Pest species represent a major ongoing threat to global biodiversity. Effective management approaches are required that regulate pest numbers, while minimizing collateral damage to nontarget species. The Trojan Female Technique (TFT) was recently proposed as a prospective approach to biological pest control. The TFT draws on the evolutionary hypothesis that maternally inherited mitochondrial genomes are prone to the accumulation of male, but not female, harming mutations. These mutations could be harnessed to provide trans-generational fertility-based control of pest species. A candidate TFT mutation was recently described in the fruit fly, Drosophila melanogaster, which confers male-only sterility in the specific isogenic nuclear background in which it is maintained. However, applicability of the TFT relies on mitochondrial mutations whose male-sterilizing effects are general across nuclear genomic contexts. We test this assumption, expressing the candidate TFT-mutation bearing haplotype alongside a range of nuclear backgrounds and comparing its fertility in males, relative to that of control haplotypes. We document consistently lower fertility for males harbouring the TFT mutation, in both competitive and noncompetitive mating contexts, across all nuclear backgrounds screened. This indicates that TFT mutations conferring reduced male fertility can segregate within populations and could be harnessed to facilitate this novel form of pest control.

  9. Acceptability of drugs for male fertility regulation: a prospectus and some preliminary data. World Health Organization Task Force on Psychosocial Research in Family Planning.

    PubMed

    1980-02-01

    Hormonal substances for male fertility regulation administered orally or by injection are currently undergoing clinical evaluation. These trials, sponsored by the World Health Organization, provide unique opportunities for intensive study of the acceptability of such an approach to fertility regulation, and of these drugs in particular. The research employs repeated interviews over a 15-month period and is conducted by social scientists collaborating with biomedical scientists at each of seven sites (Bangkok, Hong Kong, London, Mexico City, Santiago, Seoul, and Toronto). The focus is upon gauging male user's evaluations of hormonal methods (several androgen/gestagen combinations as well as cyproterone acetate) relative to their evaluations of other male methods they know about or have experienced. Of particular importance is to determine whether the hormonal methods modify or interfere with sexual desire, feelings, and behavior. The research is also assessing specific ways in which various perceived properties of fertility regulating methods relate to their acceptability in different socio-cultural settings.

  10. Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss

    SciTech Connect

    Izquierdo-Vega, Jeannett A.; Sanchez-Gutierrez, Manuel; Razo, Luz Maria del

    2008-08-01

    Fluorosis, caused by drinking water contamination with inorganic fluoride, is a public health problem in many areas around the world. The aim of the study was to evaluate the effect of environmentally relevant doses of fluoride on in vitro fertilization (IVF) capacity of spermatozoa, and its relationship to spermatozoa mitochondrial transmembrane potential ({delta}{psi}{sub m}). Male Wistar rats were administered at 5 mg fluoride/kg body mass/24 h, or deionized water orally for 8 weeks. We evaluated several spermatozoa parameters in treated and untreated rats: i) standard quality analysis, ii) superoxide dismutase (SOD) activity, iii) the generation of superoxide anion (O{sub 2}{sup {center_dot}}{sup -}), iv) lipid peroxidation concentration, v) ultrastructural analyses of spermatozoa using transmission electron microscopy, vi) {delta}{psi}{sub m}, vii) acrosome reaction, and viii) IVF capability. Spermatozoa from fluoride-treated rats exhibited a significant decrease in SOD activity ({approx} 33%), accompanied with a significant increase in the generation of O{sub 2}{sup {center_dot}} ({approx} 40%), a significant decrease in {delta}{psi}{sub m} ({approx} 33%), and a significant increase in lipid peroxidation concentration ({approx} 50%), relative to spermatozoa from the control group. Consistent with this finding, spermatozoa from fluoride-treated rats exhibited altered plasmatic membrane. In addition, the percentage of fluoride-treated spermatozoa capable of undergoing the acrosome reaction was decreased relative to control spermatozoa (34 vs. 55%), while the percentage fluoride-treated spermatozoa capable of oocyte fertilization was also significantly lower than the control group (13 vs. 71%). These observations suggest that subchronic exposure to fluoride causes oxidative stress damage and loss of mitochondrial transmembrane potential, resulting in reduced fertility.

  11. Evaluation of Aqueous Leaf Extract of Cardiospermum halicacabum (L.) on Fertility of Male Rats

    PubMed Central

    Peiris, L. Dinithi. C.; Dhanushka, M. A. T.; Jayathilake, T. A. H. D. G.

    2015-01-01

    Treatment with 100 mg/kg and 200 mg/kg body weight of aqueous leaf extract (ALE) of Cardiospermum halicacabum for 30 days produced a significant dose dependent increase in the sperm counts and sperm motility in both caput and cauda regions. Further, significant increase in serum testosterone level was evident at all applied doses. However, no significant changes in the weight of sex organs were observed. Aqueous leaf extract also increased the number of females impregnated, number of implantations, and number of viable fetuses while decreasing the total number of resorption sites in the pregnant females. However, the total cholesterol level in the serum remained unchanged and there were no records on renotoxicity; nevertheless ALE exhibited a hepatoprotective effect. It was concluded that aqueous leaf extract of Cardiospermum halicacabum enhanced sperm concentration, motility, and testosterone, leading to positive results in fertility. PMID:26064883

  12. Evaluation of sterility and fertility of male sterile lines in the USPB farm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hybrid rice has proven to have a yield advantage of 15–20% over the best inbred cultivars at the commercial scale worldwide. At present, two methods have been successfully commercialized; the three-line and two-line systems. The three-line system consists of the male sterile (MS), maintainer and res...

  13. Mating behavior and fertility of broiler breeder males reared on shortened growth cycles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the more difficult tasks when raising broiler breeder cockerels is controlling weight gain in the rearing house without inflicting excess stress. This is a period of time for the young male when many portions of reproductive system are in the formative stages and, if neglected, can have lif...

  14. Human DCXR - another 'moonlighting protein' involved in sugar metabolism, carbonyl detoxification, cell adhesion and male fertility?

    PubMed

    Ebert, Bettina; Kisiela, Michael; Maser, Edmund

    2015-02-01

    Dicarbonyl/L-xylulose reductase (DCXR; SDR20C1), a member of the short-chain dehydrogenase/reductase (SDR) superfamily catalyzes the reduction of α-dicarbonyl compounds and monosaccharides. Its role in the metabolism of L-xylulose has been known since 1970, when essential pentosuria was found to be associated with DCXR deficiency. Despite its early discovery, our knowledge about the role of human DCXR in normal physiology and pathophysiology is still incomplete. Sporadic studies have demonstrated aberrant expression in several cancers, but their physiological significance is unknown. In reproductive medicine, where DCXR is commonly referred to as 'sperm surface protein P34H', it serves as marker for epididymal sperm maturation and is essential for gamete interaction and successful fertilization. DCXR exhibits a multifunctional nature, both acting as a carbonyl reductase and also performing non-catalytic functions, possibly resulting from interactions with other proteins. Recent observations associate DCXR with a role in cell adhesion, pointing to a novel function involving tumour progression and possibly metastasis. This review summarizes the current knowledge about human DCXR and its orthologs from mouse and Caenorhabditis elegans (DHS-21) with an emphasis on its multifunctional characteristics. Due to its close structural relationship with DCXR, carbonyl reductase 2 (Cbr2), a tetrameric enzyme found in several non-primate species is also discussed. Similar to human DCXR, Cbr2 from golden hamster (P26h) and cow (P25b) is essential for sperm-zona pellucida interaction and fertilization. Because of the apparent similarity of these two proteins and the inconsistent use of alternative names previously, we provide an overview of the systematic classification of DCXR and Cbr2 and a phylogenetic analysis to illustrate their ancestry.

  15. An Epididymis-Specific Secretory Protein HongrES1 Critically Regulates Sperm Capacitation and Male Fertility

    PubMed Central

    Zhou, Yuchuan; Zheng, Min; Shi, Qixian; Zhang, Li; Zhen, Wei; Chen, Wenying; Zhang, Yonglian

    2008-01-01

    Mammalian sperm capacitation is an essential prerequisite to fertilizion. Although progress had been made in understanding the physiology and biochemistry of capacitation, little is known about the potential roles of epididymal proteins during this process. Here we report that HongrES1, a new member of the SERPIN (serine proteinase inhibitor) family exclusively expressed in the rat cauda epididymis and up-regulated by androgen, is secreted into the lumen and covers the sperm head. Co-culture of caudal sperms with HongrES1 antibody in vitro resulted in a significant increase in the percentage of capacitated spermatozoa. Furthermore, the percentage of capacitated spermatozoa clearly increased in rats when HongrES1 was down-regulated by RNAi in vivo. Remarkably, knockdown of HongrES1 in vivo led to reduced fertility accompanied with deformed appearance of fetuses and pups. These results identify HongrES1 as a novel and critical molecule in the regulation of sperm capacitation and male fertility. PMID:19116669

  16. Sequencing and annotation of the chloroplast DNAs and identification of polymorphisms distinguishing normal male-fertile and male-sterile cytoplasms of onion.

    PubMed

    von Kohn, Christopher; Kiełkowska, Agnieszka; Havey, Michael J

    2013-12-01

    Male-sterile (S) cytoplasm of onion is an alien cytoplasm introgressed into onion in antiquity and is widely used for hybrid seed production. Owing to the biennial generation time of onion, classical crossing takes at least 4 years to classify cytoplasms as S or normal (N) male-fertile. Molecular markers in the organellar DNAs that distinguish N and S cytoplasms are useful to reduce the time required to classify onion cytoplasms. In this research, we completed next-generation sequencing of the chloroplast DNAs of N- and S-cytoplasmic onions; we assembled and annotated the genomes in addition to identifying polymorphisms that distinguish these cytoplasms. The sizes (153 538 and 153 355 base pairs) and GC contents (36.8%) were very similar for the chloroplast DNAs of N and S cytoplasms, respectively, as expected given their close phylogenetic relationship. The size difference was primarily due to small indels in intergenic regions and a deletion in the accD gene of N-cytoplasmic onion. The structures of the onion chloroplast DNAs were similar to those of most land plants with large and small single copy regions separated by inverted repeats. Twenty-eight single nucleotide polymorphisms, two polymorphic restriction-enzyme sites, and one indel distributed across 20 chloroplast genes in the large and small single copy regions were selected and validated using diverse onion populations previously classified as N or S cytoplasmic using restriction fragment length polymorphisms. Although cytoplasmic male sterility is likely associated with the mitochondrial DNA, maternal transmission of the mitochondrial and chloroplast DNAs allows for polymorphisms in either genome to be useful for classifying onion cytoplasms to aid the development of hybrid onion cultivars.

  17. Deficiency of Mkrn2 causes abnormal spermiogenesis and spermiation, and impairs male fertility

    PubMed Central

    Qian, Xu; Wang, Lin; Zheng, Bo; Shi, Zhu-Mei; Ge, Xin; Jiang, Cheng-Fei; Qian, Ying-Chen; Li, Dong-Mei; Li, Wei; Liu, Xue; Yin, Yu; Zheng, Ji-Tai; Shen, Hua; Wang, Min; Guo, Xue-Jiang; He, Jun; Lin, Marie; Liu, Ling-Zhi; Sha, Jia-Hao; Jiang, Bing-Hua

    2016-01-01

    Although recent studies have shed insights on some of the potential causes of male infertility, new underlining molecular mechanisms still remain to be elucidated. Makorin-2 (Mkrn2) is an evolutionarily conserved gene whose biological functions are not fully known. We developed an Mrkn2 knockout mouse model to study the role of this gene, and found that deletion of Mkrn2 in mice led to male infertility. Mkrn2 knockout mice produced abnormal sperms characterized by low number, poor motility, and aberrant morphology. Disruption of Mkrn2 also caused failure of sperm release (spermiation failure) and misarrangement of ectoplasmic specialization (ES) in testes, thus impairing spermiogenesis and spermiation. To understand the molecular mechanism, we found that expression of Odf2, a vital protein in spermatogenesis, was significantly decreased. In addition, we found that expression levels of Odf2 were decreased in Mkrn2 knockout mice. We also found that MKRN2 was prominently expressed in the sperm of normal men, but was significantly reduced in infertile men. This result indicates that our finding is clinically relevant. The results of our study provided insights into a new mechanism of male infertility caused by the MKRN2 downregulation. PMID:28008940

  18. Occupational exposure to pesticides and consequences on male semen and fertility: a review.

    PubMed

    Mehrpour, Omid; Karrari, Parissa; Zamani, Nasim; Tsatsakis, Aristides M; Abdollahi, Mohammad

    2014-10-15

    Exposure to pesticides affects many body organs including reproductive system. Disorder of the reproductive system leads to infertility and therefore has been in the center of attention within the recent decades. Pesticides are one of the compounds that might reduce the semen quality in the exposed workers according to current knowledge. Although many underlying mechanisms have been proposed, the mechanisms of action are not clarified yet. The object of the present review was to criticize all the results of studies which evaluated the pesticide effects on male reproductive system. Results indicate that semen changes are multifactorial in the workers exposed to pesticides as there are numerous factors affecting sperm quality in occupational exposures. Majority of pesticides including organophosphoruses affect the male reproductive system by mechanisms such as reduction of sperm density and motility, inhibition of spermatogenesis, reduction of testis weights, reduction of sperm counts, motility, viability and density, and inducing sperm DNA damage, and increasing abnormal sperm morphology. Reduced weight of testes, epididymis, seminal vesicle, and ventral prostate, seminiferous tubule degeneration, change in plasma levels of testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH), decreased level and activity of the antioxidant enzymes in testes, and inhibited testicular steroidogenesis are other possible mechanisms. Moreover, DDT and its metabolites have estrogenic effects on males. Although effect of pesticides on sperm quality is undeniable, well-designed long-term studies are needed to elucidate all the possible affecting variables such as socioeconomic, cultural, nutritional, occupational, physical, and clinical characteristics alongside pesticides.

  19. Courtship raises male fertilization success through post-mating sexual selection in a spider.

    PubMed

    Schneider, Jutta M; Lesmono, Kristiani

    2009-09-07

    Courtship is well known for its positive effects on mating success. However, in polyandrous species, sexual selection continues to operate after copulation. Cryptic female choice is expected under unpredictable mating rates in combination with sequential mate encounters. However, there are very few accounts of the effects of courtship on cryptic female choice, and the available evidence is often correlative. Mature Argiope bruennichi females are always receptive and never attack or reject males before mating, although sexual cannibalism after mating occurs regularly. Still, males usually perform an energetic vibratory display prior to copulation. We tested the hypothesis that beneficial effects of courtship arise cryptically, during or after mating, resulting in increased paternity success under polyandry. Manipulating courtship duration experimentally, we found that males that mated without display had a reduced paternity share even though no differences in post-copulatory cannibalism or copulation duration were detected. This suggests that the paternity advantage associated with courtship arose through female-mediated processes after intromission, meeting the definition of cryptic female choice.

  20. RAB-Like 2 Has an Essential Role in Male Fertility, Sperm Intra-Flagellar Transport, and Tail Assembly

    PubMed Central

    Lo, Jennifer C. Y.; Jamsai, Duangporn; O'Connor, Anne E.; Borg, Claire; Clark, Brett J.; Whisstock, James C.; Field, Mark C.; Adams, Vicki; Ishikawa, Tomomoto; Aitken, R. John; Whittle, Belinda; Goodnow, Christopher C.; Ormandy, Christopher J.; O'Bryan, Moira K.

    2012-01-01

    A significant percentage of young men are infertile and, for the majority, the underlying cause remains unknown. Male infertility is, however, frequently associated with defective sperm motility, wherein the sperm tail is a modified flagella/cilia. Conversely, a greater understanding of essential mechanisms involved in tail formation may offer contraceptive opportunities, or more broadly, therapeutic strategies for global cilia defects. Here we have identified Rab-like 2 (RABL2) as an essential requirement for sperm tail assembly and function. RABL2 is a member of a poorly characterized clade of the RAS GTPase superfamily. RABL2 is highly enriched within developing male germ cells, where it localizes to the mid-piece of the sperm tail. Lesser amounts of Rabl2 mRNA were observed in other tissues containing motile cilia. Using a co-immunoprecipitation approach and RABL2 affinity columns followed by immunochemistry, we demonstrated that within developing haploid germ cells RABL2 interacts with intra-flagella transport (IFT) proteins and delivers a specific set of effector (cargo) proteins, including key members of the glycolytic pathway, to the sperm tail. RABL2 binding to effector proteins is regulated by GTP. Perturbed RABL2 function, as exemplified by the Mot mouse line that contains a mutation in a critical protein–protein interaction domain, results in male sterility characterized by reduced sperm output, and sperm with aberrant motility and short tails. Our data demonstrate a novel function for the RABL protein family, an essential role for RABL2 in male fertility and a previously uncharacterised mechanism for protein delivery to the flagellum. PMID:23055941

  1. Impaired male fertility and atrophy of seminiferous tubules caused by haploinsufficiency for Foxa3

    PubMed Central

    Behr, Rüdiger; Sackett, Sara D.; Bochkis, Irina M.; Le, Phillip Phuc; Kaestner, Klaus H.

    2007-01-01

    Foxa1, 2 and 3 (formerly HNF-3α, -β and -γ) constitute a sub-family of winged helix transcription factors with multiple roles in mammalian organ development. While all three Foxa mRNAs are present in endoderm derivatives including liver and pancreas, only Foxa3 is expressed in the testis. Here we demonstrate by genetic lineage tracing that Foxa3 is expressed in postmeiotic germ and interstitial Leydig cells. The germinal epithelium of Foxa3-deficient testes is characterized by a loss of germ cells secondary to an increase in germ cell apoptosis that ultimately leads to a Sertoli cell-only syndrome. Remarkably, not only the Foxa3−/− mice but also Foxa3+/− mice exhibited loss of germ cells. This cellular phenotype caused significantly reduced fertility and testis weight of both Foxa3−/− and Foxa3+/− mice. Using microarray analysis, we found a dramatic downregulation of the zinc finger protein 93 and the testicular tumor-associated paraneoplastic Ma antigen (PNMA) and increased expression of a number of genes including zinc finger protein 94 and several kallikrein 1-related peptidases which could account for at least part of the observed phenotype. In summary, we have identified Foxa3 as a transcriptional regulator with a dominant phenotype in germ cell maintenance and suggest FOXA3 as a potential candidate gene for subfertility in man. PMID:17488644

  2. Sensibility of male rats fertility against olive oil, Nigella sativa oil and pomegranate extract

    PubMed Central

    Mansour, Sherif W.; Sangi, Sibghatullah; Harsha, Sree; Khaleel, Mueen A.; Ibrahim, A. R. N.

    2013-01-01

    Objective To clarify the modulatory effects of daily consumption of pomegranate extract (PE), olive oil (OO) and Nagilla sativa oil (NSO) on antioxidant activity, sperm quality and pituitary-testicular axis of adult male wistar rats. Methods Thirty-two adult male Wistar rats were divided into four equal groups, eight rats each. Using rat gastric tubes, 1.0 mL distilled water, 1.0 mL PE, 0.4 mL NSO and 0.4 mL OO were orally administered daily for 6 weeks in the first, second, third and fourth groups, respectively. Reproductive organs, body weight, sperm criteria, testosterone, FSH, LH, inhibin-B, lipid peroxidation, and antioxidant enzyme activities were investigated. At the end of the study protocol, analyses occurred at the same time. Data were analysed by ANOVA test and P<0.05 was considered to be a significant value. Results In all studied groups, malondialdehyde level was significantly decreased accompanied with an increases in glutathione peroxidase and glutathione. Rats treated with PE showed an increase in catalase activities accompanied with an increase in sperm concentration which was also observed in NSO group. In PE treated group, sperm motility was also increased accompanied with decreased abnormal sperm rate. NSO, OO and PE treated groups shows an insignificant effect on testosterone, inhibin-B, FSH and LH in comparison with control group. Conclusions These results show that administration of PE, NSO and OO could modify sperm characteristics and antioxidant activity of adult male wistar rats. PMID:23836459

  3. CTCF contributes in a critical way to spermatogenesis and male fertility

    PubMed Central

    Hernández-Hernández, Abrahan; Lilienthal, Ingrid; Fukuda, Nanaho; Galjart, Niels; Höög, Christer

    2016-01-01

    The CCCTC-binding factor (CTCF) is an architectural protein that governs chromatin organization and gene expression in somatic cells. Here, we show that CTCF regulates chromatin compaction necessary for packaging of the paternal genome into mature sperm. Inactivation of Ctcf in male germ cells in mice (Ctcf-cKO mice) resulted in impaired spermiogenesis and infertility. Residual spermatozoa in Ctcf-cKO mice displayed abnormal head morphology, aberrant chromatin compaction, impaired protamine 1 incorporation into chromatin and accelerated histone depletion. Thus, CTCF regulates chromatin organization during spermiogenesis, contributing to the functional organization of mature sperm. PMID:27345455

  4. A Young Drosophila Duplicate Gene Plays Essential Roles in Spermatogenesis by Regulating Several Y-Linked Male Fertility Genes

    PubMed Central

    Yang, Shuang; Jiang, Yu; Chen, Yuan; Zhao, Ruoping; Zhang, Yue; Zhang, Guojie; Dong, Yang; Yu, Haijing; Zhou, Qi; Wang, Wen

    2010-01-01

    Gene duplication is supposed to be the major source for genetic innovations. However, how a new duplicate gene acquires functions by integrating into a pathway and results in adaptively important phenotypes has remained largely unknown. Here, we investigated the biological roles and the underlying molecular mechanism of the young kep1 gene family in the Drosophila melanogaster species subgroup to understand the origin and evolution of new genes with new functions. Sequence and expression analysis demonstrates that one of the new duplicates, nsr (novel spermatogenesis regulator), exhibits positive selection signals and novel subcellular localization pattern. Targeted mutagenesis and whole-transcriptome sequencing analysis provide evidence that nsr is required for male reproduction associated with sperm individualization, coiling, and structural integrity of the sperm axoneme via regulation of several Y chromosome fertility genes post-transcriptionally. The absence of nsr-like expression pattern and the presence of the corresponding cis-regulatory elements of the parental gene kep1 in the pre-duplication species Drosophila yakuba indicate that kep1 might not be ancestrally required for male functions and that nsr possibly has experienced the neofunctionalization process, facilitated by changes of trans-regulatory repertories. These findings not only present a comprehensive picture about the evolution of a new duplicate gene but also show that recently originated duplicate genes can acquire multiple biological roles and establish novel functional pathways by regulating essential genes. PMID:21203494

  5. The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice

    PubMed Central

    Hou, Siyuan; Xian, Li; Shi, Peiliang; Li, Chaojun; Lin, Zhaoyu; Gao, Xiang

    2016-01-01

    While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress. PMID:27226137

  6. The SLO3 sperm-specific potassium channel plays a vital role in male fertility

    PubMed Central

    Santi, Celia M; Martínez-López, Pablo; de la Vega-Beltrán, José Luis; Butler, Alice; Alisio, Arturo; Darszon, Alberto; Salkoff, Lawrence

    2010-01-01

    Here we show a unique example of male infertility conferred by a gene knock-out of the sperm-specific, pH-dependent SLO3 potassium channel. In striking contrast to wild-type sperm which undergo membrane hyperpolarization during capacitation, we found that SLO3 mutant sperm undergo membrane depolarization. Several defects in SLO3 mutant sperm are evident under capacitating conditions, including impaired motility, a bent “hairpin” shape, and failure to undergo the acrosome reaction (AR). The failure of AR is rescued by valinomycin which hyperpolarizes mutant sperm. Thus SLO3 is the principal potassium channel responsible for capacitation-induced hyperpolarization, and membrane hyperpolarization is crucial to the AR. PMID:20138882

  7. Rab geranylgeranyl transferase β subunit is essential for male fertility and tip growth in Arabidopsis.

    PubMed

    Gutkowska, Malgorzata; Wnuk, Marta; Nowakowska, Julita; Lichocka, Malgorzata; Stronkowski, Michal M; Swiezewska, Ewa

    2015-01-01

    Rab proteins, key players in vesicular transport in all eukaryotic cells, are post-translationally modified by lipid moieties. Two geranylgeranyl groups are attached to the Rab protein by the heterodimeric enzyme Rab geranylgeranyl transferase (RGT) αβ. Partial impairment in this enzyme activity in Arabidopsis, by disruption of the AtRGTB1 gene, is known to influence plant stature and disturb gravitropic and light responses. Here it is shown that mutations in each of the RGTB genes cause a tip growth defect, visible as root hair and pollen tube deformations. Moreover, FM 1-43 styryl dye endocytosis and recycling are affected in the mutant root hairs. Finally, it is demonstrated that the double mutant, with both AtRGTB genes disrupted, is non-viable due to absolute male sterility. Doubly mutated pollen is shrunken, has an abnormal exine structure, and shows strong disorganization of internal membranes, particularly of the endoplasmic reticulum system.

  8. Overexpressing the Multiple-Stress Responsive Gene At1g74450 Reduces Plant Height and Male Fertility in Arabidopsis thaliana

    PubMed Central

    Visscher, Anne M.; Belfield, Eric J.; Vlad, Daniela; Irani, Niloufer; Moore, Ian; Harberd, Nicholas P.

    2015-01-01

    A subset of genes in Arabidopsis thaliana is known to be up-regulated in response to a wide range of different environmental stress factors. However, not all of these genes are characterized as yet with respect to their functions. In this study, we used transgenic knockout, overexpression and reporter gene approaches to try to elucidate the biological roles of five unknown multiple-stress responsive genes in Arabidopsis. The selected genes have the following locus identifiers: At1g18740, At1g74450, At4g27652, At4g29780 and At5g12010. Firstly, T-DNA insertion knockout lines were identified for each locus and screened for altered phenotypes. None of the lines were found to be visually different from wildtype Col-0. Secondly, 35S-driven overexpression lines were generated for each open reading frame. Analysis of these transgenic lines showed altered phenotypes for lines overexpressing the At1g74450 ORF. Plants overexpressing the multiple-stress responsive gene At1g74450 are stunted in height and have reduced male fertility. Alexander staining of anthers from flowers at developmental stage 12–13 showed either an absence or a reduction in viable pollen compared to wildtype Col-0 and At1g74450 knockout lines. Interestingly, the effects of stress on crop productivity are most severe at developmental stages such as male gametophyte development. However, the molecular factors and regulatory networks underlying environmental stress-induced male gametophytic alterations are still largely unknown. Our results indicate that the At1g74450 gene provides a potential link between multiple environmental stresses, plant height and pollen development. In addition, ruthenium red staining analysis showed that At1g74450 may affect the composition of the inner seed coat mucilage layer. Finally, C-terminal GFP fusion proteins for At1g74450 were shown to localise to the cytosol. PMID:26485022

  9. Critical Roles of Vacuolar Invertase in Floral Organ Development and Male and Female Fertilities Are Revealed through Characterization of GhVIN1-RNAi Cotton Plants1[OPEN

    PubMed Central

    2016-01-01

    Seed number and quality are key traits determining plant fitness and crop yield and rely on combined competence in male and female fertilities. Sucrose metabolism is central to reproductive success. It remains elusive, though, how individual sucrose metabolic enzymes may regulate the complex reproductive processes. Here, by silencing vacuolar invertase (VIN) genes in cotton (Gossypium hirsutum) reproductive organs, we revealed diverse roles that VIN plays in multiple reproductive processes. A set of phenotypic and genetic studies showed significant reductions of viable seeds in GhVIN1-RNAi plants, attributed to pollination failure and impaired male and female fertilities. The former was largely owing to the spatial mismatch between style and stamen and delayed pollen release from the anthers, whereas male defects came from poor pollen viability. The transgenic stamen exhibited altered expression of the genes responsible for starch metabolism and auxin and jasmonic acid signaling. Further analyses identified the reduction of GhVIN expression in the seed coat as the major cause for the reduced female fertility, which appeared to disrupt the expression of some key genes involved in trehalose and auxin metabolism and signaling, leading to programmed cell death or growth repression in the filial tissues. Together, the data provide an unprecedented example of how VIN is required to synchronize style and stamen development and the formation of male and female fertilities for seed development in a crop species, cotton. PMID:26969720

  10. Decreased Implantation Number After In Utero Artificial Insemination Can Reflect an Impairment of Fertility in Adult Male Rats After Exogenous Leptin Exposure.

    PubMed

    Fernandez, Carla D B; Fernandes, Glaura S A; Favareto, Ana Paula A; Perobelli, Juliana E; Sanabria, Marciana; Kempinas, Wilma D G

    2017-02-01

    Leptin is a protein secreted by the adipocytes, which serves as a link between fat and brain. Its main action is to decrease appetite and increase energy expenditure, but it is also involved in the control of different neuroendocrine systems, including gonadal axis. Although the effects of leptin deficiency on reproduction are well recognized, the effect of excess leptin on male reproductive function is not clear. The aim of this study was to evaluate fertility and sperm parameters of male rats exposed to exogenous leptin. A group of adult male rats received exogenous leptin intraperitoneally (30 μg/kg/day) for 42 days, and a control group received only the vehicle during the same period. After the treatment, animals were evaluated for sperm count, sperm motility, and fertility after intrauterine artificial insemination. There was no statistically significant difference between the groups related to sperm production, sperm concentration, and sperm motility. However, fertility evaluation after artificial insemination showed a quantitative decrease in the uterus plus fetuses weight, number of implantation sites, and number of live fetuses. The fertility potential showed a reduction of about 40%, whereas the preimplantation loss rate increased more than 2-fold in leptin-treated animals. In conclusion, leptin administration to nonobese male rats impairs ability of treated animals to generate offspring, since the occurrence of implantation was diminished. So leptin can impair sperm quality, affecting the reproductive capacity.

  11. Effect of Vitamin C on Male Fertility in Rats Subjected to Forced Swimming Stress

    PubMed Central

    BB, Ghongane; BB, Nayak

    2014-01-01

    Introduction: Stress is defined as a general body response to initially threatening external or internal demands, involving the mobilization of physiological and psychological resources to deal with them. Recently, oxidative stress has become the focus of interest as a potential cause of male infertility. Normally, equilibrium exists between reactive oxygen species (ROS) production and antioxidant scavenging activities in the male reproductive organs. The ascorbic acid is a known antioxidant present in the testis with the precise role of protecting the latter from the oxidative damage. It also contributes to the support of spermatogensis at least in part through its capacity to maintain antioxidant in an active state. Materials and Methods: Group1: Normal Control animal received Distilled water, Group 2: Positive control (Only Stress), Group 3: Normal rats received an intermediate dose of Vitamin C (20mg/kg/day), Group 4: Stress + Low dose Vitamin C (10mg/kg/day), Group 5: Stress+ Intermediate dose Vitamin C (20mg/kg/day), Group 6: High dose Vitamin C (30mg/kg/day). On 16th day effect of stress on body weight, Reproductive organ weight, sperm parameters, and hormonal assay was studied. Results: In the present context, in stress group the sperm count, motility, testicular weight declined significantly. The intermediate dose and high dose of vitamin C showed significantly increased effect on the sperm count and motility. Conclusion: Various physiological changes produced force swimming indicates that swimming is an effective model for producing stress in albino rats. The results suggest that Vitamin C supplementation improves the stress induced reproductive infertility due to both their testosterone increase effect and their antioxidant effect. PMID:25177581

  12. What is harmful for male fertility: cell phone or the wireless Internet?

    PubMed

    Yildirim, Mehmet Erol; Kaynar, Mehmet; Badem, Huseyin; Cavis, Mucahıt; Karatas, Omer Faruk; Cimentepe, Ersın

    2015-09-01

    In this study, we aimed to assess the potential harmful effects of radiofrequency-electromagnetic radiation on sperm parameters. We requested semen for analyses from the male patients coming to our infertility division and also asked them to fill out an anonymous questionnaire. We queried their mobile phone and wireless Internet usage frequencies in order to determine their radiofrequency-electromagnetic radiation exposure. A total of 1082 patients filled the questionnaire but 51 of them were excluded from the study because of azoospermia. There was no significant difference between sperm counts and sperm morphology excluding sperm motility, due to mobile phone usage period, (p = 0.074, p = 0.909, and p = 0.05, respectively). The total motile sperm count and the progressive motile sperm count decreased due to the increase of internet usage (p = 0.032 and p = 0.033, respectively). In line with the total motile sperm count, progressive motile sperm count also decreased with wireless Internet usage compared with the wired Internet connection usage (p = 0.009 and p = 0.018, respectively). There was a negative correlation between wireless Internet usage duration and the total sperm count (r = -0.089, p = 0.039). We have also explored the negative effect of wireless Internet use on sperm motility according to our preliminary results.

  13. Leukocytes and oxidative stress: dilemma for sperm function and male fertility

    PubMed Central

    Henkel, Ralf R

    2011-01-01

    Spermatozoa are constantly exposed to the interphase between oxidation through high amounts of reactive oxygen species (ROS) and leukocytes, and reduction by means of scavengers and antioxidants. Considering the very special functions as being the only cells with such high polarization and exerting their functions outside the body, even in a different individual, the female genital tract, the membranes of these cells are chemically composed of an extraordinary high amount of polyunsaturated fatty acids. This in turn, renders them very susceptible to oxidative stress, which is defined as an imbalance between oxidation and reduction towards the oxidative status. As a result, ROS deriving from both leukocytes and the male germ cells themselves cause a process called ‘lipid peroxidation' and other damages to the sperm cell. On the other hand, a certain limited amount of ROS is essential in order to trigger vital physiological reactions in cells, including capacitation or the acrosome reaction in sperm. The treatment of patients with antioxidants to compensate the oxidative status caused by oxidative stress is highly debated as uncontrolled antioxidative treatment might derail the system towards the reduced status, which is also unphysiological and can even induce cancer. This paradox is called the ‘antioxidant paradox'. Therefore, a proper andrological diagnostic work-up, including the evaluation of ROS levels and the antioxidant capacity of the semen, has to be carried out beforehand, aimed at keeping the fine balance between oxidation and scavenging of vital amounts of ROS. PMID:21076433

  14. Protective Effect of Royal Jelly on In Vitro Fertilization (IVF) in Male Mice Treated with Oxymetholone

    PubMed Central

    Zahmatkesh, Ensieh; Najafi, Gholamreza; Nejati, Vahid

    2015-01-01

    Objective This study aimed to investigate the effects of royal jelly (RJ) on catalase, total antioxidant capacity and embryo development in adult mice treated with oxymetholone (OXM). Materials and Methods In this exprimental study, 32 male and 96 female adult Naval Medical Research Institute (NMRI) mice (7-9 weeks of age) with a ratio of 1:3 for fertili- zation purposes were randomly divided into 4 groups as follows: i. Control group (n=8) receiving 0.1 ml/mice saline daily by gavage for 30 day, ii. RJ group (n=8) treated with RJ at a dose of 100 mg/kg daily by gavage for 30 days, iii. OXM group (n=8) receiving OXM at the dose of 5 mg/kg daily by gavage for 30 days and iv. RJ+OXM group (n=8) receiving RJ at the dose of 100 mg/kg daily by gavage concomitant with 100 mg/kg OXM adminis- tration for 30 days. Results Analysis revealed a significant reduction in catalase, total antioxidant, as well as embryo development in OXM group (P<0.05). However, RJ group showed a salient recovery in the all of the above mentioned parameters and embryo toxicity. Conclusion The results of this study indicated a partially protective effect of RJ against OXM-induced embryo toxicity. PMID:26464831

  15. Paternal obesity negatively affects male fertility and assisted reproduction outcomes: a systematic review and meta-analysis.

    PubMed

    Campbell, Jared M; Lane, Michelle; Owens, Julie A; Bakos, Hassan W

    2015-11-01

    This systematic review investigated the effect of paternal obesity on reproductive potential. Databases searched were Pubmed, Ovid, Web of Science, Scopus, Cinahl and Embase. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Outcomes were: likelihood of infertility, embryo development, clinical pregnancy, live birth, pregnancy viability, infant development, sperm; concentration, morphology, motility, volume, DNA fragmentation, chromatin condensation, mitochondrial membrane potential (MMP), and seminal plasma factors. Thirty papers were included, with a total participant number of 115,158. Obese men were more likely to experience infertility (OR = 1.66, 95% CI 1.53-1.79), their rate of live birth per cycle of assisted reproduction technology (ART) was reduced (OR = 0.65, 95% CI 0.44-0.97) and they had a 10% absolute risk increase of pregnancy non-viability. Additionally, obese men had an increased percentage of sperm with low MMP, DNA fragmentation, and abnormal morphology. Clinically significant differences were not found for conventional semen parameters. From these findings it can be concluded that male obesity is associated with reduced reproductive potential. Furthermore, it may be informative to incorporate DNA fragmentation analysis and MMP assessment into semen testing, especially for obese men whose results suggest they should have normal fertility.

  16. Low temperatures are required to induce the development of fertile flowers in transgenic male and female early flowering poplar (Populus tremula L.).

    PubMed

    Hoenicka, Hans; Lehnhardt, Denise; Briones, Valentina; Nilsson, Ove; Fladung, Matthias

    2016-05-01

    Until now, artificial early flowering poplar systems have mostly led to the development of sterile flowers. In this study, several strategies aimed at inducting fertile flowers in pHSP::AtFT transgenic poplar were evaluated, in particular the influence of temperature and photoperiod. Our results provide evidence that temperature, and not photoperiod, is the key factor required for the development of fertile flowers in early flowering poplar. Fertile flowers were only obtained when a cold treatment phase of several weeks was used after the heat treatment phase. Heat treatments induced AtFT gene activity through activation of the heat-shock promoter (pHSP). Photoperiod did not show a similar influence on flower fertility as pollen grains were obtained under both long- and short-day conditions. Fertility was confirmed in flowers of both male and female plants. For the first time, crosses were successfully performed with transgenic female early flowering poplar. All mature flowers obtained after 8 weeks of inductive treatments were fertile. Gene expression studies also confirmed that cold temperatures influenced expression of poplar genes homologous to 'pollen development genes' from Arabidopsis thaliana (L.) Heynh. Homology and expression patterns suggested a role for PtTDF1, PtBAM1, PtSERK1/2 and PtMS1 on anther and pollen development in poplar flowers. The system developed in this study allows a fast and very reliable induction of fertile poplar flowers in a very short period of time. The non-reproductive phase, usually 7-10 years, can now be shortened to 6-10 months, and fertile flowers can be obtained independently of the season. This system is a reliable tool for breeding purposes (high-speed breeding technology), genomics and biosafety research.

  17. [Isolation and identification of specific sequences correlated to cytoplasmic male sterility and fertile maintenance in cauliflower (Brassica oleracea var. botrytis)].

    PubMed

    Wang, Chun Guo; Chen, Xiao Qiang; Li, Hui; Zhao, Qian Cheng; Sun, De Ling; Song, Wen Qin

    2008-02-01

    significant information to investigate the molecular mechanism of cytoplasmic male sterility and fertile maintenance in cauliflower.

  18. Post-translational mechanisms are associated with fertility restoration of cytoplasmic male sterility in sugar beet (Beta vulgaris).

