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Sample records for male fertility endpoints

  1. Alteration of Fertility Endpoints in Adult Male F-344 Rats by Subchronic Exposure to Inhaled Benzo(a)pyrene

    PubMed Central

    Ramesh, Aramandla; Inyang, Frank; Lunstra, Donald D.; Niaz, Mohammad S.; Kopsombut, Prapaporn M.; Jones, Kea M.; Hood, Daryl B.; Hills, Edward R.; Archibong, Anthony E.

    2012-01-01

    The objective of this study was to evaluate the reproductive risk associated with exposure of adult male Fisher-344 rats to inhaled benzo(a)pyrene (BaP). Rats were assigned randomly to a treatment or control group. Treatment consisted of sub-chronic exposure of rats via inhalation to 75μg BaP/m3, 4 hours daily for 60 days, while control animals were unexposed (UNC). Blood samples were collected immediately after the cessation of exposures (time 0) and subsequently at 24, 48, and 72 hrs, to assess the effect of bioavailable BaP on plasma testosterone and luteinizing hormone (LH) concentrations. Rats were sacrificed after the last blood collection. Testes were harvested, weighed and prepared for histology and morphometric analysis, and cauda epididymides were isolated for the determination of progressive motility and density of stored spermatozoa. BaP exposure reduced testis weight compared with UNC (Mean ± SE; 2.01 ± 0.11 vs. 3.04 ± 0.16 g; P< 0.025), and caused significant reductions in the components of the steroidogenic and spermatogenic compartments of the testis. Progressive motility and mean density of stored spermatozoa were reduced (P< 0.05). Plasma testosterone concentrations were decreased by two-thirds in BaP-exposed rats throughout the time periods studied compared with those of their UNC counterparts (P< 0.05), concomitant with increased concentrations of LH in BaP-exposed rats (P< 0.05). These data suggest that sub-chronic exposure to inhaled BaP contribute to reduced testicular and epididymal function in exposed rats. PMID:18499416

  2. Adverse Effects of a Clinically Relevant Dose of Hydroxyurea Used for the Treatment of Sickle Cell Disease on Male Fertility Endpoints

    PubMed Central

    Jones, Kea M.; Niaz, Mohammad S.; Brooks, Cynthia M.; Roberson, Shannon I.; Aguinaga, Maria P.; Hills, Edward R.; Rice, Valerie Montgomery; Bourne, Phillip; Bruce, Donald; Archibong, Anthony E.

    2009-01-01

    Two experiments were conducted to determine: 1) whether the adult male transgenic sickle cell mouse (Tg58 × Tg98; TSCM), exhibits the patterns of reproductive endpoints (hypogonadism) characteristic of men with sickle cell disease (SCD) and 2) whether hydroxyurea (HU) exacerbates this condition. In Experiment 1, blood samples were collected from adult age-matched TSCM and ICR mice (ICRM) (N = 10/group) for plasma testosterone measurements. Subsequently, mice were sacrificed, testes excised and weighed and stored spermatozoa recovered for the determination of sperm density, progressive motility and percentage of spermatozoa with normal morphology. In experiment 2, adult male TSCM were orally treated with 25 mg HU/kg body weight/day for 28 or 56 days. Control mice received the vehicle for HU (saline) as described above. At the end of the treatment periods, blood samples were collected for quantification of circulating testosterone. Subsequently, mice were sacrificed, testes and epididymides were recovered and weighed and one testis per mouse was subjected to histopathology. Stored spermatozoa were recovered for the determination of indices of sperm quality mentioned in Experiment 1. Testis weight, stored sperm density, progressive motility, percentage of spermatozoa with normal morphology and plasma testosterone concentrations of TSCM were significantly lower by 40, 65, 40, 69 and 66%, respectively than those of ICRM. These data indicate that adult TSCM used in this study suffered from hypogonadism, characteristically observed among adult male SCD patients. In Experiment 2, HU treatment significantly decreased testis weight on day 28, (0.09 ± 0.004g) that was further decreased on day 56 (0.06 ± 0.003g; treatment x time interaction) compared with controls (day 28, 0.15 ± 0.01g; day 56, 2, 0.16 ± 0.01g). Concomitant with a 52% shrinkage (P<0.001) in area of testes in 56 days of HU treatment, testes from HU-treated TSCM exhibited significant atrophic degeneration

  3. [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. PMID:23286540

  4. Vasopressin Effectively Suppresses Male Fertility

    PubMed Central

    Kwon, Woo-Sung; Park, Yoo-Jin; Kim, Yun-Hee; You, Young-Ah; Kim, In Cheul; Pang, Myung-Geol

    2013-01-01

    Arginine vasopressin (VP) is neurohypophysial hormone has been implicated in stimulating contractile activity of the male reproductive tract in the testis. Higher levels of VP decrease sperm count and motility. However, very little is known about the involvement of VP in controlling mammalian reproductive process. The goal of this study was to confirm that effect of VP receptor (AVPR2) on sperm function in capacitation condition. Deamino [Cys 1, D-ArgS] vasopressin (dDAVP), an AVPR2 agonist that operates only on AVPR2, was used. Also, Mouse spermatozoa were incubated with various concentrations of dDAVP (10−11–10−5 M) and sperm motility, capacitation status, Protein Kinase A activity (PKA), tyrosine phosphorylation, fertilization, and embryo development were assessed using computer-assisted sperm analysis, Combined Hoechst 33258/chlortetracycline fluorescence, Western blotting, and in vitro fertilization, respectively. AVPR2 was placed on the acrosome region and mid-piece in cauda epididymal spermatozoa, but the caput epididymal spermatozoa was mid-piece only. The high dDAVP treatment (10−8 and 10−5 M) significantly decreased sperm motility, intracellular pH and PKA substrates (approximately 55 and 22 kDa) and increased Ca2+ concentration. The highest concentration treatment significantly decreased PKA substrate (approximately 23 kDa) and tyrosine phosphorylation (approximately 30 kDa). VP detrimentally affected capacitation, acrosome reaction, and embryo development. Treatment with the lowest concentration (10−11 M) was not significantly different. Our data have shown that VP stimulates ion transport across sperm membrane through interactions with AVPR2. VP has a detrimental effect in sperm function, fertilization, and embryonic development, suggesting its critical role in the acquisition of fertilizing ability of mouse spermatozoa. These research findings will enable further study to determine molecular mechanism associated with fertility in

  5. Increased male fertility using fertility-related biomarkers

    PubMed Central

    Kwon, Woo-Sung; Rahman, Md Saidur; Ryu, Do-Yeal; Park, Yoo-Jin; Pang, Myung-Geol

    2015-01-01

    Conventional semen analyses are used to evaluate male factor fertility/infertility in humans and other animals. However, their clinical value remains controversial. Therefore, new tools that more accurately assess male fertility based on sperm function and fertilization mechanism are of interest worldwide. While protein markers in spermatozoa that might help differentiate fertile and infertile sperm have been identified, studies are in their infancy, and the markers require validation in field trials. In the present study, to discover more sensitive biomarkers in spermatozoa for predicting male fertility, we assessed protein expression in capacitated spermatozoa. The results demonstrated that cytochrome b-c1 complex subunit 2 (UQCRC2) was abundantly expressed in high-litter size spermatozoa (>3-fold). On the other hand, equatorin, beta-tubulin, cytochrome b-c1 complex subunit 1 (UQCRC1), speriolin, Ras-related protein Rab-2A (RAB2A), spermadhesin AQN-3, and seminal plasma sperm motility inhibitor were abundantly expressed in low-litter size spermatozoa (>3-fold). Moreover, RAB2A and UQCRC1 expression negatively correlated with litter size, while UQCRC2 expression positively correlated with litter size. Finally, the putative biomarkers predicted litter size in field trials. Our study suggests that biomarkers present in spermatozoa after capacitation can help differentiate superior male fertility from below-average fertility with high sensitivity. PMID:26489431

  6. Artificial insemination in pigs: predicting male fertility.

    PubMed

    Broekhuijse, M L W J; Feitsma, H; Gadella, B M

    2012-01-01

    Efficient artificial insemination (AI) is essential for future challenges in the pig industry. Knowledge on the exact relation between semen quality characteristics and fertility can have a major impact on both the genetic merit of future animals and the efficiency of AI. Variation in fertility is caused not only by farm- or sow-related parameters but also by boar- and semen-related parameters. In pig AI there is no gold standard concerning semen quality assessment. Assessing semen quality characteristics objectively and relating them to large field fertility datasets leads to an efficient production of insemination doses, which results in an efficient dissemination/descent of the breeding program required genes. Overall, this contributes to the development of semen quality assessments, which improves the prediction of porcine male fertility. Knowing which semen characteristics, and to what extent, contribute to male fertility and makes the field fertility more predictable. PMID:23092203

  7. Dermatological medication effects on male fertility.

    PubMed

    Millsop, Jillian Wong; Heller, Misha M; Eliason, Mark J; Murase, Jenny E

    2013-01-01

    Many drugs have been reported to impair semen parameters, leading to temporary or persistent infertility. Therefore, potential fathers may be concerned about the effect of medications on fertility. We searched the MEDLINE database of articles in English combining key terms including "male infertility," "spermatogenesis," "fertility," "drug effects," and "dermatology." Administration of methotrexate and finasteride has resulted in severe oligospermia and reversible infertility. Ketoconazole has had negative effects on sperm motility and testosterone production. Few individual case reports and a limited number of studies have demonstrated negative effects of tetracyclines, erythromycin, chloroquine, glucocorticoids, spironolactone, and antihistamines on fertility. It is important to counsel male patients when appropriate about the reversible negative effect on fertility when taking methotrexate and finasteride, and the adverse effect of ketoconazole. Patients may be reassured that taking oral retinoids, cyclosporine, azathioprine, and tumor necrosis factor alpha inhibitors should not affect their fertility. PMID:23914891

  8. Introduction: Male fertility preservation: innovations and questions.

    PubMed

    Frydman, René; Grynberg, Michaël

    2016-02-01

    It is now well established that many benign or malignant diseases may by themselves or as result of treatment, impair male fertility. Therefore, preserving the potential of becoming a genetic father represents a major issue. Besides sperm cryopreservation, which is the most reliable method for male fertility preservation, other strategies have more recently emerged, especially in prepubertal boys. Prepubertal germ cell storage from testicular sperm extraction and derivation of male gametes from stem cells may represent a future hope, although raising many ethical issues. PMID:26746134

  9. [Therapeutic issues concerning male fertility].

    PubMed

    Bernard, V; Bouvattier, C; Christin-Maitre, S

    2014-10-01

    Men reproductive health has long been ignored although it is responsible for 50% of couple's infertility. However, in recent years, the understanding of endocrine physiology underlying testis development and spermatogenesis has enabled the development of new therapeutic strategies. Some concern the management of male infertility. Others are dealing with finding an effective male contraceptive. In this review, we first present the management of infertility, in patients with congenital hypogonadotropic hypogonadism. We then describe the major improvements for Klinefelter patient's infertility. Finally, we review the different hormonal and non-hormonal methods for male contraception, currently in development. Efficacy and safety of the some non-hormonal methods remain to be demonstrated so far in humans. PMID:25617918

  10. 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)

  11. The epididymis, cytoplasmic droplets and male fertility

    PubMed Central

    Cooper, Trevor G

    2011-01-01

    The potential of spermatozoa to become motile during post-testicular maturation, and the relationship between the cytoplasmic droplet and fertilizing capacity are reviewed. Post-testicular maturation of spermatozoa involves the autonomous induction of motility, which can occur in vivo in testes with occluded excurrent ducts and in vitro in testicular explants, and artefactual changes in morphology that appear to occur in the testis in vitro. Both modifications may reflect time-dependent oxidation of disulphide bonds of head and tail proteins. Regulatory volume decrease (RVD), which counters sperm swelling at ejaculation, is discussed in relation to loss of cytoplasmic droplets and consequences for fertility. It is postulated that: (i) fertile males possess spermatozoa with sufficient osmolytes to drive RVD at ejaculation, permitting the droplet to round up and pinch off without membrane rupture; and (ii) infertile males possess spermatozoa with insufficient osmolytes so that RVD is inadequate, the droplet swells and the resulting flagellar angulation prevents droplet loss. Droplet retention at ejaculation is a harbinger of infertility caused by failure of the spermatozoon to negotiate the uterotubal junction or mucous and reach the egg. In this hypothesis, the epididymis regulates fertility indirectly by the extent of osmolyte provision to spermatozoa, which influences RVD and therefore droplet loss. Man is an exception, because ejaculated human spermatozoa retain their droplets. This may reflect their short midpiece, approximating head length, permitting a swollen droplet to extend along the entire midpiece; this not only obviates droplet migration and flagellar angulation but also hampers droplet loss. PMID:21076437

  12. Fertility treatment in male cancer survivors.

    PubMed

    Schmidt, Kirsten Louise Tryde; Carlsen, Elisabeth; Andersen, Anders Nyboe

    2007-08-01

    The present study reviews the use of assisted reproductive technology in male cancer survivors and their partners. As antineoplastic treatment with chemotherapy or radiation therapy, has the potential of inducing impairment of spermatogenesis through damage of the germinal epithelium, many male cancer survivors experience difficulties in impregnating their partners after treatment. The impairment can be temporary or permanent. While many cancer survivors regain spermatogenesis months to years after treatment, some become infertile with a-, oligo- or azoospermia. An option to secure the fertility potential of young cancer patients is to cryopreserve semen before cancer treatment for later use. A desired pregnancy may be obtained in couples where the husband has a history of cancer, using assisted reproductive technology with either fresh or cryopreserved/thawed semen. Successful outcomes have been obtained with intrauterine insemination (IUI) as well as in vitro fertilization (IVF) with or without the use of intracytoplasmic sperm injection (ICSI). In conclusion, male cancer survivors and their partners who have failed to obtain a pregnancy naturally within a reasonable time frame after end of treatment should be referred to a fertility clinic. PMID:17573855

  13. 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

  14. 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 ...

  15. 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 ...

  16. Assessment of environmental factors affecting male fertility.

    PubMed

    Dixon, R L; Sherins, R J; Lee, I P

    1979-06-01

    ppm boron displayed a significant loss of germinal elements, although most of the Leydig and Sertoli cells appeared normal. Testicular atrophy was associated with a decrease in seminiferous tubular diameter and a marked reduction of spermatocytes and spermatogenic cells. These morphologic alterations were associated with a concomitant reduction of H, SDH, and LDH-X specific activities. In contrast, the specific activities of G3PDH and MDH were significantly elevated above control. The increase in these enzyme activities can be attributed to the relative enrichment of spermatogonial cells during the loss of spermatocytes and spermiogenic cells. Boron-induced male germinal aplasia was also associated with significantly elevated plasma FSH while plasma LH and testosterone levels were not significantly altered. Plasma testosterone levels were unaltered. Male fertility studies demonstrated that at the 500 ppm boron level, fertility was unaffected. However, at 1000 and 2000 ppm boron, male fertility was significantly reduced. Most effects were reversible within 5 weeks. However, the male group receiving 2000 ppm boron for 60 days remained sterile. There was no dose-related decrease in litter size or fetal death in utero. Therefore, the boron-induced infertility was apparently not due to a dominant lethal effect but rather to germinal aplasia. Boron appears toxic to spermatogenic cells at testicular concentrations of 6-8 ppm. PMID:446458

  17. Novel class of glycosphingolipids involved in male fertility.

    PubMed

    Sandhoff, Roger; Geyer, Rudolf; Jennemann, Richard; Paret, Claudia; Kiss, Eva; Yamashita, Tadashi; Gorgas, Karin; Sijmonsma, Tjeerd P; Iwamori, Masao; Finaz, Catherine; Proia, Richard L; Wiegandt, Herbert; Gröne, Hermann-Josef

    2005-07-22

    Mice require testicular glycosphingolipids (GSLs) for proper spermatogenesis. Mutant mice strains deficient in specific genes encoding biosynthetic enzymes of the GSL pathway including Galgt1 (encoding GM2 synthase) and Siat9 (encoding GM3 synthase) have been established lacking various overlapping subsets of GSLs. Although male Galgt1-/- mice are infertile, male Siat9-/- mice are fertile. Interestingly, GSLs thought to be essential for male spermatogenesis are not synthesized in either of these mice strains. Hence, these GSLs cannot account for the different phenotypes. A novel class of GSLs was observed composed of eight fucosylated molecules present in fertile but not in infertile mutant mice. These GSLs contain polyunsaturated very long chain fatty acid residues in their ceramide moieties. GSLs of this class are expressed differentially in testicular germ cells. More importantly, the neutral subset of this new GSL class strictly correlates with male fertility. These data implicate polyunsaturated, fucosylated GSLs as essential for spermatogenesis and male mouse fertility. PMID:15917254

  18. Timing of prenatal phthalate exposure in relation to genital endpoints in male newborns.

    PubMed

    Martino-Andrade, A J; Liu, F; Sathyanarayana, S; Barrett, E S; Redmon, J B; Nguyen, R H N; Levine, H; Swan, S H

    2016-07-01

    Prior studies report that penile size and male anogenital distance (AGD), sensitive markers of androgen action in utero, may be shortened by prenatal exposure to certain phthalates, including diethylhexyl phthalate (DEHP), but no human study has investigated the importance of exposure timing in these associations. The aim of this study was to examine the significance of exposure timing on the action of prenatal phthalates in particular DEHP, on male infant penile size and AGD. In The Infant Development and the Environment Study (TIDES) we measured penile width (PW) as well as anoscrotal distance (AGDAS ) and anopenile distance (AGPAP ) in newborn males. We modeled these endpoints in relation to phthalate metabolite concentrations in maternal urine samples collected in each trimester (T1, T2, and T3) in a subset of TIDES mothers (N = 168). PW was inversely associated with T2 oxidized DEHP metabolites, mono-2-ethyl-5-oxohexyl (MEOHP, β=-0.48; 95% confidence interval, -0.93, -0.02), MEHHP (-0.48; -0.92, -0.05), mono-2-ethyl-5-carboxypentyl (MECPP, -0.51; -1.01, -0.004), although no appreciable associations were seen between PW and T1 and T3 DEHP metabolite concentrations in this subset. Concentrations of DEHP metabolites in T1 urine samples were inversely related to male AGD. For example, in T1 samples in this subset of women mono-2-ethyl-5-hydroxyhexyl (MEHHP) was inversely associated with male AGDAP (β = -1.73; 95% confidence interval, -3.45, 0.0004). However, no appreciable associations were seen between AGD measures and any DEHP metabolite in T2 and T3 samples. These data suggest that DEHP exposure is inversely associated with AGD and PW, with PW primarily associated with T2 exposure and AGD associations seen only for T1 exposure, but no associations were found between T3 DEHP metabolites and any of these genital endpoints. These findings are consistent with data on critical windows in rodent studies, supporting the biological plausibility of these

  19. 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. PMID:26787324

  20. Inbreeding effect on male and female fertility and inheritance of male sterility in Nemophila menziesii (Hydrophyllaceae).

    PubMed

    Gomez, Nadilia N; Shaw, Ruth G

    2006-05-01

    Models of the evolution of gynodioecy assume that inbreeding affects male and female fertility equally and ignore quantitative variation in sex expression. The objectives of this study were to assess inbreeding effects, genetic background, and plant maturity on male and female fertility and the mechanism of male sterility inheritance for Nemophila menziesii (Hydrophyllaceae). Frequency of male-sterile flowers, number of anthers and ovules, and percentage of viable pollen were measured on plants from different pedigrees and five inbreeding levels (F = 0, 0.0625, 0.25, 0.5, and 0.75). Quantitative variation in male sterility was evident. As inbreeding increased, anther and ovule number decreased; the effect on anther number was greater than on ovule number. Pedigrees varied in number of male-sterile flowers and inbreeding effects. Frequency of male-sterile flowers was greatest among first flowers. No trade-off between male and female fertility was detected. A model attributing male sterility to a cytoplasmic locus and restoration to male fertility to a nuclear locus accounted for the distribution of complete sterility and hermaphroditism over the pedigrees. This study suggests that models of the evolution and maintenance of gynodioecy should allow for quantitative variation in male and female fertility components due to inbreeding, pedigree, and plant maturity. PMID:21642137

  1. Male fertility: a possible role of vitamins.

    PubMed

    Kodentsova, V M; Vrzesinskaya, O A; Spirichev, V B

    1994-01-01

    This review concerns recent experimental information on some aspects revealing biochemical nature of the origin of defects responsible for the spermatozoa's loss of fertilizing potential. Possible protective effect of vitamins-antioxidants against peroxidative damage of spermatozoa playing a key role in the etiology of defective sperm function, regulating role of vitamins K and D in MM-isozyme creatine kinase activity serving as a measure of sperm biochemical maturity and normal sperm development and influence of body insufficiency of B group vitamins on energy metabolism disturbances in motile, actively metabolizing spermatozoa have been discussed. PMID:7747339

  2. Recovery of male fertility after sterilization by nuclear radiation.

    PubMed

    Macleod, J; Hotchkiss, R S; Sitterson, B W

    1964-02-29

    The potential fertility of 6 of 8 men accidentally exposed to radiation on June 16, 1958, was studied over a 3 1/2-year period. It is clear that, as measured by semen quality, evidence of recovery of spermatogenesis may be expected within 21 months, although the sperm counts at this time will probably not be consonant with a reasonable level of fertility. A satisfactory level of fertility will be reached by 30 months and a normal level by 41 months. Review of the male fertility data on the recorded cases of less than lethal nuclear radiation accidents shows that relatively small amounts of radiation will produce pronounced effects on the testes, including disturbances in the morphology of the few spermatozoa present in the ejaculate, but that ultimate recovery of some degree of fertility is possible in most cases. PMID:12255104

  3. CatSper channel, sperm function and male fertility.

    PubMed

    Singh, Akhand Pratap; Rajender, Singh

    2015-01-01

    A number of physiological events, such as sperm hyperactivation, chemotaxis towards the egg, capacitation and acrosome reaction, are triggered by activation of sperm ion channels in response to a diverse range of chemical cues. Cation channel of sperm (CatSper), a sperm-specific ion channel, is unique in orchestrating the events for fertilization, and seems to be exclusively evolved for sperm function and male fertility. CatSper acts as a polymodal, chemosensory calcium channel and plays a vital role in the regulation of sperm hyperactivation. CatSper knockout models and application of patch clamp recordings have shown that it is indispensable for male fertility, and mutations and deletions in CatSper gene(s) may lead to infertility. In fact, mutations in CatSper1 and 2 have been identified in infertile individuals; however, CatSper3 and 4 have not been explored. Restricted localization and expression of CatSper in sperm offer an added advantage to developing gamete-based safe non-hormonal contraceptives. This review concisely covers identification, structure, function, and mechanism of action of CatSper channels. The functional importance of this complex ion channel in sperm motility and male fertility is highlighted for further research on male fertility, infertility, and contraception. PMID:25457194

  4. Nutlin-3a Decreases Male Fertility via UQCRC2

    PubMed Central

    Shukla, Kamla Kant; Kwon, Woo-Sung; Rahman, Md Saidur; Park, Yoo-Jin; You, Young-Ah; Pang, Myung-Geol

    2013-01-01

    Ubiquinol-cytochrome-c reductase core protein 2 (UQCRC2) is a component of ubiquinol-cytochrome c reductase complex that is known to correlate with male fertility via spermatogenesis. Simultaneously, nutlin-3a is a small molecule antagonist of mouse double minute 2 repressor (MDM2), activate p53 and induce apoptosis responsible for spermatogenesis. To date, however there are no known effects of nutlin-3a on reproduction. Therefore, present study was designed to investigate the effect of nutlin-3a on male fertility via UQCRC2. In this in vitro trial with mice spermatozoa, we utilized CASA, CTC staining, ATP assay, western blotting, and IVF to measure the main study outcome. The short-term exposure of spermatozoa in nutlin-3a decreases sperm motion kinematics, intracellular ATP production, capacitation, the acrosome reaction, UQCRC2, and tyrosine phosphorylation (TYP) of sperm proteins in a dose-dependent manner. Notably, the decreased UQCRC2 and TYP were associated with reduced sperm kinematics, ATP production, and capacitation, which ultimately led to adverse effects on male fertility such as poor fertilization rates and embryo development. Thus, nutlin-3a may be considered as a potential male contraceptive agent due to its ability to decrease fertility secondary to changes in overall sperm physiology and embryonic development. However, the results of this preliminary study have to be confirmed by additional independent trial. PMID:24130818

  5. Nutrient supplementation: improving male fertility fourfold.

    PubMed

    Mora-Esteves, Cesar; Shin, David

    2013-07-01

    Oxidative stress can contribute to impairment in spermatogenesis leading to male-factor infertility. The effectiveness of various antioxidants (such as carnitine, vitamin C, vitamin E, selenium, carotenoids, glutathione, N-acetylcysteine, zinc, folic acid, and coenzyme Q10) is variable with respect to improving semen parameters and pregnancy rates. A recent Cochrane review determined that men taking antioxidants had a statistically significant increase in both live birth rates and pregnancy rates. For those undergoing assisted reproduction, the odds ratio that antioxidant use would improve pregnancy rates was 4.18, with a 4.85-fold improvement in live birth rate also noted. Further investigation with randomized, controlled clinical trials is needed to confirm the safety and efficacy of antioxidant supplementation in the medical management and treatment of male infertility. PMID:23775385

  6. Sex chromosome recombination failure, apoptosis, and fertility in male mice.

    PubMed

    Faisal, Imrul; Kauppi, Liisa

    2016-06-01

    Lack of crossing-over in meiosis can trigger an apoptotic response at metaphase I by the spindle assembly checkpoint (SAC). In contrast to females, segregation of sex chromosomes in males poses a particular challenge as recombination and chiasma formation is restricted to the pseudoautosomal region, the small region of homology between X and Y chromosomes. Existing data indicate that low levels of crossover failure in male meiosis can be tolerated without compromising fertility, while high levels of X-Y dissociation (in ≥70 % of cells) result in widespread apoptosis and subsequent infertility, demonstrated earlier, e.g., in Spo11β-only mice. Here, we explore the threshold of X-Y recombination failure frequency that is compatible with fertility. We show that in Spo11β-only(mb) mice with a mixed genetic background, in contrast to Spo11β-only mice with a C57BL/6 background, X-Y pairing fails in ~50 % of cells but this still allows for sperm production without any overt impact on fertility. We also review data on apoptosis and fertility from other achiasmate mouse models and propose that the incidence of homolog dissociation that can be tolerated in vivo without compromising male fertility lies between 50 and 70 %. PMID:26440410

  7. 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...

  8. Impact of cancer and cancer treatment on male fertility.

    PubMed

    Vakalopoulos, Ioannis; Dimou, Petros; Anagnostou, Ioannis; Zeginiadou, Theodosia

    2015-01-01

    While cancer, and especially testicular cancer and Hodgkin's disease, affects male fertility in many ways, the current increase of survival of male cancer patients of reproductive age or earlier has emerged as a new challenge to their subsequent ability to father children. Cancer treatments, including surgery, radiotherapy and chemotherapy, can have a transitory as well as a permanent detrimental impact on male fertility. Gonadotoxic effects and the length of time for sperm recovery after radiotherapy depends not only on initial semen quality, but also on gonadal dosage and the delivery method after chemotherapy, on the type of regimens and dosages and on the spermatogenesis phase that each drug impacts. Combination treatment with radiotherapy and chemotherapy will induce more gonadotoxicity than either modality alone. Although efforts to prevent gonadal toxicity in cancer treatment are routinely applied, sperm cryopreservation remains the gold standard to maintain male fertility after cancer survival. Fertility preservation for prepubertal boys presents the greatest problem due to the absence of mature sperm in their gonads. In this area, research efforts are concentrated on cryopreservation of immature gametes and, in particular, techniques for their maturation and proliferation after thawing. PMID:26732148

  9. ENDPOINTS OF SPERMATOXICITY IN THE RAT AFTER ACUTE EXPOSURES TO FOURTEEN MALE REPRODUCTIVE TOXICANTS

    EPA Science Inventory

    Multiple endpoints of spermatotoxicity in short in vivo tests were investigated in several chemicals which produce minimal to severe subchronic reproductive effects. Six chemicals (boric acid, dinoseb, 2,5-hexanedione, methoxychlor, metronidazole, ornidazole) produced spermatotox...

  10. Current practices in fertility preservation in male cancer patients

    PubMed Central

    Osterberg, E. Charles; Ramasamy, Ranjith; Masson, Puneet; Brannigan, Robert E.

    2014-01-01

    The incidence of a cancer diagnosis in children and young adolescents is increasing. With better treatments, the number of young cancer survivors living through reproductive age is increasing. Fertility preservation of these men and women has become essential and needs to be discussed prior to the start of cancer treatment. Here we review the current guidelines for male oncofertility patients and highlight some of the important gonadotoxic effects of chemotherapy, radiotherapy and surgery. Options for fertility preservation are also discussed along with resources that should be made available to all patients. PMID:24669115

  11. Male fertility preservation, where are we in 2014?

    PubMed

    Goossens, Ellen; Tournaye, Herman

    2014-05-01

    Male fertility preservation receives growing attention in the field of reproductive medicine. The first clinical programs were established to preserve reproductive potential in men needing gonadotoxic treatment. Sperm cryopreservation is now a standard procedure. Since a few years, several centres offer testicular tissue cryopreservation to prepubertal boys. This method is still experimental and further research is needed to implement the transplantation techniques in the clinic. With the aim to preserve or restore fertility in patients affected by other diseases (Klinefelter syndrome, Sertoli cell only syndrome), techniques for in vitro spermatogenesis are being developed. PMID:24793992

  12. 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. PMID:17022062

  13. 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

  14. 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

  15. The impact of lymphoma and treatment on male fertility.

    PubMed

    Eghbali, Houchingue; Papaxanthos-Roche, Aline

    2010-12-01

    Most patients with Hodgkin's or non-Hodgkin's lymphomas will be cured by modern chemotherapy and/or radiotherapy. Although some patients, especially those with Hodgkin's lymphoma, already have semen alterations related to their disease before treatment, sperm damage is mainly caused by anti-cancer treatments. Alkylating and similar drugs and radiation therapy are the most aggressive agents on male gonadal functions. Sperm damage is dependent on drug dose and individual sensitivity, and the recovery is unpredictable. Current approaches to fertility management include the exclusion of gonadotoxic agents whenever possible, in particular among children and preadolescent boys, and systematic sperm banking for all male patients, especially among adolescent patients and even in cases of poor sperm quality. New techniques of in vitro fertilization allow procreation even with poor sperm quality. PMID:21091152

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

    PubMed

    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

  17. 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

  18. Quebec public funding facilitates fertility preservation for male cancer patients

    PubMed Central

    Herrero, M.B.; García, A.; Buckett, W.; Tulandi, T.; Chan, P.

    2016-01-01

    Background Sperm cryopreservation remains the only clinically feasible option to preserve male fertility. The quality of counselling provided by the treating physicians and the cost of sperm cryopreservation can both influence a patient’s decision about whether to preserve sperm. On 5 August 2010, the Quebec government introduced provincial coverage of assisted reproductive technologies, with sperm cryopreservation included as a covered service. The aim of the present study was to evaluate whether and how such a program affects the behaviour of cancer patients with respect to sperm cryopreservation. Methods We analyzed the database derived from male patients undergoing sperm cryopreservation from August 2008 to August 2012 at our centre. The retrieved data included patient age, male infertility or oncologic diagnosis, sperm quality parameters, and details about the number of visits for sperm cryopreservation. Results The number of cancer patients who cryopreserved sperm before and after the policy change did not differ significantly, but a marked increase in the number of non-cancer patients was observed. Further analysis revealed that, after implementation of the public funding program, the total number of sperm cryopreservation sessions per patient increased significantly in cancer patients but not in non-cancer patients. Conclusions It appears that cancer patients who are willing to freeze sperm are keen to return for more sessions of sperm banking when no fees are associated with the service. Those findings suggest that cost reduction is an important factor for improving delivery of fertility preservation services to male cancer patients. PMID:26966400

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

    PubMed

    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

  20. 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

  1. Oestrogen action and male fertility: experimental and clinical findings.

    PubMed

    Li, Xiangdong; Li, Haiwen; Jia, Lina; Li, Xiru; Rahman, Nafis

    2015-10-01

    A proper balance between androgen and oestrogen is fundamental for normal male reproductive development and function in both animals and humans. This balance is governed by the cytochrome P450 aromatase, which is expressed also under spatio-temporal control. Oestrogen receptors ERα and/or ERβ, together with the membrane-associated G-protein-coupled functional ER (GPER), mediate the effects of oestrogen in the testis. Oestrogen action in male reproduction is more complex than previously predicted. The androgen/oestrogen balance and its regulation in the masculinisation programming window (MPW) during foetal life is the most critical period for the development of the male reproductive system. If this balance is impaired during the MPW, the male reproductive system may be negatively affected. Recent data from genetically modified mice and human infertile patients have shown that oestrogens may promote the engulfment of live Leydig cells by macrophages leading to male infertility. We also discuss recent data on environmental oestrogen exposure in men and rodents, where a rodent-human distinction is crucial and analyse some aspects of male fertility potentially related to impaired oestrogen/androgen balance. PMID:26160724

  2. 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

  3. The hazardous effects of tobacco smoking on male fertility.

    PubMed

    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

  4. 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. PMID:26101108

  5. The Control of Male Fertility by Spermatozoan Ion Channels

    PubMed Central

    Lishko, Polina V.; Kirichok, Yuriy; Ren, Dejian; Navarro, Betsy; Chung, Jean-Ju

    2014-01-01

    Ion channels control the sperm ability to fertilize the egg by regulating sperm maturation in the female reproductive tract and by triggering key sperm physiological responses required for successful fertilization such as hyperactivated motility, chemotaxis, and the acrosome reaction. CatSper, a pH-regulated, calcium-selective ion channel, and KSper (Slo3) are core regulators of sperm tail calcium entry and sperm hyperactivated motility. Many other channels had been proposed as regulating sperm activity without direct measurements. With the development of the sperm patch-clamp technique, CatSper and KSper have been confirmed as the primary spermatozoan ion channels. In addition, the voltage-gated proton channel Hv1 has been identified in human sperm tail, and the P2X2 ion channel has been identified in the midpiece of mouse sperm. Mutations and deletions in sperm-specific ion channels affect male fertility in both mice and humans without affecting other physiological functions. The uniqueness of sperm ion channels makes them ideal pharmaceutical targets for contraception. In this review we discuss how ion channels regulate sperm physiology. PMID:22017176

  6. Sperm Proteomics: Road to Male Fertility and Contraception

    PubMed Central

    Rahman, Md Saidur; Lee, June-Sub

    2013-01-01

    Spermatozoa are highly specialized cells that can be easily obtained and purified. Mature spermatozoa are transcriptionally and translationally inactive and incapable of protein synthesis. In addition, spermatozoa contain relatively higher amounts of membrane proteins compared to other cells; therefore, they are very suitable for proteomic studies. Recently, the application of proteomic approaches such as the two-dimensional polyacrylamide gel electrophoresis, mass spectrometry, and differential in-gel electrophoresis has identified several sperm-specific proteins. These findings have provided a further understanding of protein functions involved in different sperm processes as well as of the differentiation of normal state from an abnormal one. In addition, studies on the sperm proteome have demonstrated the importance of spermatozoal posttranslational modifications and their ability to induce physiological changes responsible for fertilization. Large-scale proteomic studies to identify hundreds to thousands of sperm proteins will ultimately result in the development of novel biomarkers that may help to detect fertility, the state of complete contraception, and beyond. Eventually, these protein biomarkers will allow for a better diagnosis of sperm dysfunctions and aid in drug development. This paper reviews the recent scientific publications available from the PubMed database to address sperm proteomics and its potential application to characterize male fertility and contraception. PMID:24363670

  7. In vitro fertilization for male infertility: when and how?

    PubMed

    Hall, J; Fishel, S

    1997-12-01

    The first observation that in vitro fertilization (IVF) was useful for treating oligozoospermia and oligoasthenozoospermia was reported by Fishel and Edwards in 1982. This was followed by a series of cases indicating the value of IVF in such cases. Conventional IVF has been modified and refined to achieve increased rates of conception in cases of male factor infertility. Methods such as high insemination concentration IVF for the treatment of teratozoospermia and microscopic IVF for the treatment of oligozoospermia have had some impact on fertilization and pregnancy rates; however, reports of success are varied. The recent advent of micromanipulation and, in particular, intracytoplasmic sperm injection (ICSI) has overshadowed the use of these modified IVF procedures. Because of the high fertilization and pregnancy rates achieved with ICSI, other micromanipulation techniques (subzonal insemination and partial zona dissection) have been abandoned; there have also been suggestions that other more conventional techniques, i.e. IVF, should also be abandoned and that ICSI become the sole technique for the treatment of infertility. The rapid increase in the number of centres using ICSI has led to extreme pressure for individual units to achieve high fertilization and pregnancy rates and there is a temptation to assign all patients to ICSI treatment. It is important that, in this highly competitive environment, new techniques are not applied haphazardly and reduced to the mere injection of gametes and achievement of pregnancy regardless of the cause of infertility. In his 1986 IVF--Historical Perspective, Fishel quoted Auguste Comte: 'to understand science it is necessary to know its history'. IVF has much recent history in animal and also human work. Although ICSI is the most significant therapeutic advance in male infertility treatment, its application to human IVF is only 4 years old, with a paucity of animal studies on which to rely. For this reason IVF still plays a

  8. Importance of male fertility control in family planning.

    PubMed

    Tulsiani, Daulat R P; Abou-Haila, Aida

    2014-01-01

    The world population, currently estimated to be almost seven billion, is expected to double in less than four decades. The projected population growth will cause severe competition for existing resources, not to mention the issue of overcrowding of the planet and additional greenhouse gases that will have an adverse effect on the ecological health of the planet. A recent survey conducted by the United Nations Population Control Division shows that the majority of today's young men in many countries are willing to participate in family planning by taking full control of their fertility, an important global health issue. However, the contraceptive needs of tens of millions of men/couples go unmet every single day and results in millions of unwanted pregnancies. Ever since the approval of the birth control pill by the Food and Drug Administration (FDA) in 1960, scientists have been hoping for a male equivalent. It has, however, been a difficult road, in part because of the complicated science of the male reproductive system. It is easier to control a monthly event of ovulation in women than to regulate the production of millions of fertile spermatozoa every day in men. Thus, the contraceptive options for men have not changed in decades and are still limited to the use of condoms, a timely withdrawal/pulling out (coitus interruptus) or vasectomy, a minor surgical procedure in which the vas deferens is occluded to prevent the release of spermatozoa during ejaculation. The first two approaches have a relatively higher failure rate, whereas the last approach is largely irreversible and not suitable for younger men. In this article, we will discuss various approaches currently available for men to take control of their fertility. Our intention is to discuss the details of three similar approaches that will provide safe, affordable and reversible contraception for men and are close to being approved for use by millions of men around the globe. The availability of safe

  9. 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

  10. 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. PMID:26277482

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

    PubMed

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

    2016-07-01

    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

  12. The sterile male technique: irradiation negatively affects male fertility but not male courtship.

    PubMed

    Magris, Martina; Wignall, Anne E; Herberstein, Marie E

    2015-04-01

    The sterile male technique is a common method to assign paternity, widely adopted due to its relative simplicity and low cost. Male sterility is induced by exposure to sub lethal doses of chemosterilants or irradiation, the dosage of which has to be calibrated for every species to provide successful male sterilisation, without affecting male physiology and behaviour. While the physiological effects of sterilisation are usually assessed for each study, the behavioural ones are rarely analysed in detail. Using the orb web spider Argiope keyserlingi as a model we first tested (1) the validity of the thread assay, which simulates male courtship behaviour in a standardised context, as a proxy representing courtship on a female web. We then investigated (2) the effectiveness of male sterilisation via irradiation and (3) its consequences on male courtship behaviour. Our results validate the thread assay and the sterile male technique as legitimate tools for the study of male courtship behaviour and fertilisation success. We show that these techniques are time and cost effective and reduce undesirable variation, thereby creating opportunities to study and understand the mechanisms underlying sexual selection. PMID:25794431

  13. Bile Acid Alters Male Mouse Fertility in Metabolic Syndrome Context

    PubMed Central

    Baptissart, Marine; De Haze, Angélique; Vaz, Frederic; Kulik, Wim; Damon-Soubeyrand, Christelle; Baron, Silvère; Caira, Françoise; Volle, David H.

    2015-01-01

    Bile acids have recently been demonstrated as molecules with endocrine activities controlling several physiological functions such as immunity and glucose homeostases. They act mainly through two receptors, the nuclear receptor Farnesol-X-Receptor alpha (FXRα) and the G-protein coupled receptor (TGR5). These recent studies have led to the idea that molecules derived from bile acids (BAs) and targeting their receptors must be good targets for treatment of metabolic diseases such as obesity or diabetes. Thus it might be important to decipher the potential long term impact of such treatment on different physiological functions. Indeed, BAs have recently been demonstrated to alter male fertility. Here we demonstrate that in mice with overweight induced by high fat diet, BA exposure leads to increased rate of male infertility. This is associated with the altered germ cell proliferation, default of testicular endocrine function and abnormalities in cell-cell interaction within the seminiferous epithelium. Even if the identification of the exact molecular mechanisms will need more studies, the present results suggest that both FXRα and TGR5 might be involved. We believed that this work is of particular interest regarding the potential consequences on future approaches for the treatment of metabolic diseases. PMID:26439743

  14. FACTORS ASSOCIATED WITH REDUCED FERTILITY AND IMPLANTATION RATES IN FEMALES MATED TO ACRYLAMIDE TREATED MALES

    EPA Science Inventory

    A series of studies was conducted to examine the role of copulatory dysfunction, spermatotoxicity, and/or impaired fertilization in the reduced rates of fertility and implantation observed in females mated to acrylamid-treated male rats. In initial experiments, males were gavaged...

  15. Biology of male fertility control: an overview of various male contraceptive approaches.

    PubMed

    Tulsiani, D R; Abou-Haila, A

    2015-04-01

    The population of our planet continues to grow at an alarming rate. If the growth continues at the present rate, the estimated current world population of about seven billion is expected to double in the next forty years. Accumulated data from surveys by the United Nations Population Control Division suggest that a majority of today's young men in many countries are willing to have fewer children than their parents did. However, the contraceptive options available to them have not changed in several decades. In spite of the general agreement that men, like women, must take full responsibility of their fertility, the availability of safe, reversible and affordable contraceptives for men have lagged behind because of the complexity of the science of the male reproductive system. Thus, the contraceptive needs of millions of men/couples go unmet every single day and results in millions of unwanted pregnancies. In this article, we intend to discuss new hormonal and non-hormonal contraceptive approaches that are at various stages of research and development and may someday provide new contraceptives for men. In addition, we intend to discuss many details of three safe, effective, affordable and reversible vas-based approaches that are inching closer to being approved for use by millions of men in multiple countries. Finally, our intention is to discuss the male contraceptive pill that will soon be available to men only in Indonesia. The availability of these male contraceptives will allow both men and women to take full control of their fertility and participate in slowing down the growth of world population. PMID:25516280

  16. Male fertility following spinal cord injury: an update.

    PubMed

    Ibrahim, E; Lynne, C M; Brackett, N L

    2016-01-01

    Spinal cord injury (SCI) occurs most often in young men at the peak of their reproductive health. The majority of men with SCI cannot father children naturally. Three major complications contribute to infertility in men with SCI: erectile dysfunction, ejaculatory dysfunction, and abnormal semen quality. Erectile dysfunction can be managed by regimens available to the general population, including oral administration of phosphodiesterase-5 (PDE-5) inhibitors, intracavernosal injections, vacuum devices, and penile prostheses. Semen may be obtained from anejaculatory men with SCI via the medically assisted ejaculation methods of penile vibratory stimulation (PVS) or electroejaculation (EEJ). Sperm retrieval is also possible via prostate massage or surgical sperm retrieval. Most men with SCI have abnormal semen quality characterized by normal sperm concentrations but abnormally low sperm motility and viability. Accessory gland dysfunction has been proposed as the cause of these abnormalities. Leukocytospermia is evident in most SCI patients. Additionally, elevated concentrations of pro-inflammatory cytokines and elevated concentrations of inflammasome components are found in their semen. Neutralization of these constituents has resulted in improved sperm motility. There is a recent and alarming trend in the management of infertility in couples with SCI male partners. Although many men with SCI have sufficient motile sperm in their ejaculates for attempting intrauterine insemination (IUI) or even intravaginal insemination, surgical sperm retrieval is often introduced as the first and only sperm retrieval method for these couples. Surgical sperm retrieval commits the couple to the most advanced, expensive, and invasive method of assisted conception: in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI). Couples should be informed of all options, including semen retrieval by PVS or EEJ. Intravaginal insemination or IUI should be considered when indicated

  17. Transplantation of male germ line stem cells restores fertility in infertile mice

    PubMed Central

    Ogawa, Takehiko; Dobrinski, Ina; Avarbock, Mary R.