    PubMed

    Kitazaki, Kazuyoshi; Arakawa, Takumi; Matsunaga, Muneyuki; Yui-Kurino, Rika; Matsuhira, Hiroaki; Mikami, Tetsuo; Kubo, Tomohiko

    2015-07-01

    Genetic conflict between cytoplasmically inherited elements and nuclear genes arising from their different transmission patterns can be seen in cytoplasmic male sterility (CMS), the mitochondrion-encoded inability to shed functional pollen. CMS is associated with a mitochondrial open reading frame (ORF) that is absent from non-sterility inducing mitochondria (S-orf). Nuclear genes that suppress CMS are called restorer-of-fertility (Rf) genes. Post-transcriptional and translational repression of S-orf mediates the molecular action of Rf that encodes a class of RNA-binding proteins with pentatricopeptide repeat (PPR) motifs. Besides the PPR-type of Rfs, there are also non-PPR Rfs, but the molecular interactions between non-PPR Rf and S-orf have not been described. In this study, we investigated the interaction of bvORF20, a non-PPR Rf from sugar beet (Beta vulgaris), with preSatp6, the S-orf from sugar beet. Anthers expressing bvORF20 contained a protein that interacted with preSATP6 protein. Analysis of anthers and transgenic calli expressing a FLAG-tagged bvORF20 suggested the binding of preSATP6 to bvORF20. To see the effect of bvORF20 on preSATP6, which exists as a 250-kDa protein complex in CMS plants, signal bands of preSATP6 in bvORF20-expressing and non-expressing anthers were compared by immunoblotting combined with Blue Native polyacrylamide gel electrophoresis. The signal intensity of the 250-kDa band decreased significantly, and 200- and 150-kDa bands appeared in bvORF20-expressing anthers. Transgenic callus expressing bvORF20 also generated the 200- and 150-kDa bands. The 200-kDa complex is likely to include both preSATP6 and bvORF20. Post-translational interaction between preSATP6 and bvORF20 appears to alter the higher order structure of preSATP6 that may lead to fertility restoration in sugar beet.

  19. Detection of TEM-induced reciprocal translocations in F/sub 1/ sons of CD-1 male mice: comparison of sequential fertility evaluation and cytogenetic analysis

    SciTech Connect

    Morris, S.M.; Kodell, R.L.; Domon, O.E.; Bishop, J.B.

    1988-01-01

    To determine the positive and negative classification error rates associated with the HTA in our laboratory, F/sub 1/ sons of TEM-exposed CD-1 male mice were evaluated by the sequential fertility method with subsequent cytogenetic analysis. Males who sired three litters of size 10 or less when mated to primiparous females from either the B6C3F/sub 1/ or the BCF/sub 1/ strain were classified as partial steriles. When meiotic chromosomes analyses revealed the presence of at least two cells containing multivalent figures, males were classified as translocation heterozygotes. When the fertility evaluation and the cytogenetic analysis were compared, normal fertility was observed on 5 of 83 (6.02%) translocation-bearing F/sub 1/ males mated to B6C3F/sub 1/ tester females and on 3 of 83 (3.61%) F/sub 1/ males mated to BCF/sub 1/ tester females. Thus, the false-negative error rates were 6.02% and 3.61% with these two tester strains. Multivalent figures were not observed in the meiotic chromosomes of 410 F/sub 1/ males. The false-positive error rates with these two tester strains were 2.93% for the B6C3F/sub 1/ strain and 1.71% for the BCF/sub 1/ strain. The results indicate that nonzero error rates, both false-positive and false-negative, are associated with the sequential mating method HTA. In addition, the magnitude of these error rates was influenced not only by the tester female strain but also by the genotype of the F/sub 1/ male.

  20. ICSI treatment of severe male infertility can achieve prospective embryo quality compared with IVF of fertile donor sperm on sibling oocytes

    PubMed Central

    Zheng, Ju-Fen; Chen, Xiao-Bao; Zhao, Lei-Wen; Gao, Min-Zhi; Peng, Jie; Qu, Xian-Qin; Shi, Hui-Juan; Jin, Xing-Liang

    2015-01-01

    Azoospermia, cryptozoospermia and necrospermia can markedly decrease the ability of males to achieve pregnancy in fertile females. However, patients with these severe conditions still have the option to be treated by intracytoplasmic sperm injection (ICSI) to become biological fathers. This study analyzed the fertilization ability and the developmental viabilities of the derived embryos after ICSI treatment of the sperm from these patients compared with in vitro fertilization (IVF) treatment of the proven-fertile donor sperm on sibling oocytes as a control. On the day of oocyte retrieval, the number of sperm suitable for ICSI collected from two ejaculates or testicular sperm extraction was lower than the oocytes, and therefore, excess sibling oocytes were treated by IVF with donor sperm. From 72 couples (73 cycles), 1117 metaphase II oocytes were divided into 512 for ICSI and 605 for IVF. Compared with the control, husbands’ sperm produced a lower fertilization rate in nonobstructive azoospermia (65.4% vs 83.2%; P < 0.001), crytozoospermia (68.8% vs 75.5%; P < 0.05) and necrospermia (65.0% vs 85.2%; P < 0.05). The zygotes derived in nonobstructive azoospermia had a lower cleavage rate (96.4% vs 99.4%; P < 0.05), but the rate of resultant good-quality embryos was not different. Analysis of the rates of cleaved and good-quality embryos in crytozoospermia and necrospermia did not exhibit a significant difference from the control. In conclusion, although the sperm from severe male infertility reduced the fertilization ability, the derived embryos had potential developmental viabilities that might be predictive for the expected clinical outcomes. PMID:25652630

  1. ICSI treatment of severe male infertility can achieve prospective embryo quality compared with IVF of fertile donor sperm on sibling oocytes.

    PubMed

    Zheng, Ju-Fen; Chen, Xiao-Bao; Zhao, Lei-Wen; Gao, Min-Zhi; Peng, Jie; Qu, Xian-Qin; Shi, Hui-Juan; Jin, Xing-Liang

    2015-01-01

    Azoospermia, cryptozoospermia and necrospermia can markedly decrease the ability of males to achieve pregnancy in fertile females. However, patients with these severe conditions still have the option to be treated by intracytoplasmic sperm injection (ICSI) to become biological fathers. This study analyzed the fertilization ability and the developmental viabilities of the derived embryos after ICSI treatment of the sperm from these patients compared with in vitro fertilization (IVF) treatment of the proven-fertile donor sperm on sibling oocytes as a control. On the day of oocyte retrieval, the number of sperm suitable for ICSI collected from two ejaculates or testicular sperm extraction was lower than the oocytes, and therefore, excess sibling oocytes were treated by IVF with donor sperm. From 72 couples (73 cycles), 1117 metaphase II oocytes were divided into 512 for ICSI and 605 for IVF. Compared with the control, husbands' sperm produced a lower fertilization rate in nonobstructive azoospermia (65.4% vs 83.2%; P< 0.001), crytozoospermia (68.8% vs 75.5%; P< 0.05) and necrospermia (65.0% vs 85.2%; P< 0.05). The zygotes derived in nonobstructive azoospermia had a lower cleavage rate (96.4% vs 99.4%; P< 0.05), but the rate of resultant good-quality embryos was not different. Analysis of the rates of cleaved and good-quality embryos in crytozoospermia and necrospermia did not exhibit a significant difference from the control. In conclusion, although the sperm from severe male infertility reduced the fertilization ability, the derived embryos had potential developmental viabilities that might be predictive for the expected clinical outcomes.

  2. Short communication: A missense mutation in the PROP1 (prophet of Pit 1) gene affects male fertility and milk production traits in the US Holstein population.

    PubMed

    Lan, X Y; Peñagaricano, F; DeJung, L; Weigel, K A; Khatib, H

    2013-02-01

    In previous studies, we reported significant associations of the POU1F1 pathway genes with reproduction and production traits in several dairy cattle populations. Polymorphisms in genes of this pathway were found to be associated with both female and male fertility traits in dairy cattle. The POU1F1 gene is a direct downstream target for the regulation of the prophet of Pit1 (PROP1) gene, also known as PROP paired-like homeobox 1. Interestingly, the position of PROP1 coincides with a quantitative trait locus affecting ovulation rate in cattle. Therefore, the objective of this study was to investigate whether PROP1 affects fertility and milk production traits in Holstein cattle. Using the DNA pooling sequencing approach, a missense single nucleotide polymorphism that replaces a histidine amino acid with an arginine was detected in exon 3 of PROP1. The arginine allele was found to be associated with a decrease in sire conception rate and an increase in productive life, protein yield, and net merit index in a population of 1,951 Holstein bulls. The transcription factors produced from the histidine and arginine isoforms are known to have different transcription, DNA binding, and regulation activities. As such, we propose that the association of the arginine isoform with decreased bull fertility is likely caused by reduced activity of this allele in male functions. The findings of this study suggest PROP1 polymorphisms as candidates in selection programs for fertility, health, and milk production traits in dairy cattle.

  3. Optimizing Male Fertility

    MedlinePlus

    ... intercourse increases the chance of conception. Some commercial lubricants and other substances used for lubrication such as ... ability to survive. You may want to discuss lubricant choices with your doctor since there are a ...

  4. [Intermediate endpoints in clinical research].

    PubMed

    Peters, Sanne A E; Groenwold, Rolf H H; Bots, Michiel L

    2013-01-01

    An intermediate variable such as blood pressure is part of the causal pathway of mechanisms to a clinical outcome, e.g. myocardial infarction. An intervention affects a clinical outcome through its effect on that intermediate variable. In studies designed to assess the effects of interventions an intermediate variable may be used as surrogate for clinical outcomes. Such an endpoint is also known as an intermediate endpoint. Intervention studies with intermediate endpoints are commonly performed in medical research to evaluate the effects of an intervention on clinical outcomes. Intervention studies with an intermediate endpoint are conducted in a smaller study population and with a shorter duration of follow-up than studies using clinical outcomes. An intermediate variable is not eligible as an intermediate endpoint when the intervention also affects other biological mechanisms that subsequently affect the clinical endpoint. Due to a smaller sample size and shorter study duration, side effects of intervention are more difficult to evaluate in studies with an intermediate endpoint than in studies with clinical endpoints.

  5. Fertility treatment and reproductive health of male offspring: a study of 1,925 young men from the general population.

    PubMed

    Jensen, Tina Kold; Jørgensen, Niels; Asklund, Camilla; Carlsen, Elisabeth; Holm, Mette; Skakkebaek, Niels E

    2007-03-01

    Little is known the about the reproductive health of offspring after fertility treatment. In 2001-2005, the authors approached young Danish men attending a compulsory physical examination to determine their fitness for military service. A total of 1,925 men volunteered, delivered a semen sample, had a physical examination performed and a blood sample drawn, and responded to a questionnaire. Their mothers were questioned about whether they had received fertility treatment in order to conceive their sons. Forty-seven mothers reported having received fertility treatment to conceive the index subject. After control for confounders, men whose mothers had received fertility treatment to conceive them had a 46% lower sperm concentration (95% confidence interval (CI): -63, -20) and a 45% lower total sperm count (95% CI: -64, -16). They had a smaller testis size (-0.9 ml, 95% CI: -2.2, 0.4), fewer motile sperm (-4.0%, 95% CI: -8.0, -0.1), and fewer morphologically normal spermatozoa (-2.0%, 95% CI: -4.1, 0.0). They also had a lower serum testosterone level and free androgen index (results not statistically significant). These findings should be viewed in light of the increasing use of fertility treatments. Although the cause of these findings is unknown, they raise concern about possible late effects of fertility treatment. Larger-scale studies of children born after fertility treatment should be performed.

  6. Diet-Induced Obesity in Male Mice Is Associated with Reduced Fertility and Potentiation of Acrylamide-Induced Reproductive Toxicity1

    PubMed Central

    Ghanayem, Burhan I.; Bai, Re; Kissling, Grace E.; Travlos, Greg; Hoffler, Undi

    2009-01-01

    The prevalence of human obesity and related chronic disorders such as diabetes, cardiovascular diseases, and cancer is rapidly increasing. Human studies have shown a direct relationship between obesity and infertility. The objective of the current work was to examine the effect of diet-induced obesity on male fertility and the effect of obesity on susceptibility to chemical-induced reproductive toxicity. From 5 to 30 wk of age, genetically intact male C57Bl/6J mice were fed a normal diet or one in which 60% of the kilocalories were from lard. Obese mice exhibited significant differences in the mRNA of several genes within the testes in comparison to lean males. Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. The fertility of male mice was compared through mating with control females. Acrylamide (AA)-induced reproductive toxicity was assessed in obese or lean males treated with water or 25 mg AA kg−1 day−1 via gavage for 5 days and then mated to control females. Percent body fat and weight were significantly increased in mice fed a high-fat vs. a normal diet. Obesity resulted in significant reduction in plugs and pregnancies of control females partnered with obese vs. lean males. Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. Sperm from obese males exhibited decreased motility and reduced hyperactivated progression vs. lean mice. Treatment with AA exacerbated male infertility of obese and lean mice; however, this effect was more pronounced in obese mice. Further, females partnered with AA-treated obese mice exhibited a further decrease in the percentage of live fetuses, whereas the percentage of resorptions increased. This work demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity. PMID:19696015

  7. A Single Nucleotide Polymorphism within the Novel Sex-Linked Testis-Specific Retrotransposed PGAM4 Gene Influences Human Male Fertility

    PubMed Central

    Okuda, Hidenobu; Tsujimura, Akira; Irie, Shinji; Yamamoto, Keisuke; Fukuhara, Shinichiro; Matsuoka, Yasuhiro; Takao, Tetsuya; Miyagawa, Yasushi; Nonomura, Norio; Wada, Morimasa; Tanaka, Hiromitsu

    2012-01-01

    Background The development of novel fertilization treatments, including in vitro fertilization and intracytoplasmic injection, has made pregnancy possible regardless of the level of activity of the spermatozoa; however, the etiology of male-factor infertility is poorly understood. Multiple studies, primarily through the use of transgenic animals, have contributed to a list of candidate genes that may affect male infertility in humans. We examined single nucleotide polymorphisms (SNPs) as a cause of male infertility in an analysis of spermatogenesis-specific genes. Methods and Finding We carried out the prevalence of SNPs in the coding region of phosphoglycerate mutase 4 (PGAM4) on the X chromosome by the direct sequencing of PCR-amplified DNA from male patients. Using RT-PCR and western blot analyses, we identified that PGAM4 is a functional retrogene that is expressed predominantly in the testes and is associated with male infertility. PGAM4 is expressed in post-meiotic stages, including spermatids and spermatozoa in the testes, and the principal piece of the flagellum and acrosome in ejaculated spermatozoa. A case-control study revealed that 4.5% of infertile patients carry the G75C polymorphism, which causes an amino acid substitution in the encoded protein. Furthermore, an assay for enzymatic activity demonstrated that this polymorphism decreases the enzyme’s activity both in vitro and in vivo. Conclusion These results suggest that PGAM4, an X-linked retrogene, is a fundamental gene in human male reproduction and may escape meiotic sex chromosome inactivation. These findings provide fresh insight into elucidating the mechanisms of male infertility. PMID:22590500

  8. A Combined Approach to Heat Stress Effect on Male Fertility in Nasonia vitripennis: From the Physiological Consequences on Spermatogenesis to the Reproductive Adjustment of Females Mated with Stressed Males

    PubMed Central

    Chirault, Marlène; Lucas, Christophe; Goubault, Marlène; Chevrier, Claude

    2015-01-01

    In recent years, several studies have shown a decline in reproductive success in males in both humans and wildlife. Research on male fertility has largely focused on vertebrates, although invertebrates constitute the vast majority of terrestrial biodiversity. The reduction of their reproductive capacities due to environmental stresses can have strong negative ecological impacts, and also dramatic consequences on world food production if it affects the reproductive success of biological control agents, such as parasitic wasps used to control crop pests. Here Nasonia vitripennis, a parasitic wasp of various fly species, was studied to test the effects of 24h-heat stress applied during the first pupal stage on male fertility. Results showed that only primary spermatocytes were present at the first pupal stage in all cysts of the testes. Heat stress caused a delay in spermatogenesis during development and a significant decrease in sperm stock at emergence. Females mated with these heat-stressed males showed a reduce sperm count stored in their spermatheca. Females did not appear to distinguish heat-stressed from control males and did not remate more frequently to compensate for the lack of sperm transferred. As a result, females mated with heat-stressed males produced a suboptimal lifetime offspring sex ratio compared to those mated with control males. This could further impact the population dynamics of this species. N. vitripennis appears to be an interesting biological model to study the mechanisms of subfertility and its consequence on female reproductive strategies and provides new research perspectives in both invertebrates and vertebrates. PMID:25807005

  9. Identification of Amplified Fragment Length Polymorphism (AFLP) Markers Tightly Associated with Drought Stress Gene in Male Sterile and Fertile Salvia miltiorrhiza Bunge.

    PubMed

    Zhang, Yuejin; Guo, Lijun; Shu, Zhiming; Sun, Yiyue; Chen, Yuanyuan; Liang, Zongsuo; Guo, Hongbo

    2013-03-22

    Consistent grain yield in drought environment has attracted wide attention due to global climate change. However, the important drought-related traits/genes in crops have been rarely reported. Many near-isogenic lines (NILs) of male sterile and fertile Salvia miltiorrhiza have been obtained in our previous work through testcross and backcross in continuous field experiments conducted in 2006-2009. Both segregating sterile and fertile populations were subjected to bulked segregant analysis (BSA) and amplified fragment length polymorphism (AFLP) with 384 and 170 primer combinations, respectively. One out of 14 AFLP markers (E9/M3246) was identified in treated fertile population as tightly linked to the drought stress gene with a recombination frequency of 6.98% and at a distance of 7.02 cM. One of 15 other markers (E2/M5357) was identified in a treated sterile population that is closely associated with the drought stress gene. It had a recombination frequency of 4.65% and at a distance of 4.66 cM. Interestingly, the E9/M3246 fragment was found to be identical to another AFLP fragment E11/M4208 that was tightly linked to the male sterile gene of S. miltiorrhiza with 95% identity and e-value 4 × 10-93. Blastn analysis suggested that the drought stress gene sequence showed higher identity with nucleotides in Arabidopsis chromosome 1-5.

  10. Selective restoration of male fertility in mice lacking angiotensin-converting enzymes by sperm-specific expression of the testicular isozyme.

    PubMed Central

    Ramaraj, P; Kessler, S P; Colmenares, C; Sen, G C

    1998-01-01

    Although angiotensin-converting enzyme (ACE) has been studied primarily in the context of its role in blood pressure regulation, this widely distributed enzyme has many other physiological functions. The ACE gene encodes two isozymes. The somatic isozyme is expressed in many tissues, including vascular endothelial cells, renal epithelial cells, and testicular Leydig cells, whereas the testicular or germinal angiotensin-converting enzyme is expressed only in sperm. The ACE gene knockout mice lack both isozymes and they exhibit low blood pressure, kidney dysfunctions, and male infertility. Here, we report the use of a sperm-specific promoter and interbreeding of transgenic and gene knockout mice for generating a mouse strain that expressed ACE only in sperm. The experimental mice maintained the kidney defects of ACE-/- mice, but unlike the knockout strain, the males were fertile. Thus, we established that the role of ACE in male fertility is completely dependent on its exclusive expression in sperm. Our study clearly demonstrated how transgenic and knockout techniques can be combined for ascribing a specific physiological function to the expression of a multifunctional protein in a given tissue. PMID:9664078

  11. Expression of a Catalytically Inactive Mutant Form of Glutathione Peroxidase 4 (Gpx4) Confers a Dominant-negative Effect in Male Fertility.

    PubMed

    Ingold, Irina; Aichler, Michaela; Yefremova, Elena; Roveri, Antonella; Buday, Katalin; Doll, Sebastian; Tasdemir, Adrianne; Hoffard, Nils; Wurst, Wolfgang; Walch, Axel; Ursini, Fulvio; Friedmann Angeli, José Pedro; Conrad, Marcus

    2015-06-05

    The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation. Recently, the cytosolic form of Gpx4 was identified as an upstream regulator of a novel form of non-apoptotic cell death, called ferroptosis, whereas the mitochondrial isoform of Gpx4 was previously shown to be crucial for male fertility. Here, we generated and analyzed mice with a targeted mutation of the active site selenocysteine of Gpx4 (Gpx4_U46S). Mice homozygous for Gpx4_U46S died at the same embryonic stage (E7.5) as Gpx4(-/-) embryos as expected. Surprisingly, male mice heterozygous for Gpx4_U46S presented subfertility. Subfertility was manifested in a reduced number of litters from heterozygous breeding and an impairment of spermatozoa to fertilize oocytes in vitro. Morphologically, sperm isolated from heterozygous Gpx4_U46S mice revealed many structural abnormalities particularly in the spermatozoa midpiece due to improper oxidation and polymerization of sperm capsular proteins and malformation of the mitochondrial capsule surrounding and stabilizing sperm mitochondria. These findings are reminiscent of sperm isolated from selenium-deprived rodents or from mice specifically lacking mitochondrial Gpx4. Due to a strongly facilitated incorporation of Ser in the polypeptide chain as compared with selenocysteine at the UGA codon, expression of the catalytically inactive Gpx4_U46S was found to be strongly increased. Because the stability of the mitochondrial capsule of mature spermatozoa depends on the moonlighting function of Gpx4 both as an enzyme oxidizing capsular protein thiols and as a structural protein, tightly controlled expression of functional Gpx4 emerges as a key for full male fertility.

  12. Expression of a Catalytically Inactive Mutant Form of Glutathione Peroxidase 4 (Gpx4) Confers a Dominant-negative Effect in Male Fertility*

    PubMed Central

    Ingold, Irina; Aichler, Michaela; Yefremova, Elena; Roveri, Antonella; Buday, Katalin; Doll, Sebastian; Tasdemir, Adrianne; Hoffard, Nils; Wurst, Wolfgang; Walch, Axel; Ursini, Fulvio; Friedmann Angeli, José Pedro; Conrad, Marcus

    2015-01-01

    The selenoenzyme Gpx4 is essential for early embryogenesis and cell viability for its unique function to prevent phospholipid oxidation. Recently, the cytosolic form of Gpx4 was identified as an upstream regulator of a novel form of non-apoptotic cell death, called ferroptosis, whereas the mitochondrial isoform of Gpx4 was previously shown to be crucial for male fertility. Here, we generated and analyzed mice with a targeted mutation of the active site selenocysteine of Gpx4 (Gpx4_U46S). Mice homozygous for Gpx4_U46S died at the same embryonic stage (E7.5) as Gpx4−/− embryos as expected. Surprisingly, male mice heterozygous for Gpx4_U46S presented subfertility. Subfertility was manifested in a reduced number of litters from heterozygous breeding and an impairment of spermatozoa to fertilize oocytes in vitro. Morphologically, sperm isolated from heterozygous Gpx4_U46S mice revealed many structural abnormalities particularly in the spermatozoa midpiece due to improper oxidation and polymerization of sperm capsular proteins and malformation of the mitochondrial capsule surrounding and stabilizing sperm mitochondria. These findings are reminiscent of sperm isolated from selenium-deprived rodents or from mice specifically lacking mitochondrial Gpx4. Due to a strongly facilitated incorporation of Ser in the polypeptide chain as compared with selenocysteine at the UGA codon, expression of the catalytically inactive Gpx4_U46S was found to be strongly increased. Because the stability of the mitochondrial capsule of mature spermatozoa depends on the moonlighting function of Gpx4 both as an enzyme oxidizing capsular protein thiols and as a structural protein, tightly controlled expression of functional Gpx4 emerges as a key for full male fertility. PMID:25922076

  13. A nuclear restorer-of-fertility mutation disrupts accumulation of mitochondrial ATP synthase subunit alpha in developing pollen of S male-sterile maize.

    PubMed Central

    Wen, Lanying; Ruesch, Kimberly L; Ortega, Victor M; Kamps, Terry L; Gabay-Laughnan, Susan; Chase, Christine D

    2003-01-01

    Mitochondrial biogenesis and function depend upon the interaction of mitochondrial and nuclear genomes. Forward genetic analysis of mitochondrial function presents a challenge in organisms that are obligated to respire. In the S-cytoplasmic male sterility (CMS-S) system of maize, expression of mitochondrial open reading frames (orf355-orf77) conditions collapse of developing haploid pollen. Nuclear restorer-of-fertility mutations that circumvent pollen collapse are often homozygous lethal. These spontaneous mutations potentially result from disruption of nuclear genes required for mitochondrial gene expression, in contrast to homozygous-viable restorer-of-fertility alleles that function to block or compensate for the expression of mitochondrial CMS genes. Consistent with this hypothesis, the homozygous-lethal restoring allele historically designated RfIII was shown to be recessive in diploid pollen produced by tetraploid CMS-S plants. Accordingly, the symbol for this allele has been changed to restorer-of-fertility lethal 1 (rfl1). In haploid rfl1 pollen, orf355-orf77 transcripts and mitochondrial transcripts encoding the alpha-subunit of the ATP synthase (ATPA) were decreased in abundance. Haploid rfl1 pollen failed to accumulate wild-type levels of ATPA protein, indicating that functional requirements for mitochondrial protein accumulation are relaxed in maize pollen. The CMS-S system and rfl mutations therefore allow for the selection of nuclear mutations disrupting mitochondrial biogenesis in a multicellular eukaryote. PMID:14573487

  14. Mapping QTLs for Fertility Restoration of Different Cytoplasmic Male Sterility Types in Rice Using Two Oryza sativa ×O. rufipogon Backcross Inbred Line Populations.

    PubMed

    Hu, Biao-Lin; Xie, Jian-Kun; Wan, Yong; Zhang, Jin-Wei; Zhang, Fan-Tao; Li, Xia

    2016-01-01

    Hybrid rice breeding using cytoplasmic male sterility/fertility restoration (CMS/Rf) systems plays an important role in ensuring global food security. Two backcross inbred line (BIL) populations derived from either Xieqingzao B (XB)//XB/Dongxiang wild rice (DWR) (XXD) or XB//DWR/XB (XDX) were used to detect quantitative trait loci (QTLs) for fertility restoration of Dwarf wild abortive- (DA-), Indonesia Paddy- (ID-), and DWR-type CMS in rice. Lines with ID- and DA-type CMS were testcrossed with both the XXD- and XDX-BILs, while the line with DWR-type CMS was testcrossed with the XDX-BILs only. A total of 16 QTLs for fertility restoration of CMS systems were identified, including three for DWR-type CMS, six for DA-type CMS, and seven for ID-type CMS. All of the additive alleles in the QTLs were derived from Oryza rufipogon. Eleven QTLs were clustered in five chromosomal regions, indicating that common Rf loci restored different CMS systems, and the favorable O. rufipogon alleles could be used to develop restorer lines for various CMS types by marker-assisted selection.

  15. Mapping QTLs for Fertility Restoration of Different Cytoplasmic Male Sterility Types in Rice Using Two Oryza sativa ×O. rufipogon Backcross Inbred Line Populations

    PubMed Central

    Hu, Biao-lin; Wan, Yong; Zhang, Jin-wei; Zhang, Fan-tao; Li, Xia

    2016-01-01

    Hybrid rice breeding using cytoplasmic male sterility/fertility restoration (CMS/Rf) systems plays an important role in ensuring global food security. Two backcross inbred line (BIL) populations derived from either Xieqingzao B (XB)//XB/Dongxiang wild rice (DWR) (XXD) or XB//DWR/XB (XDX) were used to detect quantitative trait loci (QTLs) for fertility restoration of Dwarf wild abortive- (DA-), Indonesia Paddy- (ID-), and DWR-type CMS in rice. Lines with ID- and DA-type CMS were testcrossed with both the XXD- and XDX-BILs, while the line with DWR-type CMS was testcrossed with the XDX-BILs only. A total of 16 QTLs for fertility restoration of CMS systems were identified, including three for DWR-type CMS, six for DA-type CMS, and seven for ID-type CMS. All of the additive alleles in the QTLs were derived from Oryza rufipogon. Eleven QTLs were clustered in five chromosomal regions, indicating that common Rf loci restored different CMS systems, and the favorable O. rufipogon alleles could be used to develop restorer lines for various CMS types by marker-assisted selection. PMID:27872859

  16. Effects of x-ray irradiation on male navel orangeworm (Lepidoptera: Pyralidae) on mating, fecundity, fertility, and inherited sterility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Male adult navel orangeworm, Amyelois transitella, were irradiated using a laboratory x-ray emitter to determine the dose needed to achieve complete egg sterility of mated female moths and inherited egg sterility of F1 generation. Adult male A. transitella were irradiated in a series of two experime...

  17. ECHIDNA protein impacts on male fertility in Arabidopsis by mediating trans-Golgi network secretory trafficking during anther and pollen development.

    PubMed

    Fan, Xinping; Yang, Caiyun; Klisch, Doris; Ferguson, Alison; Bhaellero, Rishi P; Niu, Xiwu; Wilson, Zoe A

    2014-03-01

    The trans-Golgi network (TGN) plays a central role in cellular secretion and has been implicated in sorting cargo destined for the plasma membrane. Previously, the Arabidopsis (Arabidopsis thaliana) echidna (ech) mutant was shown to exhibit a dwarf phenotype due to impaired cell expansion. However, ech also has a previously uncharacterized phenotype of reduced male fertility. This semisterility is due to decreased anther size and reduced amounts of pollen but also to decreased pollen viability, impaired anther opening, and pollen tube growth. An ECH translational fusion (ECHPro:ECH-yellow fluorescent protein) revealed developmentally regulated tissue-specific expression, with expression in the tapetum during early anther development and microspore release and subsequent expression in the pollen, pollen tube, and stylar tissues. Pollen viability and production, along with germination and pollen tube growth, were all impaired. The ech anther endothecium secondary wall thickening also appeared reduced and disorganized, resulting in incomplete anther opening. This did not appear to be due to anther secondary thickening regulatory genes but perhaps to altered secretion of wall materials through the TGN as a consequence of the absence of the ECH protein. ECH expression is critical for a variety of aspects of male reproduction, including the production of functional pollen grains, their effective release, germination, and tube formation. These stages of pollen development are fundamentally influenced by TGN trafficking of hormones and wall components. Overall, this suggests that the fertility defect is multifaceted, with the TGN trafficking playing a significant role in the process of both pollen formation and subsequent fertilization.

  18. Surrogate Endpoints in Suicide Research

    ERIC Educational Resources Information Center

    Wortzel, Hal S.; Gutierrez, Peter M.; Homaifar, Beeta Y.; Breshears, Ryan E.; Harwood, Jeri E.

    2010-01-01

    Surrogate endpoints frequently substitute for rare outcomes in research. The ability to learn about completed suicides by investigating more readily available and proximate outcomes, such as suicide attempts, has obvious appeal. However, concerns with surrogates from the statistical science perspective exist, and mounting evidence from…

  19. Effect of chronic administration of 7alpha-methyl-19-nortestosterone on serum testosterone, number of spermatozoa and fertility in adult male bonnet monkeys (Macaca radiata).

    PubMed

    Ramachandra, S G; Ramesh, V; Krishnamurthy, H N; Kumar, N; Sundaram, K; Hardy, M P; Rao, A Jagannadha

    2002-08-01

    Hormonal approaches to male contraception that are based on the suppression of LH secretion require androgen replacement treatment to maintain sexual behaviour and secondary sexual characteristics. Androgen supplementation not only involves large and frequent doses of testosterone esters but also results in undesirable effects on the prostate gland. In an attempt to avoid such problems, a synthetic androgen, 7alpha-methyl-19-nortestosterone (MENT), which is much more potent than testosterone, has been developed. In the present study, MENT was administered at different doses (25, 50, 100, 300 and 1000 microg day(-1)) either alone or in combination with oestradiol via Silastic implants for a specified period to adult male bonnet monkeys (Macaca radiata). Blood and semen samples were collected at specific intervals and analysed for serum testosterone and seminal parameters, respectively. The results of the present study clearly indicate that administration of MENT at all doses tested results in suppression of the nocturnal surge of testosterone (by day 3), as well as a decrease in the number of spermatozoa (by day 45). Co-administration of oestradiol resulted in a reduction in the dose of MENT required to suppress the nocturnal surge. None of the male bonnet monkeys treated with MENT were able to impregnate females, clearly demonstrating the efficacy of MENT in blocking fertility in male bonnet monkeys.

  20. Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort

    PubMed Central

    2014-01-01

    Background Obesity appears to be associated with male reproductive dysfunction and infertility, although this has been inconsistent and inconclusive. Insulin and leptin are known mediators and modulators of the hypothalamus-pituitary-testes axis, contributing to the regulation of male reproductive potential and overall wellbeing. These hormones are also present in semen influencing sperm functions. Although abdominal obesity is closely associated with insulin resistance (hyperinsulinaemia), hyperleptinaemia and glucose dysfunction, changes in seminal plasma concentrations of insulin, leptin and glucose in obese males has not previously been investigated. Methods This small case controlled study assessed serum and seminal concentrations of insulin, leptin and glucose in obese (BMI > =30; n = 23) and non-obese (BMI < 30; n = 19) males. Following a detailed medical history and examination, participants meeting the inclusion criteria were entered for data analysis. Body parameters such as BMI, waist and hip circumference and the waist hip ratio were measured. Serum and semen samples were collected and assayed for insulin, leptin and glucose. Semen samples also underwent a standard semen analysis, with sperm mitochondrial membrane potential (MMP) and DNA fragmentation (DF). Results Obesity was associated with increased serum and seminal insulin and leptin, with no significant difference in seminal glucose. Serum and seminal concentrations of insulin and leptin were positively correlated. Furthermore, obesity was associated with decreased sperm concentration, sperm vitality and increased MMP and DF, with a non-significant impact on motility and morphology. Conclusions Hyperinsulinaemia and hyperleptinaemia are associated with increased seminal insulin and leptin concentrations, which may negatively impact male reproductive function in obesity. Insulin was also found to be highly concentrated in the seminal plasma of both groups. This data will contribute

  1. Establishing a group of endpoints to support collective operations without specifying unique identifiers for any endpoints

    DOEpatents

    Archer, Charles J.; Blocksom, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanghon

    2016-02-02

    A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

  2. Human X-linked Intellectual Disability Factor CUL4B Is Required for Post-meiotic Sperm Development and Male Fertility

    PubMed Central

    Lin, Chien-Yu; Chen, Chun-Yu; Yu, Chih-Hsiang; Yu, I-Shing; Lin, Shu-Rung; Wu, June-Tai; Lin, Ying-Hung; Kuo, Pao-Lin; Wu, Jui-Ching; Lin, Shu-Wha

    2016-01-01

    In this study, we demonstrate that an E3-ubiquitin ligase associated with human X-linked intellectual disability, CUL4B, plays a crucial role in post-meiotic sperm development. Initially, Cul4bΔ/Y male mice were found to be sterile and exhibited a progressive loss in germ cells, thereby leading to oligoasthenospermia. Adult Cul4b mutant epididymides also contained very low numbers of mature spermatozoa, and these spermatazoa exhibited pronounced morphological abnormalities. In post-meiotic spermatids, CUL4B was dynamically expressed and mitosis of spermatogonia and meiosis of spermatocytes both appeared unaffected. However, the spermatids exhibited significantly higher levels of apoptosis during spermiogenesis, particularly during the acrosome phase through the cap phase. Comparative proteomic analyses identified a large-scale shift between wild-type and Cul4b mutant testes during early post-meiotic sperm development. Ultrastructural pathology studies further detected aberrant acrosomes in spermatids and nuclear morphology. The protein levels of both canonical and non-canonical histones were also affected in an early spermatid stage in the absence of Cul4b. Thus, X-linked CUL4B appears to play a critical role in acrosomal formation, nuclear condensation, and in regulating histone dynamics during haploid male germ cell differentiation in relation to male fertility in mice. Thus, it is possible that CUL4B-selective substrates are required for post-meiotic sperm morphogenesis. PMID:26832838

  3. Male and couple fertility impairment due to HPV-DNA sperm infection: update on molecular mechanism and clinical impact--systematic review.

    PubMed

    Gizzo, Salvatore; Ferrari, Bruno; Noventa, Marco; Ferrari, Emanuele; Patrelli, Tito Silvio; Gangemi, Michele; Nardelli, Giovanni Battista

    2014-01-01

    Recent evidences identify Human Papillomavirus (HPV) sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameters impairment is the most widely recognized effect. Regarding biomolecular implications, the available data are often conflicting. More studies are required to define the role of HPV sperm infection in clinical practice. The great majority of evidences are obtained by in vitro studies and this fact represents a limitation for the clinical management of HPVDNA sperm infection. Understanding the biological significance of HPV-DNA semen infection could permit us to explain most of the idiopathic male and couple infertility, leading to a better management of infertile men and a better timing for sperm banking storage before ART cycles.

  4. The testis anion transporter 1 (Slc26a8) is required for sperm terminal differentiation and male fertility in the mouse.

    PubMed

    Touré, Aminata; Lhuillier, Pierre; Gossen, Jan A; Kuil, Cor W; Lhôte, David; Jégou, Bernard; Escalier, Denise; Gacon, Gérard

    2007-08-01

    The Slc26 family is a conserved family of anion transporters. In the human, their physiological relevance was highlighted with the discovery of pathogenic mutations in several Slc26 transporters that lead to distinctive clinical disorders (Pendred syndrome, deafness, diastrophic dysplasia, congenital chloride diarrhoea) that are related to the specific distribution of these genes. We previously identified TAT1 as a new family member (Slc26A8), very specifically expressed in male germ cells in both the human and the mouse. To investigate Tat1 function in the male germline, we generated mice with a targeted disruption of the Tat1 gene. Heterozygous and homozygous Tat1 mutant mice were indistinguishable from wild-type littermates concerning survival rate, general appearance and gross behaviour; however, Tat1 null males were sterile due to complete lack of sperm motility and reduced sperm fertilization potential. Ultra-structural analysis revealed defects in flagellar differentiation leading to an abnormal annulus, disorganization of the midpiece-principal piece junction, hairpin bending of the sperm tail with disruption of the axial structures, and abnormal mitochondrial sheath assembly. While ATP levels were normal, ATP consumption was strongly reduced in Tat1 null spermatozoa. Interestingly, Tat1 is located at the annulus, a septin-based circular structure connecting the midpiece to the principal piece. Altogether, our results indicate that Tat1 is a critical component of the sperm annulus that is essential for proper sperm tail differentiation and motility.

  5. Human X-linked Intellectual Disability Factor CUL4B Is Required for Post-meiotic Sperm Development and Male Fertility.

    PubMed

    Lin, Chien-Yu; Chen, Chun-Yu; Yu, Chih-Hsiang; Yu, I-Shing; Lin, Shu-Rung; Wu, June-Tai; Lin, Ying-Hung; Kuo, Pao-Lin; Wu, Jui-Ching; Lin, Shu-Wha

    2016-02-02

    In this study, we demonstrate that an E3-ubiquitin ligase associated with human X-linked intellectual disability, CUL4B, plays a crucial role in post-meiotic sperm development. Initially, Cul4b(Δ)/Y male mice were found to be sterile and exhibited a progressive loss in germ cells, thereby leading to oligoasthenospermia. Adult Cul4b mutant epididymides also contained very low numbers of mature spermatozoa, and these spermatazoa exhibited pronounced morphological abnormalities. In post-meiotic spermatids, CUL4B was dynamically expressed and mitosis of spermatogonia and meiosis of spermatocytes both appeared unaffected. However, the spermatids exhibited significantly higher levels of apoptosis during spermiogenesis, particularly during the acrosome phase through the cap phase. Comparative proteomic analyses identified a large-scale shift between wild-type and Cul4b mutant testes during early post-meiotic sperm development. Ultrastructural pathology studies further detected aberrant acrosomes in spermatids and nuclear morphology. The protein levels of both canonical and non-canonical histones were also affected in an early spermatid stage in the absence of Cul4b. Thus, X-linked CUL4B appears to play a critical role in acrosomal formation, nuclear condensation, and in regulating histone dynamics during haploid male germ cell differentiation in relation to male fertility in mice. Thus, it is possible that CUL4B-selective substrates are required for post-meiotic sperm morphogenesis.