    2016-01-01

    Azoospermia or oligozoospermia due to disruption of spermatogenesis are common causes of human male infertility. We used the technique of spermatogonial transplantation in two infertile mouse strains, Steel (Sl) and dominant white spotting (W), to determine if stem cells from an infertile male were capable of generating spermatogenesis. Transplantation of germ cells from infertile Sl/Sld mutant male mice to infertile W/Wv or Wv/W54 mutant male mice restored fertility to the recipient mice. Thus, transplantation of spermatogonial stem cells from an infertile donor to a permissive testicular environment can restore fertility and result in progeny with the genetic makeup of the infertile donor male. PMID:10613820

  18. 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.

  19. 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.

  20. The Genetic Basis of Male Fertility in Relation to Haplodiploid Reproduction in Leptopilina clavipes (Hymenoptera: Figitidae)

    PubMed Central

    Pannebakker, Bart A.; Beukeboom, Leo W.; van Alphen, Jacques J. M.; Brakefield, Paul M.; Zwaan, Bas J.

    2004-01-01

    Traits under relaxed selection are expected to become reduced or disappear completely, a process called vestigialization. In parthenogenetic populations, traits historically involved in sexual reproduction are no longer under selection and potentially subject to such reduction. In Leptopilina clavipes, thelytokous (parthenogenetic) populations are infected by Wolbachia bacteria. Arrhenotokous populations do not harbor Wolbachia. When antibiotics are applied to infected females, they are cured from their infection and males arise. Such males are capable of producing offspring with uninfected females, but with lower fertilization success than sexual males. This can be attributed to the lack of selection on male fertility in thelytokous lines. In this study we used this variation in L. clavipes male fertility to determine the genetic basis of this trait. Males from cured thelytokous populations were crossed to females from uninfected populations. Using AFLP markers, a genetic linkage map was generated, consisting of five linkage groups and spanning a total distance of 219.9 cM. A single QTL of large effect (explaining 46.5% of the phenotypic variance) was identified for male fertility, which we call male fertility factor (mff). We discuss possible mechanisms underlying the effect of mff, as well as mechanisms involved in vestigialization of traits involved in sexual reproduction. PMID:15454547

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

    PubMed Central

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

    2013-01-01

    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. PMID:23630327

  2. Effect of estrogen receptor-subtype-specific ligands on fertility in adult male rats.

    PubMed

    Dumasia, Kushaan; Kumar, Anita; Kadam, Leena; Balasinor, N H

    2015-06-01

    Maintenance of normal male fertility relies on the process of spermatogenesis which is under complex endocrine control by mechanisms involving gonadotropin and steroid hormones. Although testosterone is the primary sex steroid in males, estrogen is locally produced in the testis and plays a very crucial role in male fertility. This is evident from presence of both the estrogen receptors alpha (ERα) and beta (ERβ) in the testis and their absence, as in the case of knockout mice models, leads to sterility. The present study was undertaken to understand individual roles of the two ERs in spermatogenesis and their direct contribution towards the maintenance of male fertility using receptor-subtype-specific ligands. Administration of ERα and β agonists to adult male rats for 60 days results in a significant decrease in fertility, mainly due to an increase in pre- and post-implantation loss and a concomitant decrease in litter size and sperm counts. Our results indicate that ERα is mainly involved in negative feedback regulation of gonadotropin hormones, whereas both ERs are involved in regulation of prolactin and testosterone production. Histological examinations of the testis reveal that ERβ could be involved in the process of spermiation since many failed spermatids were observed in stages IX-XI following ERβ agonist treatment. Our results indicate that overactivation of estrogen signaling through either of its receptors can have detrimental effects on the fertility parameters and that the two ERs have both overlapping and distinct roles in maintenance of male fertility. PMID:25869617

  3. 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

  4. 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 ...

  5. FORMATION AND FUNCTION OF THE MALE PRONUCLEUS DURING MAMMALIAN FERTILIZATION

    EPA Science Inventory

    A number of excellent reviews dealing with many critical aspects of fertilization in mammalian and nonmammalian species have been published (Yanagimachi, 1978, 1981, 1982,; Shapiro and Eddy, 1980; Longo, 1981a,b, 1985; Gulyas and Schmell, 1981; Wolgemuth, 1983, Wassarman, 1987). ...

  6. Timing is everything for sperm assessment in fertility studies.

    PubMed

    Mariën, Dirk; Bailey, Graham P; Eichenbaum, Gary; De Jonghe, Sandra

    2016-09-01

    The fertility study design recommended in the ICH S5(R2) Harmonised Guideline for Detection of Toxicity to Reproduction for Medicinal Products emphasizes the importance of histopathological endpoints next to a pairing assessment in evaluating male fertility. However, in a male rat fertility study with JNJ-26489112, a CNS-active agent, while there were no effects on histological endpoints, mating performance or pregnancy outcomes, sperm assessment was included. The high dose males presented with reversible decreases in epididymal, but not testicular, sperm concentration and motility and an increase in abnormal sperm morphology. In view of the differences in fertility between rats and humans, these types of sperm effects in rats suggest the potential for an impact on human male fertility that would be undetected if not for the sperm assessment. Therefore, the current example suggests that including semenology as a standard endpoint in nonclinical fertility studies may be warranted. PMID:27181369

  7. [Inheritance of reversions to male fertility in male-sterile sorghum hybrids with 9E cytoplasm male sterility induced by environmental conditions].

    PubMed

    Elkonin, L A; Gerashchenkov, G A; Domanina, I V; Rozhnova, N A

    2015-03-01

    Heritable phenotypic alterations occurring during plant ontogenesis under the influence of environmental factors are among the most intriguing genetic phenomena. It was found that male-sterile sorghum hybrids in the 9E cytoplasm from the F1 and F2 generations, which were obtained by crossing CMS lines with different fertile lines grown in field conditions, were transferred to greenhouse produce fertile tillers. Lines created by the self-pollination of revertant tillers exhibit complete male fertility upon cultivation under various environments (in the field, Tdry plot,(y) Tirrigated plot(y)). In a number of test-crosses of revertants to CMS lines in the 9E cytoplasm, restoration of male fertility in F1 hybrids was found, indicating that revertants possess functional fertility-restoring genes. A high positive correlation was found between the fertility level of the test-cross hybrids and the hydrothermal coefficient (the ratio of the sum of precipitation to the sum of temperatures) during the booting stage and pollen maturation (r = 0.75...0.91; P<0.01), suggesting that a high level of plant water availability is needed for the expression of fertility-restoring genes of revertants. These data show that the fertility-restoring genes for the 9E cytoplasm are dominant in conditions of high water availability and recessive in drought conditions; reversions to male fertility are due to up-regulation of fertility-restoring genes by a high level of water availability. Comparative MSAP-analysis of DNA of male-sterile and male-fertile test-cross hybrids using HpaII/MspI restrictases and primers to polygalacturonase gene ADPG2, which is required for cell separation during reproductive development, and gene MYB46, the transcription factor regulating secondary wall biosynthesis, revealed differences in the number and the length of amplified fragments. Changes in the methylation of these genes in conditions of drought stress are apparently the reason for male sterility of

  8. Direct but no transgenerational effects of decitabine and vorinostat on male fertility.

    PubMed

    Kläver, Ruth; Sánchez, Victoria; Damm, Oliver S; Redmann, Klaus; Lahrmann, Elisabeth; Sandhowe-Klaverkamp, Reinhild; Rohde, Christian; Wistuba, Joachim; Ehmcke, Jens; Schlatt, Stefan; Gromoll, Jörg

    2015-01-01

    Establishment and maintenance of the correct epigenetic code is essential for a plethora of physiological pathways and disturbed epigenetic patterns can provoke severe consequences, e.g. tumour formation. In recent years, epigenetic drugs altering the epigenome of tumours actively have been developed for anti-cancer therapies. However, such drugs could potentially also affect other physiological pathways and systems in which intact epigenetic patterns are essential. Amongst those, male fertility is one of the most prominent. Consequently, we addressed possible direct effects of two epigenetic drugs, decitabine and vorinostat, on both, the male germ line and fertility. In addition, we checked for putative transgenerational epigenetic effects on the germ line of subsequent generations (F1-F3). Parental adult male C57Bl/6 mice were treated with either decitabine or vorinostat and analysed as well as three subsequent untreated generations derived from these males. Treatment directly affected several reproductive parameters as testis (decitabine & vorinostat) and epididymis weight, size of accessory sex glands (vorinostat), the height of the seminiferous epithelium and sperm concentration and morphology (decitabine). Furthermore, after decitabine administration, DNA methylation of a number of loci was altered in sperm. However, when analysing fertility of treated mice (fertilisation, litter size and sex ratio), no major effect of the selected epigenetic drugs on male fertility was detected. In subsequent generations (F1-F3 generations) only subtle changes on reproductive organs, sperm parameters and DNA methylation but no overall effect on fertility was observed. Consequently, in mice, decitabine and vorinostat neither affected male fertility per se nor caused marked transgenerational effects. We therefore suggest that both drugs do not induce major adverse effects-in terms of male fertility and transgenerational epigenetic inheritance-when used in anti

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

    PubMed Central

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

    1998-01-01

    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. PMID:9539433

  10. The effects of cigarette smoking on male fertility.

    PubMed

    Kovac, Jason R; Khanna, Abhinav; Lipshultz, Larry I

    2015-04-01

    Cigarette smoking, one of the main causes of preventable morbidity and mortality, has a multitude of well-known side effects. The relationship between cigarette smoking and infertility has been studied for decades; however, large-scale, population-wide prospective studies are lacking. The majority of the current literature is in the form of retrospective studies focused on the effects of smoking on semen analyses. This article discusses the results of these studies and reviews the postulated mechanisms. The effects of smoking on assisted reproduction and in vitro fertilization outcomes are noted. The consequences of smoking while pregnant on future fertility as well as the outcomes of second-hand smoke are analyzed. The current evidence suggests that men should be advised to abstain from smoking in order to improve reproductive outcomes. PMID:25697426

  11. The effect of urethral stricture on male fertility in Ife.

    PubMed

    Badejo, O A

    1990-01-01

    Twenty patients with Urethral stricture disease presenting with difficulty in micturition, azoospermia, and oligospermia were studied. Only 5% of our patients could firmly claim to be fertile at the time of presentation with a rise to 80% fertility rate at the end of management. Fifteen percent did not notice any change in their status. Surgical approach claimed better result over conservative management because of other complications following gonococcal infections. The need for a close forensic analysis in the determination of paternity in all cases of Urethral strictures was stressed while a treatment protocol of graft urethroplasty in all cases of traumatic rupture and dilatation in cases following inflammatory lesions of the urethra was established. PMID:2090990

  12. Molecular diversity of male sterility inducing and male-fertile cytoplasms in the genus Helianthus.

    PubMed

    Horn, R.

    2002-03-01

    The organisation of mtDNA was investigated for 28 sources of cytoplasmic male sterility (CMS) and a fertile line (normal cytoplasm) of Helianthus annuus by Southern hybridisation. In addition to nine known mitochondrial genes ( atp6, atp9, cob, coxI, coxII, coxIII, 18S, 5S and nd5) three probes for the open reading frames in the rearranged area of PET1, orfH522, orfH708 and orfH873, were used. Genetic similarities of the investigat-ed cytoplasms varied between 0.3 and 1. Cluster analyses using the UPGMA method allowed the distinction of ten mitochondrial (mt) types between the 29 investigated cytoplasms. Most mitochondrial types comprise two or more CMS sources, which could not be further separated, like the PET1-like CMS sources (with the exception of ANO1 and PRR1), or ANN1/ANN2/ANN3, ANN4/ ANN5, ARG3/RIG1, BOL1/EXI1/PEF1/PEP1 and GIG1/ PET2. ANL1, ANL2 and the fertile cytoplasms are also regarded as one mitochondrial type. Unique banding patterns were only observed for ANT1 ( atp6), MAX1 ( atp6, orfH522 and orfH708) and PRR1 ( coxII). However, four of the mitochondrial types showed unique hybridisation signals: ANN4/ANN5 had characteristic bands for atp6 and orfH708, PEF1/PEP1/EXI1/BOL1 for atp6and coxII, and PET2/GIG1 for atp9. The PET1-like cytoplasms all shared the same patterns for orfH522, orfH708and cob (except ANO1). It could be demonstrated that CMS sources, like, e.g., PET2 and PEF1, are different from PET1 in mtDNA organisation and the CMS mechanism. Therefore, these CMS sources represent interesting candidates for the development of new hybrid breeding systems based on new CMS mechanisms. PMID:12582659

  13. Female life span and fertility are increased by the ejaculates of preferred males.

    PubMed

    Wagner, William E; Harper, Christopher J

    2003-09-01

    In animals with internal fertilization, sperm competition among males can favor the evolution of male ejaculate traits that are detrimental to females. Female mating preferences, in contrast, often favor traits in males that are beneficial to females, yet little is known about the effect of these preferences on the evolution of male ejaculates. A necessary condition for female preferences to affect the evolution of male ejaculate characteristics is that females select mates based on a trait correlated with ejaculate quality. Previous work has shown that females of the variable field cricket, Gryllus lineaticeps, prefer males that produce calling songs containing faster and longer chirps. In this study, we tested the hypothesis that females receive more beneficial ejaculates from preferred males. Females were placed on either a high- or a reduced-nutrition diet then mated twice to a male of known song phenotype. Females received only sperm and seminal fluid from males during these matings. There was no effect of male song phenotype on any fitness component for females on the high-nutrition diet. Reduced-nutrition females mated to males that produced preferred song types, however, lived longer, produced more eggs, produced more fertile eggs, and had a higher proportion of their eggs fertilized than those mated to other males. The life-span benefit was positively associated with male chirp duration, and the reproductive benefits were positively associated with male chirp rate. We explored two possible mechanisms for the life span and reproductive benefits. First, a path analysis suggested that part of the effect of male chirp duration on female life span may have been indirect; females mated to males that produced longer chirps showed delayed oviposition, and females that delayed oviposition lived longer. Males that produce longer chirps may thus transfer fewer or less potent oviposition stimulants to females in their seminal fluid. Second, there was a positive

  14. 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

  15. 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.

  16. Impact of garlic feeding (Allium sativum) on male fertility.

    PubMed

    Hammami, I; El May, M V

    2013-08-01

    Many medicinal plants are designed to improve health but their mechanism of action remains not clear. Among these plants, garlic (Allium sativum) has attracted particular attention of modern medicine because of its widespread use for the prevention and treatment of some human diseases such as cardiovascular diseases and cancer. However, the impact of garlic on the male reproductive system has not been clearly defined. Some studies have reported that garlic improves male sexual function and has beneficial effect in the recovery of testicular functions. However, other authors have shown that this plant impairs testicular functions (such as inhibition of testosterone production) and has spermicidal effect on spermatozoa. In this review, we attempt to clarify the current ambiguity regarding the effects of garlic and its preparations on the male reproductive system. PMID:22943423

  17. The effects of cancer and cancer therapy on male fertility

    SciTech Connect

    Thachil, J.V.; Jewett, M.A.; Rider, W.D.

    1981-08-01

    Multimodality treatments have increased the survival of cancer patients in recent years. With cure the quality of life also should be taken into consideration. Maintenance of the reproductive capacity is of great concern to many young patients. Until now the cause of sterility was attributed to the long-term side effects of treatment when recovery could not be predicted. Pre-treatment sperm banking is advised routinely for many of these patients. Our own observation as well as a few other reports show that cancer itself seems to have an adverse effect on fertility before any form of treatment. As assessed by semen quality the majority of our patients were subfertile when first seen. Hence, sperm banking may be a poor guarantee for future reproduction in these patients.

  18. 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. PMID:27044871

  19. 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

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

    PubMed

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

    2015-03-01

    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

  1. 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

  2. Morphology of the external genitalia of the adult male and female mice as an endpoint of sex differentiation

    PubMed Central

    Weiss, Dana A.; Rodriguez, Esequiel; Cunha, Tristan; Menshenina, Julia; Barcellos, Dale; Chan, Lok Yun; Risbridger, Gail; Baskin, Laurence; Cunha, Gerald

    2013-01-01

    Adult external genitalia (ExG) are the endpoints of normal sex differentiation. Detailed morphometric analysis and comparison of adult mouse ExG has revealed 10 homologous features distinguishing the penis and clitoris that define masculine vs. feminine sex differentiation. These features have enabled the construction of a simple metric to evaluate various intersex conditions in mutant or hormonally manipulated mice. This review focuses on the morphology of the adult mouse penis and clitoris through detailed analysis of histologic sections, scanning electron microscopy, and three-dimensional reconstruction. We also present previous results from evaluation of “non-traditional” mammals, such as the spotted hyena and wallaby to demonstrate the complex process of sex differentiation that involves not only androgen-dependent processes, but also estrogen-dependent and hormone-independent mechanisms. PMID:21893161

  3. Morphology of the external genitalia of the adult male and female mice as an endpoint of sex differentiation.

    PubMed

    Weiss, Dana A; Rodriguez, Esequiel; Cunha, Tristan; Menshenina, Julia; Barcellos, Dale; Chan, Lok Yun; Risbridger, Gail; Baskin, Laurence; Cunha, Gerald

    2012-05-01

    Adult external genitalia (ExG) are the endpoints of normal sex differentiation. Detailed morphometric analysis and comparison of adult mouse ExG has revealed 10 homologous features distinguishing the penis and clitoris that define masculine vs. feminine sex differentiation. These features have enabled the construction of a simple metric to evaluate various intersex conditions in mutant or hormonally manipulated mice. This review focuses on the morphology of the adult mouse penis and clitoris through detailed analysis of histologic sections, scanning electron microscopy, and three-dimensional reconstruction. We also present previous results from evaluation of "non-traditional" mammals, such as the spotted hyena and wallaby to demonstrate the complex process of sex differentiation that involves not only androgen-dependent processes, but also estrogen-dependent and hormone-independent mechanisms. PMID:21893161

  4. The role of the prostate in male fertility, health and disease.

    PubMed

    Verze, Paolo; Cai, Tommaso; Lorenzetti, Stefano

    2016-07-01

    Ejaculation is a synchronized cascade of events that has the ultimate goal of activating sperm and enabling them to reach an egg for fertilization. The seminal plasma contains a complex mixture of fluids that is secreted from the testes, epididymis and male accessory glands. The prostate gland has a pivotal role in this process, as prostatic fluid enriched in Zn(2+), citrate and kallikreins is crucial for the molecular synchronization of the functional cascade triggered by ejaculatory stimuli. The prostate is the target of a number of common diseases that can affect male fertility at different ages. In both young and aged men, prostatic diseases or an unhealthy prostate can affect spermatozoa functioning and, therefore, male fertility. Consideration of prostate physiology emphasizes a number of points: the central role of Zn(2+) and citrate in the regulation of prostate epithelium homeostasis and in ejaculation; the influence of bacteria-related prostatic inflammation on male fertility; and the potential role of prostatic inflammation in promoting the development of prostatic hyperplastic growth and carcinogenesis. PMID:27245504

  5. Parental effects on male fertility and agronomic performance of haploid-wild species hybrids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Valuable genetic diversity in diploid wild Solanum species can be accessed through crosses to haploids (2x) of the cultivated potato, S. tuberosum. These hybrids segregate for the ability to tuberize in the field. In addition, they vary in male fertility, vine size, stolon length, and tuber size. In...

  6. 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...

  7. 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...

  8. 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...

  9. Control of Male and Female Fertility by the Netrin Axon Guidance Genes

    PubMed Central

    Newquist, Gunnar; Hogan, Jesse; Walker, Kirsti; Lamanuzzi, Matthew; Bowser, Micah; Kidd, Thomas

    2013-01-01

    The netrin axon guidance genes have previously been implicated in fertility in C. elegans and in vertebrates. Here we show that adult Drosophila lacking both netrin genes, NetA and NetB, have fertility defects in both sexes together with an inability to fly and reduced viability. NetAB females produce fertilized eggs at a much lower rate than wild type. Oocyte development and ovarian innervation are unaffected in NetAB females, and the reproductive tract appears normal. A small gene, hog, that resides in an intron of NetB does not contribute to the NetAB phenotype. Restoring endogenous NetB expression rescues egg-laying, but additional genetic manipulations, such as restoration of netrin midline expression and inhibition of cell death have no effect on fertility. NetAB males induce reduced egg-laying in wild type females and display mirror movements of their wings during courtship. Measurement of courtship parameters revealed no difference compared to wild type males. Transgenic manipulations failed to rescue male fertility and mirror movements. Additional genetic manipulations, such as removal of the enabled gene, a known suppressor of the NetAB embryonic CNS phenotype, did not improve the behavioral defects. The ability to fly was rescued by inhibition of neuronal cell death and pan-neural NetA expression. Based on our results we hypothesize that the adult fertility defects of NetAB mutants are due to ovulation defects in females and a failure to properly transfer sperm proteins in males, and are likely to involve multiple neural circuits. PMID:23977313

  10. The fatty acid elongase Bond is essential for Drosophila sex pheromone synthesis and male fertility

    PubMed Central

    Ng, Wan Chin; Chin, Jacqueline S. R.; Tan, Kah Junn; Yew, Joanne Y.