  6. Transposon Tagging of a Male-Sterility, Female-Sterility Gene, St8, Revealed that the Meiotic MER3 DNA Helicase Activity Is Essential for Fertility in Soybean

    PubMed Central

    Baumbach, Jordan; Pudake, Ramesh N.; Johnson, Callie; Kleinhans, Kaylin; Ollhoff, Alexandrea; Palmer, Reid G.; Bhattacharyya, Madan K.; Sandhu, Devinder

    2016-01-01

    The W4 locus in soybean encodes a dihydroflavonol-4-reductase (DFR2) that regulates pigmentation patterns in flowers and hypocotyl. The mutable w4-m allele that governs variegated flowers has arisen through insertion of a CACTA-type transposable element, Tgm9, in DFR2. In the w4-m line, reversion from variegated to purple flower indicates excision of Tgm9, and its insertion at a new locus. Previously, we have identified a male-sterile, female-sterile mutant among the selfed progenies of a revertant plant carrying only purple flowers. Co-segregation between Tgm9 and the sterility phenotype suggested that the mutant was generated by insertion of Tgm9 at the St8 locus. The transposon was localized to exon 10 of Glyma.16G072300 that shows high identity to the MER3 DNA helicase involved in crossing over. Molecular analysis of fertile branches from two independent revertant plants confirmed precise excision of Tgm9 from the st8 allele, which restored fertility. In soybean, the gene is expressed in flower-buds, trifoliate leaves and stem. Phylogenetic analysis placed St8 in a clade with the Arabidopsis and rice MER3 suggesting that St8 is most likely the orthologous MER3 soybean gene. This study established the utility of Tgm9 in gene identification as well as in forward and reverse genetics studies. PMID:26930200

  7. Fertility and Markers of Male Reproductive Function in Inuit and European Populations Spanning Large Contrasts in Blood Levels of Persistent Organochlorines

    PubMed Central

    Bonde, Jens Peter; Toft, Gunnar; Rylander, Lars; Rignell-Hydbom, Anna; Giwercman, Aleksander; Spano, Marcello; Manicardi, Gian Carlo; Bizzaro, Davide; Ludwicki, Jan K.; Zvyezday, Valentina; Bonefeld-Jørgensen, Eva C.; Pedersen, Henning Sloth; Jönsson, Bo A.G.; Thulstrup, Ane Marie

    2008-01-01

    Objective We synthesized the main findings from an international epidemiologic study on the impact of biopersistent organic pollutants (POPs) on human reproductive function. Data sources and extraction We used a database with interview and biological data from 2,269 women and their spouses, and 18 published core papers. Data synthesis The study did not provide direct evidence of hormone-like activity of the polychlorinated biphenyl (PCB) congener CB-153 and the main dichlorodiphenyltrichloroethane (DDT) metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p′-DDE), as serum concentrations of these compounds were not consistently related to either endogenous or exogenous hormone activity in serum. Nevertheless several links bewteen POP exposure and biomarkers of male reproductive function were identified. First, an association between high CB-153 serum levels and low sperm counts was detected within a subgroup of men with short androgen receptor CAG repeat length. Second, a relationship between increased CB-153 serum concentrations and decreased sperm motility was seen in all four studied regions, and indications of reduced neutral α-glucosidase activity in seminal plasma point to a post-testicular effect. Third, damage of sperm chromatin integrity was considerably less frequent in Greenlandic Inuits compared with that in European groups, and only in the latter was impairment of sperm chromatin integrity related to POPs. Despite these effects, fertility in terms of time taken to conceive was not related to POPs except in Inuits. A likely explanation of the latter was not identified. Conclusions POPs may interfere with male reproductive function without major impact on fertility. The data do not provide direct evidence for endocrine disruption, hence other mechanisms should also be considered. PMID:18335090

  8. Drosophila mitoferrin is essential for male fertility: evidence for a role of mitochondrial iron metabolism during spermatogenesis

    PubMed Central

    2010-01-01

    Background Mammals and Drosophila melanogaster share some striking similarities in spermatogenesis. Mitochondria in spermatids undergo dramatic morphological changes and syncytial spermatids are stripped from their cytoplasm and then individually wrapped by single membranes in an individualization process. In mammalian and fruit fly testis, components of the mitochondrial iron metabolism are expressed, but so far their function during spermatogenesis is unknown. Here we investigate the role of Drosophila mitoferrin (dmfrn), which is a mitochondrial carrier protein with an established role in the mitochondrial iron metabolism, during spermatogenesis. Results We found that P-element insertions into the 5'-untranslated region of the dmfrn gene cause recessive male sterility, which was rescued by a fluorescently tagged transgenic dmfrn genomic construct (dmfrnvenus). Testes of mutant homozygous dmfrnSH115 flies were either small with unorganized content or contained some partially elongated spermatids, or testes were of normal size but lacked mature sperm. Testis squashes indicated that spermatid elongation was defective and electron micrographs showed mitochondrial defects in elongated spermatids and indicated failed individualization. Using a LacZ reporter and the dmfrnvenus transgene, we found that dmfrn expression in testes was highest in spermatids, coinciding with the stages that showed defects in the mutants. Dmfrn-venus protein accumulated in mitochondrial derivatives of spermatids, where it remained until most of it was stripped off during individualization and disposed of in waste bags. Male sterility in flies with the hypomorph alleles dmfrnBG00456 and dmfrnEY01302 over the deletion Df(3R)ED6277 was increased by dietary iron chelation and suppressed by iron supplementation of the food, while male sterility of dmfrnSH115/Df(3R)ED6277 flies was not affected by food iron levels. Conclusions In this work, we show that mutations in the Drosophila mitoferrin gene

  9. Occupational risk for male infertility: a case-control study of 218 infertile and 227 fertile men.

    PubMed

    Chia, S E; Tay, S K

    2001-11-01

    The aim of the study was to determine if certain occupations pose an increased risk for infertility (of no known cause) among a group of infertile men compared with a group of fertile men. A total of 640 consecutive men whose spouses were unable to conceive were recruited from an infertility clinic. Of these, 218 men (cases) were found to have no known cause for their infertility. A total of 227 men whose spouses were pregnant at the time of the study were recruited as controls. The Singapore Standard Occupational Classification was used to code the subjects' occupations. Semen parameters (density, total sperm counts, motility, viability, and normal morphology) in all of the cases were significantly poorer than those in the controls. The risk for infertility is associated with smoking adjusted odds ratio (OR) 2.85 and 95% confidence interval (CI) 1.91 to 4.24. Work, independently, is not a risk factor for infertility. Engineering technicians (adjusted OR, 2.75; 95% CI, 1.36 to 5.54), finance analysts (adjusted OR, 4.66; 95% CI, 1.90 to 11.40), corporate and computing managers (adjusted OR, 2.49; 95% CI, 1.04 to 5.98), and teachers (adjusted OR, 7.72; 95% CI, 1.86 to 32.10) were at a greater risk of infertility compared with "services and clerical workers." Using services and clerical workers as a reference group, certain occupations are at a higher risk for infertility. Higher work demands and possible electromagnetic field exposure could be contributory factors for infertility.

  10. Embryonic pathogenesis of hypogonadism and renal hypoplasia in hgn/hgn rats characterized by male sterility, reduced female fertility and progressive renal insufficiency.

    PubMed

    Suzuki, Hiroetsu; Yagi, Mio; Saito, Kenichi; Suzuki, Katsushi

    2007-03-01

    Congenital hypoplasia and dysplasia affect the postnatal development of organs, their physiological functioning in adulthood and the incidence of related diseases at an advanced age. Hypogonadic (hgn/hgn) rats are characterized by male sterility, reduced female fertility, progressive renal insufficiency and growth retardation, all controlled by a single recessive allele (hgn) located on chromosome 10. Since our previous studies indicated that the hypoplasia (dysplasia) of the affected organs was present at birth, we examined the embryonic pathogenesis. We mated hgn/hgn females to Brown Norway males and backcrossed F(1) males to hgn/hgn females. The resulting N(1) fetuses were genotyped using a hgn-linked microsatellite. Both sexes of hgn/hgn fetuses showed low body weight after embryonic day (ED) 15.5 and renal hypoplasia after ED 17.5. Their kidneys contained a reduced number of nephrons in a poorly formed nephrogenic zone and renal cortex. The hgn/hgn ovaries contained a small number of oogonia at ED 15.5 and oocytes after ED 17.5. Testicular growth defects were obvious after ED 17.5, and reduced numbers of Sertoli cells were detected at ED 19.5 and 21.5. The seminiferous cords in hgn/hgn testes contained more apoptotic and mitotic cells than those in +/hgn testes. These findings suggest that the phenotypes described in adult hgn/hgn rats result from embryonic hypogenesis, which continues to early postnatal stage and causes a reduction in functional tissues and cells. Since hgn/hgn rats have an insertion mutation in the microtubule-associated protein Spag5 gene, the embryonic hypogenesis described in hgn/hgn rats might result from defective cell proliferation.

  11. Registration of cytoplasmic male-sterile oilseed sunflower genetic stocks CMS GIG2 and CMS GIG2-RV, and fertility restoration lines RF GIG2-MAX 1631 and RF GIG2-MAX 1631-RV

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two cytoplasmic male-sterile (CMS) oilseed sunflower (Helianthus annuus L.) genetic stocks, CMS GIG2 (Reg. No. xxx, PI xxxx), and CMS GIG2-RV (Reg. No. xxx, PI xxxx), and corresponding fertility restoration lines RF GIG2-MAX 1631 (Reg. No. xxx, PI xxxx) and RF GIG2-MAX 1631-RV (Reg. No. xxx, PI xxx...

  12. Dietary selenium deficiency as well as excess supplementation induces multiple defects in mouse epididymal spermatozoa: understanding the role of selenium in male fertility.

    PubMed

    Shalini, Sonia; Bansal, M P

    2008-08-01

    Selenium (Se) is essential for male fertility. The present study was carried out to observe the defects associated with Se deficiency as well as excess Se supplementation by analyzing the sperm ultrastructure and chromatin organization. Different Se status mice were generated viz. Se deficient (group I), Se adequate (group II) and Se excess (group III) by feeding the respective diets for a period of 4 (group Ia, IIa and IIIa) and 8 weeks (group Ib, IIb and IIIb). Reduction in sperm concentration, motility and percentage fertility was observed in Se deficient and Se excess groups. Electron microscopy revealed mitochondrial swelling and gaps between adjacent mitochondria in mice fed Se-deficient diet for 4 weeks. At 8 weeks, several abnormalities such as loose contact of the mitochondrial helix with the plasma membrane, loss of mitochondria, retention of cytoplasmic droplet, fracturing of outer dense fibres and presence of both the midpiece and the principal piece cross-sections in a common plasma membrane were observed. In Se excess group, the predominant defect was the frequent presence of equidistant, cross-sectioned midpieces of the tail embedded in a common cytoplasm. These defects are indicative of loss of sperm motility. Spermatozoa from Se-deficient mice had incompletely condensed chromatin and indicated an increase in occurrence of DNA strand breaks. The animals fed Se excess diet also indicated increase in DNA breaks but this was significantly less than the deficient diet fed groups. Our study reveals the defects associated with Se deficiency that result in loss of reproductive ability and also reflects its possible harmful effects on spermatozoa after prolonged consumption at supranutritional level.

  13. Comparative Transcriptome Profile of the Cytoplasmic Male Sterile and Fertile Floral Buds of Radish (Raphanus sativus L.).

    PubMed

    Mei, Shiyong; Liu, Touming; Wang, Zhiwei

    2016-01-06

    Radish cytoplasmic male sterility (CMS) has been widely used for breeding in Raphanus and Brassica genera. However, the detailed regulation network of the male sterility remains to be determined. Our previous work has shown that the abnormalities in a CMS radish appeared shortly after the tetrad stage when microspores were malformed and the tapetal cells grew abnormally large. In this work, histological analysis shows that anthers are at the tetrad stage when the radish buds are about 1.5 mm in length. Furthermore, a high throughput RNA sequencing technology was employed to characterize the transcriptome of radish buds with length about 1.5 mm from two CMS lines possessing the CMS-inducing orf138 gene and corresponding near-isogenic maintainer lines. A total of 67,140 unigenes were functionally annotated. Functional terms for these genes are significantly enriched in 55 Gene Ontology (GO) groups and 323 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The transcriptome detected transcripts for 72 out of a total of 79 protein genes encoded in the chloroplast genome from radish. In contrast, the radish mitochondrial genome contains 34 protein genes, but only 16 protein transcripts were detected from the transcriptome. The transcriptome comparison between CMS and near-isogenic maintainer lines revealed 539 differentially expressed genes (DEGs), indicating that the false positive rate for comparative transcriptome profiling was clearly decreased using two groups of CMS/maintainer lines with different nuclear background. The level of 127 transcripts was increased and 412 transcripts were decreased in the CMS lines. No change in levels of transcripts except CMS-inducing orf138 was identified from the mitochondrial and chloroplast genomes. Some DEGs which would be associated with the CMS, encoding MYB and bHLH transcription factors, pentatricopeptide repeat (PPR) proteins, heat shock transcription factors (HSFs) and heat shock proteins (HSPs), are discussed. The

  14. Behavioral endpoints for radiation injury

    NASA Astrophysics Data System (ADS)

    Rabin, B. M.; Joseph, J. A.; Hunt, W. A.; Dalton, T. B.; Kandasamy, S. B.; Harris, A. H.; Ludewig, B.

    1994-10-01

    The relative behavioral effectiveness of heavy particles was evaluated. Using the taste aversion paradigm in rats, the behavioral toxicity of most types of radiation (including 20Ne and 40Ar) was similar to that of 60Co photons. Only 56Fe and 93Nb particles and fission neutrons were significantly more effective. Using emesis in ferrets as the behavioral endpoint, 56Fe particles and neutrons were again the most effective; however, 60Co photons were significantly more effective than 18 MeV electrons. These results suggest that LET does not completely predict behavioral effectiveness. Additionally, exposing rats to 10 cGy of 56Fe particles attenuated amphetamine-induced taste aversion learning. This behavior is one of a broad class of behaviors which depends on the integrity of the dopaminergic system and suggests the possibility of alterations in these behaviors following exposure to heavy particles in a space radiation environment.

  15. Statistical analysis of histopathological endpoints.

    PubMed

    Green, John W; Springer, Timothy A; Saulnier, Amy N; Swintek, Joe

    2014-05-01

    Histopathological assessments of fish from aquatic ecotoxicology studies are being performed with increasing frequency. Aquatic ecotoxicology studies performed for submission to regulatory agencies are usually conducted with multiple subjects (e.g., fish) in each of multiple vessels (replicates) within a water control and within each of several concentrations of a test substance. A number of histopathological endpoints are evaluated in each fish, and a severity score is generally recorded for each endpoint. The severity scores are often recorded using a nonquantitative scale of 0 to 4, with 0 indicating no effect, 1 indicating minimal effect, through 4 for severe effect. Statistical methods often used to analyze these scores suffer from several shortcomings: computing average scores as though scores were quantitative values, considering only the frequency of abnormality while ignoring severity, ignoring any concentration-response trend, and ignoring the possible correlation between responses of individuals within test vessels. A new test, the Rao-Scott Cochran-Armitage by Slices (RSCABS), is proposed that incorporates the replicate vessel experimental design and the biological expectation that the severity of the effect tends to increase with increasing doses or concentrations, while retaining the individual subject scores and taking into account the severity as well as frequency of scores. A power simulation and examples demonstrate the performance of the test. R-based software has been developed to carry out this test and is available free of charge at www.epa.gov/med/Prods_Pubs/rscabs.htm. The SAS-based RSCABS software is available from the first and third authors.

  16. Protective effect of royal jelly on fertility and biochemical parameters in bleomycin-‎induced male rats

    PubMed Central

    Amirshahi, Tayebeh; Najafi, Gholamreza; Nejati, Vahid

    2014-01-01

    Background: Bleomycin (BL) is a glycopeptide antibiotic obtained from the bacterium Streptomyces verticillus which is routinely used for treatment of human cancers. Royal jelly (RJ) is a production from the hypo pharyngeal, mandibular and post cerebral glands of nurse bees. RJ consists of 66% water, 15% sugars, 5% lipids, and 13% proteins, essential amino acids and vitamins. Objective: The aim of present study was to evaluate protective effect of royal jelly on sperm parameters and malondialdehyde (MDA) production in rat. Materials and Methods: Forty adult male wistar rats (220±20gr) were randomly divided into 4 groups (n=10). Control group (CG) received normal saline 10 ml/kg twice a week with Intraperitoneal (I.P) for 48 days (0.3 ml/rat(. Royal Jelly group (RJG) received jelly (100 mg/kg daily) for 48 days orally. Bleomycin group (BLG) received BL (10 mg/kg twice a week) with I.P for 48 days. Royal Jelly+ Bleomycin group (RJ+BLG) received royal Jelly (100 mg/kg /day) orally concomitant with BL administration. Sperm count, motility, and viability were investigated and chromatin quality and DNA integrity were also analyzed. Serum testosterone and MDA concentrations were measured as well. Results: BL caused decline significantly (p<0.05) sperm count, sperm viability, motility as well as testosterone concentration compared to control group while significant (p<0.05) increases in immature sperm, sperm with damaged DNA and MDA concentration were announced in BL in comparison with CG and RJ+BLG. Royal jelly improved Bleomycin-induced toxicity on sperm parameters and testosterone and MDA concentrations. Conclusion: The present results support the idea that BL adversely affects sperm parameters and MDA and the RJ with antioxidant properties has positive effects on these parameters. This article extracted from M.Sc. thesis. (Tayebeh amirshahi) PMID:24799882

  17. Neofunctionalization of duplicated Tic40 genes caused a gain-of-function variation related to male fertility in Brassica oleracea lineages.

    PubMed

    Dun, Xiaoling; Shen, Wenhao; Hu, Kaining; Zhou, Zhengfu; Xia, Shengqian; Wen, Jing; Yi, Bin; Shen, Jinxiong; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Lagercrantz, Ulf

    2014-11-01

    Gene duplication followed by functional divergence in the event of polyploidization is a major contributor to evolutionary novelties. The Brassica genus evolved from a common ancestor after whole-genome triplication. Here, we studied the evolutionary and functional features of Brassica spp. homologs to Tic40 (for translocon at the inner membrane of chloroplasts with 40 kDa). Four Tic40 loci were identified in allotetraploid Brassica napus and two loci in each of three basic diploid Brassica spp. Although these Tic40 homologs share high sequence identities and similar expression patterns, they exhibit altered functional features. Complementation assays conducted on Arabidopsis thaliana tic40 and the B. napus male-sterile line 7365A suggested that all Brassica spp. Tic40 homologs retain an ancestral function similar to that of AtTic40, whereas BolC9.Tic40 in Brassica oleracea and its ortholog in B. napus, BnaC9.Tic40, in addition, evolved a novel function that can rescue the fertility of 7365A. A homologous chromosomal rearrangement placed bnac9.tic40 originating from the A genome (BraA10.Tic40) as an allele of BnaC9.Tic40 in the C genome, resulting in phenotypic variation for male sterility in the B. napus near-isogenic two-type line 7365AB. Assessment of the complementation activity of chimeric B. napus Tic40 domain-swapping constructs in 7365A suggested that amino acid replacements in the carboxyl terminus of BnaC9.Tic40 cause this functional divergence. The distribution of these amino acid replacements in 59 diverse Brassica spp. accessions demonstrated that the neofunctionalization of Tic40 is restricted to B. oleracea and its derivatives and thus occurred after the divergence of the Brassica spp. A, B, and C genomes.

  18. Professionals' views on the issues and challenges arising from providing a fertility preservation service through sperm banking to teenage males with cancer.

    PubMed

    Crawshaw, Marilyn; Glaser, Adam; Hale, Juliet; Sloper, Patricia

    2004-03-01

    Interviews were undertaken with 22 health and social work professionals. Their analysis was completed using "selective transcription", noting understanding of process, issues and themes, and building a picture against which to consider the analysis of subsequent interviews with teenagers and parents. Professionals were also asked to identify areas for feedback from these participants. This work was part of a larger study of (i) the perceptions of adolescent males and their parents of fertility preservation services following a cancer diagnosis, and (ii) national postal surveys of common practices, areas of variance and issues experienced by professionals in UK regional paediatric oncology centres and licensed assisted conception centres. A large number of concerns were identified, which reflected professionals' difficulties in building and maintaining a relevant, adequate knowledge and skills base given the limited numbers of teenagers offered this service. The lack of appropriate training about the legal and consent frameworks, and the processes involved was also highlighted across all professional groups as was the confusion around professional and legal responsibilities for follow up. Thus, there was considerable professional uncertainty in a number of aspects of this sensitive area of service provision. Consideration needs to be given to the needs for national guidance, for training, support and updating, for liaison between the different health and social care sectors that may be involved, and for appropriate information systems. These need to be in place for each stage of the process, from diagnosis through to eventual discharge from the health system.

  19. Expanding the ecotoxicological toolbox: the inclusion of polychaete reproductive endpoints.

    PubMed

    Lewis, Ceri; Watson, Gordon J

    2012-04-01

    In the last 15 years the diversity of pollutants and routes of impact have increased. However, the polychaete families, species and endpoints investigated have remained fairly constant. Reproductive outputs are more ecologically relevant than adult physiological or biochemical changes. Nevertheless, there remains a paucity of data on the reproductive responses of the popular species to pollutants which limits our ability to understand the true ecological impacts of such contaminants on natural populations. We highlight the current knowledge gaps in our understanding of the impacts of pollutants on the 'model' species' reproductive biology and therefore the potential ecological impacts of such contaminants on their natural populations, and the potential benefits of a wider use of polychaete reproductive endpoints for ecotoxicological assessments. The following priority areas are suggested for inclusion in the polychaete ecotoxicology toolbox: 1. Include reproductive endpoints as assessments of ecotoxicology for the traditional 'model' species and those that have different reproductive traits to ensure broad ecological relevance. 2. Nereids and Arenicola marina should be used to investigate the interaction of pollutants with the endocrine/environmental control of reproduction. 3. Polychaetes are ideal for addressing the under representation of male eco-toxicity effects. 4. Emerging pollutants should be assessed with reproductive endpoints together with the traditional biomarkers. 5. Effects of pollutants on larval behaviour need to be explored considering the limited but equivocal results so far.

  20. Genetics and mapping of the R₁₁ gene conferring resistance to recently emerged rust races, tightly linked to male fertility restoration, in sunflower (Helianthus annuus L.).

    PubMed

    Qi, L L; Seiler, G J; Vick, B A; Gulya, T J

    2012-09-01

    Sunflower oil is one of the major sources of edible oil. As the second largest hybrid crop in the world, hybrid sunflowers are developed by using the PET1 cytoplasmic male sterility system that contributes to a 20 % yield advantage over the open-pollinated varieties. However, sunflower production in North America has recently been threatened by the evolution of new virulent pathotypes of sunflower rust caused by the fungus Puccinia helianthi Schwein. Rf ANN-1742, an 'HA 89' backcross restorer line derived from wild annual sunflower (Helianthus annuus L.), was identified as resistant to the newly emerged rust races. The aim of this study was to elucidate the inheritance of rust resistance and male fertility restoration and identify the chromosome location of the underlying genes in Rf ANN-1742. Chi-squared analysis of the segregation of rust response and male fertility in F(2) and F(3) populations revealed that both traits are controlled by single dominant genes, and that the rust resistance gene is closely linked to the restorer gene in the coupling phase. The two genes were designated as R ( 11 ) and Rf5, respectively. A set of 723 mapped SSR markers of sunflower was used to screen the polymorphism between HA 89 and the resistant plant. Bulked segregant analysis subsequently located R ( 11 ) on linkage group (LG) 13 of sunflower. Based on the SSR analyses of 192 F(2) individuals, R ( 11 ) and Rf5 both mapped to the lower end of LG13 at a genetic distance of 1.6 cM, and shared a common marker, ORS728, which was mapped 1.3 cM proximal to Rf5 and 0.3 cM distal to R ( 11 ) (Rf5/ORS728/R ( 11 )). Two additional SSRs were linked to Rf5 and R ( 11 ): ORS995 was 4.5 cM distal to Rf5 and ORS45 was 1.0 cM proximal to R ( 11 ). The advantage of such an introduced alien segment harboring two genes is its large phenotypic effect and simple inheritance, thereby facilitating their rapid deployment in sunflower breeding programs. Suppressed recombination was observed in LGs 2, 9

  1. Surrogate endpoint analysis: an exercise in extrapolation.

    PubMed

    Baker, Stuart G; Kramer, Barnett S

    2013-03-06

    Surrogate endpoints offer the hope of smaller or shorter cancer trials. It is, however, important to realize they come at the cost of an unverifiable extrapolation that could lead to misleading conclusions. With cancer prevention, the focus is on hypothesis testing in small surrogate endpoint trials before deciding whether to proceed to a large prevention trial. However, it is not generally appreciated that a small surrogate endpoint trial is highly sensitive to a deviation from the key Prentice criterion needed for the hypothesis-testing extrapolation. With cancer treatment, the focus is on estimation using historical trials with both surrogate and true endpoints to predict treatment effect based on the surrogate endpoint in a new trial. Successively leaving out one historical trial and computing the predicted treatment effect in the left-out trial yields a standard error multiplier that summarizes the increased uncertainty in estimation extrapolation. If this increased uncertainty is acceptable, three additional extrapolation issues (biological mechanism, treatment following observation of the surrogate endpoint, and side effects following observation of the surrogate endpoint) need to be considered. In summary, when using surrogate endpoint analyses, an appreciation of the problems of extrapolation is crucial.

  2. [Immunological surrogate endpoints to evaluate vaccine efficacy].

    PubMed

    Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai

    2015-12-01

    An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description.

  3. Characterization of null and hypomorphic alleles of the Drosophila l(2)dtl/cdt2 gene: Larval lethality and male fertility.

    PubMed

    Sloan, Roketa S; Swanson, Christina I; Gavilano, Lily; Smith, Kristen N; Malek, Pamela Y; Snow-Smith, Mayronne; Duronio, Robert J; Key, S Catherine Silver

    2012-01-01

    The Drosophila lethal(2)denticleless (l(2)dtl) gene was originally reported as essential for embryogenesis and formation of the rows of tiny hairs on the larval ventral cuticle known as denticle belts. It is now well-established that l(2)dtl (also called cdt2) encodes a subunit of a Cullin 4-based E3 ubiquitin ligase complex that targets a number of key cell cycle regulatory proteins, including p21, Cdt1, E2F1 and Set8, to prevent replication defects and maintain cell cycle control. To investigate the role of l(2)dtl/cdt2 during development, we characterized existing l(2)dtl/cdt2 mutants and generated new deletion alleles, using P-element excision mutagenesis. Surprisingly, homozygous l(2)dtl/cdt2 mutant embryos developed beyond embryogenesis, had intact denticle belts, and lacked an observable embryonic replication defect. These mutants died during larval stages, affirming that loss of l(2)dtl/cdt2 function is lethal. Our data show that L(2)dtl/Cdt2 is maternally deposited, remains nuclear throughout the cell cycle, and has a previously unreported, elevated expression in the developing gonads. We also find that E2f1 regulates l(2)dtl/cdt2 expression during embryogenesis, possibly via several highly conserved putative E2f1 binding sites near the l(2)dtl/cdt2 promoter. Finally, hypomorphic allele combinations of the l(2)dtl/cdt2 gene result in a novel phenotype: viable, low-fertility males. We conclude that "denticleless" is a misnomer, but that l(2)dtl/cdt2 is an essential gene for Drosophila development.

  4. The roles played by mitochondrial DNA and nuclear genes in reversion to fertility in S-Type male-sterile maize. Progress report, April 1, 1985--March 31, 1989

    SciTech Connect

    Laughnan, J.R.

    1995-03-01

    This is a progress report/renewal request for work of the roles played by mitochondrial DNA and nuclear genes in reversion to fertility in s-type male sterile maize. Information is included for the following major catagories of research on this project: molecular basis for nuclear reversion; molecular characterization of cytoplasmic revertants; nuclear control over cytoplasmic reversion and over replication of S1 and S2; developmental studies; transposition of nuclear restorer elements.

  5. Comparing Laboratory and Field Measured Bioaccumulation Endpoints

    EPA Science Inventory

    The report presents an approach that allows comparisons of all laboratory and field bioaccumulation endpoints measurements. The approach will enable the inclusion of large amounts of field data into evaluations of bioaccumulation potential for legacy chemicals. Currently, these...

  6. Critical endpoint behavior: A Wang Landau study

    NASA Astrophysics Data System (ADS)

    Landau, D. P.; Wang, Fugao; Tsai, Shan-Ho

    2008-07-01

    We study the critical endpoint behavior using an asymmetric Ising model with two- and three-body interactions on a triangular lattice, in the presence of an external field. The simulation method we use is Wang-Landau sampling in a two-dimensional parameter space. We observe a clear divergence of the curvature of the spectator phase boundary and of the magnetization coexistence diameter derivative at the critical endpoint, and the exponents for both divergences agree well with previous theoretical predictions.

  7. Cancer and fertility: strategies to preserve fertility.

    PubMed

    Diedrich, K; Fauser, B C J M; Devroey, P

    2011-03-01

    Fertility preservation is a key component of cancer management in young people. The Fourth Evian Annual Reproduction Workshop Meeting was held in April 2009 to discuss cancer and fertility in young adults. Specialists in oncology, assisted reproduction, embryology and clinical genetics presented published data and ongoing research on cancer and fertility, with particular focus on strategies to preserve fertility. This report is based on the expert presentations and group discussions, supplemented with publications from literature searches and the authors' knowledge. Fertility preservation should be considered for all young people undergoing potentially gonadotoxic cancer treatment. A variety of options are required to facilitate safe and effective fertility preservation for individual patients. Sperm banking is a simple and low-cost intervention. Embryo cryopreservation is the only established method of female fertility preservation. Oocyte cryopreservation offers a useful option for women without a male partner. Emergency ovarian stimulation and cryopreservation of ovarian tissue (followed by tissue transplantation or in-vitro maturation of oocytes) are experimental techniques for women who require urgent cancer treatment. Further prospective studies are required to validate cryopreservation of oocytes and ovarian tissue, in-vitro maturation of oocytes and new vitrification techniques and to identify any long-term sequelae of slow freezing of embryos.

  8. Discriminant analysis indicates a single sperm protein (SP22) is predictive of fertility following exposure to epididymal toxicants.

    PubMed

    Klinefelter, G R; Laskey, J W; Ferrell, J; Suarez, J D; Roberts, N L

    1997-01-01

    In a previous study, we found that ethane dimethanesulphonate (EDS) compromised the fertilizing ability of proximal cauda epididymal sperm from the rat within 4 days of exposure, an effect that persisted in castrated, testosterone (T)-implanted animals, establishing direct action on the epididymis. This EDS-induced reduction in fertilizing ability was highly correlated with a quantitative decrease in specific sperm protein. Here we sought to determine whether the fertility of proximal cauda epididymal sperm recovered from animals exposed to a variety of male reproductive toxicants could be predicted by assessing quantitative changes in specific sperm protein(s), or whether more common endpoints (e.g., sperm motility, sperm morphology, serum and epididymal tissue T, cauda epididymal sperm reserves) also are required to predict fertility. Intact adult male rats were dosed with EDS (25 or 50 mg/kg), chloroethylmethanesulphonate (CEMS; 12.5 or 18.75 mg/kg), or epichlorohydrin (EPI; 3 or 6 mg/kg) daily for 4 days. Castrated, T-implanted rats were dosed with hydroxyflutamide (HFLUT; 12.5 or 25 mg/kg) daily for 5 days. On day 5, proximal cauda epididymal sperm were inseminated in utero into receptive, cervically stimulated adult females, and on day 9, fertility (implants/corpora lutea) was assessed. Fertility-was decreased by the higher dose of each toxicant (P < 0.05) and also by the lower dose of EPI and HFLUT. Likewise, an acidic 22 kDa sperm protein (SP22) was decreased quantitatively (P < 0.05) in silver-stained two-dimensional gels by the higher dose of each toxicant as well as by the lower dose of EPI and HFLUT. Although sperm motility and serum T were altered by specific exposures, these endpoints were not useful in predicting fertility. In contrast, SP22 was highly correlated (P < 0.0001; r2 = 0.83) with fertility. Indeed, the amount of SP22 correctly predicted 90% and 94% of the fertile (> 50% fertility) and subfertile (< 50 fertility) animals, respectively

  9. Congenital adrenal hyperplasia: classification of studies employing psychological endpoints.

    PubMed

    Stout, Stephanie A; Litvak, Margarita; Robbins, Natashia M; Sandberg, David E

    2010-01-01

    Psychological outcomes in persons with congenital adrenal hyperplasia (CAH) have received substantial attention. The objectives of this paper were to (1) catalog psychological endpoints assessed in CAH outcome studies and (2) classify the conceptual/theoretical model shaping the research design and interpretation of CAH-related psychological effects. A total of 98 original research studies, published between 1955 and 2009, were categorized based on psychological endpoints examined as well as the research design and conceptual model guiding analysis and interpretation of data. The majority of studies (68%) investigated endpoints related to psychosexual differentiation. The preponderance of studies (76%) examined a direct relationship (i.e., inferring causality) between prenatal androgen exposure and psychological outcomes. Findings are discussed in relation to the observed imbalance between theoretical interest in the role of prenatal androgens in shaping psychosexual differentiation and a broader conceptual model that examines the role of other potential factors in mediating or moderating the influence of CAH pathophysiology on psychological outcomes in both affected females and males. The latter approach offers to identify factors amenable to clinical intervention that enhance both health and quality of life outcomes in CAH as well as other disorders of sex development.

  10. Establishing a group of endpoints in a parallel computer

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.; Xue, Hanhong

    2016-02-02

    A parallel computer executes a number of tasks, each task includes a number of endpoints and the endpoints are configured to support collective operations. In such a parallel computer, establishing a group of endpoints receiving a user specification of a set of endpoints included in a global collection of endpoints, where the user specification defines the set in accordance with a predefined virtual representation of the endpoints, the predefined virtual representation is a data structure setting forth an organization of tasks and endpoints included in the global collection of endpoints and the user specification defines the set of endpoints without a user specification of a particular endpoint; and defining a group of endpoints in dependence upon the predefined virtual representation of the endpoints and the user specification.

  11. Intracytoplasmic Sperm Injection Using DNA-Fragmented Sperm in Mice Negatively Affects Embryo-Derived Embryonic Stem Cells, Reduces the Fertility of Male Offspring and Induces Heritable Changes in Epialleles

    PubMed Central

    Fernández-González, Raúl; Laguna-Barraza, Ricardo; Pericuesta, Eva; Calero, Antonia; Ramírez, Miguel Ángel; Gutiérrez-Adán, Alfonso

    2014-01-01

    Intracytoplasmic sperm injection (ICSI) in mice using DNA-fragmented sperm (DFS) has been linked to an increased risk of genetic and epigenetic abnormalities both in embryos and offspring. This study examines: whether embryonic stem cells (ESCs) derived from DFS-ICSI embryos reflect the abnormalities observed in the DFS-ICSI progeny; the effect of DFS-ICSI on male fertility; and whether DFS-ICSI induces epigenetic changes that lead to a modified heritable phenotype. DFS-ICSI-produced embryos showed a low potential to generate ESC lines. However, these lines had normal karyotype accompanied by early gene expression alterations, though a normal expression pattern was observed after several passages. The fertility of males in the DFS-ICSI and control groups was compared by mating test. Sperm quantity, vaginal plug and pregnancy rates were significantly lower for the DFS-ICSI-produced males compared to in vivo-produced mice, while the number of females showing resorptions was higher. The epigenetic effects of DFS-ICSI were assessed by analyzing the phenotype rendered by the Axin1Fu allele, a locus that is highly sensitive to epigenetic perturbations. Oocytes were injected with spermatozoa from Axin1Fu/+ mice and the DFS-ICSI-generated embryos were transferred to females. A significantly higher proportion of pups expressed the active kinky-tail epiallele in the DFS-ICSI group than the controls. In conclusion: 1) ESCs cannot be used as a model of DFS-ICSI; 2) DFS-ICSI reduces sperm production and fertility in the male progeny; and 3) DFS-ICSI affects the postnatal expression of a defined epigenetically sensitive allele and this modification may be inherited across generations. PMID:24743851

  12. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.

    PubMed

    Dent, M P

    2007-08-01

    The upcoming European chemicals legislation REACH (Registration, Evaluation, and Authorisation of Chemicals) will require the risk assessment of many thousands of chemicals. It is therefore necessary to develop intelligent testing strategies to ensure that chemicals of concern are identified whilst minimising the testing of chemicals using animals. Xenobiotics may perturb the reproductive cycle, and for this reason several reproductive studies are recommended under REACH. One of the endpoints assessed in this battery of tests is mating performance and fertility. Animal tests that address this endpoint use a relatively large number of animals and are also costly in terms of resource, time, and money. If it can be shown that data from non-reproductive studies such as in-vitro or repeat-dose toxicity tests are capable of generating reliable alerts for effects on fertility then some animal testing may be avoided. Available rat sub-chronic and fertility data for 44 chemicals that have been classified by the European Union as toxic to fertility were therefore analysed for concordance of effects. Because it was considered appropriate to read across data for some chemicals these data sets were considered relevant for 73 of the 102 chemicals currently classified as toxic to reproduction (fertility) under this system. For all but 5 of these chemicals it was considered that a well-performed sub-chronic toxicity study would have detected pathology in the male, and in some cases, the female reproductive tract. Three showed evidence of direct interaction with oestrogen or androgen receptors (linuron, nonylphenol, and fenarimol). The remaining chemicals (quinomethionate and azafenidin) act by modes of action that do not require direct interaction with steroid receptors. However, both these materials caused in-utero deaths in pre-natal developmental toxicity studies, and the relatively low NOAELs and the nature of the hazard identified in the sub-chronic tests provides an alert

  13. Population growth rate determinants for Arbacia: Evaluating ecological relevance of toxicity test endpoints

    SciTech Connect

    Nacci, D.; Gleason, T.; Munns, W.R. Jr.

    1995-12-31

    A population dynamics model for the sea urchin, Arbacia punctulata, was recently developed incorporating life stage endpoints frequently measured in acute and chronic toxicity studies. Model elasticity analysis was used to demonstrate that population growth rate was influenced most by adult survival and least by early life stage success, calling into question the ecological relevance of results from standardized Arbacia fertilization and larval development toxicity tests. Two approaches were used to continue this evaluation. Actual and hypothetical dose-response curves for toxicant exposures over multiple life stages were used to evaluate contributions to population growth rate of stage-specific toxicant effects. Additionally, relationships between critical life stages were developed from laboratory data for Arbacia. The results of this analysis underscore the importance of understanding both endpoint sensitivity to toxicants and sensitivity of population growth rate to test endpoints in determining the ecological relevance of toxicity tests results.

  14. Molecular pathology endpoints useful for aging studies.

    PubMed

    Niedernhofer, L J; Kirkland, J L; Ladiges, W

    2016-10-06

    The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome. But for a new chemical entity, knowing what endpoints to measure remains a formidable challenge. For economy's sake, and to achieve results in a reasonable time frame, surrogate markers of lifespan and healthy aging are desperately needed. This review provides a comprehensive analysis of molecular endpoints that are currently being used as indices of age-related phenomena (e.g., morbidity, frailty, mortality) and proposes an approach for validating and prioritizing these endpoints.

  15. Enabling communication concurrency through flexible MPI endpoints

    DOE PAGES

    Dinan, James; Grant, Ryan E.; Balaji, Pavan; ...

    2014-09-23

    MPI defines a one-to-one relationship between MPI processes and ranks. This model captures many use cases effectively; however, it also limits communication concurrency and interoperability between MPI and programming models that utilize threads. Our paper describes the MPI endpoints extension, which relaxes the longstanding one-to-one relationship between MPI processes and ranks. Using endpoints, an MPI implementation can map separate communication contexts to threads, allowing them to drive communication independently. Also, endpoints enable threads to be addressable in MPI operations, enhancing interoperability between MPI and other programming models. Furthermore, these characteristics are illustrated through several examples and an empirical study thatmore » contrasts current multithreaded communication performance with the need for high degrees of communication concurrency to achieve peak communication performance.« less

  16. Enabling communication concurrency through flexible MPI endpoints

    SciTech Connect

    Dinan, James; Grant, Ryan E.; Balaji, Pavan; Goodell, David; Miller, Douglas; Snir, Marc; Thakur, Rajeev

    2014-09-23

    MPI defines a one-to-one relationship between MPI processes and ranks. This model captures many use cases effectively; however, it also limits communication concurrency and interoperability between MPI and programming models that utilize threads. Our paper describes the MPI endpoints extension, which relaxes the longstanding one-to-one relationship between MPI processes and ranks. Using endpoints, an MPI implementation can map separate communication contexts to threads, allowing them to drive communication independently. Also, endpoints enable threads to be addressable in MPI operations, enhancing interoperability between MPI and other programming models. Furthermore, these characteristics are illustrated through several examples and an empirical study that contrasts current multithreaded communication performance with the need for high degrees of communication concurrency to achieve peak communication performance.