    2015-01-01

    Insects use a spectacular variety of chemical signals to guide their social behaviours. How such chemical diversity arises is a long-standing problem in evolutionary biology. Here we describe the contribution of the fatty acid elongase Bond to both pheromone diversity and male fertility in Drosophila. Genetic manipulation and mass spectrometry analysis reveal that the loss of bond eliminates the male sex pheromone (3R,11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol (CH503). Unexpectedly, silencing bond expression severely suppresses male fertility and the fertility of conspecific rivals. These deficits are rescued on ectopic expression of bond in the male reproductive system. A comparative analysis across six Drosophila species shows that the gain of a novel transcription initiation site is correlated with bond expression in the ejaculatory bulb, a primary site of male pheromone production. Taken together, these results indicate that modification of cis-regulatory elements and subsequent changes in gene expression pattern is one mechanism by which pheromone diversity arises. PMID:26369287

  11. Male coping with cancer-fertility issues: putting the 'social' into biopsychosocial approaches.

    PubMed

    Crawshaw, Marilyn

    2013-09-01

    Biopsychosocial approaches in infertility and cancer services and research pay limited attention to 'social dimensions'. Additionally, existing cancer-related male infertility research is dominated by sperm banking studies even though fertility-related social concerns in the long term are reported to have an adverse effect on wellbeing. This paper considers whether social influences affected the fertility-related experiences of 28 men interviewed as part of a mixed-gender qualitative study of 'South Asian' and 'White' cancer survivors and their professional carers. Findings are reported under: managing stigma; sexuality and virility; ambiguity in fertile status; relationship to sperm; and meaning of fatherhood. Gender and other social influences were ambiguous, fluid and subtle--yet powerful. Combinations were neither standard nor static, indicating the dangers of practitioners stereotyping, and/or assuming homogeneity of, (in)fertile men and being unaware of their own socialized expectations. Social structures and attitudes towards valued male social roles as well as the men's psychological capacity and bodily state appear to affect experience. Men may more readily be engaged if practitioners proactively attend to the impact of social concerns, including employment and financial matters, on their perceived capacity to be fathers as a route into raising issues of sexuality and fertility. PMID:23871365

  12. Experimental methods to preserve male fertility and treat male factor infertility.

    PubMed

    Gassei, Kathrin; Orwig, Kyle E

    2016-02-01

    Infertility is a prevalent condition that has insidious impacts on the infertile individuals, their families, and society, which extend far beyond the inability to have a biological child. Lifestyle changes, fertility treatments, and assisted reproductive technology (ART) 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 men with azoospermia. PMID:26746133

  13. 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

  14. 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. PMID:23301826

  15. Targeted expression of cystatin restores fertility in cysteine protease induced male sterile tobacco plants.

    PubMed

    Shukla, Pawan; Subhashini, Mranu; Singh, Naveen Kumar; Ahmed, Israr; Trishla, Shalibhadra; Kirti, P B

    2016-05-01

    Fertility restoration in male sterile plants is an essential requirement for their utilization in hybrid seed production. In an earlier investigation, we have demonstrated that the targeted expression of a cysteine protease in tapetal cell layer resulted in complete male sterility in tobacco transgenic plants. In the present investigation, we have used a cystatin gene, which encodes for a cysteine protease inhibitor, from a wild peanut, Arachis diogoi and developed a plant gene based restoration system for cysteine protease induced male sterile transgenic tobacco plants. We confirmed the interaction between the cysteine protease and a cystatin of the wild peanut, A. diogoi through in silico modeling and yeast two-hybrid assay. Pollen from primary transgenic tobacco plants expressing cystatin gene under the tapetum specific promoter- TA29 restored fertility on cysteine protease induced male sterile tobacco plants developed earlier. This has confirmed the in vivo interaction of cysteine protease and cystatin in the tapetal cells, and the inactivation of cysteine protease and modulation of its negative effects on pollen fertility. Both the cysteine protease and cystatin genes are of plant origin in contrast to the analogous barnase-barstar system that deploys genes of prokaryotic origin. Because of the deployment of genes of plant origin, this system might not face biosafety problems in developing hybrids in food crops. PMID:26993235

  16. 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

  17. Review on research of suppression male fertility and male contraceptive drug development by natural products.

    PubMed

    Bajaj, Vijay Kumar; Gupta, Radhey S

    2013-08-01

    Male contraceptive development in the present scenario is most viable aspect of research due to uncontrolled population growth in the world. In this respect investigators are busy to find out a safe male contraceptive drug. Researchers have started their finding for a suitable drug from natural sources because these are safe and easily acceptable for common man, most of natural sources are plants and their products. In this review 137 plants and their effects on reproduction and reproductive physiology are summarized. Some of them have intense effect on male reproductive system and do not produce any side effects. Reproductive toxicological studies are also important aspects of these kinds of researches, so it is important that drugs are safe and widely acceptable. An ideal male contraceptive can influence semen, testes, hormone level, accessory reproductive organs and general physiology of animals and produced some alterations. Many plants in this review are showing antifertility as well as antispermatogenic effects, so these may be used for further study for contraceptives development but it is important to find out the mechanism of reaction and further laboratory and clinical research on some plants are needed for final male contraceptive drug development. In conclusion this review will help for finding suitable plant products for male contraceptive clinical and laboratory studies. PMID:24079200

  18. 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. PMID:26648473

  19. 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

  20. Fertility Preservation Preferences and Perspectives Among Adult Male Survivors of Pediatric Cancer and Their Parents

    PubMed Central

    Stein, Daniel M.; Victorson, David E.; Choy, Jeremy T.; Waimey, Kate E.; Pearman, Timothy P.; Smith, Kristin; Dreyfuss, Justin; Kinahan, Karen E.; Sadhwani, Divya; Woodruff, Teresa K.

    2014-01-01

    Purpose: In this study, we set out to determine the preferences, concerns, and attitudes toward fertility preservation of adult male survivors of pediatric cancer and their parents. Methods: We conducted 3 focus groups with a total of 15 male survivors of pediatric cancer (age at diagnosis: mean=14, range: 10–20; age at study: mean=35, range: 25–47) and 2 groups with a total of 7 parents of survivors. Grounded theory methodology was used for the identification and analysis of recurrent themes expressed by survivors and their parents in the course of focus group discussions. Results: Themes most frequently expressed by survivors included concern regarding long-term treatment effects and a retrospective desire for fertility impairment to have been discussed when they were originally diagnosed with cancer. Parental themes included the same hindsight desire, as well as reliance upon the treating oncologist for direction in selecting the course of treatment, and an acknowledgment that input from a specialist in fertility preservation would have been beneficial. Conclusions: Although future reproductive potential was not consistently reported as a source of apprehension when diagnosed with cancer, both survivors and their parents noted it to be a paramount concern later in life. Parents and survivors both reported that fertility preservation discussions should be routinely incorporated in the clinical context of a pediatric cancer diagnosis. PMID:24940531

  1. Injection of copper powder into epididymides via vas deferens on male fertility.

    PubMed

    Zhang, X G; Xu, Y; Qian, S Z

    1987-01-01

    In adult SD rats, a single injection of silicon rubber containing 10mg metallic copper particles via vas deferens into each cauda epididymis could induce male infertility. Although the copper contact in the cauda epididymides of treated rats was significantly higher than that in the controls, the serum copper concentration did not rise significantly, while the histology of important organs and blood testosterone levels did not change. Treated animals gained weight as fast as the controls, suggesting a low systemic toxicity of this procedure. In 5 of the 8 treated rats, fertility was restored 16 weeks after treatment with normal testicular copper concentration and testicular histology. In 3, fertility was not restored within 16 weeks and the testicular copper concentration was significantly higher than in the controls. Only in these 3 rats were different degrees of damage noted in the seminiferous epithelium and it is anticipated that the fertility will be restored after a certain period of time since sperm production was unaffected. The delayed recovery of fertility in these rats is attributed to the diffusion of copper ions into the testis. It would appear that the injection of silicon rubber containing copper particles via the vas deferens to the cauda epididymides is a potential approach for male contraception. PMID:12268654

  2. Contemporary and future insights into fertility preservation in male cancer patients

    PubMed Central

    Ong, Chloe; Durairajanayagam, Damayanthi

    2014-01-01

    In recent years, survival rates of cancer patients have increased, resulting in a shift of focus from quantity to quality of life. A key aspect of quality of life is fertility potential; patients suffering from iatrogenic infertility often become depressed. Since many cancer therapies—chemotherapy, radiotherapy and/or surgery—and even cancer itself have detrimental effects on the male reproductive system, it is important to preserve fertility before any treatment commences. Currently, the only reliable method of male fertility preservation is sperm banking. For patients who are unable to provide semen samples by the conventional method of masturbation, there are other techniques such as electroejaculation, microsurgical epididymal sperm aspiration and testicular sperm extraction that can be employed. Unfortunately, it is presently impossible to preserve the fertility potential of pre-pubertal patients. Due to the increasing numbers of adolescent cancer patients surviving treatment, extensive research is being conducted into several possible methods such as testicular tissue cryopreservation, xenografting, in vitro gamete maturation and even the creation of artificial gametes. However, in spite of its ease, safety, convenience and many accompanying benefits, sperm banking remains underutilized in cancer patients. There are several barriers involved such as the lack of information and the urgency to begin treatment, but various measures can be put in place to overcome these barriers so that sperm banking can be more widely utilized. PMID:26816750

  3. Contemporary and future insights into fertility preservation in male cancer patients.

    PubMed

    Agarwal, Ashok; Ong, Chloe; Durairajanayagam, Damayanthi

    2014-03-01

    In recent years, survival rates of cancer patients have increased, resulting in a shift of focus from quantity to quality of life. A key aspect of quality of life is fertility potential; patients suffering from iatrogenic infertility often become depressed. Since many cancer therapies-chemotherapy, radiotherapy and/or surgery-and even cancer itself have detrimental effects on the male reproductive system, it is important to preserve fertility before any treatment commences. Currently, the only reliable method of male fertility preservation is sperm banking. For patients who are unable to provide semen samples by the conventional method of masturbation, there are other techniques such as electroejaculation, microsurgical epididymal sperm aspiration and testicular sperm extraction that can be employed. Unfortunately, it is presently impossible to preserve the fertility potential of pre-pubertal patients. Due to the increasing numbers of adolescent cancer patients surviving treatment, extensive research is being conducted into several possible methods such as testicular tissue cryopreservation, xenografting, in vitro gamete maturation and even the creation of artificial gametes. However, in spite of its ease, safety, convenience and many accompanying benefits, sperm banking remains underutilized in cancer patients. There are several barriers involved such as the lack of information and the urgency to begin treatment, but various measures can be put in place to overcome these barriers so that sperm banking can be more widely utilized. PMID:26816750

  4. A fertility study of male employees engaged in the manufacture of glycerine

    SciTech Connect

    Venable, J.R.; McClimans, C.D.; Flake, R.E.; Dimick, D.B.

    1980-02-01

    The fertility status of male employees engaged in the production of chlorinated three-carbon compounds at Dow Chemical Company's Texas Division was investigated. Males who had not worked in the production of industrial chemicals for at least five years prior to the study period served as controls. Data were obtained from a reproductive medical history, from hormone determinations, from a physician's examination, and from a semen analysis. Sperm counts and percent normal sperm forms were major study variables. Comparisons were made between the control and the study groups and within the study group only for duration of exposure, strength of exposure and a combination of the two. Specific chemical exposure subgroups within the study group were also compared. Although the participation rate for the exposed group was relatively low (64%), results indicated no detrimental effect on fertility from exposure to chlorinated three-carbon compounds at levels occurring in the specified work environment.

  5. 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

  6. A chimeric ecdysone receptor facilitates methoxyfenozide-dependent restoration of male fertility in ms45 maize.

    PubMed

    Unger, Erica; Cigan, A Mark; Trimnell, Mary; Xu, Rui-ji; Kendall, Tim; Roth, Brad; Albertsen, Marc

    2002-10-01

    A mutation in the maize Ms45 gene results in abortion of microspore development and a male-sterile phenotype. MS45 protein has been localized to the tapetum and maximally expressed in anthers at the early vacuolate stage of microspore development. Molecular complementation analysis determined that a transformed copy of the gene fully restored fertility to ms45 maize. In this report, using phenotypic complementation as an assay, chimeric transcriptional activators were expressed to regulate a gal:MS45 gene and test the ability of a multi-component system to restore male fertility. A high frequency of phenotypic complementation was observed when either C1-GAL4 or VP16-GAL4 activators were transcribed by promoters that expressed at a stage of anther development that precedes the early vacuolate stage of microsporogenesis. For the conditional regulation of male fertility, these transcriptional activators were modified by the addition of regions that include the ligand-binding domain from the European corn borer ecdysone receptor to generate the nuclear receptors C1-GAL4-EcR (CGEcR) and VP16-GAL4-EcR (VGEcR). These chimeric receptors were introduced with the gal:MS45 gene into ms45 maize, and in the absence of ligand, these plants were male sterile. In contrast, application of the ecdysone agonist, methoxyfenozide, to plants containing either a constitutive (Ubiquitin1) or anther-specific (maize 5126) VGEcR resulted in the restoration of fertility to ms45 plants grown in either the greenhouse or in the field. PMID:12437077

  7. The role of male age, sperm age and mating history on fecundity and fertilization success in the hide beetle.

    PubMed Central

    Jones, Therésa M.; Elgar, Mark A.

    2004-01-01

    Models of age-related mate choice predict female preference for older males as they have proven survival ability. However, these models rarely address differences in sperm age and male mating history when evaluating the potential benefits to females from older partners. We used a novel experimental design to assess simultaneously the relative importance of these three parameters in the hide beetle, Dermestes maculatus. In a two-part experiment we first explored age-related male mating success and subsequently examined the consequences of male age, sperm age and male mating history on female fecundity and fertilization success. In a competitive mating environment, intermediate-age males gained significantly higher mating success than younger or older males. To test the consequences for females of aged-related male mating success, a second set of females were mated to males varying in age (young, intermediate-age and old), in numbers of matings and in timing of the most recent mating. We found that male age had a significant impact on female fecundity and fertilization success. Females mated to intermediate-age males laid more eggs and attained consistently higher levels of fertilization success than females with young and old mates. A male's previous mating history determined his current reproductive effort; virgin males spent longer in copula than males with prior mating opportunities. However, differences in copulation duration did not translate into increased fecundity or fertilization success. There was also little evidence to suggest that fertilization success was dependent on the age of a male's sperm. The experiment highlights the potential direct benefits accrued by females through mating with particular aged males. Such benefits are largely ignored by traditional viability models of age-related male mating success. PMID:15306356

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

    PubMed

    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

  9. Aqueous fruit extract of Mimusops elengi causes reversible suppression of spermatogenesis and fertility in male mice.

    PubMed

    Singh, N; Singh, S K

    2016-09-01

    Antifertility efficacy of oral administration of aqueous fruit extract of Mimusops elengi (200, 400 and 600 mg kg(-1) body weight/day for 35 days) was evaluated in Parkes strain male mice. Various reproductive end points such as histopathology, sperm parameters, testosterone level, haematology, serum biochemistry and fertility indices were assessed; activities of 3β- and 17β-hydroxysteroid dehydrogenases, and immunoblot expressions of StAR and P450scc in the testis were also assessed. Histologically, testes in Mimusops-treated mice showed nonuniform and diverse degenerative changes in the seminiferous tubules; both affected and normal tubules were observed in the same sections of testis. The treatment had adverse effects on testicular hydroxysteroid dehydrogenases and StAR and P450scc, serum level of testosterone and on motility, viability and number of spermatozoa in cauda epididymis. However, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine, and haematological parameters were not affected by the treatment. Also, libido was not affected in treated males, but their fertility was markedly suppressed. By 56 days of treatment withdrawal, the alterations caused in the above parameters recovered to control levels, suggesting that Mimusops treatment causes reversible suppression of spermatogenesis and fertility in Parkes mice. Further, there were no detectable signs of toxicity in treated males. PMID:27489141

  10. 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

  11. 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. PMID:22417728

  12. Information asymmetries among males: implications for fertilization success in the thirteen-lined ground squirrel.

    PubMed Central

    Schwagmeyer, P L; Parker, G A; Mock, D W

    1998-01-01

    The classical view of mammalian mating competition focuses on combat and threat. By contrast, field studies have revealed that male mating success in some species is more strongly determined by mate location ability than by physical dominance. In thirteen-lined ground squirrels, competition in locating oestrous females is exacerbated by sperm competition that favours the first male to mate with a female. We used a female-removal experiment to identify the distinguishing characteristics of males that were the first at finding and mating with females. Each focal female was observed the day before she entered oestrus; the identities of males that made contact with her and the locations of their interactions were recorded. The following morning the females were temporarily removed, and we monitored male search behaviour in their absence. Males that arrived first were those that had spent more time with the female the previous day relative to their rivals. Time invested the day before, in turn, was highly correlated with male search persistence and familiarity with the female's likely whereabouts. These results demonstrate that differential fertilization success can arise from information asymmetries among males: the advantaged individuals are those that have greater a priori knowledge of the reproductive state and spatial locations of prospective mates than rivals. PMID:9802243

  13. [Pleiotropic effect of the hooded mutation of the rat on male fertility].

    PubMed

    Prasolova, L A; Trut, L N; Os'kina, I N; Pliusnina, I Z

    2003-04-01

    Several reproductive parameters were studied in males homozygous (hh) or heterozygous (Hh) for the hooded mutation as compared with completely pigmented wild-type males (HH). Histological analysis of the testes was carried out in males of the three genotypes. The proportion of sterile males in homogeneous matings of homozygotes hh was twice as high as in matings of heterozygotes. The proportion of sterile males in matings yielding no progeny was also twice higher in homozygotes hh as compared with heterozygotes. No sterile males were detected in matings of completely pigmented wild-type animals. Unilateral cryptorchidism, a hypoplastic testis combined with a hyperplastic one, or hypoplasia of both testes were observed in some males homozygous for the hooded mutation. Morphologically, these defects were associated with underdevelopment or the complete absence of spermatogenic epithelium or with the presence of gaps and cells with large nondivided nuclei in the epithelium. The results showed that the hooded coat-color mutation exerts a pleiotropic effect on male fertility in rat. PMID:12760249

  14. NUCLEAR-MEDIATED MITOCHONDRIAL GENE REGULATION AND MALE FERTILITY IN HIGHER PLANTS: LIGHT AT THE END OF THE TUNNEL?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The exploitation of hybrid vigor in plants usually capitalizes on cytoplasmic male sterility (CMS), a maternally inherited trait characterized by the absence of functional pollen. Hybrids of many plants are produced using CMS, wherein a male-sterile line is grown adjacent to a selected male-fertile...

  15. Elevated expression of the Sertoli cell androgen receptor disrupts male fertility.

    PubMed

    Hazra, Rasmani; Upton, Dannielle; Desai, Reena; Noori, Omar; Jimenez, Mark; Handelsman, David J; Allan, Charles M

    2016-08-01

    Recently, we created a unique gain-of-function mouse model with Sertoli cell-specific transgenic androgen receptor expression (TgSCAR) showing that SCAR activity controls the synchronized postnatal development of somatic Sertoli and Leydig cells and meiotic-postmeiotic germ cells. Moderate TgSCAR (TgSCAR(m)) expression reduced testis size but had no effect on male fertility. Here, we reveal that higher TgSCAR expression (TgSCAR(H)) causes male infertility. Higher SCAR activity, shown by upregulated AR-dependent transcripts (Rhox5, Spinw1), resulted in smaller adult TgSCAR(H) testes (50% of normal) despite normal or elevated circulating and intratesticular testosterone levels. Unlike fertile TgSCAR(m) males, testes of adult TgSCAR(H) males exhibited focal regions of interstitial hypertrophy featuring immature adult Leydig cells and higher intratesticular dihydrotestosterone and 5α-androstane 3α,17β-diol levels that are normally associated with pubertal development. Mature TgSCAR(H) testes also exhibited markedly reduced Sertoli cell numbers (70%), although meiotic and postmeiotic germ cell/Sertoli cell ratios were twofold higher than normal, suggesting that elevated TgSCAR activity supports excessive spermatogenic development. Concurrent with the higher germ cell load of TgSCAR(H) Sertoli cells were increased levels of apoptotic germ cells in TgSCAR(H) relative to TgSCAR(m) testes. In addition, TgSCAR(H) testes displayed unique morphological degeneration that featured accumulated cellular and spermatozoa clusters in dilated channels of rete testes, consistent with reduced epididymal sperm numbers. Our findings reveal for the first time that excessive Sertoli cell AR activity in mature testes can reach a level that disturbs Sertoli/germ cell homeostasis, impacts focal Leydig cell function, reduces sperm output, and disrupts male fertility. PMID:27354237

  16. 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

  17. 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

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

    PubMed

    Qu, Cunmin; Fu, Fuyou; Liu, Miao; 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

  19. 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. PMID:27230702

  20. 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...

  1. 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

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

    PubMed

    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 COII(G177S), 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. COII(G177S) represents one of the clearest examples of a 'male-harming' mtDNA mutation in animals and suggest that the hypomorphic mtDNA mutations like COII(G177S) might specifically impair male gametogenesis. Intriguingly, some D. melanogaster nuclear genetic backgrounds can fully rescue COII(G177S) -associated sterility, consistent with previously proposed models that nuclear genomes can regulate the phenotypic manifestation of mtDNA mutations. PMID:27481326

  3. A New Role of the Mosquito Complement-like Cascade in Male Fertility in Anopheles gambiae

    PubMed Central

    Pompon, Julien; Levashina, Elena A.