  17. Shift endpoint trace selection algorithm and wavelet analysis to detect the endpoint using optical emission spectroscopy

    NASA Astrophysics Data System (ADS)

    Ben Zakour, Sihem; Taleb, Hassen

    2016-06-01

    Endpoint detection (EPD) is very important undertaking on the side of getting a good understanding and figuring out if a plasma etching process is done on the right way. It is truly a crucial part of supplying repeatable effects in every single wafer. When the film to be etched has been completely erased, the endpoint is reached. In order to ensure the desired device performance on the produced integrated circuit, many sensors are used to detect the endpoint, such as the optical, electrical, acoustical/vibrational, thermal, and frictional. But, except the optical sensor, the other ones show their weaknesses due to the environmental conditions which affect the exactness of reaching endpoint. Unfortunately, some exposed area to the film to be etched is very low (<0.5%), reflecting low signal and showing the incapacity of the traditional endpoint detection method to determine the wind-up of the etch process. This work has provided a means to improve the endpoint detection sensitivity by collecting a huge numbers of full spectral data containing 1201 spectra for each run, then a new unsophisticated algorithm is proposed to select the important endpoint traces named shift endpoint trace selection (SETS). Then, a sensitivity analysis of linear methods named principal component analysis (PCA) and factor analysis (FA), and the nonlinear method called wavelet analysis (WA) for both approximation and details will be studied to compare performances of the methods mentioned above. The signal to noise ratio (SNR) is not only computed based on the main etch (ME) period but also the over etch (OE) period. Moreover, a new unused statistic for EPD, coefficient of variation (CV), is proposed to reach the endpoint in plasma etches process.

  18. Fertilizer trends

    SciTech Connect

    Donaldson, R.

    1992-01-01

    This fourteenth edition of Fertilizer Trends presents historical fertilizer market data to aid industry, government, and financial market analysis and planners in their study of fertilizer and agricultural market cycles, market planning, and investment decisions. A 27-year summary of the US fertilizer market is presented in graphic and tabular form. Production, use, and trade data are included for each plant nutrient and sulfur. Canadian statistics have been included because of the important role of the Canadian fertilizer industry in the US fertilizer market. World production and consumption of nitrogen, phosphate, and potash are included because of the strong influence of world markets on the domestic market. Planted acreage and plant nutrient application rates for the major crops have been included to illustrate their effect on fertilizer use. Retail prices of the leading US fertilizer materials also are given.

  19. Fertilizer trends

    SciTech Connect

    Donaldson, R.

    1992-12-31

    This fourteenth edition of Fertilizer Trends presents historical fertilizer market data to aid industry, government, and financial market analysis and planners in their study of fertilizer and agricultural market cycles, market planning, and investment decisions. A 27-year summary of the US fertilizer market is presented in graphic and tabular form. Production, use, and trade data are included for each plant nutrient and sulfur. Canadian statistics have been included because of the important role of the Canadian fertilizer industry in the US fertilizer market. World production and consumption of nitrogen, phosphate, and potash are included because of the strong influence of world markets on the domestic market. Planted acreage and plant nutrient application rates for the major crops have been included to illustrate their effect on fertilizer use. Retail prices of the leading US fertilizer materials also are given.

  20. Courtship rate signals fertility in an externally fertilizing fish

    PubMed Central

    Weir, Laura K.; Grant, James W. A.

    2010-01-01

    Sperm limitation is widespread across many animal species. Several mechanisms of sperm allocation have been proposed, including optimal allocation according to clutch size and equal allocation across females. However, considerably less effort has been directed at investigating the behavioural signals associated with sperm limitation in males, which may include mating rate and the intensity of courtship. We investigated whether multiple successive spawnings affect individual male fertilization success, mating rates and courtship rates in Japanese medaka (Oryzias latipes). Across an average of 17 spawning events per male, fertilization success decreased from 83.7 per cent for the first spawning to 40 per cent for the last spawning while courtship rate decreased from 3.4 to 1.5 min−1. Females appeared to respond to male sperm depletion by reducing clutch size. Our results suggest that male Japanese medaka are sperm-limited, and that courtship rate may be an honest indication of fertilization ability. PMID:20410031

  1. Scaling for interfacial tensions near critical endpoints.

    PubMed

    Zinn, Shun-Yong; Fisher, Michael E

    2005-01-01

    Parametric scaling representations are obtained and studied for the asymptotic behavior of interfacial tensions in the full neighborhood of a fluid (or Ising-type) critical endpoint, i.e., as a function both of temperature and of density/order parameter or chemical potential/ordering field. Accurate nonclassical critical exponents and reliable estimates for the universal amplitude ratios are included naturally on the basis of the "extended de Gennes-Fisher" local-functional theory. Serious defects in previous scaling treatments are rectified and complete wetting behavior is represented; however, quantitatively small, but unphysical residual nonanalyticities on the wetting side of the critical isotherm are smoothed out "manually." Comparisons with the limited available observations are presented elsewhere but the theory invites new, searching experiments and simulations, e.g., for the vapor-liquid interfacial tension on the two sides of the critical endpoint isotherm for which an amplitude ratio -3.25+/-0.05 is predicted.

  2. A specific endpoint assay for ubiquitin.

    PubMed Central

    Rose, I A; Warms, J V

    1987-01-01

    Simple endpoint assays for free ubiquitin (Ub) and for the Ub-activating enzyme are described. The method for measuring Ub makes use of the reaction of iodoacetamide-treated Ub-activating enzyme (E): [3H]ATP + Ub + E----E X [3H]AMP-Ub + PPi and PPi----2Pi (in the presence of pyrophosphatase). The Ub is then measured by determining the acid-insoluble radioactivity. The reaction is accompanied by a slow enzyme-catalyzed hydrolysis of the complex to AMP plus Ub. The presence of ubiquitin-activating enzyme in excess of Ub by approximately equal to 0.1 microM assures that the steady state will be close to the endpoint for total Ub. A preparation of the activating enzyme from human erythrocytes that does not depend on affinity chromatography is described. Several applications of the assay are presented. PMID:3031643

  3. Construction of a high-resolution linkage map of Rfd1, a restorer-of-fertility locus for cytoplasmic male sterility conferred by DCGMS cytoplasm in radish (Raphanus sativus L.) using synteny between radish and Arabidopsis genomes.

    PubMed

    Cho, Youngcho; Lee, Young-Pyo; Park, Beom-Seok; Han, Tae-Ho; Kim, Sunggil

    2012-08-01

    Cytoplasmic male sterility caused by Dongbu cytoplasmic and genic male-sterility (DCGMS) cytoplasm and its nuclear restorer-of-fertility locus (Rfd1) with a linked molecular marker (A137) have been reported in radish (Raphanus sativus L.). To construct a linkage map of the Rfd1 locus, linked amplified fragment length polymorphism (AFLP) markers were screened using bulked segregant analysis. A 220-bp linked AFLP fragment sequence from radish showed homology with an Arabidopsis coding sequence. Using this Arabidopsis gene sequence, a simple PCR marker (A220) was developed. The A137 and A220 markers flanked the Rfd1 locus. Two homologous Arabidopsis genes with both marker sequences were positioned on Arabidopsis chromosome-3 with an interval of 2.4 Mb. To integrate the Rfd1 locus into a previously reported expressed sequence tag (EST)-simple sequence repeat (SSR) linkage map, the radish EST sequences located in three syntenic blocks within the 2.4-Mb interval were used to develop single nucleotide polymorphism (SNP) markers for tagging each block. The SNP marker in linkage group-2 co-segregated with male fertility in an F(2) population. Using radish ESTs positioned in linkage group-2, five intron length polymorphism (ILP) markers and one cleaved amplified polymorphic sequence (CAPS) marker were developed and used to construct a linkage map of the Rfd1 locus. Two closely linked markers delimited the Rfd1 locus within a 985-kb interval of Arabidopsis chromosome-3. Synteny between the radish and Arabidopsis genomes in the 985-kb interval were used to develop three ILP and three CAPS markers. Two ILP markers further delimited the Rfd1 locus to a 220-kb interval of Arabidopsis chromosome-3.

  4. Protein patterns as endpoints in environmental remediation

    SciTech Connect

    Bradley, B.; Brown, D.

    1995-12-31

    Biological endpoints can complement chemical analyses in monitoring environmental remediation. In some cases the levels of chemical detection are so low that the costs of clean-up to no detection would be prohibitive. And chemical tests do not indicate the availability of the contaminants to the biota. On the other hand many if not most biological tests lack specificity. The authors have investigated a protein expression assay to establish an endpoint for clean-up of sulfur mustard and breakdown products. Earthworms (Lumbricus terrestris) were exposed to sulfur mustard (SM), a breakdown product thiodiethanol (TDE), and ethylene glycol, the solvent for the two chemicals. Tissue from the lining of the coelomic cavity was taken from each of 6 worms in each treatment class. Soluble proteins were extracted and separated on one and two-dimensional (1D and 2D) gels. The 1 D gels showed no difference by eye but the patterns from control and solvent control worms on 2D gels differed from those of worms exposed to TDE and SM. The 1D gel data were digitized and analyzed by pattern recognition using artificial neural networks. The protein patterns under the two treatments and the two controls were learned in one set of data and successfully recognized in a second. This indicated that what was learned was useful in recognizing patterns induced by SM and TDE. Thus a possible endpoint for remediation would be the protein pattern at no effect levels of chemicals of interest.

  5. Biomarkers and surrogate endpoints in glaucoma clinical trials.

    PubMed

    Medeiros, Felipe A

    2015-05-01

    Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies.

  6. Understanding fertilization through intracytoplasmic sperm injection (ICSI).

    PubMed

    Neri, Queenie V; Lee, Bora; Rosenwaks, Zev; Machaca, Khaled; Palermo, Gianpiero D

    2014-01-01

    Since the establishment of in vitro fertilization, it became evident that almost half of the couples failed to achieve fertilization and this phenomenon was attributed to a male gamete dysfunction. The adoption of assisted fertilization techniques particularly ICSI has been able to alleviate male factor infertility by granting the consistent ability of a viable spermatozoon to activate an oocyte. Single sperm injection, by pinpointing the beginning of fertilization, has been an invaluable tool in clarifying the different aspects of early fertilization and syngamy. However, even with ICSI some couples fail to fertilize due to ooplasmic dysmaturity in relation to the achieved nuclear maturation marked by the extrusion of the first polar body. More uncommon are cases where the spermatozoa partially or completely lack the specific oocyte activating factor. In this work, we review the most relevant aspects of fertilization and its failure through assisted reproductive technologies. Attempts at diagnosing and treating clinical fertilization failure are described.

  7. Understanding fertilization through intracytoplasmic sperm injection (ICSI)

    PubMed Central

    Neri, Queenie V.; Lee, Bora; Rosenwaks, Zev; Machaca, Khaled; Palermo, Gianpiero D.

    2014-01-01

    Summary Since the establishment of in vitro fertilization, it became evident that almost half of the couples failed to achieve fertilization and this phenomenon was attributed to a male gamete dysfunction. The adoption of assisted fertilization techniques particularly ICSI has been able to alleviate male factor infertility by granting the consistent ability of a viable spermatozoon to activate an oocyte. Single sperm injection, by pinpointing the beginning of fertilization, has been an invaluable tool in clarifying the different aspects of early fertilization and syngamy. However, even with ICSI some couples fail to fertilize due to ooplasmic dysmaturity in relation to the achieved nuclear maturation marked by the extrusion of the first polar body. More uncommon are cases where the spermatozoa partially or completely lack the specific oocyte activating factor. In this work, we review the most relevant aspects of fertilization and its failure through assisted reproductive technologies. Attempts at diagnosing and treating clinical fertilization failure are described. PMID:24290744

  8. Ecosystem Services as Assessment Endpoints in Ecological Risk Assessment

    EPA Science Inventory

    The focus of ecological risk assessment (ERA) is on assessment endpoints, explicit expressions of environmental values to be protected. Traditionally, the ecological entities identified in assessment endpoints have been components of ecosystems deemed by risk assessors to be impo...

  9. Genetics and mapping of the R11 gene conferring resistance to recently emerged rust races, tightly linked to male fertility restoration, in sunflower (Helianthus annuus L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sunflower oil is one of the major sources of edible oil. As the second largest hybrid crop in the world, hybrid sunflowers are developed by using the PET1 cytoplasmic male sterility system that contributes a 20% yield advantage over the open-pollinated varieties. However, sunflower production in Nor...

  10. Glutathione Peroxidase 5 Is Expressed by the Entire Pig Male Genital Tract and Once in the Seminal Plasma Contributes to Sperm Survival and In Vivo Fertility

    PubMed Central

    Barranco, Isabel; Tvarijonaviciute, Asta; Perez-Patiño, Cristina; Vicente-Carrillo, Alejandro; Parrilla, Inmaculada; Ceron, Jose J.; Martinez, Emilio A.; Rodriguez-Martinez, Heriberto; Roca, Jordi

    2016-01-01

    Glutathione peroxidase-5 (GPX5) is an H2O2-scavenging enzyme identified in boar seminal plasma (SP). This study attempted to clarify its origin and role on sperm survival and fertility after artificial insemination (AI). GPX5 was expressed (Western blot and immunocytochemistry using a rabbit primary polyclonal antibody) in testes, epididymis and accessory sex glands (6 boars). SP-GPX5 concentration differed among boars (11 boars, P < 0.001), among ejaculates within boar (44 ejaculates, P < 0.001) and among portions within ejaculate (15 ejaculates). The first 10 mL of the sperm rich fraction (SRF, sperm-peak portion) had a significantly lower concentration (8.87 ± 0.78 ng/mL) than the rest of the SRF and the post-SRF (11.66 ± 0.79 and 12.37 ± 0.79 ng/mL, respectively, P < 0.005). Sperm motility of liquid-stored semen AI-doses (n = 44, at 15–17°C during 72h) declined faster in AI-doses with low concentrations of SP-GPX5 compared to those with high-levels. Boars (n = 11) with high SP-GPX5 showed higher farrowing rates and litter sizes than those with low SP-GPX5 (a total of 5,275 inseminated sows). In sum, GPX5 is widely expressed in the boar genital tract and its variable presence in SP shows a positive relationship with sperm quality and fertility outcomes of liquid-stored semen AI-doses. PMID:27627110

  11. Glutathione Peroxidase 5 Is Expressed by the Entire Pig Male Genital Tract and Once in the Seminal Plasma Contributes to Sperm Survival and In Vivo Fertility.

    PubMed

    Barranco, Isabel; Tvarijonaviciute, Asta; Perez-Patiño, Cristina; Vicente-Carrillo, Alejandro; Parrilla, Inmaculada; Ceron, Jose J; Martinez, Emilio A; Rodriguez-Martinez, Heriberto; Roca, Jordi

    2016-01-01

    Glutathione peroxidase-5 (GPX5) is an H2O2-scavenging enzyme identified in boar seminal plasma (SP). This study attempted to clarify its origin and role on sperm survival and fertility after artificial insemination (AI). GPX5 was expressed (Western blot and immunocytochemistry using a rabbit primary polyclonal antibody) in testes, epididymis and accessory sex glands (6 boars). SP-GPX5 concentration differed among boars (11 boars, P < 0.001), among ejaculates within boar (44 ejaculates, P < 0.001) and among portions within ejaculate (15 ejaculates). The first 10 mL of the sperm rich fraction (SRF, sperm-peak portion) had a significantly lower concentration (8.87 ± 0.78 ng/mL) than the rest of the SRF and the post-SRF (11.66 ± 0.79 and 12.37 ± 0.79 ng/mL, respectively, P < 0.005). Sperm motility of liquid-stored semen AI-doses (n = 44, at 15-17°C during 72h) declined faster in AI-doses with low concentrations of SP-GPX5 compared to those with high-levels. Boars (n = 11) with high SP-GPX5 showed higher farrowing rates and litter sizes than those with low SP-GPX5 (a total of 5,275 inseminated sows). In sum, GPX5 is widely expressed in the boar genital tract and its variable presence in SP shows a positive relationship with sperm quality and fertility outcomes of liquid-stored semen AI-doses.

  12. Daily exposure to summer temperatures affects the motile subpopulation structure of epididymal sperm cells but not male fertility in an in vivo rabbit model.

    PubMed

    Maya-Soriano, M J; Taberner, E; Sabés-Alsina, M; Ramon, J; Rafel, O; Tusell, L; Piles, M; López-Béjar, M

    2015-08-01

    High temperatures have negative effects on sperm quality leading to temporary or permanent sterility. The aim of the study was to assess the effect of long exposure to summer circadian heat stress cycles on sperm parameters and the motile subpopulation structure of epididymal sperm cells from rabbit bucks. Twelve White New Zealand rabbit bucks were exposed to a daily constant temperature of the thermoneutral zone (from 18 °C to 22 °C; control group) or exposed to a summer circadian heat stress cycles (30 °C, 3 h/day; heat stress group). Spermatozoa were flushed from the epididymis and assessed for sperm quality parameters at recovery. Sperm total motility and progressivity were negatively affected by high temperatures (P < 0.05), as were also specific motility parameters (curvilinear velocity, linear velocity, mean velocity, straightness coefficient, linearity coefficient, wobble coefficient, and frequency of head displacement; P < 0.05, but not the mean amplitude of lateral head displacement). Heat stress significantly increased the percentage of less-motile sperm subpopulations, although the percentage of the high-motile subpopulation was maintained, which is consistent with the fact that no effect was detected on fertility rates. However, prolificacy was reduced in females submitted to heat stress when inseminated by control bucks. In conclusion, our results suggest that environmental high temperatures are linked to changes in the proportion of motile sperm subpopulations of the epididymis, although fertility is still preserved despite the detrimental effects of heat stress. On the other hand, prolificacy seems to be affected by the negative effects of high temperatures, especially by altering female reproduction.

  13. Identification of seven genes essential for male fertility through a genome-wide association study of non-obstructive azoospermia and RNA interference-mediated large-scale functional screening in Drosophila.

    PubMed

    Yu, Jun; Wu, Hao; Wen, Yang; Liu, Yujuan; Zhou, Tao; Ni, Bixian; Lin, Yuan; Dong, Jing; Zhou, Zuomin; Hu, Zhibin; Guo, Xuejiang; Sha, Jiahao; Tong, Chao

    2015-03-01

    Non-obstructive azoospermia (NOA) is a complex and severe condition whose etiology remains largely unknown. In a genome-wide association study (GWAS) of NOA in Chinese men, few loci reached genome-wide significance, although this might be a result of genetic heterogeneity. Single nucleotide polymorphisms (SNPs) without genome-wide significance may also indicate genes that are essential for fertility, and multiple stage validation can lead to false-negative results. To perform large-scale functional screening of the genes surrounding these SNPs, we used in vivo RNA interference (RNAi) in Drosophila, which has a short maturation cycle and is suitable for high-throughput analysis. The analysis found that 7 (31.8%) of the 22 analyzed orthologous Drosophila genes were essential for male fertility. These genes corresponded to nine loci. Of these genes, leukocyte-antigen-related-like (Lar) is primarily required in germ cells to sustain spermatogenesis, whereas CG12404, doublesex-Mab-related 11E (dmrt11E), CG6769, estrogen-related receptor (ERR) and sulfateless (sfl) function in somatic cells. Interestingly, ERR and sfl are also required for testis morphogenesis. Our study thus demonstrates that SNPs without genome-wide significance in GWAS may also provide clues to disease-related genes and therefore warrant functional analysis.

  14. Magnetic-field induced critical endpoint

    NASA Astrophysics Data System (ADS)

    Rechenberger, Stefan

    2017-03-01

    The phase diagram of strong interaction matter is analyzed utilizing the Nambu-Jona-Lasinio model. Special emphasis is placed on its dependence on an external magnetic field and isospin chemical potential. Using flavor mixing induced by instanton effects the influence of isospin breaking due to the magnetic field and the isospin chemical potential is compared. It is found that at low temperatures and large quark chemical potential the magnetic field, depending on its strength, induces a new critical endpoint or a triple point.

  15. Fertility Regulation in Male Rats by Implemented Tetraazamacrocyclic Compounds of Iron(II): Synthetic, Spectroscopic, and Applied Aspects With Toxicological Screening

    PubMed Central

    Chaudhary, Ashu; Vir Singh, Ran

    2006-01-01

    Antifertility and histopathological investigations were carried out on reproductive organs of male albino rats induced by tetraazamacrocyclic complexes of iron(II). The complexes were synthesized by the template condensation of 1,2-diaminoethane, 1,3-diaminopropane with succinic acid and phthalic acid in 2 : 2 molar ratios which are abbreviated as [Fe(TAMLn)OAc] (n = 1 or 2 and TAMLn represents tetraazamacrocyclic ligand). The complexes have been characterized by elemental analysis, conductivity measurements, IR, and electronic spectra. PMID:17497000

  16. Controlling Fertility.

    ERIC Educational Resources Information Center

    Donnay, France

    1991-01-01

    Recent developments in fertility control are presented in relation to the global demographic situation. Discussion focuses on changes in scientific knowledge and concepts that have shifted the focus from birth control to planned parenthood to the notion of controlled fertility. The place of family planning programs, including their socioeconomic…

  17. Nonalcoholic Steatohepatitis and Endpoints in Clinical Trials

    PubMed Central

    Hannah, William N.; Torres, Dawn M.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in developed countries, and the rates of NAFLD continue to rise in conjunction with the obesity pandemic. While the majority of patients with isolated steatosis generally have a benign course, a diagnosis of nonalcoholic steatohepatitis (NASH) carries a significantly higher risk for progression of disease, cirrhosis, and death. Pharmacologic therapeutic interventions in NASH have largely proven to be ineffective or unappealing due to long-term side-effect profiles, and the majority of patients cannot achieve or sustain targeted weight loss goals, necessitating an urgent need for therapeutic trials and drug development. The complex molecular mechanisms leading to NASH and the long duration of time to develop complications of disease are challenges to developing meaningful clinical endpoints. Because of these challenges, surrogate endpoints that are linked to all-cause mortality, liver-related death, and complications of cirrhosis are much more likely to be beneficial in the majority of patients. PMID:28035202

  18. Strategies and Endpoints of Antifibrotic Drug Trials

    PubMed Central

    Torok, Natalie; Dranoff, Jonathan A.; Schuppan, Detlef; Friedman, Scott L.

    2015-01-01

    There is an urgent need to develop antifibrotic therapies for chronic liver disease, and to clarify which endpoints in antifibrotic trials will be acceptable to regulatory agencies. AASLD sponsored an endpoints conference to help accelerate the efficient testing of antifibrotic agents and to develop recommendations on clinical trial design for liver fibrosis. In this review we summarize the salient and novel elements of this conference and provide directions for future clinical trial design. The paper follows the structure of the conference and is organized into five areas: I) Antifibrotic trial design; II) Preclinical proof of concept studies; III) Pharmacologic targets: rationale and lessons to learn; IV) Rational drug design and development; V) Consensus and recommendations on design of clinical trials in liver fibrosis. Expert overviews and collaborative discussions helped to summarize the key unmet needs and directions for the future, including: 1) Greater clarification of at-risk populations and study groups; 2) Standardization of all elements of drug discovery and testing; 3) Standardization of clinical trial approaches; 4) Accelerated development of improved non-invasive markers; 5) Need for exploration of potential off-target toxicities of future antifibrotic drugs. PMID:25626988

  19. Radiation protection of male fertility in mouse and rat by a combination of 5-hydroxy-L-tryptophan and a thiol compound (AET).

    PubMed

    George, S; Chuttani, K; Basu, S K

    1992-01-01

    Sperm abnormalities and fall in total sperm count following different doses (4 Gy, 5 Gy and 6 Gy) of whole body gamma irradiation (WBGR) were studied in adult male Swiss strain A mice. The protecting ability of a combination of 5-hydroxy-L-tryptophan (5-HTP, 100 mg/kg) and 2-aminoethyl isothiuronium bromide hydrobromide (AET, 20 mg/kg) was also investigated. Pretreatment with a 5-HTP+AET formulation i.p., 30 min before irradiation modified the fall in sperm counts significantly. Exposures to 4 Gy, 5 Gy and 6 Gy WBGR caused marked increase of sperm abnormalities which could be significantly reduced by pretreatment with 5-HTP-AET. WBGR with 4 Gy, 5 Gy and 6 Gy produced a short period of sterility associated with oligospermia but these abnormalities were corrected by pretreatment with 5-HTP+AET. This finding was supported by breeding experiments in pretreated adult male Sprague-Dawley rats which showed delivery of normal offsprings in drug-protected irradiated groups in contrast to irradiated controls.

  20. Male fertility versus sterility, cytotype, and DNA quantitative variation in seed production in diploid and tetraploid sea lavenders (Limonium sp., Plumbaginaceae) reveal diversity in reproduction modes.

    PubMed

    Róis, Ana Sofia; Teixeira, Generosa; Sharbel, Timothy F; Fuchs, Jörg; Martins, Sérgio; Espírito-Santo, Dalila; Caperta, Ana D

    2012-12-01

    The genus Limonium Miller, a complex taxonomic group, comprises annuals and perennials that can produce sexual and/or asexual seeds (apomixis). In this study, we used diverse cytogenetic and cytometric approaches to analyze male sporogenesis and gametogenesis for characterizing male reproductive output on seed production in Limonium ovalifolium and Limonium multiflorum. We showed here that the first species is mostly composed of diploid cytotypes with 2n = 16 chromosomes and the latter species by tetraploid cytotypes with 2n = 32, 34, 35, 36 chromosomes and had a genome roughly twice as big as the former one. In both species, euploid and aneuploid cytotypes with large metacentric chromosomes having decondensed interstitial sites were found within and among populations, possibly involved in chromosomal reconstructions. L. ovalifolium diploids showed regular meiosis resulting in normal tetrads, while diverse chromosome pairing and segregation irregularities leading to the formation of abnormal meiotic products are found in balanced and non-balanced L. multiflorum tetraploids. Before anther dehiscence, the characteristic unicellular, bicellular, or tricellular pollen grains showing the typical Limonium micro- or macro-reticulate exine ornamentation patterns were observed in L. ovalifolium using scanning electron microscopy. Most of these grains were viable and able to produce pollen tubes in vitro. In both balanced and unbalanced L. multiflorum tetraploids, microspores only developed until the "ring-vacuolate stage" with a collapsed morphology without the typical exine patterns, pointing to a sporophytic defect. These microspores were unviable and therefore never germinated in vitro. L. ovalifolium individuals presented larger pollen grains than those of L. multiflorum, indicating that pollen size and ploidy levels are not correlated in the Limonium system. Cytohistological studies in mature seeds from both species revealed that an embryo and a residual endosperm

  1. Determining Significant Endpoints for Ecological risk Analyses

    SciTech Connect

    Hinton, Thimas G.; Bedford, Joel

    1999-06-01

    Our interest is in obtaining a scientifically defensible endpoint for measuring ecological risks to populations exposed to chronic, low-level radiation, and radiation with concomitant exposure to chemicals. To do so, we believe that we must understand the extent to which molecular damage is detrimental at the individual and population levels of biological organization. Ecological risk analyses based on molecular damage, without an understanding of the impacts to higher levels of biological organization, could cause cleanup strategies on DOE sites to be overly conservative and unnecessarily expensive. Our goal is to determine the relevancy of sublethal cellular damage to the performance of individuals and populations. We think that we can achieve this by using novel biological dosimeters in controlled, manipulative dose/effects experiments, and by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables such as age-specific survivorship, reproductive output, age at maturity and longevity.

  2. Comparing laboratory and field measured bioaccumulation endpoints.

    PubMed

    Burkhard, Lawrence P; Arnot, Jon A; Embry, Michelle R; Farley, Kevin J; Hoke, Robert A; Kitano, Masaru; Leslie, Heather A; Lotufo, Guilherme R; Parkerton, Thomas F; Sappington, Keith G; Tomy, Gregg T; Woodburn, Kent B

    2012-01-01

    An approach for comparing laboratory and field measures of bioaccumulation is presented to facilitate the interpretation of different sources of bioaccumulation data. Differences in numerical scales and units are eliminated by converting the data to dimensionless fugacity (or concentration-normalized) ratios. The approach expresses bioaccumulation metrics in terms of the equilibrium status of the chemical, with respect to a reference phase. When the fugacity ratios of the bioaccumulation metrics are plotted, the degree of variability within and across metrics is easily visualized for a given chemical because their numerical scales are the same for all endpoints. Fugacity ratios greater than 1 indicate an increase in chemical thermodynamic activity in organisms with respect to a reference phase (e.g., biomagnification). Fugacity ratios less than 1 indicate a decrease in chemical thermodynamic activity in organisms with respect to a reference phase (e.g., biodilution). This method provides a holistic, weight-of-evidence approach for assessing the biomagnification potential of individual chemicals because bioconcentration factors, bioaccumulation factors, biota-sediment accumulation factors, biomagnification factors, biota-suspended solids accumulation factors, and trophic magnification factors can be included in the evaluation. The approach is illustrated using a total 2393 measured data points from 171 reports, for 15 nonionic organic chemicals that were selected based on data availability, a range of physicochemical partitioning properties, and biotransformation rates. Laboratory and field fugacity ratios derived from the various bioaccumulation metrics were generally consistent in categorizing substances with respect to either an increased or decreased thermodynamic status in biota, i.e., biomagnification or biodilution, respectively. The proposed comparative bioaccumulation endpoint assessment method could therefore be considered for decision making in a

  3. Small tubules, surprising discoveries: from efferent ductules in the turkey to the discovery that estrogen receptor alpha is essential for fertility in the male

    PubMed Central

    Hess, R.A.

    2017-01-01

    Efferent ductules are small, delicate tubules that connect rete testis with the head of the epididymis, first identified by de Graaf in 1668. Although difficult to find in routine dissection, the ductules are an essential component of the male reproductive tract and in larger mammals occupy up more than 50% of the caput epididymidis. My introduction to research began with the study of efferent ductules in the domestic turkey, and to my surprise these small structures with kidney-like function become the core for numerous discoveries throughout my scientific career. In this review, only two discoveries that I found interesting will be discussed: cilia that line the efferent ductule lumen and estrogen receptors that play an essential role in regulating fluid reabsorption. A potential link between these two discoveries was uncovered in the study of efferent ductule effects observed in the estrogen receptor knockout mouse and following toxic exposure to the fungicide benomyl. PMID:28191043

  4. Novel Role for p110β PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells

    PubMed Central

    Guillermet-Guibert, Julie; Smith, Lee B.; Halet, Guillaume; Whitehead, Maria A.; Pearce, Wayne; Rebourcet, Diane; León, Kelly; Crépieux, Pascale; Nock, Gemma; Strömstedt, Maria; Enerback, Malin; Chelala, Claude; Graupera, Mariona; Carroll, John; Cosulich, Sabina; Saunders, Philippa T. K.; Huhtaniemi, Ilpo; Vanhaesebroeck, Bart

    2015-01-01

    The organismal roles of the ubiquitously expressed class I PI3K isoform p110β remain largely unknown. Using a new kinase-dead knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interact. PMID:26132308

  5. Fertility Awareness

    MedlinePlus

    ... when ovulation happens. Couples use a calendar, a thermometer to measure body temperature, the thickness of cervical ... fertility awareness — such as ovulation detection kits and thermometers, for example — are available in drugstores. But they ...

  6. Predicting fertility.

    PubMed

    Maheshwari, Abha; Bhattacharya, Siladitya; Johnson, Neil P

    2008-06-01

    Various predictors of fertility have been described, suggesting that none are ideal. The literature on tests of ovarian reserve is largely limited to women undergoing in vitro fertilization, and is reliant on the use of surrogate markers, such as cycle cancellation and number of oocytes retrieved, as reference standards. Currently available prediction models are far from ideal; most are applicable only to subfertile women seeking assisted reproduction, and lack external validation. Systematic reviews and meta-analyses of predictors of fertility are limited by their heterogeneity in terms of the population sampled, predictors tested and reference standards used. There is an urgent need for consensus in the design of these studies, definition of abnormal tests, and, above all, a need to use robust outcomes such as live birth as the reference standard. There are no reliable predictors of fertility that can guide women as to how long childbearing can be deferred.

  7. Fertility Awareness

    MedlinePlus

    ... time the couple using only fertility awareness for birth control who does not want to get pregnant should ... period. In general, how well each type of birth control method works depends on a lot of things. ...

  8. Effect of Pre-Fixation Delay and Freezing on Mink Testicular Endpoints for Environmental Research

    PubMed Central

    Spörndly-Nees, Ellinor; Ekstedt, Elisabeth; Magnusson, Ulf; Fakhrzadeh, Azadeh; Luengo Hendriks, Cris L.; Holm, Lena

    2015-01-01

    There is growing interest in using wild animals to monitor the real-life cocktail effect of environmental chemicals on male reproduction. However, practical difficulties, such as long distances to the laboratory, generally prolong the time between euthanisation and specimen handling. For instance, tissue fixation is often performed on frozen material or on material where deterioration has started, which may affect tissue morphology. This study examined the effect of pre-fixation delay and freezing on mink testicular endpoints in order to determine robust endpoints in suboptimally handled specimens. Sexually mature farmed mink (n=30) selected at culling were divided into six groups and subjected to different time intervals between euthanisation and fixation or freezing: 0 hours (fixed immediately post mortem), 6 hours, 18 hours, 30 hours, 42 hours, or frozen 6 hours post mortem and thawed overnight. Unaffected endpoints when pre-fixation storage was extended to 30 hours included: area and diameter of the seminiferous tubules, length and weight of the testes, and acrosomes marked with Gata-4. Epithelial height, Sertoli cells marked with Gata-4 and cell morphology were affected endpoints after 6 hours of storage. Freezing the tissue prior to fixation severely altered cell morphology and reduced testicular weight, tubular diameter and area. Morphological changes seen after 6 hours included shredded germ cells and excess cytoplasm in seminiferous tubular lumen, chromatin rearrangements and increased germ cell death. Extended delay before fixation and freezing affected many endpoints in the mink testicular tissue. Some of these endpoints may mimic chemically induced effects, which is important to consider when evaluating specimens from wild animals for environmental toxicity. PMID:25933113

  9. RNA editing events in mitochondrial genes by ultra-deep sequencing methods: a comparison of cytoplasmic male sterile, fertile and restored genotypes in cotton.

    PubMed

    Suzuki, Hideaki; Yu, Jiwen; Ness, Scott A; O'Connell, Mary A; Zhang, Jinfa

    2013-09-01

    Cytoplasmic male sterility (CMS) is a maternally inherited trait resulting in failure to produce functional pollen and is widely used in the production of hybrid seed. Improper RNA editing is implicated as the molecular basis for some CMS systems. However, the mechanism of CMS in cotton is unknown. This study compared RNA editing events in eight mitochondrial genes (atp1, 4, 6, 8, 9, and cox1, 2, 3) among three lines (maintainer B, CMS A, and restorer R). These events were quantified by ultra-deep sequencing of mitochondrial transcripts and sequencing of cloned versions of these genes as cDNAs. A comparison of genomic PCR and RT-PCR products detected 72 editing sites in coding sequences in the eight genes and four partial editing sites in the 3'-untranslated region of atp6. The most frequent alteration (61.4 %) resulted in changes of hydrophilic amino acids to hydrophobic amino acids and the most common alteration was proline (P) to leucine (L) (26.7 %). In atp6, RNA editing created a stop codon from a glutamine in the genomic sequence. Statistical analysis of the frequencies of RNA editing events detected differences between mtDNA genes, but no differences between cotton cytoplasms that could account for the CMS phenotype or restoration. This study represents the first work to use next-generation sequencing to identify RNA editing positions and efficiency, and possible association with CMS and restoration in plants.

  10. Population-scale assessment endpoints in ecological risk assessment part II: selection of assessment endpoint attributes.

    PubMed

    Landis, Wayne G; Kaminski, Laurel A

    2007-07-01

    Because ecological services often are tied to specific species, the risk to populations is a critical endpoint and important feature of ecological risk assessments. In Part 1 of this series it was demonstrated that population scale assessment endpoints are important expressions of the valued components of ecological structures. This commentary reviews several of the characteristics of populations that can be evaluated and used in population scale risk assessments. Two attributes are evaluated as promising. The 1st attribute is the change in potential productivity of the population over a specified time period. The 2nd attribute is the change in the age structure of a population, expressed graphically or as a normalized effects vector (NEV). The NEV is a description of the change in age structure due to a toxicant or other stressor and appears to be characteristic of specific stressor effects.

  11. Ecosystem services as assessment endpoints for ecological risk assessment.

    PubMed

    Munns, Wayne R; Rea, Anne W; Suter, Glenn W; Martin, Lawrence; Blake-Hedges, Lynne; Crk, Tanja; Davis, Christine; Ferreira, Gina; Jordan, Steve; Mahoney, Michele; Barron, Mace G

    2016-07-01

    Ecosystem services are defined as the outputs of ecological processes that contribute to human welfare or have the potential to do so in the future. Those outputs include food and drinking water, clean air and water, and pollinated crops. The need to protect the services provided by natural systems has been recognized previously, but ecosystem services have not been formally incorporated into ecological risk assessment practice in a general way in the United States. Endpoints used conventionally in ecological risk assessment, derived directly from the state of the ecosystem (e.g., biophysical structure and processes), and endpoints based on ecosystem services serve different purposes. Conventional endpoints are ecologically important and susceptible entities and attributes that are protected under US laws and regulations. Ecosystem service endpoints are a conceptual and analytical step beyond conventional endpoints and are intended to complement conventional endpoints by linking and extending endpoints to goods and services with more obvious benefit to humans. Conventional endpoints can be related to ecosystem services even when the latter are not considered explicitly during problem formulation. To advance the use of ecosystem service endpoints in ecological risk assessment, the US Environmental Protection Agency's Risk Assessment Forum has added generic endpoints based on ecosystem services (ES-GEAE) to the original 2003 set of generic ecological assessment endpoints (GEAEs). Like conventional GEAEs, ES-GEAEs are defined by an entity and an attribute. Also like conventional GEAEs, ES-GEAEs are broadly described and will need to be made specific when applied to individual assessments. Adoption of ecosystem services as a type of assessment endpoint is intended to improve the value of risk assessment to environmental decision making, linking ecological risk to human well-being, and providing an improved means of communicating those risks. Integr Environ Assess Manag

  12. ABNORMAL POLLEN VACUOLATION1 (APV1) is required for male fertility by contributing to anther cuticle and pollen exine formation in maize.

    PubMed

    Somaratne, Yamuna; Tian, Youhui; Zhang, Hua; Wang, Mingming; Huo, Yanqing; Cao, Fengge; Zhao, Li; Chen, Huabang

    2017-01-12

    Anther cuticle and pollen exine are the major protective barriers against various stresses. The proper functioning of genes expressed in the tapetum is vital for the development of pollen exine and anther cuticle. In this study, we report a tapetum-specific gene, Abnormal Pollen Vacuolation1 (APV1), in maize that affects anther cuticle and pollen exine formation. The apv1 mutant was completely male sterile. Its microspores were swollen, less vacuolated, with a flat and empty anther locule. In the mutant, the anther epidermal surface was smooth, shiny, and plate-shaped compared with the three-dimensional crowded ridges and randomly formed wax crystals on the epidermal surface of the wild-type. The wild-type mature pollen had elaborate exine patterning, whereas the apv1 pollen surface was smooth. Only a few unevenly distributed Ubisch bodies were formed on the apv1 mutant, leading to a more apparent inner surface. A significant reduction in the cutin monomers was observed in the mutant. APV1 encodes a member of the P450 subfamily, CYP703A2-Zm, which contains 530 amino acids. APV1 appeared to be widely expressed in the tapetum at the vacuolation stage, and its protein signal co-localized with the endoplasmic reticulum (ER) signal. RNA-Seq data revealed that most of the genes in the fatty acid metabolism pathway were differentially expressed in the apv1 mutant. Altogether, we suggest that APV1 functions in the fatty acid hydroxylation pathway which is involved in forming sporopollenin precursors and cutin monomers that are essential for the development of pollen exine and anther cuticle in maize.

  13. Ordered kinematic endpoints for 5-body cascade decays

    NASA Astrophysics Data System (ADS)

    Klimek, Matthew D.

    2016-12-01

    We present expressions for the kinematic endpoints of 5-body cascade decay chains proceeding through all possible combinations of 2-body and 3-body decays, with one stable invisible particle in the final decay stage. When an invariant mass can be formed in multiple ways by choosing different final state particles from a common vertex, we introduce techniques for finding the sub-leading endpoints for all indistinguishable versions of the invariant mass. In contrast to short decay chains, where sub-leading endpoints are linearly related to the leading endpoints, we find that in 5-body decays, they provide additional independent constraints on the mass spectrum.

  14. Voluntary control of static endpoint stiffness during force regulation tasks.

    PubMed

    Perreault, Eric J; Kirsch, Robert F; Crago, Patrick E

    2002-06-01

    The goals of this study were to determine the degree to which subjects could voluntarily modulate static endpoint stiffness orientation and to quantify the effects of simultaneously generated voluntary endpoint forces on this ability. Static endpoint stiffness, which characterizes the relationship between externally imposed displacements of the hand and the elastic forces generated in response, was estimated in real time during the application of planar, stochastic perturbations of endpoint position. This estimation was accomplished using a real-time parametric identification algorithm on measured force and position data. Subjects were provided with real-time visual feedback of endpoint stiffness, and their ability to modulate the orientation of maximum static stiffness was measured for different endpoint force magnitudes and directions. We found that individuals can voluntarily change stiffness orientation but that the magnitude of these changes is small, the range of available stiffness orientations decreases as endpoint force exertion increases, and endpoint force direction significantly constrains direction and magnitude of the stiffness orientations that can be achieved. Given these findings it appears unlikely that static endpoint stiffness orientation is controlled independently of force by voluntary neural mechanisms during postural tasks.

  15. Genetic damage and the expression of behavioral abnormalities in the progeny of male rats exposed to ionizing radiation

    SciTech Connect

    Lowery, M.C.

    1987-01-01

    To determine the possible genetic nature of behavioral anomalies, an identifiable genetic endpoint, inherited chromosome translocations in the offspring, was selected to evaluate the relationship to behavior. Young adult male Fischer 344 rats were exposed to 50-300 rads of ionizing radiation. Two weeks following their irradiation, the males were mated with four virgin females for one week. During this time, fertilizing sperm were derived from post-meiotic spermatids, the stage of the spermatogenic cycle most sensitive to the mutagenic effects of radiation. Behavioral analyses of the resulting 390 offspring consisted of both motor reflex and motor coordination measurements as well as learning and retention parameters. Significant differences in performance were seen in several of the motor reflex measurements in progeny of males exposed to some of the higher doses of irradiation. A similar phenomenon was observed in the performance of a single learned behavior.

  16. Translational endpoints in fragile X syndrome.

    PubMed

    de Esch, Celine E F; Zeidler, Shimriet; Willemsen, Rob

    2014-10-01

    Fragile X syndrome (FXS) occurs in less than 10% of the intellectually disabled (ID) population. The cause of FXS is a CGG trinucleotide repeat longer than 200 CGG units within the first exon of the FMR1 gene, which leads to hypermethylation and consequently silencing of the FMR1 gene. The lack of FMR1's gene product, the fragile X mental retardation protein (FMRP) in neurons is the cause of the ID in patients with FXS. FMRP plays an important role in local protein synthesis at the synapse including modulation of synaptic plasticity. The advancing knowledge about the cellular function of FMRP has led to the identification of translational endpoints for future therapeutic intervention strategies. This review highlights the challenging routes to the identification of reliable outcome measures in preclinical studies using both cellular models and Fmr1 knockout mice. Finally, clinical studies carried out to correct intellectual and behavioral deficits in patients with FXS, using a variety of existing and new drugs, are discussed.

  17. Targeted ablation of plasma membrane Ca2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4.

    PubMed

    Okunade, Gbolahan W; Miller, Marian L; Pyne, Gail J; Sutliff, Roy L; O'Connor, Kyle T; Neumann, Jonathan C; Andringa, Anastasia; Miller, Daniel A; Prasad, Vikram; Doetschman, Thomas; Paul, Richard J; Shull, Gary E

    2004-08-06

    The relative importance of plasma membrane Ca2+-ATPase (PMCA) 1 and PMCA4 was assessed in mice carrying null mutations in their genes (Atp2b1 and Atp2b4). Loss of both copies of the gene encoding PMCA1 caused embryolethality, whereas heterozygous mutants had no overt disease phenotype. Despite widespread and abundant expression of PMCA4, PMCA4 null (Pmca4-/-) mutants exhibited no embryolethality and appeared outwardly normal. Loss of PMCA4 impaired phasic contractions and caused apoptosis in portal vein smooth muscle in vitro; however, this phenotype was dependent on the mouse strain being employed. Pmca4-/- mice on a Black Swiss background did not exhibit the phenotype unless they also carried a null mutation in one copy of the Pmca1 gene. Pmca4-/- male mice were infertile but had normal spermatogenesis and mating behavior. Pmca4-/- sperm that had not undergone capacitation exhibited normal motility but could not achieve hyperactivated motility needed to traverse the female genital tract. Ultrastructure of the motility apparatus in Pmca4-/- sperm tails was normal, but an increased incidence of mitochondrial condensation indicated Ca2+ overload. Immunoblotting and immunohistochemistry showed that PMCA4 is the most abundant isoform in testis and sperm and that it is localized to the principle piece of the sperm tail, which is also the location of the major Ca2+ channel (CatSper) required for sperm motility. These results are consistent with an essential housekeeping or developmental function for PMCA1, but not PMCA4, and show that PMCA4 expression in the principle piece of the sperm tail is essential for hyperactivated motility and male fertility.

  18. Transgenic Pearl Millet Male Fertility Restorer Line (ICMP451) and Hybrid (ICMH451) Expressing Brassica juncea Nonexpressor of Pathogenesis Related Genes 1 (BjNPR1) Exhibit Resistance to Downy Mildew Disease

    PubMed Central

    Khareedu, Venkateswara Rao; Vudem, Dashavantha Reddy

    2014-01-01

    Brassica juncea Nonexpressor of pathogenesis-related genes 1 (BjNPR1) has been introduced into pearl millet male fertility restorer line ICMP451 by Agrobacterium tumefaciens-mediated genetic transformation. Transgenic pearl millet plants were regenerated from the phosphinothricin-resistant calli obtained after co-cultivation with A. tumefaciens strain LBA4404 harbouring Ti plasmid pSB111-bar-BjNPR1. Molecular analyses confirmed the stable integration and expression of BjNPR1 in transgenic pearl millet lines. Transgenes BjNPR1 and bar were stably inherited and disclosed co-segregation in subsequent generations in a Mendelian fashion. Transgenic pearl millet hybrid ICMH451-BjNPR1 was developed by crossing male-sterile line 81A X homozygous transgenic line ICMP451-BjNPR1. T3 and T4 homozygous lines of ICMP451-BjNPR1 and hybrid ICMH451-BjNPR1 exhibited resistance to three strains of downy mildew pathogen, while the untransformed ICMP451 and the isogenic hybrid ICMH451 plants were found susceptible. Following infection with S. graminicola, differential expression of systemic acquired resistance pathway genes, UDP-glucose salicylic acid glucosyl transferase and pathogenesis related gene 1 was observed in transgenic ICMP451-BjNPR1 and untransformed plants indicating the activation of systemic acquired resistance pathway contributing to the transgene-mediated resistance against downy mildew. The transgenic pearl millet expressing BjNPR1 showed resistance to multiple strains of S. graminicola and, as such, seems promising for the development of durable downy mildew resistant hybrids. PMID:24603762

  19. Doubled Haploid ‘CUDH2107’ as a Reference for Bulb Onion (Allium cepa L.) Research: Development of a Transcriptome Catalogue and Identification of Transcripts Associated with Male Fertility

    PubMed Central

    Khosa, Jiffinvir S.; Lee, Robyn; Bräuning, Sophia; Lord, Janice; Pither-Joyce, Meeghan; McCallum, John; Macknight, Richard C.

    2016-01-01

    Researchers working on model plants have derived great benefit from developing genomic and genetic resources using ‘reference’ genotypes. Onion has a large and highly heterozygous genome making the sharing of germplasm and analysis of sequencing data complicated. To simplify the discovery and analysis of genes underlying important onion traits, we are promoting the use of the homozygous double haploid line ‘CUDH2107’ by the onion research community. In the present investigation, we performed transcriptome sequencing on vegetative and reproductive tissues of CUDH2107 to develop a multi-organ reference transcriptome catalogue. A total of 396 million 100 base pair paired reads was assembled using the Trinity pipeline, resulting in 271,665 transcript contigs. This dataset was analysed for gene ontology and transcripts were classified on the basis of putative biological processes, molecular function and cellular localization. Significant differences were observed in transcript expression profiles between different tissues. To demonstrate the utility of our CUDH2107 transcriptome catalogue for understanding the genetic and molecular basis of various traits, we identified orthologues of rice genes involved in male fertility and flower development. These genes provide an excellent starting point for studying the molecular regulation, and the engineering of reproductive traits. PMID:27861615

  20. Sperm gamma-aminobutyric acid type A receptor delta subunit (GABRD) and its interaction with purinergic P2X2 receptors in progesterone-induced acrosome reaction and male fertility.

    PubMed

    Xu, Wenming; Wang, Ke; Chen, Yan; Liang, Xiao Tong; Yu, Mei Kuen; Yue, Huanxun; Tierney, M Louise

    2017-02-13

    The mechanism underlying the non-genomic action of progesterone in sperm functions and related Ca2+ mobilisation remains elusive. Herein we report the expression of gamma-aminobutyric acid type A receptor delta subunit (GABRD) in human and rodent sperm and its involvement in mediating the progesterone-induced acrosome reaction. GABRD was localised in the sperm head/neck region. A δ(392-422)-specific inhibitory peptide against GABRD blocked the progesterone-induced acrosome reaction and the associated increase in intracellular Ca2+. Similarly, an inhibitory effect against both progesterone-induced Ca2+ influx and the acrosome reaction was observed with a P2X2 receptor antagonist. The lack of synergism between the GABRD and P2X2 inhibitors suggests that these two receptors are playing a role in the same pathway. Furthermore, a co-immunoprecipitation experiment demonstrated that GABRD could undergo protein-protein interactions with the Ca2+-conducting P2X2 receptor. This interaction between the receptors could be reduced following progesterone (10μM) inducement. Significantly reduced GABRD expression was observed in spermatozoa from infertile patients with reduced acrosome reaction capacity, suggesting that normal expression of GABRD is critical for the sperm acrosome reaction and thus male fertility. The results of the present study indicate that GABRD represents a novel progesterone receptor or modulator in spermatozoa that is responsible for the progesterone-induced Ca2+ influx required for the acrosome reaction through its interaction with the P2X2 receptor.

  1. Computer Model for Prediction of PCB Dechlorination and Biodegradation Endpoints

    SciTech Connect

    Just, E.M.; Klasson, T.

    1999-04-19

    Mathematical modeling of polychlorinated biphenyl (PCB) transformation served as a means of predicting possible endpoints of bioremediation, thus allowing evaluation of several of the most common transformation patterns. Correlation between laboratory-observed and predicted endpoint data was, in some cases, as good as 0.98 (perfect correlation = 1.0).

  2. Sperm macromolecules associated with bull fertility.

    PubMed

    Kaya, Abdullah; Memili, Erdoğan

    2016-06-01

    Bull fertility, ability of the sperm to fertilize and activate the egg that sustain embryo development, is vitally important for effective and efficient production of cattle. Fertility is a complex trait with low heritability. Despite recent advances in genomic selection and possibility of enormous paternal benefits to profitable cattle production, there exist no reliable tests for evaluating semen quality and predicting bull fertility. This review focuses on sperm macromolecules such as transcripts, proteins and the epigenome, i.e., the functional genome that are associated with bull fertility. Generating new information in these systems is important beyond agriculture because such progress advances the fundamental science of the mammalian male gamete while at the same time introduces biotechnology into livestock production. Sperm macromolecules and epigenome markers associated with bull fertility can be used alone or in combination with the current SNP microarrays to determine sperm quality and to indicate bull fertility.

  3. Effects of simulated weightlessness on meiosis. Fertilization, and early development in mice

    NASA Technical Reports Server (NTRS)

    Wolgemuth, D. J.

    1986-01-01

    The initial goal was to construct a clinostat which could support mammalian cell culture. The clinostat was selected as a means by which to simulate microgravity conditions within the laboratory, by constant re-orientation of cells with respect to the gravity vector. The effects of this simulated microgravity on in-vitro meiotic maturation of oocytes, using mouse as the model system, was investigated. The effects of clinostat rotation on fertilization in-vitro was then examined. Specific endpoints included examining the timely appearance of male and female pronuclei (indicating fertilization) and the efficiency of extrusion of the second polar body. Particular attention was paid to detecting anomalies of fertilization, including parthenogenetic activation and multiple pronuclei. Finally, for the preliminary studies on mouse embryogenesis, a key feature of the clinostat was modified, that of the position of the cells during rotation. A means was found to immobilize the cells during the clinostat reotation, permitting the cells to remain at the axis of rotation yet not interfering with cellular development.

  4. Fertility and the family.

    PubMed

    Kono, S

    1991-09-01

    The developed countries of Asia include Japan and the newly industrialized economies of Hong Kong, Taiwan, Republic of Korea, and Singapore. These 5 societies share various similarities that have helped in their socioeconomic development. The 1st includes a significant and quite rapid socioeconomic development (per capita gross national product, urbanization, demographic transition, educational attainment, and industrialization). The 2nd similarity is the extremely high levels of education. Indeed those 5 societies boast the most highly educated populations in Asia. 3rd, they have achieved below replacement fertility. In fact, they never really had very high birth rates anyhow. 4th, extended families are the norm despite rapid transformation of their societies. Confucianism, the 5th similarity, advocates multigenerational families. Children understand that it is their duty to always take care of their parents. Parents know that they have a right to ask for their children's help at any time. In 1981, a demographer hypothesized that 1 of the leading signs of fertility decline is the nucleation of the family. yet in these 5 societies nucleation did not appear before fertility decline. In fact, in Japan, fertility is higher in those homes where the grandmother watches her grandchildren while the daughter or daughter-in-law is at work. Some have compared the role of Confucianism in socioeconomic development with that of Protestantism in the industrialization of Europe. Both stress hard work, simplicity, frugality, discipline, and regularity in daily life. Yet Confucianism sees women as bearers of children and servants to men. Women in these societies protest this mindset by postponing marriage and having few children. If these societies wish to increase fertility, they need to restructure their male oriented societies.

  5. A novel test of the phenotype-linked fertility hypothesis reveals independent components of fertility.

    PubMed Central

    Pizzari, Tommaso; Jensen, Per; Cornwallis, Charles K.

    2004-01-01

    The phenotype-linked fertility hypothesis predicts that male sexual ornaments signal fertilizing efficiency and that the coevolution of male ornaments and female preference for such ornaments is driven by female pursuit of fertility benefits. In addition, directional testicular asymmetry frequently observed in birds has been suggested to reflect fertilizing efficiency and to covary with ornament expression. However, the idea of a phenotypic relationship between male ornaments and fertilizing efficiency is often tested in populations where environmental effects mask the underlying genetic associations between ornaments and fertilizing efficiency implied by this idea. Here, we adopt a novel design, which increases genetic diversity through the crossing of two divergent populations while controlling for environmental effects, to test: (i) the phenotypic relationship between male ornaments and both, gonadal (testicular mass) and gametic (sperm quality) components of fertilizing efficiency; and (ii) the extent to which these components are phenotypically integrated in the fowl, Gallus gallus. We show that consistent with theory, the testosterone-dependent expression of a male ornament, the comb, predicted testicular mass. However, despite their functional inter-dependence, testicular mass and sperm quality were not phenotypically integrated. Consistent with this result, males of one parental population invested more in testicular and comb mass, whereas males of the other parental population had higher sperm quality. We found no evidence that directional testicular asymmetry covaried with ornament expression. These results shed new light on the evolutionary relationship between male fertilizing efficiency and ornaments. Although testosterone-dependent ornaments may covary with testicular mass and thus reflect sperm production rate, the lack of phenotypic integration between gonadal and gametic traits reveals that the expression of an ornament is unlikely to reflect the

  6. The application of GBS markers for extending the dense genetic map of rye (Secale cereale L.) and the localization of the Rfc1 gene restoring male fertility in plants with the C source of sterility-inducing cytoplasm.

    PubMed

    Milczarski, Paweł; Hanek, Monika; Tyrka, Mirosław; Stojałowski, Stefan

    2016-11-01

    Genotyping by sequencing (GBS) is an efficient method of genotyping in numerous plant species. One of the crucial steps toward the application of GBS markers in crop improvement is anchoring them on particular chromosomes. In rye (Secale cereale L.), chromosomal localization of GBS markers has not yet been reported. In this paper, the application of GBS markers generated by the DArTseq platform for extending the high-density map of rye is presented. Additionally, their application is used for the localization of the Rfc1 gene that restores male fertility in plants with the C source of sterility-inducing cytoplasm. The total number of markers anchored on the current version of the map is 19,081, of which 18,132 were obtained from the DArTseq platform. Numerous markers co-segregated within the studied mapping population, so, finally, only 3397 unique positions were located on the map of all seven rye chromosomes. The total length of the map is 1593 cM and the average distance between markers is 0.47 cM. In spite of the resolution of the map being not very high, it should be a useful tool for further studies of the Secale cereale genome because of the presence on this map of numerous GBS markers anchored for the first time on rye chromosomes. The Rfc1 gene was located on high-density maps of the long arm of the 4R chromosome obtained for two mapping populations. Genetic maps were composed of DArT, DArTseq, and PCR-based markers. Consistent mapping results were obtained and DArTs tightly linked to the Rfc1 gene were successfully applied for the development of six new PCR-based markers useful in marker-assisted selection.

  7. Equipment management risk rating system based on engineering endpoints.

    PubMed

    James, P J

    1999-01-01

    The equipment management risk ratings system outlined here offers two significant departures from current practice: risk classifications are based on intrinsic device risks, and the risk rating system is based on engineering endpoints. Intrinsic device risks are categorized as physical, clinical and technical, and these flow from the incoming equipment assessment process. Engineering risk management is based on verification of engineering endpoints such as clinical measurements or energy delivery. This practice eliminates the ambiguity associated with ranking risk in terms of physiologic and higher-level outcome endpoints such as no significant hazards, low significance, injury, or mortality.

  8. Gender attitudes and fertility aspirations among young men in five high fertility East African countries.

    PubMed

    Snow, Rachel C; Winter, Rebecca A; Harlow, Siobán D

    2013-03-01

    The relationship between women's attitudes toward gender equality and their fertility aspirations has been researched extensively, but few studies have explored the same associations among men. Using recent Demographic and Health Survey data from five high fertility East African countries, we examine the association between young men's gender attitudes and their ideal family size. Whereas several DHS gender attitude responses were associated with fertility aspirations in select countries, men's greater tolerance of wife beating was consistently associated with higher fertility aspirations across all countries, independent of education, income, or religion. Our findings highlight the overlapping values of male authority within marriage and aspirations for large families among young adult males in East Africa. Total lifetime fertility in East Africa remains among the highest worldwide: thus, governments in the region seeking to reduce fertility may need to explicitly scrutinize and address the reproduction of prevailing masculine values.

  9. Semen collection and fertility in naturally fertile sandhill cranes

    USGS Publications Warehouse

    Chen, G.; Gee, G.F.; Nicolich, Jane M.; Taylor, J.A.; Urbanek, R.P.; Stahlecker, D.W.

    1997-01-01

    Aviculturists often ask if semen collection will interfere with fertility in naturally fertile pairs of cranes. We used 12 naturally fertile Florida sandhill crane (Grus canadensis pratensis) pairs for this study, 6 control and 6 experimental. All pairs had produced fertile eggs in previous years and were in out-of-doors pens scattered throughout different pen complexes, within auditory range but physically isolated. Semen was collected on Tuesday mornings and Friday afternoons from 26 February 1993 to 4 June 1993. We used standard artificial insemination methods to collect and to evaluate the semen and spermatozoa. Semen collection did not affect semen quality or quantity. Semen volume, sperm density, sperm motility, sperm morphology, sperm live, sperm number per collection, and male response to semen collection exhibited significant daily variation (P < 0.05). Although semen collection began 13 days before the first egg in the experimental group, we observed no differences in the date of first egg laid or in fertility between experimental and control groups. Also, we observed no differences in the interval between clutches or in the percentage of broken eggs between experimental and control groups. Sires consistently producing better semen samples produced fewer fertile eggs than sires producing poorer semen samples (r = 0.60).

  10. Patient reported outcomes as endpoints in medical research.

    PubMed

    Fairclough, Diane L

    2004-04-01

    This review covers a number of the many design and analytic issues associated with clinical trials that incorporate patient reported outcomes as primary or secondary endpoints. We use a clinical trial designed to evaluate a new therapy for the prevention of migraines to illustrate how endpoints are defined by the objectives of the study, the methods for handling longitudinal assessments with multiple scales or outcomes, and the methods of analysis in the presence of missing data.

  11. DIFFERENTIAL SENSITIVITY OF MALE GERM CELLS TO MAINSTREAM AND SIDESTREAM TOBACCO SMOKE IN THE MOUSE

    SciTech Connect

    Polyzos, Aris; Schmid, Thomas Ernst; Pina-Guzman, Belem; Quintanilla-Vega, Betzabet; Marchetti, Francesco

    2009-03-13

    Cigarette smoking in men has been associated with increased chromosomal abnormalities in sperm and with increased risks for spontaneous abortions, birth defects and neonatal death. Little is known, however, about the reproductive consequences of paternal exposure to second-hand smoke. We used a mouse model to investigate the effects of paternal exposure to sidestream (SS) smoke, the main constituent of second-hand smoke, on the genetic integrity and function of sperm, and to determine whether male germ cells were equally sensitive to mainstream (MS) and SS smoke. A series of sperm DNA quality and reproductive endpoints were investigated after exposing male mice for two weeks to MS or SS smoke. Our results indicated that: (i) only SS smoke significantly affected sperm motility; (ii) only MS smoke induced DNA strand breaks in sperm; (iii) both MS and SS smoke increased sperm chromatin structure abnormalities; and (iv) MS smoke affected both fertilization and the rate of early embryonic development, while SS smoke affected fertilization only. These results show that MS and SS smoke have differential effects on the genetic integrity and function of sperm and provide further evidence that male exposure to second-hand smoke, as well as direct cigarette smoke, may diminish a couple's chance for a successful pregnancy and the birth of a healthy baby.

  12. Accurate measurement method for tube's endpoints based on machine vision

    NASA Astrophysics Data System (ADS)

    Liu, Shaoli; Jin, Peng; Liu, Jianhua; Wang, Xiao; Sun, Peng

    2017-01-01

    Tubes are used widely in aerospace vehicles, and their accurate assembly can directly affect the assembling reliability and the quality of products. It is important to measure the processed tube's endpoints and then fix any geometric errors correspondingly. However, the traditional tube inspection method is time-consuming and complex operations. Therefore, a new measurement method for a tube's endpoints based on machine vision is proposed. First, reflected light on tube's surface can be removed by using photometric linearization. Then, based on the optimization model for the tube's endpoint measurements and the principle of stereo matching, the global coordinates and the relative distance of the tube's endpoint are obtained. To confirm the feasibility, 11 tubes are processed to remove the reflected light and then the endpoint's positions of tubes are measured. The experiment results show that the measurement repeatability accuracy is 0.167 mm, and the absolute accuracy is 0.328 mm. The measurement takes less than 1 min. The proposed method based on machine vision can measure the tube's endpoints without any surface treatment or any tools and can realize on line measurement.

  13. Comparative endpoint sensitivity of in vitro estrogen agonist assays.

    PubMed

    Dreier, David A; Connors, Kristin A; Brooks, Bryan W

    2015-07-01

    Environmental and human health implications of endocrine disrupting chemicals (EDCs), particularly xenoestrogens, have received extensive study. In vitro assays are increasingly employed as diagnostic tools to comparatively evaluate chemicals, whole effluent toxicity and surface water quality, and to identify causative EDCs during toxicity identification evaluations. Recently, the U.S. Environmental Protection Agency (USEPA) initiated ToxCast under the Tox21 program to generate novel bioactivity data through high throughput screening. This information is useful for prioritizing chemicals requiring additional hazard information, including endocrine active chemicals. Though multiple in vitro and in vivo techniques have been developed to assess estrogen agonist activity, the relative endpoint sensitivity of these approaches and agreement of their conclusions remain unclear during environmental diagnostic applications. Probabilistic hazard assessment (PHA) approaches, including chemical toxicity distributions (CTD), are useful for understanding the relative sensitivity of endpoints associated with in vitro and in vivo toxicity assays by predicting the likelihood of chemicals eliciting undesirable outcomes at or above environmentally relevant concentrations. In the present study, PHAs were employed to examine the comparative endpoint sensitivity of 16 in vitro assays for estrogen agonist activity using a diverse group of compounds from the USEPA ToxCast dataset. Reporter gene assays were generally observed to possess greater endpoint sensitivity than other assay types, and the Tox21 ERa LUC BG1 Agonist assay was identified as the most sensitive in vitro endpoint for detecting an estrogenic response. When the sensitivity of this most sensitive ToxCast in vitro endpoint was compared to the human MCF-7 cell proliferation assay, a common in vitro model for biomedical and environmental monitoring applications, the ERa LUC BG1 assay was several orders of magnitude less

  14. TCRC Fertility Page

    MedlinePlus

    The Testicular Cancer Resource Center The TCRC Fertility Page Testicular Cancer and fertility are interrelated in numerous ways. TC usually ... Orchiectomy: As I mentioned, many men who have testicular cancer also already have fertility problems. In some, the ...

  15. Surrogate Endpoint Evaluation: Principal Stratification Criteria and the Prentice Definition.

    PubMed

    Gilbert, Peter B; Gabriel, Erin E; Huang, Ying; Chan, Ivan S F

    2015-09-01

    A common problem of interest within a randomized clinical trial is the evaluation of an inexpensive response endpoint as a valid surrogate endpoint for a clinical endpoint, where a chief purpose of a valid surrogate is to provide a way to make correct inferences on clinical treatment effects in future studies without needing to collect the clinical endpoint data. Within the principal stratification framework for addressing this problem based on data from a single randomized clinical efficacy trial, a variety of definitions and criteria for a good surrogate endpoint have been proposed, all based on or closely related to the "principal effects" or "causal effect predictiveness (CEP)" surface. We discuss CEP-based criteria for a useful surrogate endpoint, including (1) the meaning and relative importance of proposed criteria including average causal necessity (ACN), average causal sufficiency (ACS), and large clinical effect modification; (2) the relationship between these criteria and the Prentice definition of a valid surrogate endpoint; and (3) the relationship between these criteria and the consistency criterion (i.e., assurance against the "surrogate paradox"). This includes the result that ACN plus a strong version of ACS generally do not imply the Prentice definition nor the consistency criterion, but they do have these implications in special cases. Moreover, the converse does not hold except in a special case with a binary candidate surrogate. The results highlight that assumptions about the treatment effect on the clinical endpoint before the candidate surrogate is measured are influential for the ability to draw conclusions about the Prentice definition or consistency. In addition, we emphasize that in some scenarios that occur commonly in practice, the principal strata sub-populations for inference are identifiable from the observable data, in which cases the principal stratification framework has relatively high utility for the purpose of effect

  16. Image Segmentation Using Parametric Contours With Free Endpoints.

    PubMed

    Benninghoff, Heike; Garcke, Harald

    2016-04-01

    In this paper, we introduce a novel approach for active contours with free endpoints. A scheme for image segmentation is presented based on a discrete version of the Mumford-Shah functional where the contours can be both closed and open curves. Additional to a flow of the curves in normal direction, evolution laws for the tangential flow of the endpoints are derived. Using a parametric approach to describe the evolving contours together with an edge-preserving denoising, we obtain a fast method for image segmentation and restoration. The analytical and numerical schemes are presented followed by numerical experiments with artificial test images and with a real medical image.

  17. Image Segmentation Using Parametric Contours With Free Endpoints

    NASA Astrophysics Data System (ADS)

    Benninghoff, Heike; Garcke, Harald

    2016-04-01

    In this paper, we introduce a novel approach for active contours with free endpoints. A scheme is presented for image segmentation and restoration based on a discrete version of the Mumford-Shah functional where the contours can be both closed and open curves. Additional to a flow of the curves in normal direction, evolution laws for the tangential flow of the endpoints are derived. Using a parametric approach to describe the evolving contours together with an edge-preserving denoising, we obtain a fast method for image segmentation and restoration. The analytical and numerical schemes are presented followed by numerical experiments with artificial test images and with a real medical image.

  18. Toxic trace metals and human oocytes during in vitro fertilization (IVF).

    PubMed

    Bloom, Michael S; Parsons, Patrick J; Steuerwald, Amy J; Schisterman, Enrique F; Browne, Richard W; Kim, Keewan; Coccaro, Gregory A; Conti, Giulia C; Narayan, Natasha; Fujimoto, Victor Y

    2010-06-01

    Trace exposures to the toxic metals mercury (Hg), cadmium (Cd) and lead (Pb) may threaten human reproductive health. The aim of this study is to generate biologically-plausible hypotheses concerning associations between Hg, Cd, and Pb and in vitro fertilization (IVF) endpoints. For 15 female IVF patients, a multivariable log-binomial model suggests a 75% reduction in the probability for a retrieved oocyte to be in metaphase-II arrest for each microg/dL increase in blood Pb concentration (relative risk (RR)=0.25, 95% confidence interval (CI) 0.03-2.50, P=0.240). For 15 male IVF partners, each microg/L increase in urine Cd concentration is associated with an 81% decrease in the probability for oocyte fertilization (RR=0.19, 95% CI 0.03-1.35, P=0.097). Because of the magnitude of the effects, these results warrant a comprehensive study with sufficient statistical power to further evaluate these hypotheses.

  19. Obesity and fertility.

    PubMed

    Best, Damian; Bhattacharya, Siladitya

    2015-10-01

    The prevalence of overweight and obesity in women of reproductive age has increased over the past 30 years. Infertility affects 1 in 7 couples, and female obesity is associated with anovulation. The mechanisms by which excessive fat delays time to pregnancy (TTP) appear rooted in ovulatory problems and direct effects on oocytes, causing poorer embryo development, as well as in effects on the endometrium. Weight loss in women has been shown to improve conception, but not necessarily live birth rates following fertility treatment, and further research in this area is needed. The obesity epidemic has been accompanied by a potential rise in male infertility, which has been attributed to hormonal disturbances and compromised semen parameters.

  20. Comprehensive proteomic analysis of bovine spermatozoa of varying fertility rates and identification of biomarkers associated with fertility

    PubMed Central

    Peddinti, Divyaswetha; Nanduri, Bindu; Kaya, Abdullah; Feugang, Jean M; Burgess, Shane C; Memili, Erdogan

    2008-01-01

    Background Male infertility is a major problem for mammalian reproduction. However, molecular details including the underlying mechanisms of male fertility are still not known. A thorough understanding of these mechanisms is essential for obtaining consistently high reproductive efficiency and to ensure lower cost and time-loss by breeder. Results Using high and low fertility bull spermatozoa, here we employed differential detergent fractionation multidimensional protein identification technology (DDF-Mud PIT) and identified 125 putative biomarkers of fertility. We next used quantitative Systems Biology modeling and canonical protein interaction pathways and networks to show that high fertility spermatozoa differ from low fertility spermatozoa in four main ways. Compared to sperm from low fertility bulls, sperm from high fertility bulls have higher expression of proteins involved in: energy metabolism, cell communication, spermatogenesis, and cell motility. Our data also suggests a hypothesis that low fertility sperm DNA integrity may be compromised because cell cycle: G2/M DNA damage checkpoint regulation was most significant signaling pathway identified in low fertility spermatozoa. Conclusion This is the first comprehensive description of the bovine spermatozoa proteome. Comparative proteomic analysis of high fertility and low fertility bulls, in the context of protein interaction networks identified putative molecular markers associated with high fertility phenotype. PMID:18294385

  1. Sharp bounds on causal effects using a surrogate endpoint.

    PubMed

    Kuroki, Manabu

    2013-11-10

    This paper considers a problem of evaluating the causal effect of a treatment X on a true endpoint Y using a surrogate endpoint S, in the presence of unmeasured confounders between S and Y. Such confounders render the causal effect of X on Y unidentifiable from the causal effect of X on S and the joint probability of S and Y. To evaluate the causal effect of X on Y in such a situation, this paper derives closed-form formulas for the sharp bounds on the causal effect of X on Y based on both the causal effect of X on S and the joint probability of S and Y under various assumptions. In addition, we show that it is not always necessary to observe Y to test the null causal effect of X on Y under the monotonicity assumption between X and S. These bounds enable clinical practitioners and researchers to assess the causal effect of a treatment on a true endpoint using a surrogate endpoint with minimum computational effort.

  2. Predictive Modeling of Apical Toxicity Endpoints Using Data ...

    EPA Pesticide Factsheets

    The US EPA and other regulatory agencies face a daunting challenge of evaluating potential toxicity for tens of thousands of environmental chemicals about which little is currently known. The EPA’s ToxCast program is testing a novel approach to this problem by screening compounds using a variety of in vitro assays and using the results to prioritize chemicals for further, more detailed testing. Phase I of ToxCast is testing 320 chemicals (mainly pesticide active ingredients) against ~400 cell-based and biochemical assays. In order to anchor these studies, we are using in vivo guideline study data for subchronic, chronic, cancer, reproductive and developmental endpoints. This data is compiled in the EPA toxicity reference database, ToxRefDB. The main goal of ToxCast is the discovery and validation of “signatures” linking in vitro assay data to in vivo toxicity endpoints. These signatures will be collections of assays that are correlated with particular endpoints. These assay collections should also help define molecular-and cellular-level mechanisms of toxicity. This talk will discuss our strategy to use a combination of statistical and machine learning methods, coupled with biochemical network or systems biology approaches. Our initial examples will focus signatures for endpoints from 2 year rodent cancer bioassays. Most of the data we have analyzed is in dose or concentration response series, so to effectively use this data we have developed novel appro

  3. Is Suicide Ideation a Surrogate Endpoint for Geriatric Suicide?

    ERIC Educational Resources Information Center

    Links, Paul S.; Heisel, Marnin J.; Quastel, Adam

    2005-01-01

    The present study explored the validity of treating suicide ideation as a surrogate endpoint that can serve as a proxy for suicide in clinical intervention research with suicidal seniors. Two criteria; that suicide ideation is modulated by the proposed intervention and that modulation of suicide ideation leads to a quantitative reduction in…

  4. Developing a Cognition Endpoint for Traumatic Brain Injury Clinical Trials.

    PubMed

    Silverberg, Noah D; Crane, Paul K; Dams-O'Connor, Kristen; Holdnack, James; Ivins, Brian J; Lange, Rael T; Manley, Geoffrey T; McCrea, Michael; Iverson, Grant L

    2017-01-15

    Cognitive impairment is a core clinical feature of traumatic brain injury (TBI). After TBI, cognition is a key determinant of post-injury productivity, outcome, and quality of life. As a final common pathway of diverse molecular and microstructural TBI mechanisms, cognition is an ideal endpoint in clinical trials involving many candidate drugs and nonpharmacological interventions. Cognition can be reliably measured with performance-based neuropsychological tests that have greater granularity than crude rating scales, such as the Glasgow Outcome Scale-Extended, which remain the standard for clinical trials. Remarkably, however, there is no well-defined, widely accepted, and validated cognition endpoint for TBI clinical trials. A single cognition endpoint that has excellent measurement precision across a wide functional range and is sensitive to the detection of small improvements (and declines) in cognitive functioning would enhance the power and precision of TBI clinical trials and accelerate drug development research. We outline methodologies for deriving a cognition composite score and a research program for validation. Finally, we discuss regulatory issues and the limitations of a cognition endpoint.

  5. ECOLOGICAL ENDPOINT MODELING: EFFECTS OF SEDIMENT ON FISH POPULATIONS

    EPA Science Inventory

    Sediment is one of the main stressors of concern for TMDLs (Total Maximum Daily Loads) for streams, and often it is a concern because of its impact on biological endpoints. The National Research Council (NRC) has recommended that the EPA promote the development of models that ca...

  6. Comparison and Evaluation of Laboratory and Field Measured Bioaccumulation Endpoints

    EPA Science Inventory

    Evaluation of bioaccumulation endpoints on a fugacity basis allows provides a framework to assess the biomagnification potential of a chemical and assess data deficiencies, i.e., uncertainties and lack of data. In addition, it is suggested that additional guidance is needed in o...

  7. Improving Endpoint Detection to Support Automated Systematic Reviews

    PubMed Central

    Lucic, Ana; Blake, Catherine L.

    2016-01-01

    Authors of biomedical articles use comparison sentences to communicate the findings of a study, and to compare the results of the current study with earlier studies. The Claim Framework defines a comparison claim as a sentence that includes at least two entities that are being compared, and an endpoint that captures the way in which the entities are compared. Although automated methods have been developed to identify comparison sentences from the text, identifying the role that a specific noun plays (i.e. entity or endpoint) is much more difficult. Automated methods have been successful at identifying the second entity, but classification models were unable to clearly differentiate between the first entity and the endpoint. We show empirically that establishing if head noun is an amount or measure provides a statistically significant improvement that increases the endpoint precision from 0.42 to 0.56 on longer and from 0.51 to 0.58 on shorter sentences and recall from 0.64 to 0.71 on longer and from 0.69 to 0.74 on shorter sentences. The differences were not statistically significant for the second compared entity. PMID:28269949

  8. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... well-controlled clinical trials establishing that the biological product has an effect on a...

  9. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... well-controlled clinical trials establishing that the biological product has an effect on a...

  10. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based...

  11. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... well-controlled clinical trials establishing that the biological product has an effect on a...

  12. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based...

  13. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based...

  14. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based...

  15. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... well-controlled clinical trials establishing that the biological product has an effect on a...

  16. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity. 314.510 Section 314.510...

  17. Embryonic exposure to dimethoate and/or deltamethrin impairs sexual development and programs reproductive success in adult male offspring mice.

    PubMed

    Ben Slima, A; Ben Abdallah, F; Keskes-Ammar, L; Mallek, Z; El Feki, A; Gdoura, R

    2012-05-01

    Pesticides can be toxic to desirable plants and animals, including humans. The aim of this study was to investigate the reproductive effects of low doses of pesticides on male offspring of exposed pregnant mice. Three groups of five female mice were treated daily by oral gavage with dimethoate (5 mg kg(-1) per day), deltamethrin (5 mg kg(-1) per day) and their mixture at 5 mg kg(-1) per day from day 3 to day 21 of pregnancy. Fertility, sexual behaviour and a number of reproductive endpoints, such as organ weights, sperm evaluations and testicular histology, were examined on four adult male offspring of exposed pregnant mice. When compared with control, a dose of deltamethrin 5 mg kg j(-1) causes a decrease in the absolute and relative weight of the testes of exposed mice and it affects their fertility by reducing the density, mobility and vitality of sperm and increasing the number of abnormal forms of these cells (P ≤ 0.01). The same results were obtained in mice exposed to a dose of 5 mg kg j(-1) combination of dimethoate and deltamethrin. This study demonstrated that deltamethrin and combination of dimethoate and deltamethrin caused a decrease in the absolute and relative weight of the testes, which affected the sperm parameters of male offspring of exposed mice to a low dose of these pesticides during pregnancy.