    2015-01-01

    Thioester-containing protein 1 (TEP1) is a key immune factor that determines mosquito resistance to a wide range of pathogens, including malaria parasites. Here we report a new allele-specific function of TEP1 in male fertility. We demonstrate that during spermatogenesis TEP1 binds to and removes damaged cells through the same complement-like cascade that kills malaria parasites in the mosquito midgut. Further, higher fertility rates are mediated by an allele that renders the mosquito susceptible to Plasmodium. By elucidating the molecular and genetic mechanisms underlying TEP1 function in spermatogenesis, our study suggests that pleiotropic antagonism between reproduction and immunity may shape resistance of mosquito populations to malaria parasites. PMID:26394016

  4. A New Role of the Mosquito Complement-like Cascade in Male Fertility in Anopheles gambiae.

    PubMed

    Pompon, Julien; Levashina, Elena A

    2015-01-01

    Thioester-containing protein 1 (TEP1) is a key immune factor that determines mosquito resistance to a wide range of pathogens, including malaria parasites. Here we report a new allele-specific function of TEP1 in male fertility. We demonstrate that during spermatogenesis TEP1 binds to and removes damaged cells through the same complement-like cascade that kills malaria parasites in the mosquito midgut. Further, higher fertility rates are mediated by an allele that renders the mosquito susceptible to Plasmodium. By elucidating the molecular and genetic mechanisms underlying TEP1 function in spermatogenesis, our study suggests that pleiotropic antagonism between reproduction and immunity may shape resistance of mosquito populations to malaria parasites. PMID:26394016

  5. Diversifying Sunflower Germplasm by Integration and Mapping of a Novel Male Fertility Restoration Gene

    PubMed Central

    Liu, Zhao; Wang, Dexing; Feng, Jiuhuan; Seiler, Gerald J.; Cai, Xiwen; Jan, Chao-Chien

    2013-01-01

    The combination of a single cytoplasmic male-sterile (CMS) PET-1 and the corresponding fertility restoration (Rf) gene Rf1 is used for commercial hybrid sunflower (Helianthus annuus L., 2n = 34) seed production worldwide. A new CMS line 514A was recently developed with H. tuberosus cytoplasm. However, 33 maintainers and restorers for CMS PET-1 and 20 additional tester lines failed to restore the fertility of CMS 514A. Here, we report the discovery, characterization, and molecular mapping of a novel Rf gene for CMS 514A derived from an amphiploid (Amp H. angustifolius/P 21, 2n = 68). Progeny analysis of the male-fertile (MF) plants (2n = 35) suggested that this gene, designated Rf6, was located on a single alien chromosome. Genomic in situ hybridization (GISH) indicated that Rf6 was on a chromosome with a small segment translocation on the long arm in the MF progenies (2n = 34). Rf6 was mapped to linkage group (LG) 3 of the sunflower SSR map. Eight markers were identified to be linked to this gene, covering a distance of 10.8 cM. Two markers, ORS13 and ORS1114, were only 1.6 cM away from the gene. Severe segregation distortions were observed for both the fertility trait and the linked marker loci, suggesting the possibility of a low frequency of recombination or gamete selection in this region. This study discovered a new CMS/Rf gene system derived from wild species and provided significant insight into the genetic basis of this system. This will diversify the germplasm for sunflower breeding and facilitate understanding of the interaction between the cytoplasm and nuclear genes. PMID:23307903

  6. 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.

  7. The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis.

    PubMed

    Ding, Guo-Lian; Liu, Ye; Liu, Miao-E; Pan, Jie-Xue; Guo, Meng-Xi; Sheng, Jian-Zhong; Huang, He-Feng

    2015-01-01

    The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring. PMID:25814158

  8. The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis

    PubMed Central

    Ding, Guo-Lian; Liu, Ye; Liu, Miao-E; Pan, Jie-Xue; Guo, Meng-Xi; Sheng, Jian-Zhong; Huang, He-Feng

    2015-01-01

    The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring. PMID:25814158

  9. 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.

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

    PubMed

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

    2000-07-01

    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. PMID:11013879

  11. 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.

  12. Female Japanese quail (Coturnix japonica) mated with males that harassed them are unlikely to lay fertilized eggs.

    PubMed

    Persaud, Kamini N; Galef, Bennett G

    2005-11-01

    Results of previous studies of courtship and mating in Japanese quail (Coturnix japonica) suggest that females avoid conspecific males because, while courting and mating, males engage in behaviors that are potentially injurious to females. However, prior experiments provided no direct evidence that females avoided harassing males. Here the authors show that a female quail choosing between a previous sex partner and an unfamiliar male avoids the former if he engaged in relatively many potentially injurious acts while courting and mating, (Experiments 1 and 2) and that males behaving aggressively toward mates are less likely than are gentler males to fertilize the females' eggs (Experiment 3). Male sexual harassment appears to be a tactic both aversive to female quail and relatively ineffective in fertilizing them. PMID:16366777

  13. 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

  14. Argonautes promote male fertility and provide a paternal memory of germline gene expression in C. elegans

    PubMed Central

    Conine, Colin C.; Moresco, James J.; Gu, Weifeng; Shirayama, Masaki; Conte, Darryl; Yates, John R.; Mello, Craig C.

    2014-01-01

    SUMMARY During each life cycle germ cells preserve and pass on both genetic and epigenetic information. In C. elegans, the ALG-3/4 Argonaute proteins are expressed during male gametogenesis and promote male fertility. Here we show that the CSR-1 Argonaute functions with ALG-3/4 to positively regulate target genes required for spermiogenesis. Our findings suggest that ALG-3/4 functions during spermatogenesis to amplify a small-RNA signal that represents an epigenetic memory of male-specific gene expression. CSR-1, which is abundant in mature sperm, appears to transmit this memory to offspring. Surprisingly, in addition to small RNAs targeting male-specific genes, we show that males also harbor an extensive repertoire of CSR-1 small RNAs targeting oogenesis-specific mRNAs. Together these findings suggest that C. elegans sperm transmit not only the genome but also epigenetic binary signals in the form of Argonaute/small-RNA complexes that constitute a memory of gene expression in preceding generations. PMID:24360276

  15. Comparison of fertilization outcome between microdrop and open insemination methods in non-male factor IVF patients.

    PubMed

    Li, Yubin; Li, Tao; Mai, Qingyun; Long, Lingli; Ou, Jianping

    2014-06-01

    Both microdrop and open methods are commonly used for in vitro fertilization (IVF) protocols for embryo culture as well as oocyte insemination. However, few comparative studies evaluating the microdrop or open method of insemination on the fertilization outcome and subsequent embryo development have been performed. A randomized study was conducted to compare microdrop and open fertilization with respect to fertilization rate and embryo development among non-male factor patients undergoing in vitro fertilization and embryo transfer (IVF-ET). The results presented in this study demonstrate that the fertilization failure rate [total fertilization failure rate (TFF) plus low fertilization rate (<25% oocytes fertilized)] in the microdrop insemination group was higher than in the open insemination group (11.9% versus 3.3%, p < 0.001), while the good quality embryo rate and pregnancy rate did not differ significantly between the groups. As a highly complicated process involving many extrinsic and intrinsic factors, further studies are needed to confirm the effects of these insemination methods on the rate of fertilization failure. PMID:24499510

  16. Feeding programs promoting daily feed intake stability in rabbit males reduce sperm abnormalities and improve fertility.

    PubMed

    Pascual, J J; Marco-Jiménez, F; Martínez-Paredes, E; Ródenas, L; Fabre, C; Juvero, M A; Cano, J L

    2016-08-01

    males may be useful to fit their needs and provide a constant daily supply of nutrients, with some sperm morphologic characteristics being improved, as well as the fertility of their pooled semen. PMID:27040647

  17. Self-Fertilization and the Role of Males in Populations of Tadpole Shrimp (Branchiopoda: Notostraca: Triops).

    PubMed

    Horn, Rebekah L; Cowley, David E

    2016-11-01

    Self-fertilization has both negative and positive fitness effects on species evolution. Selfing can increase inbreeding depression, thereby decreasing genetic diversity. In contrast, self-fertilization can preserve beneficial gene combinations and facilitate colonization success. Within the class of crustaceans Branchiopoda, selfing is a primary reproductive mode. Some species of Triops, in the family Notostraca, are a few of the animal species thought to have a mixed mating system between hermaphrodites and males termed androdioecy. The objective of this study is to validate the reproductive mode utilized by Triops newberryi in southern New Mexico by the use of progeny arrays and population simulations. Individuals were reared in the lab from dried soil collected from temporary ponds inhabited by T. newberryi The adults reared and the encysted embryos contained within their brood pouches were genotyped using 7 T. newberryi specific microsatellite markers to determine the relatedness between parent and offspring. Overall microsatellite diversity was low with few heterozygous individuals and limited polymorphisms. Simulated populations and allele segregation analysis suggest hermaphroditism is the primary reproductive mode for T. newberryi In addition, based on the offspring's alleles, there was no direct evidence that a male (ovisacless) T. newberryi outcrossed with a female. Population simulations further suggest that the rate of successful outcrossing events must be low and could explain why outcrossing was not observed in the laboratory rearing trials. PMID:27358476

  18. Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility

    PubMed Central

    Ciraolo, Elisa; Morello, Fulvio; Hobbs, Robin M.; Wolf, Frieder; Marone, Romina; Iezzi, Manuela; Lu, Xiaoyun; Mengozzi, Giulio; Altruda, Fiorella; Sorba, Giovanni; Guan, Kaomei; Pandolfi, Pier Paolo; Wymann, Matthias P.

    2010-01-01

    Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110β develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110β-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110β is crucially needed in c-Kit–mediated spermatogonial expansion, as c-Kit–positive cells are lost in the adult testis and activation of Akt by SCF is blocked by a p110β inhibitor. These data establish that activation of the p110β PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers. PMID:20053680

  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. 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

  1. A low molecular weight proteome comparison of fertile and male sterile 8 anthers of Zea mays

    PubMed Central

    Wang, Dongxue; Adams, Christopher M.; Fernandes, John F.; Egger, Rachel L.; Walbot, Virginia

    2014-01-01

    Summary During maize anther development, somatic locular cells differentiate to support meiosis in the pollen mother cells. Meiosis is an important event during anther growth and is essential for plant fertility as pollen contains the haploid sperm. A subset of maize male sterile mutants exhibit meiotic failure, including ms8 (male sterile 8) in which meiocytes arrest as dyads and the locular somatic cells exhibit multiple defects. Systematic proteomic profiles were analysed in biological triplicates plus technical triplicates comparing ms8 anthers with fertile sibling samples at both the premeiotic and meiotic stages; proteins from 3.5 to 20 kDa were fractionated by 1-D PAGE, cleaved with Lys-C and then sequenced using a LTQ Orbitrap Velos MS paradigm. Three hundred and 59proteins were identified with two or more assigned peptides in which each of those peptides were counted at least two or more times (0.4% peptide false discovery rate (FDR) and 0.2% protein FDR); 2761 proteins were identified with one or more assigned peptides (0.4% peptide FDR and 7.6% protein FDR). Stage-specific protein expression provides candidate stage markers for early anther development, and proteins specifically expressed in fertile compared to sterile anthers provide important clues about the regulation of meiosis. 49% of the proteins detected by this study are new to an independent whole anther proteome, and many small proteins missed by automated maize genome annotation were validated; these outcomes indicate the value of focusing on low molecular weight proteins. The roles of distinctive expressed proteins and methods for mass spectrometry of low molecular weight proteins are discussed. PMID:22748129

  2. New insights into male (in)fertility: the importance of NO

    PubMed Central

    Buzadzic, B; Vucetic, M; Jankovic, A; Stancic, A; Korac, A; Korac, B; Otasevic, V

    2015-01-01

    Infertility is a global problem that is on the rise, especially during the last decade. Currently, infertility affects approximately 10–15% of the population worldwide. The frequency and origin of different forms of infertility varies. It has been shown that reactive oxygen and nitrogen species (ROS and RNS) are involved in the aetiology of infertility, especially male infertility. Various strategies have been designed to remove or decrease the production of ROS and RNS in spermatozoa, in particular during in vitro fertilization. However, in recent years it has been shown that spermatozoa naturally produce a variety of ROS/RNS, including superoxide anion radical (O2⋅−), hydrogen peroxide and NO. These reactive species, in particular NO, are essential in regulating sperm capacitation and the acrosome reaction, two processes that need to be acquired by sperm in order to achieve fertilization potential. In addition, it has recently been shown that mitochondrial function is positively correlated with human sperm fertilization potential and quality and that NO and NO precursors increase sperm motility by increasing energy production in mitochondria. We will review the new link between sperm NO-driven redox regulation and infertility herein. A special emphasis will be placed on the potential implementation of new redox-active substances that modulate the content of NO in spermatozoa to increase fertility and promote conception. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 PMID:24601995

  3. Expression of Zinc Finger Protein 105 in the Testis and its Role in Male Fertility

    PubMed Central

    Zhou, Huaxin; Liu, Lan-Hsin; Zhang, Heng; Lei, Zhenmin; Lan, Zi-Jian

    2011-01-01

    Using an in silico approach, we identified a putative zinc finger domain-containing transcription factor (zinc finger protein 105, ZFP105) that was enriched in the adult mouse testis. RT-PCR analyses showed that Zfp105 was indeed highly expressed in adult mouse testis and that its expression was regulated during postnatal development. To further characterize Zfp105 expression, we generated a Zfp105:β-galactosidase (LacZ) knock-in reporter mouse line (Zfp105LacZ/+) in which a Zfp105:LacZ fusion gene was expressed. Whole-mount LacZ analyses of adult Zfp105LacZ/+ tissues showed robust LacZ staining in the testis, very weak staining in the ovary and no staining in the spleen, liver, kidney, heart, lung, thymus, adrenal gland, uterus or oviduct. Sectional LacZ staining showed that ZFP105 was highly expressed in pachytene spermatocytes. ZNF35, the human ortholog of ZFP105, was also expressed in male germ cells of normal human testis. More importantly, reduced male fertility and sloughed spermatogenic cells were observed in adult Zfp105LacZ/LacZ mice. Taken together, our results suggest that ZFP105 is a male germ-cell factor and plays a role in male reproduction. PMID:20186958

  4. Sodium–hydrogen exchanger NHA1 and NHA2 control sperm motility and male fertility

    PubMed Central

    Chen, Su-Ren; Chen, M; Deng, S-L; Hao, X-X; Wang, X-X; Liu, Y-X

    2016-01-01

    Our previous work identified NHA1, a testis-specific sodium–hydrogen exchanger, is specifically localized on the principal piece of mouse sperm flagellum. Our subsequent study suggested that the number of newborns and fertility rate of NHA1-vaccinated female mice are significantly stepped down. In order to define the physiological function of NHA1 in spermatozoa, we generated Nha1Fx/Fx, Zp3-Cre (hereafter called Nha1 cKO) mice and found that Nha1 cKO males were viable and subfertile with reduced sperm motility. Notably, cyclic AMP (cAMP) synthesis by soluble adenylyl cyclase (sAC) was attenuated in Nha1 cKO spermatozoa and cAMP analogs restored sperm motility. Similar to Nha1 cKO males, Nha2Fx/Fx, Zp3-Cre (hereafter called Nha2 cKO) male mice were subfertile, indicating these two Nha genes may be functionally redundant. Furthermore, we demonstrated that male mice lacking Nha1 and Nha2 genes (hereafter called Nha1/2 dKO mice) were completely infertile, with severely diminished sperm motility owing to attenuated sAC-cAMP signaling. Importantly, principal piece distribution of NHA1 in spermatozoa are phylogenetically conserved in spermatogenesis. Collectively, our data revealed that NHA1 and NHA2 function as a key sodium–hydrogen exchanger responsible for sperm motility after leaving the cauda epididymidis. PMID:27010853

  5. Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive.

    PubMed

    Miyata, Haruhiko; Satouh, Yuhkoh; Mashiko, Daisuke; Muto, Masanaga; Nozawa, Kaori; Shiba, Kogiku; Fujihara, Yoshitaka; Isotani, Ayako; Inaba, Kazuo; Ikawa, Masahito

    2015-10-23

    Calcineurin inhibitors, such as cyclosporine A and FK506, are used as immunosuppressant drugs, but their adverse effects on male reproductive function remain unclear. The testis expresses somatic calcineurin and a sperm-specific isoform that contains a catalytic subunit (PPP3CC) and a regulatory subunit (PPP3R2). We demonstrate herein that male mice lacking Ppp3cc or Ppp3r2 genes (knockout mice) are infertile, with reduced sperm motility owing to an inflexible midpiece. Treatment of mice with cyclosporine A or FK506 creates phenocopies of the sperm motility and morphological defects. These defects appear within 4 to 5 days of treatment, which indicates that sperm-specific calcineurin confers midpiece flexibility during epididymal transit. Male mouse fertility recovered a week after we discontinued treatment. Because human spermatozoa contain PPP3CC and PPP3R2 as a form of calcineurin, inhibition of this sperm-specific calcineurin may lead to the development of a reversible male contraceptive that would target spermatozoa in the epididymis. PMID:26429887

  6. The Rapamycin-Sensitive Complex of Mammalian Target of Rapamycin Is Essential to Maintain Male Fertility.

    PubMed

    Schell, Christoph; Kretz, Oliver; Liang, Wei; Kiefer, Betina; Schneider, Simon; Sellung, Dominik; Bork, Tillmann; Leiber, Christian; Rüegg, Markus A; Mallidis, Con; Schlatt, Stefan; Mayerhofer, Artur; Huber, Tobias B; Grahammer, Florian

    2016-02-01

    The mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin and its analogs are being increasingly used in solid-organ transplantation. A commonly reported side effect is male subfertility to infertility, yet the precise mechanisms of mTOR interference with male fertility remain obscure. With the use of a conditional mouse genetic approach we demonstrate that deficiency of mTORC1 in the epithelial derivatives of the Wolffian duct is sufficient to cause male infertility. Analysis of spermatozoa from Raptor fl/fl*KspCre mice revealed an overall decreased motility pattern. Both epididymis and seminal vesicles displayed extensive organ regression with increasing age. Histologic and ultrastructural analyses demonstrated increased amounts of destroyed and absorbed spermatozoa in different segments of the epididymis. Mechanistically, genetic and pharmacologic mTORC1 inhibition was associated with an impaired cellular metabolism and a disturbed protein secretion of epididymal epithelial cells. Collectively, our data highlight the role of mTORC1 to preserve the function of the epididymis, ductus deferens, and the seminal vesicles. We thus reveal unexpected new insights into the frequently observed mTORC1 inhibitor side effect of male infertility in transplant recipients. PMID:26683665

  7. 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. PMID:19789214

  8. Selenium-enriched probiotics improves murine male fertility compromised by high fat diet.

    PubMed

    Ibrahim, Hala A M; Zhu, Yongxing; Wu, Cong; Lu, Chenhui; Ezekwe, Michael O; Liao, Shengfa F; Huang, Kehe; Haung, Kehe

    2012-06-01

    A total of 75 male mice were allotted to five groups of 15 each in a completely randomized experimental design to study the effects of probiotics, inorganic selenium, and selenium-enriched probiotics on male fertility in hyperlipidemic status. The mice in group 1 were fed a normal basal diet and served as negative control. The mice in group 2 were fed a high fat diet and served as positive control. The mice in groups 3, 4, and 5 were fed the high fat diet supplemented with probiotics, inorganic selenium, and selenium-enriched probiotics, respectively. The high fat diet was composed of 15% lard, 1% cholesterol, 0.3% cholic acid, and 83.7% basal diet. Over 90% of the selenium in the selenium-enriched probiotics was present in forms of organic selenium. After the mice were fed these diets for 75 days, serumal total cholesterol, triglycerides, low density lipoprotein, high density lipoprotein, and testosterone levels, plus sperm index (count, motility and abnormalities), penis length, and weight and histopathology of testes were measured. The results showed that in the mice fed the high fat diet were significant (P < 0.01) elevations of serumal total cholesterol, triglycerides and low density lipoprotein, and decreases of high density lipoprotein. The high fat diet caused a decline in serumal testosterone level, reduced semen quality, and atrophy and degeneration of seminiferous tubules. No effects on penis length or relative weight of testis were observed. Supplementation of probiotics, inorganic selenium, or selenium-enriched probiotics to the high fat diet significantly alleviated (P < 0.05) the adverse effects of hyperlipidemia by reducing testicular tissue injury, increasing serumal testosterone level, and improving sperm indexes. It was concluded that hyperlipidemia had significant adverse effects on male fertility, which could be ameliorated at various degrees by feeding the diets supplemented with probiotics, inorganic selenium, or selenium-enriched probiotics

  9. G9a-mediated histone methylation regulates cadmium-induced male fertility damage in pubertal mice.

    PubMed

    Li, Min; Liu, Chuan; Yang, Lingling; Zhang, Lei; Chen, Chunhai; He, Mindi; Lu, Yonghui; Feng, Wei; Pi, Huifeng; Zhang, Yanwen; Zhong, Min; Yu, Zhengping; Zhou, Zhou

    2016-06-11

    Increasing evidence suggests that cadmium (Cd) is associated with male fertility damage. However, the effects of histone modification on Cd-induced male fertility damage remain obscure. This study aims to evaluate the roles of histone methylation mediated by euchromatin histone methyltransferase (EHMT2/G9a) in regulating Cd-induced male fertility damage. We exposed 4-week-old male C57BL/6J mice to Cd by intraperitoneal injection at 2mg/kg for 1, 3 and 5days. Our data showed that Cd exposure decreased the numbers of impregnated females and litter sizes, which was concomitant with sperm count reduction, histological changes in the cauda epididymal ducts and seminiferous epithelium, and testicular cell apoptosis as evaluated by terminal dUTP nick-end labeling (TUNEL) assay and immunoblotting with increased levels of cleaved caspase 3, PARP and Bax and a decreased level of Bcl-2. Cd-induced male fertility damage was accompanied by enhanced G9a activity followed by increased histone H3 lysine 9 monomethylation (H3K9me1) and dimethylation (H3K9me2) in testes. Furthermore, inhibition of G9a by BIX-01294 normalized H3K9me1 and H3K9me2 to basal levels and prevented Cd-induced male fertility damage and testicular cell apoptosis. Our present study revealed that G9a-mediated histone methylation plays a critical role in Cd-induced male fertility damage and testicular cell apoptosis. PMID:27060504

  10. Self-fertilization in human: having a male embryo without a father.

    PubMed

    Irmak, M Kemal

    2010-11-01

    ovulation, estrogens increase the motility of the oviduct on the left side which results in a negative pressure in the tube and oocyte and sperms are picked-up into the tube with the help of this vacuum effect, taking both gametes to the fertilization site in the oviduct. Since the sperm contains a Y chromosome, this fertilization gives rise to a XY male embryo. PMID:20452130

  11. Fertility as a Priority among At-Risk Adolescent Males Newly Diagnosed with Cancer and Their Parents

    PubMed Central

    Klosky, James L.; Simmons, Jessica L.; Russell, Kathryn M.; Foster, Rebecca H.; Sabbatini, Gina M.; Canavera, Kristin E.; Hodges, Jason R.; Schover, Leslie R.; McDermott, Michael J.