  18. [Male contraception].

    PubMed

    Demoulin, A

    1984-04-01

    Among the reasons why male hormonal contraception has lagged behind female methods are the necessity of preserving virility, the fact that spermatogenesis is a continuous process, the need to control secondary effects and toxicity, and the requirement that modes of administration be acceptable to both partners. Among currently available reversible mehtods, withdrawal is undoubtedly the most ancient. It is still widespread but cannot be recommended because of its limited effectiveness. The condom is used by about 10% of couples worldwide as a principal or temporary method, but its inter-ference with sensation has limited its acceptance. Condoms are nevertheless highly effective when used with a spermicide. Various androgens are currently under investigation. High doses of testosterone can induce azoospermia without affecting libido but their side effects may be serious. The use of combinations of steroids permits doses to be reduced and offers promise for the future. The combination of oral medroxyprogesterone acetate and percutaneous testosterone is one of the better approaches; the combination is effective and nontoxic but has the disadvantage of percutaneous administration. Gossypol, a pigment extracted from the cotton plant, has been used as a contraceptive in China with a reported efficacy of 99.89%, recovery of fertility within 3 months, and no effect on future fertility. However, its toxicity appears to be significant in the animal and its reversibility is uncertain. A search is on for analogs which would preserve the contraceptive effects while eliminating toxic effects. Several gonadotropin releasing hormone (GnRH) analogs under investigation for their interference with spermatogenesis have given promising results. Several chemicals tested for contraceptive effects have had unacceptably high toxicity. Chinese investigators have reported good results with various physical methods of interfering with sperm production, but their reversibility and innocuity

  19. Automatic endpoint detection to support the systematic review process.

    PubMed

    Blake, Catherine; Lucic, Ana

    2015-08-01

    Preparing a systematic review can take hundreds of hours to complete, but the process of reconciling different results from multiple studies is the bedrock of evidence-based medicine. We introduce a two-step approach to automatically extract three facets - two entities (the agent and object) and the way in which the entities are compared (the endpoint) - from direct comparative sentences in full-text articles. The system does not require a user to predefine entities in advance and thus can be used in domains where entity recognition is difficult or unavailable. As with a systematic review, the tabular summary produced using the automatically extracted facets shows how experimental results differ between studies. Experiments were conducted using a collection of more than 2million sentences from three journals Diabetes, Carcinogenesis and Endocrinology and two machine learning algorithms, support vector machines (SVM) and a general linear model (GLM). F1 and accuracy measures for the SVM and GLM differed by only 0.01 across all three comparison facets in a randomly selected set of test sentences. The system achieved the best performance of 92% for objects, whereas the accuracy for both agent and endpoints was 73%. F1 scores were higher for objects (0.77) than for endpoints (0.51) or agents (0.47). A situated evaluation of Metformin, a drug to treat diabetes, showed system accuracy of 95%, 83% and 79% for the object, endpoint and agent respectively. The situated evaluation had higher F1 scores of 0.88, 0.64 and 0.62 for object, endpoint, and agent respectively. On average, only 5.31% of the sentences in a full-text article are direct comparisons, but the tabular summaries suggest that these sentences provide a rich source of currently underutilized information that can be used to accelerate the systematic review process and identify gaps where future research should be focused.

  20. Defining Surrogate Endpoints for Clinical Trials in Severe Falciparum Malaria

    PubMed Central

    Plewes, Katherine; Maude, Richard J.; Hanson, Josh; Herdman, M. Trent; Leopold, Stije J.; Ngernseng, Thatsanun; Charunwatthana, Prakaykaew; Phu, Nguyen Hoan; Ghose, Aniruddha; Hasan, M. Mahtab Uddin; Fanello, Caterina I.; Faiz, Md Abul; Hien, Tran Tinh; Day, Nicholas P. J.; White, Nicholas J.; Dondorp, Arjen M.

    2017-01-01

    Background Clinical trials in severe falciparum malaria require a large sample size to detect clinically meaningful differences in mortality. This means few interventions can be evaluated at any time. Using a validated surrogate endpoint for mortality would provide a useful alternative allowing a smaller sample size. Here we evaluate changes in coma score and plasma lactate as surrogate endpoints for mortality in severe falciparum malaria. Methods Three datasets of clinical studies in severe malaria were re-evaluated: studies from Chittagong, Bangladesh (adults), the African ‘AQUAMAT’ trial comparing artesunate and quinine (children), and the Vietnamese ‘AQ’ study (adults) comparing artemether with quinine. The absolute change, relative change, slope of the normalization over time, and time to normalization were derived from sequential measurements of plasma lactate and coma score, and validated for their use as surrogate endpoint, including the proportion of treatment effect on mortality explained (PTE) by these surrogate measures. Results Improvements in lactate concentration or coma scores over the first 24 hours of admission, were strongly prognostic for survival in all datasets. In hyperlactataemic patients in the AQ study (n = 173), lower mortality with artemether compared to quinine closely correlated with faster reduction in plasma lactate concentration, with a high PTE of the relative change in plasma lactate at 8 and 12 hours of 0.81 and 0.75, respectively. In paediatric patients enrolled in the ‘AQUAMAT’ study with cerebral malaria (n = 785), mortality was lower with artesunate compared to quinine, but this was not associated with faster coma recovery. Conclusions The relative changes in plasma lactate concentration assessed at 8 or 12 hours after admission are valid surrogate endpoints for severe malaria studies on antimalarial drugs or adjuvant treatments aiming at improving the microcirculation. Measures of coma recovery are not valid

  1. Fertilizer summary data 1990

    SciTech Connect

    Berry, J.T.; Hargett, N.L.

    1991-05-01

    Fertilizer Summary Data, published biennially by the National Fertilizer and Environmental Research Center (NFERC), combines fertilizer application and consumption statistics, crop acreage, and farm income/expense data by state and region for the period 1970 through 1990. This sixteenth edition contains statistics on commercial fertilizers sold for farm and nonfarm use, fertilizer distribution by class, and the leading fertilizer grades. Fertilizers are classified as single- or multiple-nutrient materials. Single-nutrient fertilizers, such as anhydrous ammonia (82-0-0), contain only one primary plant nutrient. Multiple-nutrient fertilizers contain two or more plant nutrients and include the ammonium phosphates and grades manufactured by dry or fluid mixing or chemical processing. In some cases, States report materials used in blending multiple-nutrient fertilizers as single-nutrient ingredients lather than the final manufactured product. Fertilizer consumption statistics for 1970 through 1980 are from US Department of Agriculture annual reports. Annual consumption data for 1985 through 1990 are based on the tabulation of individual state fertilizer tonnage reports submitted annually to TVA for inclusion in the National record of fertilizer consumption, Commercial Fertilizers. Crop statistics, fertilizer application rates, and farm income and expense data are supplied by the National Agricultural Statistics Service and the Economic Research Service, USDA.

  2. Ovarian fluid allows directional cryptic female choice despite external fertilization.

    PubMed

    Alonzo, Suzanne H; Stiver, Kelly A; Marsh-Rollo, Susan E

    2016-08-16

    In species with internal fertilization, females can favour certain males over others, not only before mating but also within the female's reproductive tract after mating. Here, we ask whether such directional post-mating (that is, cryptic) female mate choice can also occur in species with external fertilization. Using an in vitro sperm competition experiment, we demonstrate that female ovarian fluid (ovarian fluid) changes the outcome of sperm competition by decreasing the importance of sperm number thereby increasing the relative importance of sperm velocity. We further show that ovarian fluid does not differentially affect sperm from alternative male phenotypes, but generally enhances sperm velocity, motility, straightness and chemoattraction. Under natural conditions, female ovarian fluid likely increases the paternity of the preferred parental male phenotype, as these males release fewer but faster sperm. These results imply females have greater control over fertilization and potential to exert selection on males in species with external fertilization than previously thought possible.

  3. Ovarian fluid allows directional cryptic female choice despite external fertilization

    PubMed Central

    Alonzo, Suzanne H.; Stiver, Kelly A.; Marsh-Rollo, Susan E.

    2016-01-01

    In species with internal fertilization, females can favour certain males over others, not only before mating but also within the female's reproductive tract after mating. Here, we ask whether such directional post-mating (that is, cryptic) female mate choice can also occur in species with external fertilization. Using an in vitro sperm competition experiment, we demonstrate that female ovarian fluid (ovarian fluid) changes the outcome of sperm competition by decreasing the importance of sperm number thereby increasing the relative importance of sperm velocity. We further show that ovarian fluid does not differentially affect sperm from alternative male phenotypes, but generally enhances sperm velocity, motility, straightness and chemoattraction. Under natural conditions, female ovarian fluid likely increases the paternity of the preferred parental male phenotype, as these males release fewer but faster sperm. These results imply females have greater control over fertilization and potential to exert selection on males in species with external fertilization than previously thought possible. PMID:27529581

  4. Impaired fertilizing ability of superoxide dismutase 1-deficient mouse sperm during in vitro fertilization.

    PubMed

    Tsunoda, Satoshi; Kawano, Natsuko; Miyado, Kenji; Kimura, Naoko; Fujii, Junichi

    2012-11-01

    The oxidative modification of gametes by a reactive oxygen species is a major deleterious factor that decreases the successful rate of in vitro fertilization. Superoxide dismutase 1 (SOD1) plays a pivotal role in antioxidation by scavenging the superoxide anion, and its deficiency causes infertility in female mice, but the significance of the enzyme in male mice remains unclear. In the present study, we characterized Sod1(-/-) (Sod1-KO) male reproductive organs and compiled the first report of the impaired fertilizing ability of Sod1-KO sperm in in vitro fertilization. Insemination of wild-type oocytes with Sod1-KO sperm exhibited lower rates of fertility compared with insemination by wild-type sperm. The low fertilizing ability found for Sod1-KO sperm was partially rescued by reductant 2-mercaptoethanol, which suggested the oxidative modification of sperm components. The numbers of motile and progressive sperm decreased during the in vitro fertilization process, and a decline in ATP content and elevation in lipid peroxidation occurred in the Sod1-KO sperm in an incubation time-dependent manner. Tyrosine phosphorylation, which is a hallmark for sperm capacitation, was also impaired in the Sod1-KO sperm. These results collectively suggest that machinery involved in sperm capacitation and motility are vulnerable to oxidative damage during the in vitro fertilization process, which could increase the rate of inefficient fertilization.

  5. TENORM: Fertilizer and Fertilizer Production Wastes

    EPA Pesticide Factsheets

    Phosphate rock is used in the production of phosphate fertilizers. Due to its chemical properties, phosphate rock may contain significant quantities of naturally occurring radioactive materials (NORM).

  6. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans.

    PubMed

    Swan, Shanna H

    2008-10-01

    After briefly discussing human exposure to phthalates--diesters of 1,2-benzenedicarboxylic acid (phthalic acid)--this article first presents recent findings from the Study for Future Families, a multi-center pregnancy study in which the human analogue of the phthalate syndrome was first identified. This is one of an increasing number of studies that have investigated human endpoints in relation to environmental exposure to these ubiquitous compounds. This literature, which includes a range of human health endpoints following prenatal, neonatal, childhood, and adult exposures, is then summarized. At least one significant association has been reported for urinary metabolites of di-n-butyl phthalate (DBP), butylbenzyl phthalate (BzBP), diethyl phthlate (DEP), and di-isononyl phthalate (DINP) and for three of the urinary metabolites of di(2-ethylhexyl) phthalate (DEHP). Many of the findings reported in humans--most of which have been in males--are consistent with the anti-androgenic action that has been demonstrated for several phthalates. Replication of the results described here and further mechanistic studies are needed to strengthen links between phthalates and adverse health outcomes.

  7. Endpoints for Mouse Abdominal Tumor Models: Refinement of Current Criteria

    PubMed Central

    Paster, Eden V; Villines, Kimberly A; Hickman, Debra L

    2009-01-01

    Accurate, rapid, and noninvasive health assessments are required to establish more appropriate endpoints in mouse cancer models where tumor size is not easily measured. We evaluated potential endpoints in mice with experimentally induced peritoneal lymphoma, an abdominal tumor model, by comparing body weight, body condition, and behavior with those of a control group of mice not developing lymphoma. Our hypothesis was that body weight would increase or plateau, whereas body condition and behavioral scores would decrease, as disease progressed. Results indicated that body weight did not differ significantly between the control and experimental groups, but the experimental group experienced significant decreases in both body condition and behavioral scores. Our results support the use of body condition and behavioral scoring as adjunctive assessment methods for mice involved in abdominal lymphoma tumor studies in which health may decline despite an increase or plateau in body weight. PMID:19619413

  8. A new end-point for ELISA titrations.

    PubMed

    Vidal, José

    2004-01-01

    This report describes a new ELISA procedure based on end-point titrations. This end-point ELISA takes advantage of the change of color intensity that occurs when peroxidase-containing wells of an ELISA plate are revealed with diaminobenzidine-nickel and further intensification with silver: as antibody concentration and, therefore, peroxidase concentration, decreased, the color became stronger in some wells and, afterwards (i.e., at lower antibody and peroxidase concentrations), the color faded toward clear background. It is proposed that the reciprocal of the sample dilution at which the color intensifies can be used as a measure of the sample antibody content. This report verifies the validity and precision of that procedure.

  9. Changing the endpoints for determining effective obesity management.

    PubMed

    Ross, Robert; Blair, Steve; de Lannoy, Louise; Després, Jean-Pierre; Lavie, Carl J

    2015-01-01

    Health authorities worldwide recommend weight loss as a primary endpoint for effective obesity management. Despite a growing public awareness of the importance of weight loss and the spending of billions of dollars by Americans in attempts to lose weight, obesity prevalence continues to rise. In this report we argue that effective obesity management in today's environment will require a shift in focus from weight loss as the primary endpoint, to improvements in the causal behaviors; diet and exercise/physical activity (PA). We reason that increases in PA combined with a balanced diet are associated with improvement in many of the intermediate risk factors including cardiorespiratory fitness (CRF) associated with obesity despite minimal or no weight loss. Consistent with this notion, we suggest that a focus on healthy behaviors for the prevention of additional weight gain may be an effective way of managing obesity in the short term.

  10. Urinary paraben concentrations and in vitro fertilization outcomes among women from a fertility clinic

    PubMed Central

    Mínguez-Alarcón, Lidia; Chiu, Yu-Han; Messerlian, Carmen; Williams, Paige L.; Sabatini, Mary E.; Toth, Thomas L.; Ford, Jennifer B.; Calafat, Antonia M.; Hauser, Russ

    2015-01-01

    Objective To explore the relationship between urinary paraben concentrations and IVF outcomes among women attending an academic fertility center. Design Prospective cohort study. Setting Fertility clinic in a hospital setting. Patient(s) A total of 245 women contributing 356 IVF cycles. Intervention(s) None. Quantification of urinary concentrations of parabens by isotope-dilution tandem mass spectrometry, and assessment of clinical endpoints of IVF treatments abstracted from electronic medical records at the academic fertility center. Main Outcome Measure(s) Total and mature oocyte counts, proportion of high quality embryos, fertilization rates, and rates of implantation, clinical pregnancy and live births. Results The geometric mean of the urinary concentrations of methyl (MP), propyl (PP) and butyl paraben (BP) in our study population were 133, 24 and 1.5 µg/L, respectively. In models adjusted for age, body mass index, race/ethnicity, smoking status and primary infertility diagnosis, urinary MP, PP and BP concentrations were not associated with IVF outcomes, specifically total and mature oocyte counts, proportion of high embryo quality and fertilization rates. Moreover, no significant associations were found between urinary paraben concentrations and rates of implantation, clinical pregnancy and live births. Conclusion(s) Urinary paraben concentrations were not associated with IVF outcomes among women undergoing infertility treatments. PMID:26654974

  11. Research priorities in biomarkers and surrogate end-points.

    PubMed

    Aronson, Jeffrey K

    2012-06-01

    Ideal tests of the effects of therapeutic interventions measure the desired outcomes; however, the desired outcomes are not always easily measured or may be long-term objectives. Biomarkers and surrogate end-points are often cheaper and easier to measure and can be measured over a shorter time span. They can be used in screening, diagnosing, staging, and monitoring diseases, in monitoring responses to interventions, and in various aspects of drug discovery and development. They can be extrinsic to the body or intrinsic, and can relate to any point in the pharmacological chain, at the molecular, cellular, tissue, or organ level. Problems arise when the relation between the pathophysiology of the disease and the mechanism of action of the intervention is not properly understood; when adverse effects obviate therapeutic effects; when confounding factors, such as other drugs, alter the surrogate independently of the final end-point; when a biomarker persists after resolution of the disease; and when the concentration-effect curves for the effects of an intervention on the primary outcome and the surrogate are different. Use of biomarkers may also be hindered by poor reproducibility of measurement techniques. Challenges for clinical pharmacologists are to devise biomarker tests that are reliable, reproducible, sensitive, and specific, and surrogate end-points that are associated with the clinical outcomes of concern and useful. A robust taxonomy is needed of the relations that link the pathophysiology of disease, the mechanisms of action of interventions and their adverse effects, the desired clinical outcomes, and the surrogate end-points that predict them.

  12. Modeling Robot Dynamic Performance for Endpoint Force Control

    DTIC Science & Technology

    1988-08-01

    we consider is robot endpoint force control, also known as manipulator compliant motion control. Force control research has been quite popular...manipulator through a programmed trajectory consisting of a sequence of joint positions and velocities. Position and velocity sensors located at the robot ...may be located. 1.1 Force Control Research Background Research in robot compliant motion control has been in these areas: " Passive compliance schemes

  13. Lifestyle, environment, and male reproductive health.

    PubMed

    Barazani, Yagil; Katz, Benjamin Farrel; Nagler, Harris Mark; Stember, Doron Sol

    2014-02-01

    A large number of environmental and lifestyle factors may negatively affect spermatogenesis and male fertility. This article enumerates the current state of knowledge regarding those that have been identified, and extrapolates the predicted magnitude of these effects over the next 20 years based on current societal trends. However, it is likely that additional factors have yet to be recognized. Additional research is needed to further define and clarify environmental factors that affect male fertility in order to mitigate their effects.

  14. Challenges assessing clinical endpoints in early Huntington disease

    PubMed Central

    Paulsen, Jane S.; Wang, Chiachi; Duff, Kevin; Barker, Roger; Nance, Martha; Beglinger, Leigh; Moser, David; Williams, Janet K.; Simpson, Sheila; Langbehn, Douglas; van Kammen, Daniel P.

    2010-01-01

    The primary aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest-studied HD participants likely to be recruited into clinical trials. Since the advent of genetic testing for HD, it is possible to identify gene carriers prior to the diagnosis of disease, which opens up the possibility of clinical trials of disease-modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multi-national, 32-site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene-positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real-life function. PMID:20623772

  15. Exposing the cancer genome atlas as a SPARQL endpoint

    PubMed Central

    Deus, Helena F.; Veiga, Diogo F.; Freire, Pablo R.; Weinstein, John N.; Mills, Gordon B.; Almeida, Jonas S.

    2011-01-01

    The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. PMID:20851208

  16. Triennial Reproduction Symposium: sperm characteristics that limit success of fertilization.

    PubMed

    Flowers, W L

    2013-07-01

    Current industry estimates of reproductive performance for cattle, sheep, and swine operations indicate that males contribute significantly to fertility failures. This appears to be due to the use of subfertile individuals and emphasizes the need for additional research in identifying characteristics of sperm that compromise fertilization. In theory, sperm characteristics, such as motility or the percentage of normal sperm, form a positive relationship with fertility that reaches a certain maximal fertility (i.e., an asymptotic relationship). It is clear that variation exists among males in terms of how fertility responds to increasing sperm dosage or numbers of normal sperm, both in the slope of the curve and the point at which the fertility reaches a maximum. Variations along the linear portion of fertility curves are due to compensable traits that are involved with the ability of sperm to penetrate the zona pellucida. It appears that most fertility curves reach their plateau when 70% of sperm possess a given compensable trait. The level of fertility at which the plateau occurs is determined by noncompensable traits that are associated with binding of sperm to the oolemma, syngamy, and subsequent development of the zygote. Several studies have shown differences in fertility among males that have similar levels of compensable traits but differed in their noncompensable characteristics. Compensable and noncompensable traits can estimate either individual or functional characteristics of sperm. Intuitively, functional traits such as in vitro penetration should provide a better indication of fertilization than individual ones such as motility. However, correlations of both types with fertility are very similar. Reasons for this may be related to how characteristics of sperm cells are influenced by the female reproductive tract after insemination. Sperm capacitation is a functional trait in boars that is quite different in vitro versus in vivo. If this relationship

  17. Plant fertilizer poisoning

    MedlinePlus

    Plant fertilizers and household plant foods are used to improve plant growth. Poisoning can occur if someone swallows these products. Plant fertilizers are mildly poisonous if small amounts are swallowed. ...

  18. What Is Fertility Preservation?

    MedlinePlus

    ... cancer.net/navigating-cancer-care/dating-sex-and-reproduction/fertility-concerns-and-preservation-men [top] ASCO. (2016). ... cancer.net/navigating-cancer-care/dating-sex-and-reproduction/fertility-concerns-and-preservation-women [top] National Cancer ...

  19. The risky reliance on small surrogate endpoint studies when planning a large prevention trial.

    PubMed

    Baker, Stuart G; Kramer, Barnett S

    2013-02-01

    The definitive evaluation of treatment to prevent a chronic disease with low incidence in middle age, such as cancer or cardiovascular disease, requires a trial with a large sample size of perhaps 20,000 or more. To help decide whether to implement a large true endpoint trial, investigators first typically estimate the effect of treatment on a surrogate endpoint in a trial with a greatly reduced sample size of perhaps 200 subjects. If investigators reject the null hypothesis of no treatment effect in the surrogate endpoint trial they implicitly assume they would likely correctly reject the null hypothesis of no treatment effect for the true endpoint. Surrogate endpoint trials are generally designed with adequate power to detect an effect of treatment on surrogate endpoint. However, we show that a small surrogate endpoint trial is more likely than a large surrogate endpoint trial to give a misleading conclusion about the beneficial effect of treatment on true endpoint, which can lead to a faulty (and costly) decision about implementing a large true endpoint prevention trial. If a small surrogate endpoint trial rejects the null hypothesis of no treatment effect, an intermediate-sized surrogate endpoint trial could be a useful next step in the decision-making process for launching a large true endpoint prevention trial.

  20. Quantifying male attractiveness.

    PubMed Central

    McNamara, John M; Houston, Alasdair I; Marques Dos Santos, Miguel; Kokko, Hanna; Brooks, Rob

    2003-01-01

    Genetic models of sexual selection are concerned with a dynamic process in which female preference and male trait values coevolve. We present a rigorous method for characterizing evolutionary endpoints of this process in phenotypic terms. In our phenotypic characterization the mate-choice strategy of female population members determines how attractive females should find each male, and a population is evolutionarily stable if population members are actually behaving in this way. This provides a justification of phenotypic explanations of sexual selection and the insights into sexual selection that they provide. Furthermore, the phenotypic approach also has enormous advantages over a genetic approach when computing evolutionarily stable mate-choice strategies, especially when strategies are allowed to be complex time-dependent preference rules. For simplicity and clarity our analysis deals with haploid mate-choice genetics and a male trait that is inherited phenotypically, for example by vertical cultural transmission. The method is, however, easily extendible to other cases. An example illustrates that the sexy son phenomenon can occur when there is phenotypic inheritance of the male trait. PMID:14561306

  1. The molecular basis of fertilization (Review)

    PubMed Central

    Georgadaki, Katerina; Khoury, Nikolas; Spandidos, Demetrios A.; Zoumpourlis, Vasilis

    2016-01-01

    Fertilization is the fusion of the male and female gamete. The process involves the fusion of an oocyte with a sperm, creating a single diploid cell, the zygote, from which a new individual organism will develop. The elucidation of the molecular mechanisms of fertilization has fascinated researchers for many years. In this review, we focus on this intriguing process at the molecular level. Several molecules have been identified to play a key role in each step of this intriguing process (the sperm attraction from the oocyte, the sperm maturation, the sperm and oocyte fusion and the two gamete pronuclei fusion leading to the zygote). Understanding the molecular mechanisms of the cell-cell interactions will provide a better understanding of the causes of fertility issues due to fertilization defects. PMID:27599669

  2. [Orchitis and male infertility].

    PubMed

    Schuppe, H-C; Pilatz, A; Hossain, H; Meinhardt, A; Bergmann, M; Haidl, G; Weidner, W

    2010-05-01

    Infections and inflammations of the genital tract are considered the most frequent causes of reduced male fertility, but conclusive epidemiological data are not available. In view of the exposure of germ cells to pathogenic components as well as the cells and mediators involved in the inflammatory processes, irreversible damage to spermatogenesis and corresponding decline of ejaculate quality are to be expected, particularly in cases of chronic orchitis. While the consequences of orchitis and epididymo-orchitis that exhibit clinical symptoms due to systemic or local infections are well known, including testicular atrophy and complete loss of fertility, those cases of inflammatory reactions of the testicles that manifest an asymptomatic or subclinical course, or are not even due to an infection, have received little attention until now. However, systematic histopathological analyses have shown a high prevalence of asymptomatic inflammatory reactions in testicular biopsies from infertile men. The mostly focal lymphocytic infiltrates correlate with the degree of damage to spermatogenesis and corresponding clinical and endocrinological parameters of testicular function. Noninvasive diagnostic techniques are not yet available so that chronic asymptomatic inflammations of the testicles as the primary cause or cofactor of male fertility disorders are underestimated. Except for administration of pathogen-specific antibiotics, treatment recommendations are to a large extent still lacking.

  3. A unique mechanism of successful fertilization in a domestic bird

    PubMed Central

    Sasanami, Tomohiro; Izumi, Shunsuke; Sakurai, Naoki; Hirata, Toshifumi; Mizushima, Shusei; Matsuzaki, Mei; Hiyama, Gen; Yorinaga, Eriko; Yoshimura, Takashi; Ukena, Kazuyoshi; Tsutsui, Kazuyoshi

    2015-01-01

    Fertilization is an indispensable step for formation of a zygote in sexual reproduction, leading to species survival. When mating occurs, sperm is transported to the female reproductive tracts via the seminal plasma (SP). SP is derived from male accessory sex glands and it plays pivotal roles for fertilization in animals. However, molecular mechanisms of SP or a fluid derived from male accessory sex glands for successful fertilization remain unclear. Here, we report that in male quail the cloacal gland (CG) produces prostaglandin F2α (PGF2α) that contributes to successful fertilization. PGF2α, as well as the secretion of CG (CGS), induced vaginal contractions and caused the opening of the entrance of the sperm storage tubules, the structures responsible for the long-term sperm storage and fertilization. The removal of CGS from the male before mating reduced the fertility, but the supplementation of CGS or PGF2α rescued the subfertility. We further showed that male CG contains glucose that is utilized as energy source for the intrinsic sperm mobility after transportation to female vagina. This mechanism, in concert with the excitatory effects of PGF2α enables successful fertilization in the domestic bird. PMID:25572424

  4. A unique mechanism of successful fertilization in a domestic bird.

    PubMed

    Sasanami, Tomohiro; Izumi, Shunsuke; Sakurai, Naoki; Hirata, Toshifumi; Mizushima, Shusei; Matsuzaki, Mei; Hiyama, Gen; Yorinaga, Eriko; Yoshimura, Takashi; Ukena, Kazuyoshi; Tsutsui, Kazuyoshi

    2015-01-09

    Fertilization is an indispensable step for formation of a zygote in sexual reproduction, leading to species survival. When mating occurs, sperm is transported to the female reproductive tracts via the seminal plasma (SP). SP is derived from male accessory sex glands and it plays pivotal roles for fertilization in animals. However, molecular mechanisms of SP or a fluid derived from male accessory sex glands for successful fertilization remain unclear. Here, we report that in male quail the cloacal gland (CG) produces prostaglandin F2α (PGF2α) that contributes to successful fertilization. PGF2α, as well as the secretion of CG (CGS), induced vaginal contractions and caused the opening of the entrance of the sperm storage tubules, the structures responsible for the long-term sperm storage and fertilization. The removal of CGS from the male before mating reduced the fertility, but the supplementation of CGS or PGF2α rescued the subfertility. We further showed that male CG contains glucose that is utilized as energy source for the intrinsic sperm mobility after transportation to female vagina. This mechanism, in concert with the excitatory effects of PGF2α enables successful fertilization in the domestic bird.

  5. Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

    DOEpatents

    Archer, Charles J; Blocksome, Michael E; Ratterman, Joseph D; Smith, Brian E

    2014-02-11

    Endpoint-based parallel data processing in a parallel active messaging interface ('PAMI') of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective opeartion through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

  6. Endpoint-based parallel data processing in a parallel active messaging interface of a parallel computer

    DOEpatents

    Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.; Smith, Brian E.

    2014-08-12

    Endpoint-based parallel data processing in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including a specification of data communications parameters for a thread of execution on a compute node, including specifications of a client, a context, and a task, the compute nodes coupled for data communications through the PAMI, including establishing a data communications geometry, the geometry specifying, for tasks representing processes of execution of the parallel application, a set of endpoints that are used in collective operations of the PAMI including a plurality of endpoints for one of the tasks; receiving in endpoints of the geometry an instruction for a collective operation; and executing the instruction for a collective operation through the endpoints in dependence upon the geometry, including dividing data communications operations among the plurality of endpoints for one of the tasks.

  7. Clinical research and methodology: What usage and what hierarchical order for secondary endpoints?

    PubMed

    Laporte, Silvy; Diviné, Marine; Girault, Danièle

    2016-02-01

    In a randomised clinical trial, when the result of the primary endpoint shows a significant benefit, the secondary endpoints are scrutinised to identify additional effects of the treatment. However, this approach entails a risk of concluding that there is a benefit for one of these endpoints when such benefit does not exist (inflation of type I error risk). There are mainly two methods used to control the risk of drawing erroneous conclusions for secondary endpoints. The first method consists of distributing the risk over several co-primary endpoints, so as to maintain an overall risk of 5%. The second is the hierarchical test procedure, which consists of first establishing a hierarchy of the endpoints, then evaluating each endpoint in succession according to this hierarchy while the endpoints continue to show statistical significance. This simple method makes it possible to show the additional advantages of treatments and to identify the factors that differentiate them.

  8. SPERM COUNT DISTRIBUTIONS IN FERTILE MEN

    EPA Science Inventory

    Sperm concentration and count are often used as indicators of environmental impacts on male reproductive health. Existing clinical databases may be biased towards subfertile men with low sperm counts and less is known about expected sperm count distributions in cohorts of fertil...

  9. SPERMATOZOAL RNA PROFILES OF NORMAL FERTILE MEN

    EPA Science Inventory

    What Constitutes the Normal Fertile Male?

    G. Charles Ostermeier1, David J. Dix2, David Miller3, Purvesh Khatri4, and Stephen A. Krawetz1.

    1Departments of Obstetrics and Gynaecology, Center for Molecular Medicine and Genetics, & Institute for Scientific Computing, Wa...

  10. Low rates of multiple fertilization in parous Anopheles albimanus.

    PubMed

    Villarreal, C; Fuentes-Maldonado, G; Rodriguez, M H; Yuval, B

    1994-03-01

    We determined how frequently parous female Anopheles albimanus fertilize their eggs with sperm from more than one male. To establish paternity we relied on 2 phenotypically distinct laboratory strains. Nulliparous females were allowed to mate freely with males from one strain, and after oviposition they were offered a 2nd mating with males of the other strain. Fertilization patterns were determined by the phenotypes of offspring. Only 0.6% of females ovipositing for a 2nd time (n = 312) used sperm from the 2nd male, as did 4% of females completing a 3rd gonotrophic cycle (n = 25). In this species receptivity is not routinely renewed following oviposition.

  11. Evaluation of a multi-endpoint assay in rats, combining the bone-marrow micronucleus test, the Comet assay and the flow-cytometric peripheral blood micronucleus test.

    PubMed

    Bowen, Damian E; Whitwell, James H; Lillford, Lucinda; Henderson, Debbie; Kidd, Darren; Mc Garry, Sarah; Pearce, Gareth; Beevers, Carol; Kirkland, David J

    2011-05-18

    With the publication of revised draft ICH guidelines (Draft ICH S2), there is scope and potential to establish a combined multi-end point in vivo assay to alleviate the need for multiple in vivo assays, thereby reducing time, cost and use of animals. Presented here are the results of an evaluation trial in which the bone-marrow and peripheral blood (via MicroFlow(®) flow cytometry) micronucleus tests (looking at potential chromosome breakage and whole chromosome loss) in developing erythrocytes or young reticulocytes were combined with the Comet assay (measuring DNA strand-breakage), in stomach, liver and blood lymphocytes. This allowed a variety of potential target tissues (site of contact, site of metabolism and peripheral distribution) to be assessed for DNA damage. This combination approach was performed with minimal changes to the standard and regulatory recommended sampling times for the stand-alone assays. A series of eight in vivo genotoxins (2-acetylaminofluorene, benzo[a]pyrene, carbendazim, cyclophosphamide, dimethylnitrosamine, ethyl methanesulfonate, ethyl nitrosourea and mitomycin C), which are known to act via different modes of action (direct- and indirect-acting clastogens, alkylating agents, gene mutagens, cross-linking and aneugenic compounds) were tested. Male rats were dosed at 0, 24 and 45 h, and bone marrow and peripheral blood (micronucleus endpoint), liver, whole blood and stomach (Comet endpoint) were sampled at three hours after the last dose. Comet and micronucleus responses were as expected based on available data for conventional (acute) stand-alone assays. All compounds were detected as genotoxic in at least one of the endpoints. The importance of evaluating both endpoints was highlighted by the uniquely positive responses for certain chemicals (benzo[a]pyrene and 2-acetylaminofluorene) with the Comet endpoint and certain other chemicals (carbendazim and mitomycin C) with the micronucleus endpoint. The data generated from these

  12. New science-based endpoints to accelerate oncology drug development.

    PubMed

    Kelloff, Gary J; Sigman, Caroline C

    2005-03-01

    Although several new oncology drugs have reached the market, more than 80% of drugs for all indications entering clinical development do not get marketing approval, with many failing late in development often in Phase III trials, because of unexpected safety issues or difficulty determining efficacy, including confounded outcomes. These factors contribute to the high costs of oncology drug development and clearly show the need for faster, more cost-effective strategies for evaluating oncology drugs and better definition of patients who will benefit from treatment. Remarkable advances in the understanding of neoplastic progression at the cellular and molecular levels have spurred the discovery of molecularly targeted drugs. This progress along with advances in imaging and bioassay technologies are the basis for describing and evaluating new biomarker endpoints as well as for defining other biomarkers for identifying patient populations, potential toxicity, and providing evidence of drug effect and efficacy. Definitions and classifications of these biomarkers for use in oncology drug development are presented in this paper. Science-based and practical criteria for validating biomarkers have been developed including considerations of mechanistic plausibility, available methods and technology, and clinical feasibility. New promising tools for measuring biomarkers have also been developed and are based on genomics and proteomics, direct visualisation by microscopy (e.g., confocal microscopy and computer-assisted image analysis of cellular features), nanotechnologies, and direct and remote imaging (e.g., fluorescence endoscopy and anatomical, functional and molecular imaging techniques). The identification and evaluation of potential surrogate endpoints and other biomarkers require access to and analysis of large amounts of data, new technologies and extensive research resources. Further, there is a requirement for a convergence of research, regulatory and drug developer

  13. Exploring a possible origin of the QCD critical endpoint

    SciTech Connect

    Bugaev, K. A. Petrov, V. K. Zinovjev, G. M.

    2013-03-15

    We develop a new model of the QCD critical endpoint by matching the deconfinement phase transition line of quark-gluon bags with the similar line at which the bag surface tension coefficient vanishes. Unlike all previous studies of such models the deconfined phase in our approach is defined not by an essential singularity of the isobaric partition function but its simple pole. As an unexpected result we find out that the first-order phase transition which is usually defined by a discontinuity of the first derivative of the bag system pressure results from a discontinuity of the derivative of surface tension coefficient of quark-gluon bags.

  14. Two-temperature LATE-PCR endpoint genotyping

    PubMed Central

    Sanchez, J Aquiles; Abramowitz, Jessica D; Salk, Jesse J; Reis, Arthur H; Rice, John E; Pierce, Kenneth E; Wangh, Lawrence J

    2006-01-01

    Background In conventional PCR, total amplicon yield becomes independent of starting template number as amplification reaches plateau and varies significantly among replicate reactions. This paper describes a strategy for reconfiguring PCR so that the signal intensity of a single fluorescent detection probe after PCR thermal cycling reflects genomic composition. The resulting method corrects for product yield variations among replicate amplification reactions, permits resolution of homozygous and heterozygous genotypes based on endpoint fluorescence signal intensities, and readily identifies imbalanced allele ratios equivalent to those arising from gene/chromosomal duplications. Furthermore, the use of only a single colored probe for genotyping enhances the multiplex detection capacity of the assay. Results Two-Temperature LATE-PCR endpoint genotyping combines Linear-After-The-Exponential (LATE)-PCR (an advanced form of asymmetric PCR that efficiently generates single-stranded DNA) and mismatch-tolerant probes capable of detecting allele-specific targets at high temperature and total single-stranded amplicons at a lower temperature in the same reaction. The method is demonstrated here for genotyping single-nucleotide alleles of the human HEXA gene responsible for Tay-Sachs disease and for genotyping SNP alleles near the human p53 tumor suppressor gene. In each case, the final probe signals were normalized against total single-stranded DNA generated in the same reaction. Normalization reduces the coefficient of variation among replicates from 17.22% to as little as 2.78% and permits endpoint genotyping with >99.7% accuracy. These assays are robust because they are consistent over a wide range of input DNA concentrations and give the same results regardless of how many cycles of linear amplification have elapsed. The method is also sufficiently powerful to distinguish between samples with a 1:1 ratio of two alleles from samples comprised of 2:1 and 1:2 ratios of the

  15. Evaluating endocrine endpoints relative to reproductive success in Japanese quail exposed to estrogenic chemicals [poster

    USGS Publications Warehouse

    Henry, P.F.P.; Russek-Cohen, E.; Casey, C.S.; Abdelnabi, M.A.; Ottinger, M.A.

    2000-01-01

    The standard US EPA guidelines for avian reproductive testing may not be sufficiently sensitive to detect effects of sublethal and chronic exposure to endocrine disrupting toxins. There is a need to evaluate endocrine endpoints as potential markers for contaminant effects, and to determine their effectiveness and sensitivity when applied to wildlife. To this end, a three generational test was conducted using the Japanese quail (Coturnix japonica) and a proven estrogenic PCB. Birds were exposed during embryonic development via maternal deposition and/or direct egg injection at day 4. Standard measures of reproductive success and productivity used in toxicological studies, as well as multiple measures of physiological and behavioral responses used in endocrine studies were collected. Long term effects on growth and apparent development were similar between treated and control offspring. Fertility of treated eggs decreased from 75%+ 4.4 (x + se) for P1, to 59% + 12.5 for F1 and 54% + 14.2 for F2. All paired control birds mated to produce viable eggs, whereas 27 % of the F1 and 41 % of the F2 treated pairs failed to produce at least 1 viable egg. Although some decreases in productivity can be related to direct toxic exposure, the response from one generation to the next was not linear with treatment, indicating a potential effect from behavioral or other endocrine alterations.

  16. Sneaker "jack" males outcompete dominant "hooknose" males under sperm competition in Chinook salmon (Oncorhynchus tshawytscha).