    2014-01-01

    Purpose Infertility is a frequent consequence of cancer therapy and is often associated with psychological distress. Although adult survivors prioritize fertility and parenthood, this issue remains unexplored among adolescent males. This study examined future fertility as a priority (relative to other life goals) at time of diagnosis for at-risk adolescents and their parents. Methods Newly diagnosed adolescent males (n=96; age=13.0-21.9 years) at increased risk for infertility secondary to cancer treatment prioritized eight life goals: to have school/work success, children, friends, wealth, health, a nice home, faith, and a romantic relationship. Patients' parents (fathers, n=30; mothers, n=61) rank-ordered the same priorities for their children. Results “Having children” was ranked as a “top 3” life goal among 43.8% of adolescents, 36.7% of fathers, and 21.3% of mothers. Fertility ranked 3rd among adolescents, 4th among fathers, and 5th among mothers. Future health was ranked the top priority across groups, distinct from all other goals (ps<.001), and fertility ranked higher than home ownership and wealth for all groups (ps<.001). For adolescents, low/moderate fertility risk perception was associated with higher fertility rankings than no/high risk perceptions (p=.01). Conclusions Good health is the most important life goal among adolescents newly diagnosed with cancer and their parents. In this relatively small sample, adolescents prioritized fertility as a top goal, parents also rated fertility as being more important than home ownership and financial wealth. Health care providers should communicate fertility risk and preservation options at diagnosis and facilitate timely discussion among families, who may differ in prioritization of future fertility. PMID:25082365

  12. Effect of long-term ingestion of chromium compounds on aggression, sex behavior and fertility in adult male rat.

    PubMed

    Bataineh, H; al-Hamood, M H; Elbetieha, A; Bani Hani, I

    1997-08-01

    The effects of long-term ingestion of chromium chloride (trivalent compound) and potassium dichromate (hexavalent compound) was investigated on sexual behavior, aggressive behavior and fertility in male rats. Adult male rats were exposed to chromium chloride and potassium dichromate in drinking water at a concentration of 1000 ppm for 12 weeks. The exposure of male rats to chromium chloride and potassium dichromate reduced the number of mounts. The exposure of male rats to potassium dichromate increased the time to ejaculation. On the other hand, the exposure of male rats to chromium chloride and potassium dichromate increased the post ejaculatory interval. The number of animals ejaculating were reduced in chromium chloride and potassium dichromate exposed male rats. The exposure of male rats to chromium chloride and potassium dichromate decreased lateralizations, boxing bouts and fights with stud male. The exposure of male rats to chromium chloride and potassium dichromate had no effect on fertility. Testes, seminal vesicle and preputial gland weights were significantly reduced in chromium chloride- and potassium dichromate-exposed males. In conclusion, the long-term ingestion of chromium chloride and potassium dichromate would have adverse effects on sexual behavior and territorial aggression in adult male rat. PMID:9292274

  13. Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice

    PubMed Central

    Roqueta-Rivera, Manuel; Stroud, Chad K.; Haschek, Wanda M.; Akare, Sandeep J.; Segre, Mariangela; Brush, Richard S.; Agbaga, Martin-Paul; Anderson, Robert E.; Hess, Rex A.; Nakamura, Manabu T.

    2010-01-01

    Delta-6 desaturase-null mice (−/−) are unable to synthesize highly unsaturated fatty acids (HUFAs): arachidonic acid (AA), docosahexaenoic acid (DHA), and n6-docosapentaenoic acid (DPAn6). The −/− males exhibit infertility and arrest of spermatogenesis at late spermiogenesis. To determine which HUFA is essential for spermiogenesis, a diet supplemented with either 0.2% (w/w) AA or DHA was fed to wild-type (+/+) and −/− males at weaning until 16 weeks of age (n = 3–5). A breeding success rate of DHA-supplemented −/− was comparable to +/+. DHA-fed −/− showed normal sperm counts and spermiogenesis. Dietary AA was less effective in restoring fertility, sperm count, and spermiogenesis than DHA. Testis fatty acid analysis showed restored DHA in DHA-fed −/−, but DPAn6 remained depleted. In AA-fed −/−, AA was restored at the +/+ level, and 22:4n6, an AA elongated product, accumulated in testis. Cholesta-3,5-diene was present in testis of +/+ and DHA-fed −/−, whereas it diminished in −/− and AA-fed −/−, suggesting impaired sterol metabolism in these groups. Expression of spermiogenesis marker genes was largely normal in all groups. In conclusion, DHA was capable of restoring all observed impairment in male reproduction, whereas 22:4n6 formed from dietary AA may act as an inferior substitute for DHA. PMID:19690334

  14. 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

  15. 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. PMID:25966625

  16. 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. PMID:26205254

  17. Characterization of a Novel Thermosensitive Restorer of Fertility for Cytoplasmic Male Sterility in Maize

    PubMed Central

    Gabay-Laughnan, Susan; Kuzmin, Evgeny V.; Monroe, Jessica; Roark, Leah; Newton, Kathleen J.

    2009-01-01

    S-type cytoplasmic male sterility (CMS-S) in maize is associated with high levels of a 1.6-kb RNA in mitochondria. This RNA contains two chimeric open reading frames (ORFs), orf355 and orf77. The previously described nuclear restorer-of-fertility allele Rf3 causes the processing of all transcripts that contain these chimeric ORFs. The Lancaster Surecrop-derived inbred line A619 carries a restorer that is distinct from Rf3 in that it selectively reduces only the CMS-S-specific 1.6-kb RNA. We have found that 10 additional Lancaster lines carry a single restoring allele traceable to either of two inbred lines, C103 and Oh40B. The C103 and Oh40B restorers are allelic to each other, but not to Rf3. Thus, this restoring allele, designated Rf9, represents a second naturally occurring CMS-S restorer in maize. Rf9 is a less effective restorer of fertility than is Rf3; its expression is influenced by both inbred nuclear background and temperature. Rf9 acts to reduce the amounts of orf355/orf77-containing linear mitochondrial subgenomes, which are generated by recombination of circular subgenomes with CMS-S-specific linear plasmids. The 1.6-kb RNA, which is transcribed only from linear ends, is correspondingly reduced. PMID:19255365

  18. [Animal experimental studies on the effects of noise stress on male fertility].

    PubMed

    Günther, E

    1976-01-01

    Psychic stress is able to cause male infertility. Stieve found out aspermatogenesis in executed men. Cockett et al. immobilized 5 Macaca-Monkeys 15 to 40 days in capsule module under simulated space flight conditions and detected severe testicular degeneration. Carosi and Calabro reported about workers exposed to industrial noise over a period of years; the number of offspring was found to be much lower than in non exposed families. We examined the effect of noise on the fertility of 21 male guinea pigs. Sounding of 110 dB lasted 3-5 hours daily over a period of 22-31 days. Histological examination of the testicular tissue did not show any disorder of spermatogenesis. We believe that the negative result is attributed to failings in the test arrangement. Sounding only lasted for a maximum of 31 days. However, the duration of spermatogenesis in guinea pigs is about 40 days. Moreover the sounding maximum was only 5 hours per day, yet the time of recovery took 4-5 times longer every day. Consequently the daily short-term depression of the neuroendrocrinium affected the gonadotropine secretion in similarity to the daily biorhythmic variation. Therefore the expected inhibition of fertility by the neuroendrocrinic way could not be demonstrated. Our experiments also revealed another problem. In noise-exposed guinea pigs there was 8.2 per cent tubuli contorti without complete spermatogenesis. Moreover, in the control group even 9.9 per cent of the tubuli was found to be sperm-free. It is not clear why such a contrary reaction occurred. However, it is possible that hormonal stimulation increased temporarily as a result of noise stress. It should be noted that this effect has also been reported by Arguellis. PMID:962176

  19. When to ask male adolescents to provide semen sample for fertility preservation?

    PubMed Central

    Dabaja, Ali A.; Wosnitzer, Matthew S.; Bolyakov, Alexander; Schlegel, Peter N.

    2014-01-01

    Background Fertility preservation in adolescents undergoing sterilizing radiation and/or chemotherapy is the standard of care in oncology. The opportunity for patients to provide a semen sample by ejaculation is a critical issue in adolescent fertility preservation. Methods Fifty males with no medical or sexual developmental abnormalities were evaluated. The subjects were screened for evidence of orgasmic, erectile, and ejaculatory dysfunction. A detailed sexual development history was obtained under an Institutional Review Board (IRB)-approved protocol. Results Fifty males, aged 18-65 years (mean 39±16.03 years) volunteered to be part of this study. The mean reported age for the onset of puberty was 12.39 years (95% CI, 11.99-12.80 years), 13.59 years (95% CI, 13.05-14.12 years) for the first ejaculation, 12.56 years (95% CI, 11.80-13.32 years) for the start of masturbation, and 17.26 years (95% CI, 16.18-18.33 years) for the first experienced intercourse. Seventy-five percent of the cohort reached puberty by the age of 13.33, experienced masturbation by 14.5, first ejaculated by the age of 14.83, and had intercourse at age of 19.15 years. The first experienced ejaculation fell 1.5 years after the onset of puberty in 80% present of the cohort, and 84% starts masturbation 1.5 years after the onset of puberty. The mean response between the younger and the older subject was not statistical significance. Conclusions It is appropriate to consider a request for semen specimens by masturbation from teenagers at one year and six months after the onset of puberty; the onset age of puberty plus 1.5 years is an important predictor of ejaculation and sample collection for cryopreservation. PMID:26813354

  20. Expression of zinc finger protein 105 in the testis and its role in male fertility.

    PubMed

    Zhou, Huaxin; Liu, Lan-Hsin; Zhang, Heng; Lei, Zhenmin; Lan, Zi-Jian

    2010-06-01

    Using an in silico approach, we identified a putative zinc finger domain-containing transcription factor (zinc finger protein 105, ZFP105) enriched in the adult mouse testis. RT-PCR analyses showed that Zfp105 was indeed highly expressed in adult mouse testis and that its expression was regulated during postnatal development. To further characterize Zfp105 expression, we generated a Zfp105:beta-galactosidase (LacZ) knock-in reporter mouse line (Zfp105(LacZ/+)) in which a Zfp105:LacZ fusion gene was expressed. Whole-mount LacZ analyses of adult Zfp105(LacZ/+) tissues showed robust LacZ staining in the testis, very weak staining in the ovary, and no staining in the spleen, liver, kidney, heart, lung, thymus, adrenal gland, uterus, or oviduct. Sectional LacZ staining showed that ZFP105 was highly expressed in pachytene spermatocytes. ZNF35, the human ortholog of Zfp105, was also highly expressed in human testis. Immunofluorescence analysis showed that ZNF35 was located primarily in the cytoplasm of male germ cells. More importantly, reduced male fertility was observed in adult Zfp105(LacZ/LacZ) mice. Histological studies showed the presence of undifferentiated spermatogenic cells in the lumen of seminiferous tubules at stage VII and in the epididymal lumen of adult Zfp105(LacZ/LacZ) mice. Taken together, our results suggest that ZFP105 is a male germ-cell factor and plays a role in male reproduction. PMID:20186958

  1. The SCF/c-KIT system in the male: Survival strategies in fertility and cancer.

    PubMed

    Cardoso, Henrique J; Figueira, Marília I; Correia, Sara; Vaz, Cátia V; Socorro, Sílvia

    2014-12-01

    Maintaining the delicate balance between cell survival and death is of the utmost importance for the proper development of germ cells and subsequent fertility. On the other hand, the fine regulation of tissue homeostasis by mechanisms that control cell fate is a factor that can prevent carcinogenesis. c-KIT is a type III receptor tyrosine kinase activated by its ligand, stem cell factor (SCF). c-KIT signaling plays a crucial role in cell fate decisions, specifically controlling cell proliferation, differentiation, survival, and apoptosis. Indeed, deregulating the SCF/c-KIT system by attenuation or overactivation of its signaling strength is linked to male infertility and cancer, and rebalancing its activity via c-KIT inhibitors has proven beneficial in treating human tumors that contain gain-of-function mutations or overexpress c-KIT. This review addresses the roles of SCF and c-KIT in the male reproductive tract, and discusses the potential application of c-KIT target therapies in disorders of the reproductive system. PMID:25359157

  2. The Forkhead Transcription Factor, FOXP3: A Critical Role in Male Fertility in Mice1

    PubMed Central

    Jasurda, Jake S.; Jung, Deborah O.; Froeter, Erin D.; Schwartz, David B.; Hopkins, Torin D.; Farris, Corrie L.; McGee, Stacey; Narayan, Prema; Ellsworth, Buffy S.

    2013-01-01

    ABSTRACT Fertility is dependent on the hypothalamic-pituitary-gonadal axis. Each component of this axis is essential for normal reproductive function. Mice with a mutation in the forkhead transcription factor gene, Foxp3, exhibit autoimmunity and infertility. We have previously shown that Foxp3 mutant mice have significantly reduced expression of pituitary gonadotropins. To address the role of Foxp3 in gonadal function, we examined the gonadal phenotype of these mice. Foxp3 mutant mice have significantly reduced seminal vesicle and testis weights compared with Foxp3+/Y littermates. Spermatogenesis in Foxp3 mutant males is arrested prior to spermatid elongation. Activation of luteinizing hormone signaling in Foxp3 mutant mice by treatment with human chorionic gonadotropin significantly increases seminal vesicle and testis weights as well as testicular testosterone content and seminiferous tubule diameter. Interestingly, human chorionic gonadotropin treatments rescue spermatogenesis in Foxp3 mutant males, suggesting that their gonadal phenotype is due primarily to a loss of pituitary gonadotropin stimulation rather than an intrinsic gonadal defect. PMID:24258212

  3. TAp73 is required for spermatogenesis and the maintenance of male fertility

    PubMed Central

    Inoue, Satoshi; Tomasini, Richard; Rufini, Alessandro; Elia, Andrew J.; Agostini, Massimiliano; Amelio, Ivano; Cescon, Dave; Dinsdale, David; Zhou, Lily; Harris, Isaac S.; Lac, Sophie; Silvester, Jennifer; Li, Wanda Y.; Sasaki, Masato; Haight, Jillian; Brüstle, Anne; Wakeham, Andrew; Mckerlie, Colin; Jurisicova, Andrea; Melino, Gerry; Mak, Tak W.

    2014-01-01

    The generation of viable sperm proceeds through a series of coordinated steps, including germ cell self-renewal, meiotic recombination, and terminal differentiation into functional spermatozoa. The p53 family of transcription factors, including p53, p63, and p73, are critical for many physiological processes, including female fertility, but little is known about their functions in spermatogenesis. Here, we report that deficiency of the TAp73 isoform, but not p53 or ΔNp73, results in male infertility because of severe impairment of spermatogenesis. Mice lacking TAp73 exhibited increased DNA damage and cell death in spermatogonia, disorganized apical ectoplasmic specialization, malformed spermatids, and marked hyperspermia. We demonstrated that TAp73 regulates the mRNA levels of crucial genes involved in germ stem/progenitor cells (CDKN2B), spermatid maturation/spermiogenesis (metalloproteinase and serine proteinase inhibitors), and steroidogenesis (CYP21A2 and progesterone receptor). These alterations of testicular histology and gene expression patterns were specific to TAp73 null mice and not features of mice lacking p53. Our work provides previously unidentified in vivo evidence that TAp73 has a unique role in spermatogenesis that ensures the maintenance of mitotic cells and normal spermiogenesis. These results may have implications for the diagnosis and management of human male infertility. PMID:24449892

  4. 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

  5. Isolation and molecular tagging of Rf4, a new male fertility restoration gene from wild sunflower Helianthus maximiliani L.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In sunflower, CMS PET1 and the associated fertility restoration gene Rf1 is the only source extensively used in commercial hybrid production. The search for new cytoplasmic male sterility (CMS) and restorer sources to broaden the genetic diversity is needed to insure efficient hybrid seed production...

  6. EXTENSIN18 is required for full male fertility as well as normal vegetative growth in Arabidopsis.

    PubMed

    Choudhary, Pratibha; Saha, Prasenjit; Ray, Tui; Tang, Yuhong; Yang, David; Cannon, Maura C

    2015-01-01

    EXTENSINS (EXTs) are a 65-member subfamily of hydroxyproline-rich glycoproteins (HRGPs) of which 20 putatively form crosslinking networks in the cell wall. These 20 classical EXTs are involved at the start of new wall assembly as evidenced by a requirement for EXT3 during cytokinesis, and the ability of some EXTs to polymerize in vitro into dendritic patterns. EXT3 was previously shown to form pulcherosine (three Tyrosines) cross-links. Little direct data exists on the other 19 classical EXTs. Here, we describe the phenotypes of ext18 mutants and rescued progeny as well as associated expression profiles of all 20 classical EXT genes. We found that EXT18 is required for full male fertility, as well as for normal vegetative growth. EXT18 has potential to form crosslinking networks via di-iso-di-tyrosine (four Tyrosines) covalent bonds, and not via pulcherosine due to deficit of lone Tyrosines. This together with ext18 defective pollen grains and pollen tubes, and reduced plant size, suggests that EXT18-type EXTs are important contributors to wall integrity, in pollen and other rapidly extending walls. The data also show that a knockout of EXT18 had a pleiotropic affect on the expression of several EXTs, as did the reintroduction of the native EXT18 gene, thus supporting the thesis that transcription of groups of EXTs are co-regulated and work in different combinations to make distinctive inputs into wall assembly of different cell types. These insights contribute to basic knowledge of cell wall self-assembly in different cell types, and potentially enable biotechnological advances in biomass increase and plant fertility control. PMID:26257758

  7. EXTENSIN18 is required for full male fertility as well as normal vegetative growth in Arabidopsis

    PubMed Central

    Choudhary, Pratibha; Saha, Prasenjit; Ray, Tui; Tang, Yuhong; Yang, David; Cannon, Maura C.

    2015-01-01

    EXTENSINS (EXTs) are a 65-member subfamily of hydroxyproline-rich glycoproteins (HRGPs) of which 20 putatively form crosslinking networks in the cell wall. These 20 classical EXTs are involved at the start of new wall assembly as evidenced by a requirement for EXT3 during cytokinesis, and the ability of some EXTs to polymerize in vitro into dendritic patterns. EXT3 was previously shown to form pulcherosine (three Tyrosines) cross-links. Little direct data exists on the other 19 classical EXTs. Here, we describe the phenotypes of ext18 mutants and rescued progeny as well as associated expression profiles of all 20 classical EXT genes. We found that EXT18 is required for full male fertility, as well as for normal vegetative growth. EXT18 has potential to form crosslinking networks via di-iso-di-tyrosine (four Tyrosines) covalent bonds, and not via pulcherosine due to deficit of lone Tyrosines. This together with ext18 defective pollen grains and pollen tubes, and reduced plant size, suggests that EXT18-type EXTs are important contributors to wall integrity, in pollen and other rapidly extending walls. The data also show that a knockout of EXT18 had a pleiotropic affect on the expression of several EXTs, as did the reintroduction of the native EXT18 gene, thus supporting the thesis that transcription of groups of EXTs are co-regulated and work in different combinations to make distinctive inputs into wall assembly of different cell types. These insights contribute to basic knowledge of cell wall self-assembly in different cell types, and potentially enable biotechnological advances in biomass increase and plant fertility control. PMID:26257758

  8. 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

  9. 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. PMID:26582516

  10. Adult male mice conceived by in vitro fertilization exhibit increased glucocorticoid receptor expression in fat tissue.

    PubMed

    Simbulan, R K; Liu, X; Feuer, S K; Maltepe, E; Donjacour, A; Rinaudo, P

    2016-02-01

    Prenatal development is highly plastic and readily influenced by the environment. Adverse conditions have been shown to alter organ development and predispose offspring to chronic diseases, including diabetes and hypertension. Notably, it appears that the changes in glucocorticoid hormones or glucocorticoid receptor (GR) levels in peripheral tissues could play a role in the development of chronic diseases. We have previously demonstrated that in vitro fertilization (IVF) and preimplantation embryo culture is associated with growth alterations and glucose intolerance in mice. However, it is unknown if GR signaling is affected in adult IVF offspring. Here we show that GR expression is increased in inbred (C57Bl6/J) and outbred (CF-1× B6D2F1/J) blastocysts following in vitro culture and elevated levels are also present in the adipose tissue of adult male mice. Importantly, genes involved in lipolysis and triglyceride synthesis and responsive to GR were also increased in adipose tissue, indicating that increased GR activates downstream gene pathways. The promoter region of GR, previously reported to be epigenetically modified by perinatal manipulation, showed no changes in DNA methylation status. Our findings demonstrate that IVF results in a long-term change in GR gene expression in a sex- and tissue-specific manner. These changes in adipose tissues may well contribute to the metabolic phenotype in mice conceived by IVF. PMID:26511158

  11. 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.