    PubMed

    Young, Brent; Conti, David V; Dean, Matthew D

    2013-12-01

    In a variety of taxa, males deploy alternative reproductive tactics to secure fertilizations. In many species, small "sneaker" males attempt to steal fertilizations while avoiding encounters with larger, more aggressive, dominant males. Sneaker males usually face a number of disadvantages, including reduced access to females and the higher likelihood that upon ejaculation, their sperm face competition from other males. Nevertheless, sneaker males represent an evolutionarily stable strategy under a wide range of conditions. Game theory suggests that sneaker males compensate for these disadvantages by investing disproportionately in spermatogenesis, by producing more sperm per unit body mass (the "fair raffle") and/or by producing higher quality sperm (the "loaded raffle"). Here, we test these models by competing sperm from sneaker "jack" males against sperm from dominant "hooknose" males in Chinook salmon. Using two complementary approaches, we reject the fair raffle in favor of the loaded raffle and estimate that jack males were ∼1.35 times as likely as hooknose males to fertilize eggs under controlled competitive conditions. Interestingly, the direction and magnitude of this skew in paternity shifted according to individual female egg donors, suggesting cryptic female choice could moderate the outcomes of sperm competition in this externally fertilizing species.

  17. THE 6-MINUTE WALK TEST AND OTHER CLINICAL ENDPOINTS IN DUCHENNE MUSCULAR DYSTROPHY: RELIABILITY, CONCURRENT VALIDITY, AND MINIMAL CLINICALLY IMPORTANT DIFFERENCES FROM A MULTICENTER STUDY

    PubMed Central

    McDonald, Craig M; Henricson, Erik K; Abresch, R Ted; Florence, Julaine; Eagle, Michelle; Gappmaier, Eduard; Glanzman, Allan M; Spiegel, Robert; Barth, Jay; Elfring, Gary; Reha, Allen; Peltz, Stuart W

    2013-01-01

    Introduction: An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6-minute walk test (6MWT) and other endpoints. Methods: Screening and baseline evaluations included the 6-minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate–determined energy expenditure index, and other exploratory endpoints. Results: The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 meters based on 2 statistical distribution methods. Conclusions: The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints. The 6MWD is an optimal primary endpoint for Duchenne muscular dystrophy (DMD) clinical trials that are focused therapeutically on preservation of ambulation and slowing of disease progression. Muscle Nerve 48: 357–368, 2013 PMID:23674289

  18. Fertility Herbs: Do They Enhance Fertility?

    MedlinePlus

    ... pregnant. I've seen many ads for fertility herbs and supplements. Do they work? Answers from Jani ... it's not surprising that some people look to herbs and supplements as a possible alternative treatment to ...

  19. Female effects, but no intrinsic male effects on paternity outcome in crickets.

    PubMed

    Simmons, L W; Lovegrove, M; Almbro, M

    2014-08-01

    Competitive fertilization success can depend on the relative abilities of competing males to fertilize available ova, and on mechanisms of cryptic female choice that moderate paternity. Competitive fertilization success is thus an emergent property of competing male genotypes, female genotype and their interactions. Accurate estimates of intrinsic male effects on competitive fertilization success are therefore problematic. We used a cross-classified nonbreeding design in which rival male family background was standardized to partition variation in competitive fertilization success among male and female family backgrounds in the field cricket Teleogryllus oceanicus. Male effects were close to zero, supporting previous quantitative genetic designs in which male competitors were assigned at random. In contrast, some 22% of the variance in competitive fertilization success was explained by female effects, suggesting that paternity in this species is influenced strongly by cryptic female choice.

  20. New Insights into the Mechanism of Fertilization in Nematodes

    PubMed Central

    Singaravelu, Gunasekaran; Singson, Andrew

    2012-01-01

    Fertilization results from the fusion of male and female gametes in all sexually reproducing organisms. Much of nematode fertility work was focused on Caenorhabditis elegans and Ascaris suum. The C. elegans hermaphrodite produces a limited number of sperm initially, and then commits to the exclusive production of oocytes. The post-meiotic differentiation called spermiogenesis converts sessile spermatids into motile spermatozoa. The motility of spermatozoa depends on dynamic assembly and disassembly of a MSP (Major Sperm Protein)-based cytoskeleton uniquely found in nematodes. Both self-derived and male-derived spermatozoa are stored in spermatheca, the site of fertilization in hermaphrodites. The oocytes are arrested in meiotic prophase I until a sperm derived signal relieves the inhibition allowing the meiotic maturation to occur. Oocyte undergoes meiotic maturation, enters into spermatheca, gets fertilized, completes meiosis and exits into uterus as a zygote. This review focuses on our current understanding of the events around fertilization in nematodes. PMID:21749902

  1. Assessment of toxicity test endpoints for freshwater mussel larvae (glochidia).

    PubMed

    Fritts, Andrea K; Barnhart, M Christopher; Bradley, Megan; Liu, Na; Cope, W Gregory; Hammer, Edward; Bringolf, Robert B

    2014-01-01

    The objectives of the present study were to determine if the viability of freshwater mussel larvae (glochidia) is an ecologically relevant endpoint for toxicity tests and to define the appropriate duration of those tests. The authors assessed 1) how viability (the shell closure response to sodium chloride) compares with infectivity (ability to attach to a host fish and successfully metamorphose to the juvenile stage), and 2) the decline of viability and infectivity over time after glochidia were released from female mussels. Glochidia of 7 mussel species were isolated from females, placed in water, and subsampled daily for 2 d to 5 d. Viability, when ≥90%, was generally a good predictor of infectivity; however, when viability was <90%, infectivity was often disproportionately low, especially for glochidia collected near the end of the brooding period. Viability and infectivity declined more rapidly in natural water and sediment compared to reconstituted water. Following 24-h exposure to a toxicant (sodium chloride or copper), infectivity of the viable glochidia did not differ among concentrations of toxicants. The results indicate that viability is a valid proxy for infectivity and an ecologically relevant endpoint for standard toxicity tests with freshwater mussels for any test duration with control viability >90%.

  2. Design and analysis of crossover trials for absorbing binary endpoints.

    PubMed

    Nason, Martha; Follmann, Dean

    2010-09-01

    The crossover is a popular and efficient trial design used in the context of patient heterogeneity to assess the effect of treatments that act relatively quickly and whose benefit disappears with discontinuation. Each patient can serve as her own control as within-individual treatment and placebo responses are compared. Conventional wisdom is that these designs are not appropriate for absorbing binary endpoints, such as death or HIV infection. We explore the use of crossover designs in the context of these absorbing binary endpoints and show that they can be more efficient than the standard parallel group design when there is heterogeneity in individuals' risks. We also introduce a new two-period design where first period "survivors" are rerandomized for the second period. This design combines the crossover design with the parallel design and achieves some of the efficiency advantages of the crossover design while ensuring that the second period groups are comparable by randomization. We discuss the validity of the new designs and evaluate both a mixture model and a modified Mantel-Haenszel test for inference. The mixture model assumes no carryover or period effects while the Mantel-Haenszel approach conditions out period effects. Simulations are used to compare the different designs and an example is provided to explore practical issues in implementation.

  3. Immediate skin responses to laser and light treatments: Warning endpoints: How to avoid side effects.

    PubMed

    Wanner, Molly; Sakamoto, Fernanda H; Avram, Mathew M; Anderson, R Rox

    2016-05-01

    Lasers are versatile, commonly used treatment tools in dermatology. While it is tempting to follow manufacturer's guidelines or other "recipes" for laser treatment, this approach alone can be a recipe for disaster. Specific and immediate skin responses or endpoints exist and are clinically useful because they correlate with underlying mechanisms that are either desirable (ie, therapeutic), undesirable (ie, warning signs of injury or side effects), or incidental. The observation of clinical endpoints is a safe and reliable guide for appropriate treatment. This article presents the warning endpoints during specific dermatologic laser treatments, and the accompanying article presents the therapeutic endpoints, their underlying mechanisms, and the utility of these endpoints.

  4. Fertility Issues in Adolescent and Young Adult Cancer Survivors

    PubMed Central

    Benedict, Catherine; Shuk, Elyse

    2016-01-01

    Purpose: Many adolescent and young adult (AYA) cancer survivors place great importance on fertility. This study explored AYAs' discussions of fertility in the context of discussing their survivorship experiences. Methods: Secondary analyses of a qualitative study of young adult survivors of adolescent cancers (“AYA survivors”) was performed using semistructured individual interviews and focus groups. Analyses were conducted using grounded theory using thematic content analysis with an inductive data-driven approach. Results: Participants (n = 43) were 16–24 years old, diagnosed with cancer between ages 14 and 18 years, and were at least 6 months post-treatment. Before treatment, 5 males banked sperm and no females preserved fertility. More males (50%) than females (39%) reported uncertainty about their fertility. Three major categories emerged from the data: fertility concerns, emotions raised when discussing fertility, and strategies used to manage fertility concerns. Fertility concerns focused on dating/partner reactions, health risks, and what potential infertility would mean for their life narrative. Emotions included distress, feeling overwhelmed and hopeful/wishful thinking. Females were more likely to feel distressed and overwhelmed than males. Strategies to manage concerns included acceptance/“making do,” desire to postpone concerns, and reliance on assisted reproductive technology. Conclusions: Most AYAs in our study reported a number of reproductive concerns and fertility-related distress after treatment, which may affect other areas of psychosocial functioning. Females may be more at-risk for distress than males, particularly in situations of uncertainty and limited knowledge. Future work should explore how to best incorporate fertility-related informational and support services more fully into survivorship care. Implications for survivorship care are discussed. PMID:26812452

  5. [Fertility decline in Spain].

    PubMed

    Arango, J

    1987-01-01

    The historical processes of secular fertility decline in Spain and Portugal are not well understood. Very few microdemographic studies of small geographic regions or particular social strata have been done. A contribution by David Reher to the First Spanish-Portuguese-Italian Historical Demography Conference on the fertility decline in the interior province of Cuenca, Spain, uses the own-children method to analyze changes in marital fertility in the 19th and 20th centuries. Reher discovered a slight fertility decline of perhaps 15% which occurred between the end of the 18th century and 1860-75. The fertility decline did not resume until after the Spanish Civil War, and then it was a very gradual and continuous process. When instead of the total female population, women aged 35-39 were studied, unequivocal signs of fertility control appeared. Conscious fertility control thus appears to have begun among older women limiting rather than spacing births. Reher's analysis by social groups demonstrates that fertility declined first and more rapidly in the nonagricultural and urban populations and among the higher income groups. The fertility decline in Cuenca was certainly not identical to that in most of Spain, but may have been fairly typical of a large part of the interior. Another contribution to the Historical Demography Conference, by Anna Cabre and Isabel Pujadas, analyzes fertility trends and cyclical fluctuations in 20th century Cataluna, arguing that they must be placed in historical perspective if recent changes are to be understood and plausible projections made. Their work demonstrates the value of selecting a relatively homogeneous geographic unit for analysis. The contribution of Margarita Delgado to the conference analyzed interregional fertility differences in contemporary Spain. The high legitimate fertility of the south of Spain is accentuated by high nuptiality rates. In central Spain, the combination of high legitimate fertility rates and low

  6. Computation of eigenfunctions and eigenvalues for the Sturm-Liouville problem with Dirichlet boundary conditions at the left endpoint and Neumann conditions at the right endpoint

    NASA Astrophysics Data System (ADS)

    Khapaev, M. M.; Khapaeva, T. M.

    2016-10-01

    A functional-based variational method is proposed for finding the eigenfunctions and eigenvalues in the Sturm-Liouville problem with Dirichlet boundary conditions at the left endpoint and Neumann conditions at the right endpoint. Computations are performed for three potentials: sin(( x-π)2/π), cos(4 x), and a high nonisosceles triangle.

  7. 21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or irreversible morbidity. 601.41 Section 601.41 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED)...

  8. Female labour force participation and fertility.

    PubMed

    Concepcion, M B

    1974-01-01

    The levels of labor force participation by women in selected Asian countries were recorded in a series of censuses taken over a period of years. These levels were less influenced than male employment levels by economic conditions and more influenced by cultural traits of the country. Postwar trends seem to have fallen in Korea, risen in Singapore and the Philippines, and remained steady in Japan, Malaya, and Thailand. The limitations of these data are mentioned. In Thailand and West Malaysia greater percentages of women worked in agricultural than non-agricultural employment; in the Philippines, where women did not work so much in agricultural pursuits, their jobs were still in traditional rather than in development industries. In the cities of Bangkok, Manila, and Kuala Lumpur, fertility was lower for working than for non-working women. In rural agricultural areas, the fertility of working women was minimally higher, probably due to economic need of lar ger families. It is concluded that urban life separates the employment and the family roles of working women, leading to lowered fertility; this does not occur in rural areas. The creation of new roles for women alternative or supplementary to marriage and motherhood would result in lowered fertility. In high fertility Asian countries, policies directed toward greater participation of women in non-agricultural work and great er exposure to an urban lifestyle might achieve fertility reductions.

  9. The effects of semen collection on fertility in captive, naturally fertile, sandhill cranes

    USGS Publications Warehouse

    Chen, G.; Gee, G.F.; Nicolich, Jane M.; Taylor, J.A.

    2001-01-01

    We tested to see if semen collection interferes with fertility in naturally fertile pairs of cranes. We used 12 naturally fertile, Florida sandhill crane (Grus canadensis pratensis) pairs for this study, 6 control and 6 experimental. All pairs had previously produced fertile eggs. Semen was collected on Tuesday mornings and Friday afternoons from 26 February 1993 to 4 June 1993. We used standard artificial insemination methods to collect and to evaluate the semen and spermatozoa. Semen collection had minimal effect on semen quality and semen quantity. Semen volume, sperm density, sperm motility, sperm morphology, sperm viability, sperm number per collection, and male response to semen collection exhibited significant daily variation. Although semen collection began 13 days before the first egg in the experimental group, we did not observe differences in the date of first egg laid or in fertility between experimental and control groups. Also, we observed no statistically significant differences in the interval between clutches or in the percentage of broken eggs between experimental and control groups. However, 4 eggs were broken by adults during the disturbance associated with capturing birds for semen collection. We found that females with mates from which we consistently gathered better semen samples produced fewer fertile eggs than females with sires producing poorer semen samples (r = 0.60). We interpret these results to mean that males that were successfully breeding with their mates had little left at the time of our collection.

  10. Trends in Utilization of Surrogate Endpoints in Contemporary Cardiovascular Clinical Trials.

    PubMed

    Patel, Ravi B; Vaduganathan, Muthiah; Samman-Tahhan, Ayman; Kalogeropoulos, Andreas P; Georgiopoulou, Vasiliki V; Fonarow, Gregg C; Gheorghiade, Mihai; Butler, Javed

    2016-06-01

    Surrogate endpoints facilitate trial efficiency but are variably linked to clinical outcomes, and limited data are available exploring their utilization in cardiovascular clinical trials over time. We abstracted data regarding primary clinical, intermediate, and surrogate endpoints from all phase II to IV cardiovascular clinical trials from 2001 to 2012 published in the 8 highest Web of Science impact factor journals. Two investigators independently classified the type of primary endpoint. Of the 1,224 trials evaluated, 677 (55.3%) primary endpoints were clinical, 165 (13.5%) intermediate, and 382 (31.2%) surrogate. The relative proportions of these endpoints remained constant over time (p = 0.98). Trials using surrogate endpoints were smaller (187 vs 1,028 patients) and enrolled patients more expeditiously (1.4 vs 0.9 patients per site per month) compared with trials using clinical endpoints (p <0.001 for both comparisons). Surrogate endpoint trials were independently more likely to meet their primary endpoint compared to trials with clinical endpoints (adjusted odds ratio 1.56, 95% CI 1.05 to 2.34; p = 0.03). Rates of positive results in clinical endpoint trials have decreased over time from 66.1% in 2001 to 2003 to 47.2% in 2010 to 2012 (p = 0.001), whereas these rates have remained stable over the same period for surrogate (72.0% to 69.3%, p = 0.27) and intermediate endpoints (74.4% to 71.4%, p = 0.98). In conclusion, approximately a third of contemporary cardiovascular trials use surrogate endpoints. These trials are completed more expeditiously and are more likely to meet their primary outcomes. The overall scientific contribution of these surrogate endpoint trials requires further attention given their variable association with definitive outcomes.

  11. Mexican plants and human fertility.

    PubMed

    Crabbe, P

    1979-07-01

    Synthetic steroids are obtainable cheaply and in abundance from sapogenins, substances originating from plants of the Discorea family. Some 40 years ago, Russell Marker, an American chemist, discovered this source, which grows abundantly in Mexican jungles and is now exploited and cultivated commercially. Today synthetic steroids prepared from extracts from a wide range of vegetable sources are used in the treatment of rheumatoid arthritis, allergies, inflammatory diseases, sterility, and various heart conditions, and form the basis of modern oral contraceptives. Nevertheless, oral contraceptives in current use are still fairly costly, and women have to be educated in their use. What is needed urgently is a cheaper contraceptive pill with a long-term effect, and research is continuing. For example, scientists from the People's Republic of China have reported significant anti-fertility effects associated with 2 substances, anordin and dinordin, prepared with steroids derived from the sisal plants Agave sisilana and Agave americana. These agents, whose anti-fertility properties have been confirmed by scientists in Sweden and the United States, constitute a new family of contraceptives with the great advantage of having to be taken only once or twice instead of 20 times per month necessary with the ordinary pill. Also from China, scientists have reported the effectiveness of gossypol as an orally administered male contraceptive, although gossypol is not a steroid. It may become, however, a leading candidate for a male contraceptive.

  12. Counseling Males.

    ERIC Educational Resources Information Center

    Scher, Murray, Ed.

    1981-01-01

    Contains 16 articles about counseling males including: (1) gender role conflict; (2) sex-role development; (3) counseling adolescent, adult, and gay males; (4) teenage fathers; (5) female therapists and male clients; (6) career development; (7) hypermasculinity; (8) counseling physically abusive men, uncoupling men; (9) group therapy, men's…

  13. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model

    PubMed Central

    Gulani, Jatinder; King, Gregory; Hieber, Kevin; Chappell, Mark; Ossetrova, Natalia

    2016-01-01

    Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6–14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2–4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies. PMID:27579862

  14. Correlation of Hip Fracture with Other Fracture Types: Toward a Rational Composite Hip Fracture Endpoint

    PubMed Central

    Colón-Emeric, Cathleen; Pieper, Carl F.; Grubber, Janet; Van Scoyoc, Lynn; Schnell, Merritt L; Van Houtven, Courtney Harold; Pearson, Megan; Lafleur, Joanne; Lyles, Kenneth W.; Adler, Robert A.

    2016-01-01

    Purpose With ethical requirements to the enrollment of lower risk subjects, osteoporosis trials are underpowered to detect reduction in hip fractures. Different skeletal sites have different levels of fracture risk and response to treatment. We sought to identify fracture sites which cluster with hip fracture at higher than expected frequency; if these sites respond to treatment similarly, then a composite fracture endpoint could provide a better estimate of hip fracture reduction. Methods Cohort study using Veterans Affairs and Medicare administrative data. Male Veterans (n=5,036,536) aged 50-99 years receiving VA primary care between1999-2009 were included. Fractures were ascertained using ICD9 and CPT codes and classified by skeletal site. Pearson correlation coefficients, logistic regression and kappa statistics, were used to describe the correlation between each fracture type and hip fracture within individuals, without regards to the timing of the events. Results 595,579 (11.8%) men suffered 1 or more fractures and 179,597 (3.6%) suffered 2 or more fractures during the time under study. Of those with one or more fractures, rib was the most common site (29%), followed by spine (22%), hip (21%) and femur (20%). The fracture types most highly correlated with hip fracture were pelvic/acetabular (Pearson correlation coefficient 0.25, p<0.0001), femur (0.15, p<0.0001), and shoulder (0.11, p<0.0001). Conclusions Pelvic, acetabular, femur, and shoulder fractures cluster with hip fractures within individuals at greater than expected frequency. If we observe similar treatment risk reductions within that cluster, subsequent trials could consider use of a composite endpoint to better estimate hip fracture risk. PMID:26151123

  15. Simultaneous determination of androgenic and estrogenic endpoints in the threespine stickleback (Gasterosteus aculeatus) using quantitative RT-PCR.

    PubMed

    Hogan, Natacha S; Wartman, Cheryl A; Finley, Megan A; van der Lee, Jennifer G; van den Heuvel, Michael R

    2008-12-11

    A method to evaluate the expression of three hormone responsive genes, vitellogenin (estrogens), spiggin (androgens), and an androgen receptor (ARbeta) using real-time PCR in threespine stickleback is presented. Primers were designed from previously characterised spiggin and ARbeta sequences, while a homology cloning strategy was used to isolate a partial gene sequence for stickleback vitellogenin (Vtg). Spiggin mRNA was significantly higher in kidneys of field-caught males compared to females by greater than five orders of magnitude while ARbeta levels were only 1.4-fold higher in males. Female fish had four order of magnitude higher liver Vtg expression than wild-captured males. To determine the sensitivity of these genes to induction by hormones, male and female sticklebacks were exposed to 1, 10 and 100 ng/L of methyltestosterone (MT) or estradiol (E2) in a flow-through exposure system for 7 days. Spiggin induction in females, and Vtg induction in males were both detectable at 10 ng/L of MT and E2, respectively. MT exposure did not induce ARbeta expression in the kidneys of female stickleback. In vitro gonadal steroid hormones production was measured in testes and ovaries of exposed stickleback to compare gene expression endpoints to an endpoint of hormonal reproductive alteration. Reduction in testosterone production in ovaries at all three MT exposure concentrations, and ovarian estradiol synthesis at the 100 ng/L exposure were the only effects observed in the in vitro steroidogenesis for either hormone exposure. Application of these methods to assess both androgenic, estrogenic, and anti-steroidogenic properties of environmental contaminants in a single fish species will be a valuable tool for identifying compounds causing reproductive dysfunction in fishes.

  16. Fertilization in echinoderms.

    PubMed

    Santella, Luigia; Vasilev, Filip; Chun, Jong T

    2012-08-31

    For more than 150 years, echinoderm eggs have served as overly favored experimental model systems in which to study fertilization. Sea urchin and starfish belong to the same phylum and thus share many similarities in their fertilization patterns. However, several subtle but fundamental differences do exist in the fertilization of sea urchin and starfish, reflecting their phylogenetic bifurcation approximately 500 million years ago. In this article we review some of the seminal and recent findings that feature similarities and differences in sea urchin and starfish at fertilization.

  17. Fertilizer Use and Water Quality.

    ERIC Educational Resources Information Center

    Reneau, Fred; And Others

    This booklet presents informative materials on fertilizer use and water quality, specifically in regard to environmental pollution and protection in Illinois. The five chapters cover these topics: Fertilizer and Water Quality, Fertilizer Use, Fertilizers and the Environment, Safety Practices, and Fertilizer Management Practices. Key questions are…

  18. Semi-inclusive hadronic B decays in the endpoint region

    SciTech Connect

    Chay, Junegone; Kim, Chul; Leibovich, Adam K.; Zupan, Jure

    2006-10-01

    We consider in the soft-collinear effective theory semi-inclusive hadronic B decays, B{yields}XM, in which an energetic light meson M near the endpoint recoils against an inclusive jet X. We focus on a subset of decays where the spectator quark from the B meson ends up in the jet. The branching ratios and direct CP asymmetries are computed to next-to-leading order accuracy in {alpha}{sub s} and to leading order in 1/m{sub b}. The contribution of charming penguins is extensively discussed, and a method to extract it in semi-inclusive decays is suggested. Subleading 1/m{sub b} corrections and SU(3) breaking effects are discussed.

  19. DETERMINING SIGNIFICANT ENDPOINTS FOR ECOLOGICAL RISK ANALYS ES

    SciTech Connect

    Hinton, Thomas G.

    2000-12-31

    Our interest is in obtaining a scientifically defensible endpoint for measuring ecological risks to populations exposed to chronic, low-level radiation, and radiation with concomitant exposure to chemicals. To do so, we believe that we must understand the extent to which molecular damage is detrimental at the individual and population levels of biological organization. Ecological risk analyses based on molecular damage, without an understanding of the impacts to higher levels of biological organization, could cause cleanup strategies on DOE sites to be overly conservative and unnecessarily expensive. Our goal is to determine the relevancy of sublethal cellular damage to the performance of individuals and populations. We think that we can achieve this by using novel biological dosimeters in controlled, manipulative dose/effects experiments, and by coupling changes in metabolic rates and energy allocation patterns to meaningful population response variables (such as age-specific survivorship, reproductive output, age at maturity and longevity).

  20. Are Hemodynamics Surrogate Endpoints in Pulmonary Arterial Hypertension?

    PubMed Central

    Ventetuolo, Corey E.; Gabler, Nicole B.; Fritz, Jason S.; Smith, K. Akaya; Palevsky, Harold I.; Klinger, James R.; Halpern, Scott D.; Kawut, Steven M.

    2014-01-01

    Background While frequently assessed in trials and clinical practice, hemodynamic response to therapy has never been validated as a surrogate endpoint for clinical events in pulmonary arterial hypertension (PAH). Methods and Results We performed a patient-level pooled analysis of four randomized placebo-controlled trials to determine if treatment-induced changes in hemodynamic values at 12 weeks accounted for the relationship between treatment assignment and the probability of early clinical events (death, lung transplantation, atrial septostomy, PAH hospitalization, withdrawal for clinical worsening, escalation in PAH therapy). We included 1119 subjects with PAH. The median (interquartile range) age was 48 (37 – 59), and 23% were men. 656 (59%) received active therapy (101 [15%] iloprost, 118 [18%] sitaxsentan, 204 [31%] sildenafil, and 233 [36%] subcutaneous treprostinil). Active treatment significantly lowered right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance and increased cardiac output and index (p < 0.01 for all). Changes in hemodynamic values (except for RAP and mPAP) were significantly associated with the risk of a clinical event (p ≤ 0.01 for all). While active treatment approximately halved the odds of a clinical event compared to placebo (p < 0.001), changes in hemodynamics accounted for only 1.2 – 13.9% of the overall treatment effect. Conclusions Treatment-induced changes in hemodynamics at 12 weeks only partially explain the impact of therapy on the probability of early clinical events in PAH. These findings suggest that resting hemodynamics are not valid surrogate endpoints for short-term events in PAH clinical trials. PMID:24951771

  1. Introduction: Ejaculatory problems and male infertility.

    PubMed

    Sigman, Mark

    2015-11-01

    There are a variety of dysfunctions of the ejaculatory process which may negatively impact male fertility but are not commonly discussed. The meanings of the terms used to describe these conditions are often unclear. This month's Views and Reviews define the commonly used and confused terms. The initial article explains normal male function with an emphasis on the ejaculatory process. Following articles discuss the causes, evaluation and management of the male with ejaculatory dysfunction.

  2. Fertility Treatments for Females

    MedlinePlus

    ... are some causes of infertility?​​​ What is fertility preservation? When should I consult a health care provider?​ ... are some causes of infertility?​​​ What is fertility preservation? When should I consult a health care provider?​ ...

  3. Infertility and Fertility

    MedlinePlus

    ... are some causes of infertility?​​​ What is fertility preservation? When should I consult a health care provider?​ ... are some causes of infertility?​​​ What is fertility preservation? When should I consult a health care provider?​ ...

  4. [Socioeconomic variables and fertility].

    PubMed

    Arguello, O

    1980-08-01

    While making comparative analyses of data collected by the World Fertility Survey regarding Latin America, a group of investigators of CELADE (Centro Latinoamericano de Demografia) realized that the selection of economic variables for the study of fertility had serious limitations. Such limitations did not allow the elaboration of a theory which took into account the complicated process of fertility, in all its socioeconomic, cultural, and psychological manifestations. Thus, this paper intends to lay the theoretical basis for the selection of all relevant variables, distinguishing, for example, the average fertility of women according to area of residence, place of early socialization, migrant status, social status, occupation of husband, level of instruction, occupation, and all changes in occupational activities of women in fertile age.

  5. Molecular biology of male infertility.

    PubMed

    Feng, H L

    2003-01-01

    About 15% of couples have reduced fertility and in approximately one-half of all cases the reason is male infertility, usually of genetic origin. Thus, in the context of research in genes involved in reproduction and sex determination, genetic anomalies in gametogenesis are being extensively studied. The most frequent pathogenic causes of male infertility are Y-chromosomal microdeletions (8-15%) in the long arm of the Y chromosome, which, by loss of specific DNA segments, leads to loss of vital genes for sperm production. Infertile men, who attend infertility clinics, rise to 15% among those with azoospermia or spermatogenesis problem. The new technique of intracytoplasmic sperm injection has allowed many infertile men to achieve their dreams of fatherhood. However, the spermatogenic defect is genetic anomalies, which might be a potential risk of transmitting this defect to future offspring. Therefore, genetic counseling of all couples with the diagnosis of male infertility is recommended before their enrolment in intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection. The important role of genetic abnormalities in the causation of human male infertility is increasingly recognized. While much remains to be learned in this fast-moving field, considerable progress has been made in the clinical delineation of genetic forms of male infertility and in the characterization of the responsible genes and their mutations or deletions. This review should provide insight into the understanding of parthenogenesis of male infertility in the human.

  6. Smoking and Male Infertility: An Evidence-Based Review

    PubMed Central

    Harlev, Avi; Gunes, Sezgin Ozgur; Shetty, Amit; du Plessis, Stefan Simon

    2015-01-01

    Many studies have reported that the contents of cigarette smoke negatively affect sperm parameters, seminal plasma, and various other fertility factors. Nevertheless, the actual effect of smoking on male fertility is not clear. The effect of smoking on semen parameters is based on the well-established biological finding that smoking increases the presence of reactive oxygen species, thereby resulting in oxidative stress (OS). OS has devastating effects on sperm parameters, such as viability and morphology, and impairs sperm function, hence reducing male fertility. However, not all studies have come to the same conclusions. This review sheds light upon the arguable association between smoking and male fertility and also assesses the impact of non-smoking routes of tobacco consumption on male infertility. It also highlights the evidence that links smoking with male infertility, including newly emerging genetic and epigenetic data, and discusses the clinical implications thereof. PMID:26770934

  7. Lycopene and male infertility

    PubMed Central

    Durairajanayagam, Damayanthi; Agarwal, Ashok; Ong, Chloe; Prashast, Pallavi

    2014-01-01

    Excessive amounts of reactive oxygen species (ROS) cause a state of oxidative stress, which result in sperm membrane lipid peroxidation, DNA damage and apoptosis, leading to decreased sperm viability and motility. Elevated levels of ROS are a major cause of idiopathic male factor infertility, which is an increasingly common problem today. Lycopene, the most potent singlet oxygen quencher of all carotenoids, is a possible treatment option for male infertility because of its antioxidant properties. By reacting with and neutralizing free radicals, lycopene could reduce the incidence of oxidative stress and thus, lessen the damage that would otherwise be inflicted on spermatozoa. It is postulated that lycopene may have other beneficial effects via nonoxidative mechanisms in the testis, such as gap junction communication, modulation of gene expression, regulation of the cell cycle and immunoenhancement. Various lycopene supplementation studies conducted on both humans and animals have shown promising results in alleviating male infertility—lipid peroxidation and DNA damage were decreased, while sperm count and viability, and general immunity were increased. Improvement of these parameters indicates a reduction in oxidative stress, and thus the spermatozoa is less vulnerable to oxidative damage, which increases the chances of a normal sperm fertilizing the egg. Human trials have reported improvement in sperm parameters and pregnancy rates with supplementation of 4–8 mg of lycopene daily for 3–12 months. However, further detailed and extensive research is still required to determine the dosage and the usefulness of lycopene as a treatment for male infertility. PMID:24675655

  8. Anatomy of an experimental two-link flexible manipulator under end-point control

    NASA Technical Reports Server (NTRS)

    Oakley, Celia M.; Cannon, Robert H., Jr.

    1990-01-01

    The design and experimental implementation of an end-point controller for two-link flexible manipulators are presented. The end-point controller is based on linear quadratic Gaussian (LQG) theory and is shown to exhibit significant improvements in trajectory tracking over a conventional controller design. To understand the behavior of the manipulator structure under end-point control, a strobe sequence illustrating the link deflections during a typical slew maneuver is included.

  9. Impact of weighted composite compared to traditional composite endpoints for the design of randomized controlled trials.

    PubMed

    Bakal, Jeffrey A; Westerhout, Cynthia M; Armstrong, Paul W

    2015-12-01

    Composite endpoints are commonly used in cardiovascular clinical trials. When using a composite endpoint a subject is considered to have an event when the first component endpoint has occurred. The use of composite endpoints offers the ability to incorporate several clinically important endpoint events thereby augmenting the event rate and increasing statistical power for a given sample size. One assumption of the composite is that all component events are of equal clinical importance. This assumption is rarely achieved given the diversity of component endpoints included. One means of adjusting for this diversity is to adjust the outcomes using severity weights determined a priori. The use of a weighted endpoint also allows for the incorporation of multiple endpoints per patient. Although weighting the outcomes lowers the effective number of events, it offers additional information that reduces the variance of the estimate. We created a series of simulation studies to examine the effect on power as the individual components of a typical composite were changed. In one study, we noted that the weighted composite was able to offer discriminative power when the component outcomes were altered, while the traditional method was not. In the other study, we noted that the weighted composite offered a similar level of power to the traditional composite when the change was driven by the more severe endpoints.

  10. Fertilizer nitrogen isotope signatures.

    PubMed

    Bateman, Alison S; Kelly, Simon D

    2007-09-01

    There has been considerable recent interest in the potential application of nitrogen isotope analysis in discriminating between organically and conventionally grown crops. A prerequisite of this approach is that there is a difference in the nitrogen isotope compositions of the fertilizers used in organic and conventional agriculture. We report new measurements of delta15N values for synthetic nitrogen fertilizers and present a compilation of the new data with existing literature nitrogen isotope data. Nitrogen isotope values for fertilizers that may be permitted in organic cultivation systems are also reported (manures, composts, bloodmeal, bonemeal, hoof and horn, fishmeal and seaweed based fertilizers). The delta15N values of the synthetic fertilizers in the compiled dataset fall within a narrow range close to 0 per thousand with 80% of samples lying between-2 and 2 per thousand and 98.5% of the data having delta15N values of less than 4 per thousand (mean=0.2 per thousand n=153). The fertilizers that may be permitted in organic systems have a higher mean delta15N value of 8.5 per thousand and exhibit a broader range in delta15N values from 0.6 to 36.7 per thousand (n=83). The possible application of the nitrogen isotope approach in discriminating between organically and conventionally grown crops is discussed in light of the fertilizer data presented here and with regard to other factors that are also important in determining crop nitrogen isotope values.

  11. Effects of un-ionized ammonia on histological, endocrine, and whole organism endpoints in slimy sculpin (Cottus cognatus).

    PubMed

    Spencer, P; Pollock, R; Dubé, M

    2008-12-11

    Ammonia is known to be an important toxicant in aquatic environments. Although ammonia toxicity has been well studied in many fish species, effects of chronic exposure on slimy sculpin (Cottus cognatus), a critical biomonitoring species for northern aquatic habitats, are not well known. Further, with increasing mining development in Canada's north, this information is critical to better predict potential effects of mine effluent discharges on northern fish species. Slimy sculpin were exposed to six concentrations of un-ionized ammonia (NH(3)) relevant to concentrations found in northern mining effluents: control (0 ppm), 0.278 ppm, 0.556 ppm, 0.834 ppm, 1.112 ppm, and 1.668 ppm. An LC(50) of 1.529 ppm was calculated from mortality data. Histopathological examination of gills indicated significant tissue damage, measured as lamellar fusion and epithelial lifting, at 0.834 ppm, 1.112 ppm, and 1.668 ppm. Using gill endpoints, NOEC and LOEC were calculated as 0.556 ppm and 0.834 ppm, respectively. An EC(50) of 0.775 ppm was determined for lamellar fusion and an EC(50) of 0.842 ppm for epithelial lifting. Hemorrhage of gills was present in mortalities, which occurred at 1.668 ppm of un-ionized ammonia. A significant decrease in liver somatic index (LSI) was seen in both male and female fish at 0.834 ppm and 1.112 ppm, respectively. Gonadosomatic index (GSI) in female fish significantly increased at 1.668 ppm un-ionized ammonia with an associated significant increase in total wholebody testosterone concentrations. GSI in male fish also significantly increased at 1.668 ppm but no differences were seen in testosterone concentrations. No significant differences were seen in gonad histopathological assessments or condition factor. Gill histopathology endpoints may be a more sensitive indicator for detecting effects in slimy sculpin exposed to ammonia than traditional chronic endpoints. Results from this study indicate that ammonia concentrations commonly reported in northern

  12. Clinical guide to fertility preservation in hematopoietic cell transplant recipients.

    PubMed

    Joshi, S; Savani, B N; Chow, E J; Gilleece, M H; Halter, J; Jacobsohn, D A; Pidala, J; Quinn, G P; Cahn, J-Y; Jakubowski, A A; Kamani, N R; Lazarus, H M; Rizzo, J D; Schouten, H C; Socie, G; Stratton, P; Sorror, M L; Warwick, A B; Wingard, J R; Loren, A W; Majhail, N S

    2014-04-01

    With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to increase steadily. Infertility is a frequent problem that long-term HCT survivors and their partners face and it can negatively impact on the quality of life. The most optimal time to address fertility issues is before the onset of therapy for the underlying disease; however, fertility preservation should also be addressed before HCT in all children and patients of reproductive age, with referral to a reproductive specialist for patients interested in fertility preservation. In vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking are acceptable methods for fertility preservation in adult women/pubertal females. Sperm banking is the preferred method for adult men/pubertal males. Frequent barriers to fertility preservation in HCT recipients may include the perception of lack of time to preserve fertility given an urgency to move ahead with transplant, lack of patient-physician discussion because of several factors (for example, time constraints, lack of knowledge), inadequate access to reproductive specialists, and costs and lack of insurance coverage for fertility preservation. There is a need to raise awareness in the medical community about fertility preservation in HCT recipients.

  13. The evolutionary role of males in C. elegans

    PubMed Central

    Chasnov, Jeffrey R.

    2013-01-01

    Although the nematode worm Caenorhabditis elegans reproduces primarily as a self-fertilizing hermaphrodite, males are maintained in natural populations at low frequency. In this commentary, I discuss the evolutionary forces that maintain males and the role males might play in this mating system. PMID:24058855

  14. Development of Effects-Based Nutrient Criteria using Biological Endpoints

    NASA Astrophysics Data System (ADS)

    Miltner, R.

    2005-05-01

    Ohio employs biological endpoints to judge the status of aquatic life in rivers and streams. Specifically, numeric criteria derived from biological indices have been incorporated into Ohio's water quality standards for fish and macroinvertebrate communities. When appropriate, chemical-specific water quality standards derived from dose-response curves are used in concert with the biological indices to ascribe the causes and sources of impairment to polluted streams. However, water quality criteria have not been established for all polluting agents, especially those, like nutrients, that do not elicit a simple dose-response curve. In such cases, where biological impairment is observed, the linkage between the impairment and causal agent is made inferentially. Ohio EPA is currently studying the relationship between nutrient concentrations, periphytic chlorophyll a concentrations, and biological indices to ascertain whether a direct relationship exists between nutrient concentration and the biological health of fish and macroinvertebrate communities, with the eventual goal of adopting effects-based nutrient criteria in Ohio's water quality standards. Results from the first field season show a strong relationship between chlorophyll a concentrations, and physical and land use variables. Additionally, 48 h dissolved oxygen flux correlated with periphytic chlorophyll a concentrations and the degree of canopy cover.