  12. Male sexual ornament size is positively associated with reproductive morphology and enhanced fertility in the stalk-eyed fly Teleopsis dalmanni

    PubMed Central

    2008-01-01

    Background Exaggerated male ornaments and displays often evolve in species where males only provide females with ejaculates during reproduction. Although "good genes" arguments are typically invoked to explain this phenomenon, a simpler alternative is possible if variation in male reproductive quality (e.g. sperm number, ejaculate content, mating rate) is an important determinant of female reproductive success. The "phenotype-linked fertility hypothesis" states that female preference for male ornaments or displays has been selected to ensure higher levels of fertility and has driven the evolution of exaggerated male traits. Females of the stalk-eyed fly Teleopsis dalmanni must mate frequently to maintain high levels of fertility and prefer to mate with males exhibiting large eyespan, a condition-dependent sexual ornament. If eyespan indicates male reproductive quality, females could directly increase their reproductive success by mating with males with large eyespan. Here we investigate whether male eyespan indicates accessory gland and testis length, and then ask whether mating with large eyespan males affects female fertility. Results Male eyespan was a better predictor of two key male reproductive traits – accessory gland and testis length – than was body size alone. This positive relationship held true over three levels of increasing environmental stress during the maturation of the adult accessory glands and testes. Furthermore, females housed with a large eyespan male exhibited higher levels of fertility than those with small eyespan males. Conclusion Male eyespan in stalk-eyed flies is subject to strong directional mate preference and is a reliable indicator of male reproductive quality – both because males with larger eyespan have bigger accessory glands and testes, and also as they confer higher fertility on females. Fertility enhancement may have arisen because males with larger eyespan mated more often and/or because they transferred more sperm or

  13. Experimentally controlled downregulation of the histone chaperone FACT in Plasmodium berghei reveals that it is critical to male gamete fertility

    PubMed Central

    Laurentino, Eliane C; Taylor, Sonya; Mair, Gunnar R; Lasonder, Edwin; Bartfai, Richard; Stunnenberg, Hendrik G; Kroeze, Hans; Ramesar, Jai; Franke-Fayard, Blandine; Khan, Shahid M; Janse, Chris J; Waters, Andrew P

    2011-01-01

    Human FACT (facilitates chromatin transcription) consists of the proteins SPT16 and SSRP1 and acts as a histone chaperone in the (dis)assembly of nucleosome (and thereby chromatin) structure during transcription and DNA replication. We identified a Plasmodium berghei protein, termed FACT-L, with homology to the SPT16 subunit of FACT. Epitope tagging of FACT-L showed nuclear localization with high expression in the nuclei of (activated) male gametocytes. The gene encoding FACT-L could not be deleted indicating an essential role during blood-stage development. Using a ‘promoter-swap’ approach whereby the fact-l promoter was replaced by an ‘asexual blood stage-specific’ promoter that is silent in gametocytes, transcription of fact-l in promoter-swap mutant gametocytes was downregulated compared with wild-type gametocytes. These mutant male gametocytes showed delayed DNA replication and gamete formation. Male gamete fertility was strongly reduced while female gamete fertility was unaffected; residual ookinetes generated oocysts that arrested early in development and failed to enter sporogony. Therefore FACT is critically involved in the formation of fertile male gametes and parasite transmission. ‘Promoter swapping’ is a powerful approach for the functional analysis of proteins in gametocytes (and beyond) that are essential during asexual blood-stage development. PMID:21899698

  14. Sexual maturation and fertility of male and female mice exposed prenatally and postnatally to trivalent and hexavalent chromium compounds.

    PubMed

    Al-Hamood, M H; Elbetieha, A; Bataineh, H

    1998-01-01

    The reproductive toxicity of trivalent and hexavalent chromium compounds was investigated in male and female mice exposed to 1000 ppm chromium chloride and potassium dichromate via their mother during gestational and lactational periods. Fertility was reduced in male offspring exposed to either trivalent or hexavalent chromium compounds. Body weights and weights of testes, seminal vesicles and preputial glands were reduced in trivalent-exposed male offspring. The exposure of female mice offspring to trivalent and hexavalent chromium compounds delayed sexual maturation. Fertility was reduced in female offspring exposed to either trivalent or hexavalent chromium compounds. The exposure of female mice to hexavalent chromium compound reduced the number of implantations and viable fetuses respectively. Body weight and weights of ovaries and uteri were reduced in trivalent-exposed female offspring. The results indicate that under our experimental conditions, the exposure of male and female mice offspring to either trivalent or hexavalent chromium compounds during gestational and lactational periods impair reproductive functions and fertility in adulthood. PMID:9801270

  15. Are old males still good males and can females tell the difference? Do hidden advantages of mating with old males off-set costs related to fertility, or are we missing something else?

    PubMed

    Johnson, Sheri L; Gemmell, Neil J

    2012-07-01

    Sperm function generally declines with male age. Paradoxically, females of many species still choose to mate with old males rather than young males. Females choosing old mates may suffer reduced fertilization rates and an increased incidence of birth defects in offspring, lowering fitness which may in turn lead to conflict between the sexes. This apparent paradox has generated much interest from theorists, but whether this paradox presents in nature remains equivocal. Empirical studies have found mixed support for both a decline in fertility with male age and age-based female mate preference. Here, we examine recent evidence for this paradox, identify confounding variables, highlight areas that deserve further investigation, and suggest avenues for future research. PMID:22581618

  16. Effects of X-Ray Irradiation on Male Navel Orangeworm Moths (Lepidoptera: Pyralidae) on Mating, Fecundity, Fertility, and Inherited Sterility.

    PubMed

    Light, Douglas M; Ovchinnikova, Inna; Jackson, Eric S; Haff, Ronald P

    2015-10-01

    Male adult navel orangeworm, Amyelois transitella (Walker), were irradiated using a laboratory scale x-ray irradiation unit to determine the required dose for complete egg sterility of mated female moths and inherited sterility of F1 and F2 generations. Adult male A. transitella were irradiated in two separate experiments at 100-300 Gy and 50-175 Gy. Mating frequency, fecundity, and fertility of normal females crossed with irradiated parental males was compared with the mating of nonirradiated moths. Mating frequency was 100% for females crossed with nonirradiated control males. At male treatment doses of ≥150 Gy the percentage of females found unmated increased, while multiple-mated females decreased. Female fecundity was not affected while fertility was affected in a dose-dependent relationship to exposure of parental males to x-ray irradiation. Embryonic development of eggs to the prehatch stage and egg eclosion did not occur at radiation doses ≥125 Gy. Emergence of F1 adults was low and occurred only for progeny of parental males exposed to doses ≤100 Gy, with no emergence at ≥125 Gy. Though fecundity appeared similar for control and irradiated F1 females, no F2 eggs hatched for the test exposures of 50-100 Gy. Based on our results, a dose of ≥125 Gy had efficacy in inducing both primary parental sterility in treated male moths and inherited sterility in F1 male and female moths. Results suggest that A. transitella might be considered a candidate for the sterile insect technique using adults irradiated at these relatively low x-ray exposure doses. PMID:26453709

  17. Male and female experiences of having fertility matters raised alongside a cancer diagnosis during the teenage and young adult years.

    PubMed

    Crawshaw, M A; Glaser, A W; Hale, J P; Sloper, P

    2009-07-01

    Discussion and management of potential reproductive health sequelae of adolescent cancer are essential and challenging components of care for the multidisciplinary team. Despite this, research has been limited to specific experiences (e.g. sperm banking) or fertility-related concerns of adult survivors. This grounded theory study of 38 male and female survivors of adolescent cancer aged 16-30 years drew on in-depth single interviews to map the range of experiences of being advised that treatment might affect fertility. Strong support for being told at around diagnosis was found regardless of gender, age, incapacity or availability of fertility preservation services. Age and life stage appeared less significant for impact than the perceived level of threat to personal and social well-being. Women were more likely to achieve lower levels of comprehension about the physiological impact, to report later distress from lack of fertility preservation services and to revisit more frequently those decisions made by the few offered fertility preservation. Men found decision making about sperm banking straightforward on the whole and reported satisfaction with having the choice regardless of outcome. Findings suggest that young people can cope with this information alongside diagnosis especially when professional and parental support is proportionate to the particular impact on them. PMID:19594609

  18. Restoration of spermatogenesis and male fertility using an androgen receptor transgene.

    PubMed

    Walker, William H; Easton, Evan; Moreci, Rebecca S; Toocheck, Corey; Anamthathmakula, Prashanth; Jeyasuria, Pancharatnam

    2015-01-01

    Androgens signal through the androgen receptor (AR) to regulate male secondary sexual characteristics, reproductive tract development, prostate function, sperm production, bone and muscle mass as well as body hair growth among other functions. We developed a transgenic mouse model in which endogenous AR expression was replaced by a functionally modified AR transgene. A bacterial artificial chromosome (BAC) was constructed containing all AR exons and introns plus 40 kb each of 5' and 3' regulatory sequence. Insertion of an internal ribosome entry site and the EGFP gene 3' to AR allowed co-expression of AR and EGFP. Pronuclear injection of the BAC resulted in six founder mice that displayed EGFP production in appropriate AR expressing tissues. The six founder mice were mated into a Sertoli cell specific AR knockout (SCARKO) background in which spermatogenesis is blocked at the meiosis stage of germ cell development. The AR-EGFP transgene was expressed in a cyclical manner similar to that of endogenous AR in Sertoli cells and fertility was restored as offspring were produced in the absence of Sertoli cell AR. Thus, the AR-EGFP transgene under the control of AR regulatory elements is capable of rescuing AR function in a cell selective, AR-null background. These initial studies provide proof of principle that a strategy employing the AR-EGFP transgene can be used to understand AR functions. Transgenic mice expressing selective modifications of the AR-EGFP transgene may provide crucial information needed to elicit the molecular mechanisms by which AR acts in the testis and other androgen responsive tissues. PMID:25803277

  19. 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

  20. Familiarity affects the assessment of female facial signals of fertility by free-ranging male rhesus macaques

    PubMed Central

    Higham, James P.; Hughes, Kelly D.; Brent, Lauren J. N.; Dubuc, Constance; Engelhardt, Antje; Heistermann, Michael; Maestriperi, Dario; Santos, Laurie R.; Stevens, Martin

    2011-01-01

    Animals signal their reproductive status in a range of sensory modalities. Highly social animals, such as primates, have access not only to such signals, but also to prior experience of other group members. Whether this experience affects how animals interpret reproductive signals is unknown. Here, we explore whether familiarity with a specific female affects a male's ability to assess that female's reproductive signals. We used a preferential looking procedure to assess signal discrimination in free-ranging rhesus macaques, a species in which female facial luminance covaries with reproductive status. We collected images of female faces throughout the reproductive cycle, and using faecal hormone analysis to determine ovulation, categorized images as coming from a female's pre-fertile, ovulating, or post-fertile period. We printed colour-calibrated stimuli of these faces, reproducing stimuli perceptually the same in colour and luminance to the original appearance of females. These images were presented to males who were either unfamiliar or familiar with stimuli females. Overall, males distinguished ovulatory from pre-ovulatory faces. However, a significant proportion of males did so only among males familiar with stimuli females. These experiments demonstrate that familiarity may increase a receiver's ability to use a social partner's signals to discern their reproductive status. PMID:21471112

  1. Gendered Divisions of Fertility Work: Socioeconomic Predictors of Female versus Male Sterilization

    ERIC Educational Resources Information Center

    Bertotti, Andrea M.

    2013-01-01

    Domestic labor researchers have examined a multitude of duties disproportionately performed by women, yet the responsibility associated with navigating a couple's fertility--fertility work--has been overlooked. Using data from the 2006-2010 National Survey of Family Growth ("N" = 1,415), the author examined how racial and socioeconomic factors…

  2. 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

  3. RAN-Binding Protein 9 is Involved in Alternative Splicing and is Critical for Male Germ Cell Development and Male Fertility

    PubMed Central

    Bao, Jianqiang; Tang, Chong; Li, Jiachen; Zhang, Ying; Bhetwal, Bhupal P.; Zheng, Huili; Yan, Wei

    2014-01-01

    As a member of the large Ran-binding protein family, Ran-binding protein 9 (RANBP9) has been suggested to play a critical role in diverse cellular functions in somatic cell lineages in vitro, and this is further supported by the neonatal lethality phenotype in Ranbp9 global knockout mice. However, the exact molecular actions of RANBP9 remain largely unknown. By inactivation of Ranbp9 specifically in testicular somatic and spermatogenic cells, we discovered that Ranbp9 was dispensable for Sertoli cell development and functions, but critical for male germ cell development and male fertility. RIP-Seq and proteomic analyses revealed that RANBP9 was associated with multiple key splicing factors and directly targeted >2,300 mRNAs in spermatocytes and round spermatids. Many of the RANBP9 target and non-target mRNAs either displayed aberrant splicing patterns or were dysregulated in the absence of Ranbp9. Our data uncovered a novel role of Ranbp9 in regulating alternative splicing in spermatogenic cells, which is critical for normal spermatogenesis and male fertility. PMID:25474150

  4. 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). PMID:24814801

  5. 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

  6. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice.

    PubMed

    Miyata, Haruhiko; Castaneda, Julio M; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M

    2016-07-12

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201-12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract-enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the "gold standard" to determine whether a gene's function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  7. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice

    PubMed Central

    Miyata, Haruhiko; Castaneda, Julio M.; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R.; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L.; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M.; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M.

    2016-01-01

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201–12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract–enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the “gold standard” to determine whether a gene’s function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  8. 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 ...

  9. Case Series of Fertility Treatment in HIV-Discordant Couples (Male Positive, Female Negative): The Ontario Experience

    PubMed Central

    Newmeyer, Trent; Tecimer, Sandy N.; Jaworsky, Denise; Chihrin, Steven; Gough, Kevin; Rachlis, Anita; Martin, James; Mohammed, Saira; Loutfy, Mona R.

    2011-01-01

    The success of combination antiretroviral therapies for the treatment of human immunodeficiency virus (HIV) has resulted in prolonged life expectancy (over 40 years from diagnosis) and an improved quality of life for people living with HIV. The risk of vertical HIV transmission during pregnancy has been reduced to less than 1%. As a result of these breakthroughs and as many of these individuals are of reproductive age, fertility issues are becoming increasingly important for this population. One population in which conception planning and reduction of horizontal HIV transmission warrants further research is HIV-discordant couples where the male partner is HIV-positive and the female partner is HIV-negative. Sperm washing is a technique carried out in a fertility clinic that separates HIV from the seminal fluid. Although sperm washing followed by intrauterine insemination significantly reduces the risk of horizontal HIV transmission, there has been limited access to the procedure in North America. Furthermore, little is known about the conception decision-making experiences of HIV-discordant couples who might benefit from sperm washing. Chart reviews and semi-structured interviews were completed with 12 HIV-discordant couples in Ontario, Canada. Couples were recruited through HIV clinics and one fertility clinic that offered sperm washing. Participants identified a number of factors that affected their decision-making around pregnancy planning. Access to sperm washing and other fertility services was an issue (cost, travel and few clinics). Participants identified a lack of information on the procedure (availability, safety). Sources of support (social networks, healthcare providers) were unevenly distributed, especially among those who did not disclose their HIV status to friends and family. Finally, the stigmatisation of HIV continues to have a negative affect on HIV-discordant couples and their intentions to conceive. Access to sperm washing and fertility service

  10. Case series of fertility treatment in HIV-discordant couples (male positive, female negative): the Ontario experience.

    PubMed

    Newmeyer, Trent; Tecimer, Sandy N; Jaworsky, Denise; Chihrin, Steven; Gough, Kevin; Rachlis, Anita; Martin, James; Mohammed, Saira; Loutfy, Mona R

    2011-01-01

    The success of combination antiretroviral therapies for the treatment of human immunodeficiency virus (HIV) has resulted in prolonged life expectancy (over 40 years from diagnosis) and an improved quality of life for people living with HIV. The risk of vertical HIV transmission during pregnancy has been reduced to less than 1%. As a result of these breakthroughs and as many of these individuals are of reproductive age, fertility issues are becoming increasingly important for this population. One population in which conception planning and reduction of horizontal HIV transmission warrants further research is HIV-discordant couples where the male partner is HIV-positive and the female partner is HIV-negative. Sperm washing is a technique carried out in a fertility clinic that separates HIV from the seminal fluid. Although sperm washing followed by intrauterine insemination significantly reduces the risk of horizontal HIV transmission, there has been limited access to the procedure in North America. Furthermore, little is known about the conception decision-making experiences of HIV-discordant couples who might benefit from sperm washing. Chart reviews and semi-structured interviews were completed with 12 HIV-discordant couples in Ontario, Canada. Couples were recruited through HIV clinics and one fertility clinic that offered sperm washing. Participants identified a number of factors that affected their decision-making around pregnancy planning. Access to sperm washing and other fertility services was an issue (cost, travel and few clinics). Participants identified a lack of information on the procedure (availability, safety). Sources of support (social networks, healthcare providers) were unevenly distributed, especially among those who did not disclose their HIV status to friends and family. Finally, the stigmatisation of HIV continues to have a negative affect on HIV-discordant couples and their intentions to conceive. Access to sperm washing and fertility service

  11. 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.

  12. Consequences of hyperthyroidism in male and female fertility: pathophysiology and current management.

    PubMed

    Mintziori, G; Kita, M; Duntas, L; Goulis, D G

    2016-08-01

    Thyroid hormone acts on the oocytes, sperm and embryo during fertilization, implantation and placentation. Both hypothyroidism and hyperthyroidism may influence fertility. However, evidence of the association of hyperthyroidism with infertility is scarce and sometimes conflicting. Thyroid hormone influences human reproduction via a variety of mechanisms at both the central and the peripheral level. Infertility may occur in hyperthyroid men and women, but it is usually reversible upon restoration of euthyroidism. This review aims to summarize the available data on the association of hyperthyroidism and infertility in both men and women and to provide practical suggestions for the management of these patients. PMID:26956000

  13. EndPoints 2000

    Energy Science and Technology Software Center (ESTSC)

    2009-08-13

    The application leads the user through a logical framework to determine the minimum effort and cost necessary to reach the desired end state for each space, system, and facility. Endpoints are used to plan the project work, track and manage the determination, management, verification, and closure of D&D endpoints, consistent with DOE End Point guidance documents.

  14. 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.

  15. 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...

  16. 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...

  17. Seed-Set Evaluation of Four Male-Sterile, Female-Fertile Soyban Lines Using Alfalfa Leaf-Cutter Bees and Honey Bees as Pollinators

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Male-sterile, female-fertile plants have been used to produce hybrid soybean seed. Manual cross-pollination using male-sterile plants to produce large quantities of hybrid seed is difficult and time-consuming, because of the low success rate in cross-pollination. Insect pllinators may be suitable ...

  18. A null mutation in the first enzyme of flavonoid biosynthesis does not affect male fertility in Arabidopsis.

    PubMed Central

    Burbulis, I E; Iacobucci, M; Shirley, B W

    1996-01-01

    Flavonoids are a major class of secondary metabolites that serves a multitude of functions in higher plants, including a recently discovered role in male fertility. Surprisingly, Arabidopsis plants deficient in flavonoid biosynthesis appear to be fully fertile. Using RNA gel blot analysis and polymerase chain reaction-based assays, we have shown that a mutation at the 3' splice acceptor site in the Arabidopsis chalcone synthase gene completely disrupts synthesis of the active form of the enzyme. We also confirmed that this enzyme, which catalyzes the first step of flavonoid biosynthesis, is encoded by a single-copy gene. HPLC analysis of whole flowers and stamens was used to show that plants homozygous for the splice site mutation are completely devoid of flavonoids. This work provides compelling evidence that despite the high levels of these compounds in the pollen of most plant species, flavonoids are not universally required for fertility. The role of flavonoids in plant reproduction may therefore offer an example of convergent functional evolution in secondary metabolism. PMID:8672888

  19. 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. PMID:25351529

  20. Adaptive Regulation of Testis Gene Expression and Control of Male Fertility by the Drosophila Harpin RNA Pathway

    PubMed Central

    Wen, Jiayu; Duan, Hong; Bejarano, Fernando; Okamura, Katsutomo; Fabian, Lacramioara; Brill, Julie A.; Bortolamiol-Becet, Diane; Martin, Raquel; Ruby, J. Graham; Lai, Eric C.

    2014-01-01

    SUMMARY Although endogenous siRNAs (endo-siRNAs) have been described in many species, still little is known about their endogenous utility. Here, we show that Drosophila hairpin RNAs (hpRNAs) generate an endo-siRNA class with predominant expression in testes. Although hpRNAs are universally recently evolved, we identify highly complementary protein-coding targets for all hpRNAs. Importantly, we find broad evidence for evolutionary divergences that preferentially maintain compensatory pairing between hpRNAs and targets, serving as first evidence for adaptive selection for siRNA-mediated target regulation in metazoans. We demonstrate organismal impact of hpRNA activity, since knockout of hpRNA1 derepresses its target ATP synthase-β in testes and compromises spermatogenesis and male fertility. Moreover, we reveal surprising male-specific impact of RNAi factors on germ cell development and fertility, consistent with testis-directed function of the hpRNA pathway. Finally, the collected hpRNA loci chronicle an evolutionary timeline that reflects their origins from prospective target genes, mirroring a strategy described for plant miRNAs. PMID:25544562

  1. Fertility of male and female mice heterozygous for the reciprocal translocation T(7;17)3BKM.

    PubMed

    Koleva, M; Benova, D

    1992-01-01

    The present paper describes the fertility of male and female mice heterozygous for the reciprocal translocation T(7;17)3BKM. This translocation was induced by gamma rays in the spermatozoa of an irradiated parent. It is characterized by "asymmetrical" localization of the breakpoints, distally in Chromosome 7 (7F5) and proximally in Chromosome 17 (17B1). The data presented here relate only those matings in which, for both partners, heterozygosity or normality could be confirmed cytogenetically. The results indicate that both male and female translocation heterozygotes are fertile, their mean litter size being reduced to about 50% of that of normal littermates. This leads to the conclusion that the multivalents mainly undergo either alternate or adjacent-1 2:2 segregation. No viable tertiary trisomics were observed among the progeny of the translocation carriers. Analysis of the frequency of the different types of multivalents in diakinesis-metaphase I spermatocytes showed a significant predominance of chain-type figures (CIV and CIII+I), with chains of four elements (CIV) being more frequent than other configurations. This demonstrates that the small marker chromosome remains attached by one of its segments to the tetravalent. PMID:1486808

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

    PubMed

    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

  3. 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

  4. Linkage analysis between the partial restoration (pr) and the restorer-of-fertility (Rf) loci in pepper cytoplasmic male sterility.