  15. Responsiveness of endpoints in osteoporosis clinical trials--an update.

    PubMed

    Cranney, A; Welch, V; Tugwell, P; Wells, G; Adachi, J D; McGowan, J; Shea, B

    1999-01-01

    As an update of our earlier paper, published as part of the Outcome Measures in Rheumatology Clinical Trials (OMERACT 3) proceedings in 1996, we surveyed the types of outcomes incorporated in recent clinical trials. A literature search was conducted on MEDLINE and Current Contents, from January 1996 to March 1998, using the search strategy recommended by the Cochrane Collaboration for the identification of randomized controlled trials (RCT). Two independent reviewers selected trials according to inclusion criteria. The same reviewers extracted data on clinical and radiographic fractures, pain, quality of life, and bone mineral density (BMD). Seventy-four RCT conducted on bone loss in postmenopausal women were identified. Most trials incorporated biochemical markers and BMD as outcome measures. Fewer trials included vertebral fractures, pain, height, and quality of life. The responsiveness is presented in terms of the sample size needed per group to show a statistically significant difference. The most responsive outcomes were pain, BMD, and biochemical markers. The number needed to treat to prevent one vertebral fracture ranged from 13 to 54, depending on the intervention and population. Investigators should examine the characteristics of the patient population and the nature of the intervention in determining the sample size required to demonstrate a significant effect. The selection of endpoints should be based on their responsiveness, feasibility, and the importance of using standardized outcomes. Standardized outcomes greatly facilitate the synthesis of available information into systematic reviews by groups such as the Cochrane Collaboration.

  16. Identification of sequence-related amplified polymorphism and insertion-deletion markers linked to the male fertility restorer gene of pol-like CMS06J45 in heading Chinese cabbage (Brassica rapa subsp pekinensis).

    PubMed

    Xu, X Y; Zhang, Y; Zhang, L G; Fang, Z Y

    2014-11-14

    In order to map the restorer gene BrRfp of the polima (pol)-like cytoplasmic male sterility (CMS) 06J45 line in heading Chinese cabbage, an F2 segregating population with 258 individuals of CMS06J45 and the restorer line 01S325 were tested by sequence-related amplified polymorphism (SRAP) and insertion-deletion (InDel) technologies combined with the bulked segregant analysis method. As a result, two SRAP markers, me3em3.366 and pm88bg5.263, that were linked with the BrRfp gene were identified from 463 SRAP primer pairs. By cloning, sequencing, and basic local alignment search tool analysis, the two markers were targeted to the BGIScaffold000053 of Brassica rapa in the Brassica database. Using the BGIScaffold000053 sequence, four InDel primer pairs were designed and identified to be linked with the BrRfp gene in this population. Linkage analysis showed that these markers were distributed on both sides of the BrRfp gene, the linkage distances of two nearest markers InDel878.1125 and InDel920.713 were 0.82 and 0.46 cM, respectively, and the BrRfp gene was restricted to a 243-kb genomic region of B. rapa. These specific markers provided basic information for map-based cloning of the BrRfp gene and will be very valuable for the marker-assisted selection of a new restorer line in heading Chinese cabbage.

  17. Fertility Clinic Success Rates

    MedlinePlus

    ... Birth Defects ART and Autism 2013 Assisted Reproductive Technology Fertility Clinic Success Rates Report Recommend on Facebook ... RSS ABOUT About CDC Jobs Funding LEGAL Policies Privacy FOIA No Fear Act OIG 1600 Clifton Road ...

  18. Chapter VII. Predicting Fertility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Section 2. Visual and Microscopic Approaches for Differentiating Unfertilized Germinal Discs and Early dead Embryos from Pre-Incubated Blastoderms Section 3. Predicting the Duration of fertility by Counting Sperm in the Outer Perivitelline Layer of Laid Eggs...

  19. Optimizing Natural Fertility

    MedlinePlus

    ... heavy alcohol consumption (> 2 drinks per day), heavy caffeine consumption, and the use of recreational drugs such as marijuana have all been associated with reduced fertility. Therefore, women (and ... alcohol and caffeine use, and avoid smoking and all recreational drugs ...

  20. Impaired fertility in T-stock female mice after superovulation

    SciTech Connect

    Wyrobek, A J; Bishop, J B; Marchetti, F; Zudova, D

    2003-12-05

    Superovulation of female mice with exogenous gonadotrophins is routinely used for increasing the number of eggs ovulated by each female in reproductive and developmental studies. We report an unusual effect of superovulation on fertilization in mice. In vivo matings of superovulated T-stock females with B6C3F1 males resulted in a 2-fold reduction (P<0.001) in the frequencies of fertilized eggs compared to control B6C3F1 matings. In addition, {approx}22 hr after mating only 15% of fertilized eggs recovered in T-stock females had reached the metaphase stage of the first cleavage division versus 87% in B6C3F1 females (P < 0.0001). Matings with T-stock males did not improve the reproductive performance of T-stock females. To investigate the possible cause(s) for the impaired fertilization and zygotic development, the experiments were repeated using in vitro fertilization. Under these conditions, the frequencies of fertilized eggs were not different in superovulated T-stock and B6C3F1 females (51.7% {+-} 6.0 and 64.5% {+-}3.8, P=0.10). There was a 7-fold increase in the frequencies of fertilized T-stock eggs that completed the first cell cycle of development after in vitro versus in vivo fertilization. These results rule out an intrinsic deficiency of the T-stock oocyte as the main reason for the impaired fertility after in vivo matings and suggest that superovulation of T-stock females induces a hostile oviductal and uterine environment with dramatic effects on fertilization and zygotic development.

  1. Statistical evaluation of surrogate endpoints with examples from cancer clinical trials.

    PubMed

    Buyse, Marc; Molenberghs, Geert; Paoletti, Xavier; Oba, Koji; Alonso, Ariel; Van der Elst, Wim; Burzykowski, Tomasz

    2016-01-01

    A surrogate endpoint is intended to replace a clinical endpoint for the evaluation of new treatments when it can be measured more cheaply, more conveniently, more frequently, or earlier than that clinical endpoint. A surrogate endpoint is expected to predict clinical benefit, harm, or lack of these. Besides the biological plausibility of a surrogate, a quantitative assessment of the strength of evidence for surrogacy requires the demonstration of the prognostic value of the surrogate for the clinical outcome, and evidence that treatment effects on the surrogate reliably predict treatment effects on the clinical outcome. We focus on these two conditions, and outline the statistical approaches that have been proposed to assess the extent to which these conditions are fulfilled. When data are available from a single trial, one can assess the "individual level association" between the surrogate and the true endpoint. When data are available from several trials, one can additionally assess the "trial level association" between the treatment effect on the surrogate and the treatment effect on the true endpoint. In the latter case, the "surrogate threshold effect" can be estimated as the minimum effect on the surrogate endpoint that predicts a statistically significant effect on the clinical endpoint. All these concepts are discussed in the context of randomized clinical trials in oncology, and illustrated with two meta-analyses in gastric cancer.

  2. Use of sublethal endpoints in sediment toxicity testing with the amphipod Hyalella azteca

    SciTech Connect

    Kemble, N.E.; Brunson, E.B.; Dwyer, F.J.; Ehrhardt, E.A.; Hardesty, D.K.; Haverland, P.S.; Ingersoll, C.G.

    1995-12-31

    ASTM and EPA standard methods for sediment toxicity tests with Hyalella azteca typically recommend use of lethality as the endpoint in a 10-d exposure. However, data from 10- to 28-d exposures with amphipods indicate sublethal endpoints (i.e., growth, sexual maturation, or reproduction) identify additional samples as toxic. The authors compared the frequency that lethal and sublethal endpoints identified a sediment sample as toxic in 14- and 28-d amphipod exposures. In the 14-d amphipod exposures, lethality identified 20% of the samples as toxic, and sublethal endpoints identified an additional 16% of the samples as toxic using sublethal endpoints only. Similarly, in the 28-d exposures, lethality identified 14% of the samples as toxic and sublethal endpoints identified an additional 18% of the samples as toxic. The authors are also currently evaluating Sediment Effect Concentrations (SECs) relative to both lethal and sublethal endpoints in H. azteca exposures. These SECs will be used to evaluate reliability in estimating toxicity of samples. Potential factors which may confound interpretation of sublethal endpoints in sediment tests include: (1) changes in sediment chemistry resulting from long-term storage or feeding (2) the influence of physical characteristics of sediment (grain size), and (3) effects of ammonia or hydrogen sulfide.

  3. 78 FR 46351 - Trial Designs and Endpoints for Liver Disease Secondary to Nonalcoholic Steatohepatitis; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ... HUMAN SERVICES Food and Drug Administration Trial Designs and Endpoints for Liver Disease Secondary to... Research in cosponsorship with the American Association for the Study of Liver Diseases (AASLD) is announcing a 2-day public workshop entitled ``Trial Designs and Endpoints for Liver Disease Secondary...

  4. Partitioning sexual selection into its mating success and fertilization success components.

    PubMed

    Pischedda, Alison; Rice, William R

    2012-02-07

    Postcopulatory sexual selection due to sperm competition and/or cryptic female choice has been documented in a diversity of taxonomic groups and is considered a pivotal component of sexual selection. Despite this apparent importance, the relative contribution of postcopulatory fertilization success to overall sexual selection has not yet been measured in any species. Here, we used a laboratory-adapted population of the promiscuous fruit fly Drosophila melanogaster to partition the variance in male reproductive success into mating success (a major component of precopulatory sexual selection) and fertilization success (a major component of postcopulatory sexual selection). We found that fertilization success contributed nearly as strongly as mating success to a male's net performance in sexual selection, but that most of this postcopulatory component was attributable to variation in male mating order (the tendency to be the last male to mate a female). After adjusting for mating order, only ≈2% of the residual variation in male reproductive success was attributable to differential fertilization success. We found no correlation between male mating success and fertilization success in this system. Unlike natural populations of Drosophila, our laboratory population is adapted to a semelparous lifecycle, so our findings will be most applicable to other promiscuous species with strong sperm precedence and one short breeding period per year or lifetime. In these species, fertilization success may have as much influence on male reproductive success as mating success, but the timing of mating (mating order) may be the predominant factor contributing to variation in fertilization success.

  5. Condoms - male

    MedlinePlus

    Prophylactics; Rubbers; Male condoms; Contraceptive - condom; Contraception - condom; Barrier method - condom ... rubber Polyurethane Condoms are the only method of birth control for men that are not permanent. They can ...

  6. A Few Endpoint Geodesic Restriction Estimates for Eigenfunctions

    NASA Astrophysics Data System (ADS)

    Chen, Xuehua; Sogge, Christopher D.

    2014-07-01

    We prove a couple of new endpoint geodesic restriction estimates for eigenfunctions. In the case of general 3-dimensional compact manifolds, after a TT* argument, simply by using the L 2-boundedness of the Hilbert transform on , we are able to improve the corresponding L 2-restriction bounds of Burq, Gérard and Tzvetkov (Duke Math J 138:445-486, 2007) and Hu (Forum Math 6:1021-1052, 2009). Also, in the case of 2-dimensional compact manifolds with nonpositive curvature, we obtain improved L 4-estimates for restrictions to geodesics, which, by Hölder's inequality and interpolation, implies improved L p -bounds for all exponents p ≥ 2. We do this by using oscillatory integral theorems of Hörmander (Ark Mat 11:1-11, 1973), Greenleaf and Seeger (J Reine Angew Math 455:35-56, 1994) and Phong and Stein (Int Math Res Notices 4:49-60, 1991), along with a simple geometric lemma (Lemma 3.2) about properties of the mixed-Hessian of the Riemannian distance function restricted to pairs of geodesics in Riemannian surfaces. We are also able to get further improvements beyond our new results in three dimensions under the assumption of constant nonpositive curvature by exploiting the fact that, in this case, there are many totally geodesic submanifolds.

  7. Observations on Three Endpoint Properties and Their Relationship to Regulatory Outcomes of European Oncology Marketing Applications

    PubMed Central

    Stolk, Pieter; McAuslane, James Neil; Schellens, Jan; Breckenridge, Alasdair M.; Leufkens, Hubert

    2015-01-01

    Background. Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy’s clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes. Materials and Methods. We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013). Results. Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments. There was no difference (p = .3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p < .05) improvements in primary endpoints (p < .0001 difference between the approved and failed groups). Conclusion. Three key endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint outcome, and its statistical significance) are consistent with the European Medicines Agency guidance and, notwithstanding the contribution of unique disease-specific circumstances, are associated with a predictable positive outcome for oncology MAAs. Implications for Practice: Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many

  8. Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans

    PubMed Central

    Yang, Zhendong; Xue, Kathy S.; Sun, Xiulan; Tang, Lili; Wang, Jia-Sheng

    2015-01-01

    Aflatoxins B1 (AFB1), deoxynivalenol (DON), fumonisin B1 (FB1), T-2 toxin (T-2), and zearalenone (ZEA) are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB1 toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB1, FB1, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model. PMID:26633509

  9. Latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint.

    PubMed

    Hu, Chuanpu; Szapary, Philippe O; Mendelsohn, Alan M; Zhou, Honghui

    2014-08-01

    Informative exposure-response modeling of clinical endpoints is important in drug development. There has been much recent progress in latent variable modeling of ordered categorical endpoints, including the application of indirect response (IDR) models and accounting for residual correlations between multiple categorical endpoints. This manuscript describes a framework of latent-variable-based IDR models that facilitate easy simultaneous modeling of a continuous and a categorical clinical endpoint. The model was applied to data from two phase III clinical trials of subcutaneously administered ustekinumab for the treatment of psoriatic arthritis, where Psoriasis Area and Severity Index scores and 20, 50, and 70 % improvement in the American College of Rheumatology response criteria were used as efficacy endpoints. Visual predictive check and external validation showed reasonable parameter estimation precision and model performance.

  10. Multi-Toxic Endpoints of the Foodborne Mycotoxins in Nematode Caenorhabditis elegans.

    PubMed

    Yang, Zhendong; Xue, Kathy S; Sun, Xiulan; Tang, Lili; Wang, Jia-Sheng

    2015-12-02

    Aflatoxins B₁ (AFB₁), deoxynivalenol (DON), fumonisin B₁ (FB₁), T-2 toxin (T-2), and zearalenone (ZEA) are the major foodborne mycotoxins of public health concerns. In the present study, the multiple toxic endpoints of these naturally-occurring mycotoxins were evaluated in Caenorhabditis elegans model for their lethality, toxic effects on growth and reproduction, as well as influence on lifespan. We found that the lethality endpoint was more sensitive for T-2 toxicity with the EC50 at 1.38 mg/L, the growth endpoint was relatively sensitive for AFB₁ toxic effects, and the reproduction endpoint was more sensitive for toxicities of AFB₁, FB₁, and ZEA. Moreover, the lifespan endpoint was sensitive to toxic effects of all five tested mycotoxins. Data obtained from this study may serve as an important contribution to knowledge on assessment of mycotoxin toxic effects, especially for assessing developmental and reproductive toxic effects, using the C. elegans model.

  11. Hybridization using cytoplasmic male sterility and herbicide tolerance from nuclear genes

    SciTech Connect

    Beversdorf, W.D.; Erickson, L.R.; Grant, I.

    1987-04-14

    An improved process is described for producing a substantially homogeneous population of plants of a predetermined hybrid variety of a crop which is capable of undergoing both self-pollination and cross-pollination. This process comprises: growing in a first planting area a substantially random population of cytoplasmic male sterile plants which exhibit tolerance to at least one herbicide attributable solely to homozygous dominant nuclear genes, and male fertile plants which are capable of pollinating the cytoplasmic male sterile plants and which lack the herbicide tolerance because the presence of homozygous recessive nuclear genes for such trait. The cytoplasmic male sterile plants and the male fertile plants are pollinated with pollen derived from the male fertile plants. Seed is formed on the cytoplasmic male sterile plants and on the male fertile plants. Harvesting in bulk the seed is formed on the plants of the first planting area.

  12. Long sperm fertilize more eggs in a bird

    PubMed Central

    Bennison, Clair; Hemmings, Nicola; Slate, Jon; Birkhead, Tim

    2015-01-01

    Sperm competition, in which the ejaculates of multiple males compete to fertilize a female's ova, results in strong selection on sperm traits. Although sperm size and swimming velocity are known to independently affect fertilization success in certain species, exploring the relationship between sperm length, swimming velocity and fertilization success still remains a challenge. Here, we use the zebra finch (Taeniopygia guttata), where sperm size influences sperm swimming velocity, to determine the effect of sperm total length on fertilization success. Sperm competition experiments, in which pairs of males whose sperm differed only in length and swimming speed, revealed that males producing long sperm were more successful in terms of (i) the number of sperm reaching the ova and (ii) fertilizing those ova. Our results reveal that although sperm length is the main factor determining the outcome of sperm competition, complex interactions between male and female reproductive traits may also be important. The mechanisms underlying these interactions are poorly understood, but we suggest that differences in sperm storage and utilization by females may contribute to the outcome of sperm competition. PMID:25621327

  13. Male contraception.

    PubMed

    Wang, Christina; Swerdloff, Ronald S

    2002-04-01

    Currently approved male-directed contraceptive methods include condoms and vas occlusion. Vas occlusion is very effective but is intended to be non-reversible. Condoms have a relatively high failure rate, at least partially due to compliance problems and are not accepted by many couples. The only other male-oriented methods in clinical trials utilize the administration of testosterone alone or its combination with another gonadotropin-suppressing agent such as a progestin or a gonadotropin-releasing hormone antagonist. Studies published in the 1990s demonstrated that a testosterone-containing hormonal contraceptive method suppressed spermatogenesis to azoospermia in most men and severe oligozoospermia in the remaining. The contraceptive efficacy after treatment with testosterone alone was comparable to that of female hormonal methods. Having proven that reversible male contraception is a reality, present trials are attempting to identify the best androgen delivery system and the most effective androgen plus progestin preparation. It is likely that the first marketed male hormonal contraceptive method will be a long-acting (injectable or implant) combination of an androgen plus a progestin. Research is continuing to identify other target areas for male contraceptive development, including agents with post-testicular and epididymal sites of action.

  14. Revisiting Suppression of Interspecies Hybrid Male Lethality in Caenorhabditis Nematodes.

    PubMed

    Ryan, Lauren E; Haag, Eric S

    2017-02-16

    Within the nematode genus Caenorhabditis, C. briggsae and C. nigoni are among the most closely related species known. They differ in sexual mode, with C. nigoni retaining the ancestral XO male-XX female outcrossing system, while C. briggsae recently evolved self-fertility and an XX-biased sex ratio. Wild-type C. briggsae and C. nigoni can produce fertile hybrid XX female progeny, but XO progeny are either 100% inviable (when C. briggsae is the mother) or viable but sterile (when C. nigoni is the mother). A recent study provided evidence suggesting that loss of the Cbr-him-8 meiotic regulator in C. briggsae hermaphrodites allowed them to produce viable and fertile hybrid XO male progeny when mated to C. nigoni Because such males would be useful for a variety of genetic experiments, we sought to verify this result. Preliminary crosses with wild-type C. briggsae hermaphrodites occasionally produced fertile males, but they could not be confirmed to be interspecies hybrids. Using an RNA interference protocol that eliminates any possibility of self-progeny in Cbr-him-8 hermaphrodites, we find sterile males bearing the C. nigoni X chromosome, but no fertile males bearing the C. briggsae X, as in wild-type crosses. Our results suggest that the apparent rescue of XO hybrid viability and fertility is due to incomplete purging of self-sperm prior to mating.

  15. End-points and clinical trial design in pulmonary arterial hypertension: have we made progress?

    PubMed

    Peacock, A J; Naeije, R; Galiè, N; Rubin, L

    2009-07-01

    There is enormous interest in the treatment of pulmonary arterial hypertension (PAH), so it is appropriate to consider the design of trials of new therapies and the end-points to be measured when trying to decide whether or not a therapy is effective. In May 2003, the first meeting devoted solely to the discussion of end-points and trial design in PAH was held in Gleneagles, UK. At that time, most of the randomised controlled trials in PAH had used 6-min walking distance and/or resting haemodynamics as their primary end-points. The present article considers the progress that has been made since 2003. It deals with aspects of clinical trial design (such as noninferiority, superiority and withdrawal trials), considers end-points used in previous and current studies (such as 6-min walking distance, time to clinical worsening, haemodynamics, imaging and plasma brain natriuretic peptide), and considers what end-points might be used in the future. The second end-points meeting was held in Turnberry, UK, in June 2007. It had a similar format to the first meeting. Much of what is presented here is a summary of the workshops from that meeting. An attempt has been made to both summarise the current state of end-points and trial design and suggest new ways in which they could be improved. The present article forms one of a series being published in the European Respiratory Journal on pulmonary hypertension.

  16. Female Fertility Affects Men's Linguistic Choices

    PubMed Central

    Coyle, Jacqueline M.; Kaschak, Michael P.

    2012-01-01

    We examined the influence of female fertility on the likelihood of male participants aligning their choice of syntactic construction with those of female confederates. Men interacted with women throughout their menstrual cycle. On critical trials during the interaction, the confederate described a picture to the participant using particular syntactic constructions. Immediately thereafter, the participant described to the confederate a picture that could be described using either the same construction that was used by the confederate or an alternative form of the construction. Our data show that the likelihood of men choosing the same syntactic structure as the women was inversely related to the women's level of fertility: higher levels of fertility were associated with lower levels of linguistic matching. A follow-up study revealed that female participants do not show this same change in linguistic behavior as a function of changes in their conversation partner's fertility. We interpret these findings in the context of recent data suggesting that non-conforming behavior may be a means of men displaying their fitness as a mate to women. PMID:22347361

  17. Female fertility affects men's linguistic choices.

    PubMed

    Coyle, Jacqueline M; Kaschak, Michael P

    2012-01-01

    We examined the influence of female fertility on the likelihood of male participants aligning their choice of syntactic construction with those of female confederates. Men interacted with women throughout their menstrual cycle. On critical trials during the interaction, the confederate described a picture to the participant using particular syntactic constructions. Immediately thereafter, the participant described to the confederate a picture that could be described using either the same construction that was used by the confederate or an alternative form of the construction. Our data show that the likelihood of men choosing the same syntactic structure as the women was inversely related to the women's level of fertility: higher levels of fertility were associated with lower levels of linguistic matching. A follow-up study revealed that female participants do not show this same change in linguistic behavior as a function of changes in their conversation partner's fertility. We interpret these findings in the context of recent data suggesting that non-conforming behavior may be a means of men displaying their fitness as a mate to women.

  18. Trust and Fertility Dynamics

    PubMed Central

    Billari, Francesco C.; Pessin, Léa

    2016-01-01

    We argue that the divergence in fertility trends in advanced societies is influenced by the interaction of long-standing differences in generalized trust with the increase in women’s educational attainment. Our argument builds on the idea that trust enhances individuals’ and couples’ willingness to outsource childcare to outside their extended family. This becomes critically important as women’s increased education enhances the demand for combining work and family life. We test our hypothesis using data from the World Values Survey and European Values Study on 36 industrialized countries between the years 1981 and 2009. Multilevel statistical analyses reveal that the interaction between national-level generalized trust and cohort-level women’s education is positively associated with completed fertility. As education among women expands, high levels of generalized trust moderate fertility decline. PMID:28003707

  19. Ovarian cancer clinical trial endpoints: Society of Gynecologic Oncology white paper

    PubMed Central

    Herzog, Thomas J.; Armstrong, Deborah K.; Brady, Mark F.; Coleman, Robert L.; Einstein, Mark H.; Monk, Bradley J.; Mannel, Robert S.; Thigpen, J. Tate; Umpierre, Sharee A.; Villella, Jeannine A.; Alvarez, Ronald D.

    2015-01-01

    Objective To explore the value of multiple clinical endpoints in the unique setting of ovarian cancer. Methods A clinical trial workgroup was established by the Society of Gynecologic Oncology to develop a consensus statement via multiple conference calls, meetings and white paper drafts. Results Clinical trial endpoints have profound effects on late phase clinical trial design, result interpretation, drug development, and regulatory approval of therapeutics. Selection of the optimal clinical trial endpoint is particularly provocative in ovarian cancer where long overall survival (OS) is observed. The lack of new regulatory approvals and the lack of harmony between regulatory bodies globally for ovarian cancer therapeutics are of concern. The advantages and disadvantages of the numerous endpoints available are herein discussed within the unique context of ovarian cancer where both crossover and post-progression therapies potentially uncouple surrogacy between progression-free survival (PFS) and OS, the two most widely supported and utilized endpoints. The roles of patient reported outcomes (PRO) and health related quality of life (HRQoL) are discussed, but even these widely supported parameters are affected by the unique characteristics of ovarian cancer where a significant percentage of patients may be asymptomatic. Original data regarding the endpoint preferences of ovarian cancer advocates is presented. Conclusions Endpoint selection in ovarian cancer clinical trials should reflect the impact on disease burden and unique characteristics of the treatment cohort while reflecting true patient benefit. Both OS and PFS have led to regulatory approvals and are clinically important. OS remains the most objective and accepted endpoint because it is least vulnerable to bias; however, the feasibility of OS in ovarian cancer is compromised by the requirement for large trial size, prolonged time-line for final analysis, and potential for unintended loss of treatment effect

  20. Sublethal Toxicity Endpoints of Heavy Metals to the Nematode Caenorhabditis elegans.

    PubMed

    Jiang, Ying; Chen, Jiandong; Wu, Yue; Wang, Qiang; Li, Huixin

    2016-01-01

    Caenorhabditis elegans, a free-living nematode, is commonly used as a model organism in ecotoxicological studies. The current literatures have provided useful insight into the relative sensitivity of several endpoints, but few direct comparisons of multiple endpoints under a common set of experimental conditions. The objective of this study was to determine appropriate sublethal endpoints to develop an ecotoxicity screening and monitoring system. C. elegans was applied to explore the sublethal toxicity of four heavy metals (copper, zinc, cadmium and chromium). Two physiological endpoints (growth and reproduction), three behavioral endpoints (head thrash frequency, body bend frequency and feeding) and two enzymatic endpoints (acetylcholine esterase [AChE] and superoxide dismutase [SOD]) were selected for the assessment of heavy metal toxicity. The squared correlation coefficients (R2) between the responses observed and fitted by Logit function were higher than 0.90 and the RMSE were lower than 0.10, indicating a good significance statistically. There was no significant difference among the half effect concentration (EC50) endpoints in physiological and behavioral effects of the four heavy metals, indicating similar sensitivity of physiological and behavioral effects. AChE enzyme was more sensitive to copper, zinc, and cadmium than to other physiological and behavioral effects, and SOD enzyme was most sensitive to chromium. The EC50 of copper, zinc, and cadmium, to the AChE enzyme in the nematodes were 0.68 mg/L, 2.76 mg/L, and 0.92 mg/L respectively and the EC50 of chromium to the SOD enzyme in the nematode was 1.58 mg/L. The results of this study showed that there was a good concentration-response relationship between all four heavy metals and the sublethal toxicity effects to C. elegans. Considering these sublethal endpoints in terms of simplicity, accuracy, repeatability and costs of the experiments, feeding is the relatively ideal sublethal toxicity endpoint of

  1. Fertility incentives and disincentives.

    PubMed

    Financioglu, N

    1984-06-01

    Some 40 countries use some form of incentives and disincentives in support of population policies, about half with the aim of reducing fertility and half with the aim of increasing it. These schemes range from limitations on tax and family allowances or maternity benefits after a given family size has been reached to payments to acceptors of fertility control methods. Some schemes aim to eliminate or reduce the cost and inconvenience people may face in achieving their fertility preferences, whereas others contain an element of deterrence. It is difficult to isolate and measure the impact of incentives on fertility from the effects of other factors such as family planning service availability or modernization. Studies in pronatalist countries suggest that incentive schemes produce short-term fertility increases without a change in average family size. Monetary incentives must be constantly increased to keep pace with inflation, placing a heavy burden on government budgets. Administrative capacity to operate the scheme is critical in terms of both manpower and efficient systems for record keeping, monitoring, and close supervision to prevent abuse. There is also considerable debate on the moral and ethical implications of incentives and disincentives as policy tools. Incentives offered for the acceptance of a particular fertility control method potentially contravene the principle of voluntary and informed consent. In addition, the relative value of the reward is greater for those in the lower income groups. The discriminatory nature of certain types of incentives and disincentives is illustrated by measures introduced in Singapore that give highest priority in school enrollment to the children of highly educated mothers with 2-3 children. This ruling is expected to further intensify the controversy surrounding incentive and disincentive schemes.

  2. Adolescent fertility: worldwide concerns.

    PubMed

    Senderowitz, J; Paxman, J M

    1985-04-01

    There is growing concern over the adverse health, social, economic, and demographic effects of adolescent fertility. Morbidity and mortality rates ar significantly higher for teenage mothers and their infants, and early initiation of childbearing generally means truncated education, lower future family income, and larger completed family size. Adolescent fertility rates, which largely reflect marriage patterns, range from 4/1000 in Mauritania; in sub-Saharan Africa, virtually all rates are over 100. In most countries, adolescent fertility rates are declining due to rising age at marriage, increased educational and economic opportunities for young women, changes in social customs, increased use of contraception, and access to abortion. However, even if fertility rates were to decline dramatically among adolescent women in developing countries, their sheer numbers imply that their fertility will have a major impact on world population growth in the years ahead. The number of women in the world ages 15-19 years is expected to increase from 245 million in 1985 to over 320 million in the years 2020; 82% of these women live in developing countries. As a result of more and earlier premarital sexual activity, fostered by the lengthening gap between puberty and marriage, diminished parental and social controls, and increasing peer and media pressure to be sexually active, abortion and out-of-wedlock childbearing are increasing among teenagers in many developed and rapidly urbanizing developing countries. Laws and policies regarding sex education in the schools and access to family planning services by adolescents can either inhibit or support efforts to reduce adolescent fertility. Since contraceptive use is often sporadic and ineffective among adolescents, family planning services are crucial. Such programs should aim to reduce adolescents' dependence on abortion through preventive measures and increase awareness of the benefits of delayed sexual activity. Similarly, sex

  3. Fertility variation and status number in clonal seed orchards of Pinus sylvestris.

    PubMed

    Bilir, Nebi; Temiraga, Halime

    2012-11-15

    The present study was carried out to evaluate fertility variation, status number and gene diversity based on strobili productions in two clonal seed orchards of Scots pine (Pinus sylvestris L.). There were large differences among clones for the female and male strobili productions in the orchards. Positive and significant (p< or =0.05) correlations were found between female and male strobili production (r = 0.76, 0.55). Female fertility variation (1.03, 1.07) was larger than male fertility variation (1.02, 1.03) in the orchards. The status numbers estimated based on the total fertility were very high (97 and 98% of census numbers). The large fertility variation could be balanced by different treatments such as mixing seed equally from clones or genetinc thinning.

  4. Declining fertility in Nepal.

    PubMed

    Das Dangol, B; Retherford, R D; Thapa, S

    1997-03-01

    This article relies on data from the 1991 Nepal Fertility, Family Planning, and Health Survey (NFFPHS) and the 1996 Nepal Living Standards Survey (NLSS) to assess trends in fertility in Nepal. The NFFPHS shows heaping at ages 5, 8, 10, and 12 years and a larger proportion of infants. The NLSS shows a different pattern of misreporting of youth and a stronger but similar pattern of age heaping as the NFFPHS for adults. Children ever born by maternal age indicates a degree of completeness and the deletion by older women of deceased children and married children living outside the household. Findings suggest less complete reporting in the NLSS. Age-specific fertility rates are calculated based on birth histories (BH) and the own-children (OC) method based on life tables. Findings indicate that BH and OC estimates of the cumulative fertility rate (CFR) derived from the NLSS and the NFFPHS were comparable for estimating trends in the total fertility rate (TFR). The trends from the two data sets overlapped fairly well during 1983-89. Fertility trends by single years of age showed considerably annual fluctuations due to age misreporting. The CFR and TFR for aggregated time periods showed little or no decline for the earlier 5-year period, a steeper decline in the second period, and variations in trends by data set for the third period from 1983 to 1989. One curve showed no decline and the other showed fertility decline. Fitting a straight line to the trend for 1977-91 shows that CFR declined by 1.61 children from 5.29 children in 1977 to 3.68 children in 1991. TFR declined by 1.90 children from 6.68 children in 1977 to 4.78 children in 1991. The author cautions that the point of fertility decline was not determined exactly, but data suggest that decline occurred around 1980, and the rate was fast thereafter. TFR declined by 2.70 children in urban areas and 1.83 children in rural areas.

  5. Kisspeptin and fertility.

    PubMed

    Hameed, Saira; Jayasena, Channa N; Dhillo, Waljit S

    2011-02-01

    The kisspeptins are a family of peptide hormones, which in recent years have been shown to play a critical role in the regulation of the hypothalamic-pituitary-gonadal axis, thus in turn influencing fertility and reproduction. This review examines the physiological role of kisspeptin and the kisspeptin receptor in the control of gonadotrophin and gonadal steroid hormone secretion and the implications of these findings with respect to fertility. In addition, the potential therapeutic use of kisspeptin in the treatment of reproductive disorders will be examined.

  6. Fertility regulation technology: status and prospects.

    PubMed

    Segal, S J; Nordberg, O S

    1977-03-01

    The current status of and prospects for contraceptive methods is reviewed. Regulations governing the development, safety, and effectiveness of contraceptive methods are discussed, as well as the nature of the female and male reproductive system. Methods reviewed include coitus interruptus, the condom, spermicidal contraceptive agents, postcoital douching, the vaginal diaphragm, male and female sterilization, the rhythm method, oral contraceptives, IUDs, induced abortion, progesterone-releasing IUDs, postcoital estrogens, abortifacient agents (prostaglandins), immunization against human chorionic gonadotropin (HCG), pharmacologic suppression of the corpus luteum, long-acting injections of Depo-Provera, implantation of capsules containing norgestrel, the intravaginal ring, intracervical devices, release of contraceptive steroids through an arm bracelet, and male contraceptive agents. New areas of contraceptive research include influencing the release of luteininzing hormone-releasing hormone, ''turning-off'' corpus luteum function in early pregnancy by competitors for HCG, affecting sperm or ovarian membranes to prevent fertilization, and interferring with sperm and egg development.

  7. A Dynamical Modeling Approach for Analysis of Longitudinal Clinical Trials in the Presence of Missing Endpoints.

    PubMed

    Banks, H T; Hu, Shuhua; Rosenberg, Eric

    2017-01-01

    Randomized longitudinal clinical trials are the gold standard to evaluate the effectiveness of interventions among different patient treatment groups. However, analysis of such clinical trials becomes difficult in the presence of missing data, especially in the case where the study endpoints become difficult to measure because of subject dropout rates or/and the time to discontinue the assigned interventions are different among the patient groups. Here we report on using a validated mathematical model combined with an inverse problem approach to predict the values for the missing endpoints. A small randomized HIV clinical trial where endpoints for most of patients are missing is used to demonstrate this approach.

  8. The Cultural Bind on the American Male

    ERIC Educational Resources Information Center

    Chenoweth, Gene

    2012-01-01

    In this article, the author talks about the cultural bind on the American male. The process starts with conception. If the spermatozoid that fertilizes the egg contains only X chromosomes a girl will be produced. If a single Y chromosome out of the 24 produced by the father is included, the baby will be a boy. From this point on the girls have a…

  9. Epidemiologic methods for investigating male fecundity

    PubMed Central

    Olsen, Jørn; Ramlau-Hansen, Cecilia Høst

    2014-01-01

    Fertility is a couple concept that has been measured since the beginning of demography, and male fecundity (his biological capacity to reproduce) is a component of the fertility rate. Unfortunately, we have no way of measuring the male component directly, although several indirect markers can be used. Population registers can be used to monitor the proportion of childless couples, couples who receive donor semen, trends in dizygotic twinning, and infertility diagnoses. Studies using time-to-pregnancy (TTP) may identify couple subfecundity, and TTP data will correlate with sperm quality and quantity as well as sexual activity and a number of other conditions. Having exposure data available for couples with a fecund female partner would make TTP studies of interest in identifying exposures that may affect male fecundity. Biological indicators such as sperm quality and quantity isolate the male component of fertility, and semen data therefore remain an important source of information for research. Unfortunately, often over half of those invited to provide a sperm sample will refuse, and the study is then subject to a selection that may introduce bias. Because the most important time windows for exposures that impair semen production could be early fetal life, puberty, and the time of ejaculation; longitudinal data over decades of time are required. The ongoing monitoring of semen quality and quantity should continue, and surveys monitoring fertility and waiting TTP should also be designed. PMID:24369129

  10. Male circumcision.

    PubMed

    2012-09-01

    Male circumcision consists of the surgical removal of some, or all, of the foreskin (or prepuce) from the penis. It is one of the most common procedures in the world. In the United States, the procedure is commonly performed during the newborn period. In 2007, the American Academy of Pediatrics (AAP) convened a multidisciplinary workgroup of AAP members and other stakeholders to evaluate the evidence regarding male circumcision and update the AAP's 1999 recommendations in this area. The Task Force included AAP representatives from specialty areas as well as members of the AAP Board of Directors and liaisons representing the American Academy of Family Physicians, the American College of Obstetricians and Gynecologists, and the Centers for Disease Control and Prevention. The Task Force members identified selected topics relevant to male circumcision and conducted a critical review of peer-reviewed literature by using the American Heart Association's template for evidence evaluation. Evaluation of current evidence indicates that the health benefits of newborn male circumcision outweigh the risks; furthermore, the benefits of newborn male circumcision justify access to this procedure for families who choose it. Specific benefits from male circumcision were identified for the prevention of urinary tract infections, acquisition of HIV, transmission of some sexually transmitted infections, and penile cancer. Male circumcision does not appear to adversely affect penile sexual function/sensitivity or sexual satisfaction. It is imperative that those providing circumcision are adequately trained and that both sterile techniques and effective pain management are used. Significant acute complications are rare. In general, untrained providers who perform circumcisions have more complications than well-trained providers who perform the procedure, regardless of whether the former are physicians, nurses, or traditional religious providers. Parents are entitled to factually correct

  11. Soil microbes and plant fertilization.

    PubMed

    Miransari, Mohammad

    2011-12-01

    With respect to the adverse effects of chemical fertilization on the environment and their related expenses, especially when overused, alternative methods of fertilization have been suggested and tested. For example, the combined use of chemical fertilization with organic fertilization and/or biological fertilization is among such methods. It has been indicated that the use of organic fertilization with chemical fertilization is a suitable method of providing crop plants with adequate amount of nutrients, while environmentally and economically appropriate. In this article, the importance of soil microbes to the ecosystem is reviewed, with particular emphasis on the role of plant growth-promoting rhizobacteria, arbuscular mycorrhizal fungi, and endophytic bacteria in providing necessary nutrients for plant growth and yield production. Such microbes are beneficial to plant growth through colonizing plant roots and inducing mechanisms by which plant growth increases. Although there has been extensive research work regarding the use of microbes as a method of fertilizing plants, it is yet a question how the efficiency of such microbial fertilization to the plant can be determined and increased. In other words, how the right combination of chemical and biological fertilization can be determined. In this article, the most recent advances regarding the effects of microbial fertilization on plant growth and yield production in their combined use with chemical fertilization are reviewed. There are also some details related to the molecular mechanisms affecting the microbial performance and how the use of biological techniques may affect the efficiency of biological fertilization.

  12. Recovery of fertility by Mediterranean flour moths transferred from continuous light to light:dark

    SciTech Connect

    Riemann, J.G.; Johnson, M.; Thorson, B.

    1981-05-01

    Male Mediterranean flour moths, Anagasta kuehniella (Zeller), placed in continuous light (LL) from the early pupal stage on were partially sterile as adults. When old adult moths were transferred to alternating light and dark (LD), fertility was not recovered, but fertility was recovered when fairly young males were similarly transferred. Multiple matings of males indicated that recovery was correlated with sperm in the testes at the LL to LD transfer becoming available for ejaculations. Few morphological abnormalities were found in the sperm of LL males, but there was less activity than in the sperm of LD males. At 1 week after eclosion, the testes of LL males contained more sperm bundles than did the testes of LD males, but the LL males had somewhat fewer bundles overall in their reproductive tracts. Disruption of the circadian rhythm regulating movement of sperm from the testes was suggested as the most probable cause of the sterility of LL males.