    PubMed

    Lee, Jundae; Yoon, Jae Bok; Park, Hyo Guen

    2008-08-01

    Cytoplasmic male sterility (CMS) in chili pepper is restored by one major dominant nuclear gene, restorer-of-fertility (Rf), together with some modifier genes and is also affected by temperature. As a result, male fertility was identified as having several phenotypes. That identified and used in the present study allowed partial restoration of fertility, producing plants that simultaneously produce normal and aborted pollen grains, with most grains stuck to the anther wall, even after dehiscence, resulting in low seed set per fruit. The trait was visible only in the presence of Paterson's sterile cytoplasm and was controlled by a recessive nuclear gene, partial restoration (pr). A CAPS marker, PR-CAPS, closely linked to the trait, has been developed by Lee et al. (2008). In this study, linkage analysis was performed in 205 F(2) individuals derived from the 'Buja' Korean commercial F(1) chili pepper variety using the PR-CAPS marker and the three Rf-linked markers (OPP13-CAPS, AFRF8-CAPS, and CRF-SCAR) previously reported. Consequently, we found that these four markers were tightly linked. This result means that the pr gene might be tightly linked to the Rf locus or the third allele of Rf locus. The sequence diversity of the pr- and Rf-linked markers was also analyzed. The internal sequences of OPP13-CAPS (1,180 bp) and PR-CAPS (640 bp) markers in 91 Korean inbred lines were clearly divided into three haplotypes. According to the sequencing results, a new PR-CAPS (MseI or SphI digestion) marker was designed to distinguish the three haplotypes. This marker will be useful for marker-assisted selection to develop new maintainers and restorers in commercial hybrid pepper breeding using CMS. PMID:18465115

  5. Effect of gibberellic acid on the quality of sperm and in vitro fertilization outcome in adult male rats.

    PubMed

    Hosseinchi, Mohammadreza; Soltanalinejad, Farhad; Najafi, Gholamreza; Roshangar, Leila

    2013-01-01

    Gibberellic acid (GA3) is a group of plant hormones identified in various plants. The aim of this study was to determine the effects of GA3 on sperm parameters and in vitro fertilization (IVF). Fifty six adult male rats were divided into seven groups as, control, treatment and sham. Following 15, 30 and 45 days of GA3 and methanol alcohol (MA) administration, rats were euthanized and epididymis tail was transferred to human tubular fluid (HTF) medium containing 4 mg mL(-1) bovine serum albumin (BSA) .Total number of sperms, the percentage of live sperms, immature sperms and sperms with damaged chromatin and IVF were examined. The oocytes were obtained from immature rats after the injection of pregnant mare's serum (PMSG) and human chorionic gonadotropin (HCG) hormones. Human tubular fluid was used as the fertilization medium and zygotes transferred to fresh 1-cell rat embryos culture medium (mR1ECM) to reach the blastocyst stage. This study showed that GA3 could decrease the number of total sperms on days 30 and 45 in treated group comparison with the control and sham groups. Additionally, GA3 increased the immature sperms and sperms with damaged chromatin. The percentage of fertilization, two-cell embryos and blastocyst resulting from the treatment group on days 30 and 45 also decreased and showed significant differences with the control and sham groups (p < 0.05). The results obtained from this study indicated that the oral use of GA3 could reduce the fertility in rats by influencing the sperm number and the quality of sperm's chromatins. PMID:25568681

  6. Effect of gibberellic acid on the quality of sperm and in vitro fertilization outcome in adult male rats

    PubMed Central

    Hosseinchi, Mohammadreza; Soltanalinejad, Farhad; Najafi, Gholamreza; Roshangar, Leila

    2013-01-01

    Gibberellic acid (GA3) is a group of plant hormones identified in various plants. The aim of this study was to determine the effects of GA3 on sperm parameters and in vitro fertilization (IVF). Fifty six adult male rats were divided into seven groups as, control, treatment and sham. Following 15, 30 and 45 days of GA3 and methanol alcohol (MA) administration, rats were euthanized and epididymis tail was transferred to human tubular fluid (HTF) medium containing 4 mg mL-1 bovine serum albumin (BSA) .Total number of sperms, the percentage of live sperms, immature sperms and sperms with damaged chromatin and IVF were examined. The oocytes were obtained from immature rats after the injection of pregnant mare's serum (PMSG) and human chorionic gonadotropin (HCG) hormones. Human tubular fluid was used as the fertilization medium and zygotes transferred to fresh 1-cell rat embryos culture medium (mR1ECM) to reach the blastocyst stage. This study showed that GA3 could decrease the number of total sperms on days 30 and 45 in treated group comparison with the control and sham groups. Additionally, GA3 increased the immature sperms and sperms with damaged chromatin. The percentage of fertilization, two-cell embryos and blastocyst resulting from the treatment group on days 30 and 45 also decreased and showed significant differences with the control and sham groups (p < 0.05). The results obtained from this study indicated that the oral use of GA3 could reduce the fertility in rats by influencing the sperm number and the quality of sperm’s chromatins. PMID:25568681

  7. Transgenic male-sterile plant induced by an unedited atp9 gene is restored to fertility by inhibiting its expression with antisense RNA.

    PubMed Central

    Zabaleta, E; Mouras, A; Hernould, M; Suharsono; Araya, A

    1996-01-01

    We have previously shown that the expression of an unedited atp9 chimeric gene correlated with male-sterile phenotype in transgenic tobacco plant. To study the relationship between the expression of chimeric gene and the male-sterile trait, hemizygous and homozygous transgenic tobacco lines expressing the antisense atp9 RNA were constructed. The antisense producing plants were crossed with a homozygous male-sterile line, and the F1 progeny was analyzed. The offspring from crosses between homozygous lines produced only male-fertile plants, suggesting that the expression antisense atp9 RNA abolishes the effect of the unedited chimeric gene. In fact, the plants restored to male fertility showed a dramatic reduction of the unedited atp9 transcript levels, resulting in normal flower development and seed production. These results support our previous observation that the expression of unedited atp9 gene can induce male sterility. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8855343

  8. Epididymal protein Rnase10 is required for post-testicular sperm maturation and male fertility.

    PubMed

    Krutskikh, Anton; Poliandri, Ariel; Cabrera-Sharp, Victoria; Dacheux, Jean Louis; Poutanen, Matti; Huhtaniemi, Ilpo

    2012-10-01

    Eutherian spermatozoa are dependent on the environment of the proximal epididymis to complete their maturation; however, no specific epididymal factors that mediate this process have so far been identified. Here, we show that targeted disruption of the novel gene Rnase10 encoding a secreted proximal epididymal protein in the mouse results in a binding defect in spermatozoa and their inability to pass through the uterotubal junction in the female. The failure to gain the site of fertilization in the knockout spermatozoa is associated with a gradual loss of ADAM3 and ADAM6 proteins during epididymal transit. In the distal epididymis, these spermatozoa appear to lack calcium-dependent associations with the immobilizing glutinous extracellular material and are released as single, vigorously motile cells that display no tendency for head-to-head agglutination and lack affinity to the oviductal epithelium. In sperm-egg binding assay, they are unable to establish a tenacious association with the zona pellucida, yet they are capable of fertilization. Furthermore, these sperm show accelerated capacitation resulting in an overall in vitro fertilizing ability superior to that of wild-type sperm. We conclude that the physiological role of sperm adhesiveness is in the mechanism of restricted sperm entry into the oviduct rather than in sperm-egg interaction. PMID:22750516

  9. 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. PMID:26001873

  10. Evaluation of possible toxic effects of spearmint (Mentha spicata) on the reproductive system, fertility and number of offspring in adult male rats

    PubMed Central

    Nozhat, Fatemeh; Alaee, Sanaz; Behzadi, Khodabakhsh; Azadi Chegini, Najmeh

    2014-01-01

    Objective: In this study we investigated the effects of spearmint (Mentha spicata Labiatae) on the reproductive system, fertility and number of offspring in adult male rats. Materials and Methods: Adult Wistar male rats in one control (C) and three experimental groups (I, II and III) received 0, 10, 20 and 40 mg/kg spearmint extract orally for 45 days, respectively. Following this treatment, the animals’ weights, and the standard weight of reproductive tissues, sperm count, sperm motility and serum testosterone concentration were measured, and reproductive tissues were examined histopathologically. To evaluate the effects of spearmint on fertility of male rats and growth of their offspring, male rats of the control and experimental groups mated with untreated female rats. Results: Results showed that spearmint did not affect the rats’ body and reproductive tissue weights. The sperm count, fast and slow progressive motility of sperm and serum testosterone concentration decreased while number of non-progressive sperm and immotile sperm increased in the experimental groups compared to the control group, but none of these changes were statistically significant. Histopathological studies showed no severe changes in reproductive tissues between control and experimental groups. Number and growth of offspring born from mating of male rats with untreated female rats showed no difference. Conclusion: We concluded that spearmint has no significant toxic effect on the reproductive system, fertility and number of offspring in adult male rats at the above mentioned dose levels. However high levels of this extract may have adverse effects on male fertility. PMID:25386406

  11. 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...

  12. Lack of sexual experience does not reduce the responses of LH, estrus or fertility in anestrous goats exposed to sexually active males.

    PubMed

    Fernández, Ilda G; Luna-Orozco, Juan Ramón; Vielma, Jesús; Duarte, Gerardo; Hernández, Horacio; Flores, José Alfredo; Gelez, Hélène; Delgadillo, José Alberto

    2011-11-01

    We investigated whether LH secretion, estrous behavior and fertility would differ between sexually inexperienced and experienced anestrous goats exposed to the males. Male goats were rendered sexually active during the reproductive rest season by exposure to 2.5 months of artificial long days. Two groups of anovulatory sexually inexperienced and sexually experienced does were exposed to males during 15 days (n = 20 per group). LH pulsatility was determined every 15 min from 4h before to 8h after introducing males (Day 0). Estrous behavior was recorded twice daily. Pregnancy rates were determined on Day 50. Fertility was determined at parturition. Male sexual behavior was registered on days 1 and 2 during 1h. Before introducing the males, the number of LH pulses did not differ between groups. After introduction of the males, all females increased their LH pulsatility, but the number of pulses did not differ between sexually inexperienced and experienced goats. The proportion of females displaying estrous behavior with a high pregnancy rate and fertility did not differ between inexperienced and experienced goats. The sexual behavior of the males did not differ significantly between those interacting with sexually inexperienced or experienced goats. We conclude that goats can show substantial endocrine and reproductive responses to males, even in the absence of previous sexual experience, when sexually active bucks are used. PMID:21821035

  13. Assessment of aggression, sexual behavior and fertility in adult male rat following long-term ingestion of four industrial metals salts.

    PubMed

    Bataineh, H; Al-Hamood, M H; Elbetieha, A M

    1998-10-01

    1. The effect of long-term ingestion of the industrial metals salts, manganese sulfate, aluminum chloride, lead acetate and copper chloride was investigated on aggression, sexual behavior and fertility in male rat. Adult male rats ingested solutions of these salts along with drinking water at a concentration of 1000 p.p.m. for 12 weeks. 2. Male rat sexual behavior was suppressed after the ingestion of manganese sulfate, aluminum chloride, lead acetate and copper chloride. The ingestion of solutions of these salts markedly prolonged the intromission and ejaculation latencies. Aluminum chloride and copper chloride reduced the copulatory efficiency. 3. Male rat aggression was also abolished after the ingestion of manganese sulfate, aluminum chloride, lead acetate and copper chloride. The ingestion of solutions of these salts markedly suppressed lateralizations, boxing bouts, fight with stud male and ventral presenting postures. 4. Fertility was reduced in male rats ingested with lead acetate. The total number of resorptions was increased in female rats impregnated by males ingested with manganese sulfate and lead acetate. 5. Body, absolute or relative testes, seminal vesicles weights were dropped in adult male rats ingested with manganese sulfate, aluminum chloride, lead acetate and copper chloride. However, the absolute or relative preputial gland weights were not affected. Collectively, these results suggest that the long-term ingestion of manganese sulfate, aluminum chloride, lead acetate and copper chloride would have adverse effects on sexual behavior, territorial aggression, fertility and the reproductive system of the adult male rat. PMID:9821021

  14. 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

  15. 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. PMID:26939127

  16. The capability of reprogramming the male chromatin after fertilization is dependent on the quality of oocyte maturation.

    PubMed

    Gioia, Luisa; Barboni, Barbara; Turriani, Maura; Capacchietti, Giulia; Pistilli, Maria Gabriella; Berardinelli, Paolo; Mattioli, Mauro

    2005-07-01

    The present experiments compared the ability of pig oocytes matured either in vivo or in vitro to structurally reorganize the penetrated sperm chromatin into male pronucleus (PN) and to carry out, in parallel, the epigenetic processes of global chromatin methylation and acetylation, 12-14 h after in vitro fertilization (IVF). In addition, PN distribution of histone deacetylase (HDAC), a major enzyme interfacing DNA methylation and histone acetylation, was investigated. The ability of the oocyte to operate an efficient block to polyspermy was markedly affected by maturation. The monospermic fertilization rate was significantly higher for in vivo than for in vitro matured (IVM) oocytes (P < 0.01) which, furthermore, showed a reduced ability to transform the chromatin of penetrated sperm into male PN (P < 0.01). Indirect immunofluorescence analysis of global DNA methylation, histone acetylation and HDAC distribution (HDAC-1, -2 and -3), carried out in monospermic zygotes that reached the late PN stage, showed that IVM oocytes also had a reduced epigenetic competence. In fact, while in about 80% of in vivo matured and IVF oocytes the male PN underwent a process of active demethylation and showed a condition of histone H4 hyperacetylation, only 40% of IVM/IVF zygotes displayed a similar PN remodelling asymmetry. Oocytes that carried out the first part of maturation in vivo (up to germinal vesicle breakdown; GVBD) and then completed the process in vitro, displayed the same PN asymmetry as oocytes matured entirely in vivo. A crucial role of HDAC in the establishment of PN acetylation asymmetry seems to be confirmed by the use of HDAC inhibitors as well as by the abnormal distribution of the enzyme between the two PN in IVM zygotes. Collectively, these data demonstrated that some pig IVM oocytes fail to acquire full remodelling competence which is independent from their ooplasmic ability to morphologically reorganize the sperm nucleus into PN. PMID:15985629

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

    PubMed Central

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

    2013-01-01

    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 oestrogens-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. PMID:22449655

  18. Negative biomarker-based male fertility evaluation: sperm phenotypes associated with molecular-level anomalies

    PubMed Central

    Sutovsky, Peter; Aarabi, Mahmoud; Miranda-Vizuete, Antonio; Oko, Richard

    2015-01-01

    Biomarker-based sperm analysis elevates the treatment of human infertility and ameliorates reproductive performance in livestock. The negative biomarker-based approach focuses on proteins and ligands unique to defective spermatozoa, regardless of their morphological phenotype, lending itself to analysis by flow cytometry (FC). A prime example is the spermatid specific thioredoxin SPTRX3/TXNDC8, retained in the nuclear vacuoles and superfluous cytoplasm of defective human spermatozoa. Infertile couples with high semen SPTRX3 are less likely to conceive by assisted reproductive therapies (ART) and more prone to recurrent miscarriage while low SPTRX3 has been associated with multiple ART births. Ubiquitin, a small, proteolysis-promoting covalent posttranslational protein modifier is found on the surface of defective posttesticular spermatozoa and in the damaged protein aggregates, the aggresomes of spermiogenic origin. Semen ubiquitin content correlates negatively with fertility and conventional semen parameters, and with sperm binding of lectins LCA (Lens culinaris agglutinin; reveals altered sperm surface) and PNA (Arachis hypogaea/peanut agglutinin; reveals acrosomal malformation or damage). The Postacrosomal Sheath WWI Domain Binding Protein (PAWP), implicated in oocyte activation during fertilization, is ectopic or absent from defective human and animal spermatozoa. Consequently, FC-parameters of PAWP correlate with ART outcomes in infertile couples and with fertility in bulls. Assays based on the above biomarkers have been combined into multiplex FC semen screening protocols, and the surface expression of lectins and ubiquitin has been utilized to develop nanoparticle-based bull semen purification method validated by field artificial insemination trials. These advances go hand-in-hand with the innovation of FC-technology and genomics/proteomics-based biomarker discovery. PMID:25999356

  19. 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

  20. The importance of the one carbon cycle nutritional support in human male fertility: a preliminary clinical report

    PubMed Central

    2014-01-01

    Background Sperm chromatin structure is often impaired; mainly due to oxidative damage. Antioxidant treatments do not consistently produce fertility improvements and, when given at high doses, they might block essential oxidative processes such as chromatin compaction. This study was intended to assess the effect on male sub-fertility of a pure one carbon cycle nutritional support without strong antioxidants. Methods Male partners of couples resistant to at least 2 assisted reproductive technology (ART) attempts, with no evidence of organic causes of infertility and with either DNA fragmentation index (DFI) measured by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) or nuclear decondensation index (SDI) measured by aniline blue staining exceeding 20%, were invited to take part in a trial of a nutritional support in preparation for a further ART attempt. The treatment consisted of a combination of B vitamins, zinc, a proprietary opuntia fig extract and small amounts of N-acetyl-cysteine and Vitamin E (Condensyl™), all effectors of the one carbon cycle. Results 84 patients were enrolled, they took 1 or 2 Condensyl™ tablets per day for 2 to 12 months. Positive response rates were 64.3% for SDI, 71.4% for DFI and 47.6% for both SDI and DFI. Eighteen couples (21%) experienced a spontaneous pregnancy before the planned ART cycle, all ended with a live birth. The remaining 66 couples underwent a new ART attempt (4 IUI; 18 IVF; 44 ICSI) resulting in 22 further clinical pregnancies and 15 live births. The clinical pregnancy rate (CPR) and the live birth rate (LBR) were 47.6% and 39.3% respectively. The full responders, i.e. the 40 patients achieving an improvement of both SDI and DFI, reported a CPR of 70% and a LBR of 57.5% (p < 0.001). Conclusions Nutritional support of the one carbon cycle without strong antioxidants improves both the SDI and the DFI in ART resistant male partners and results in high pregnancy rates suggesting a positive

  1. The Male Sterility Locus ms3 is Present in a Fertility Controlling Gene Cluster in Soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean [Glycine max (L.) Merr.] is a self-pollinated plant. Manual cross-pollination is used to produce limited quantities of hybrid seed. To produce large quantities of hybrid seed, insect-mediated cross-pollination is necessary. An efficient nuclear male-sterile system for hybrid seed producti...

  2. 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...

  3. 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...

  4. 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.

  5. 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. PMID:24433209

  6. 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

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

    PubMed

    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

  8. Ehd4 is required to attain normal pre-pubertal testis size but dispensable for fertility in male mice

    PubMed Central

    George, Manju; Rainey, Mark A.; Naramura, Mayumi; Ying, GuoGuang; Harms, Don W.; Vitaterna, Martha H.; Doglio, Lynn; Crawford, Susan E.; Hess, Rex A.; Band, Vimla; Band, Hamid

    2010-01-01

    The four highly homologous members of the C-terminal EH domain-containing (EHD) protein family (EHD1-4) regulates endocytic recycling. To delineate the role of EHD4 in normal physiology and development, mice with a conditional knockout of the Ehd4 gene were generated. PCR of genomic DNA and Western blotting of organ lysates from Ehd4−/− mice confirmed EHD4 deletion. Ehd4−/− mice were viable and born at expected Mendelian ratios; however, males showed a 50% reduction in testis weight, obvious from postnatal day 31. An early (day 10) increase in germ cell proliferation and apoptosis and a later increase in apoptosis (day 31) were seen in the Ehd4−/− testis. Other defects included a progressive reduction in seminiferous tubule diameter, dysregulation of seminiferous epithelium and head abnormalities in elongated spermatids. As a consequence, lower sperm counts and reduced fertility were observed in Ehd4−/− males. Interestingly, EHD protein expression was seen to be temporally regulated in the testis and levels peaked between days 10 and 15. In the adult testis, EHD4 was highly expressed in primary spermatocytes and EHD4 deletion altered the levels of other EHD proteins in an age-dependent manner. We conclude that high levels of EHD1in the adult Ehd4−/− testis functionally compensate for lack of EHD4 and prevents the development of severe fertility defects. Our results suggest a role for EHD4 in the proper development of post-mitotic and post-meiotic germ cells and implicate EHD protein-mediated endocytic recycling as an important process in germ cell development and testis function. PMID:20213691

  9. Understanding the Role of Heat Shock Protein Isoforms in Male Fertility, Aging and Apoptosis

    PubMed Central

    Purandhar, Kaveri; Jena, Prasant Kumar; Prajapati, Bhumika; Rajput, Parth

    2014-01-01

    Heat shock proteins (HSPs) play a role in the homeostasis, apoptosis regulation and the maintenance of the various other physiological processes. Aging is accompanied by a decrease in the resistance to environmental stress, while mitochondria are primary targets in the process of aging, their expression decreasing with age. Mitochondrion also plays a significant role in the process of spermatogenesis. HSPs have been shown to be involved in apoptosis with some of acting as apoptotic inhibitors and are involved in cytoprotection. In this review we discuss the roles of Hsp 27, 60, 70, and 90 in aging and male infertility and have concluded that these particular HSPs can be used as a molecular markers for mitochondrially- mediated apoptosis, aging and male infertility. PMID:25606560

  10. Basic concepts and recent advancements in the study of male fertility

    PubMed Central

    Kovac, Jason R; Lipshultz, Larry I

    2016-01-01

    Many controversial topics regarding Andrology in general, and male infertility more specifically have been discussed and debated for decades. Numerous manuscripts and entire journals have been dedicated to the dissemination of standardized information with multiple reviews covering similar topics. This massive amount of data leads to difficulty identifying pertinent clinical practice guidelines. Furthermore, detailed instructions on how to manage common clinical conditions tend to be diluted by copious amounts of text and superfluous information. PMID:27048783

  11. LRGUK-1 Is Required for Basal Body and Manchette Function during Spermatogenesis and Male Fertility

    PubMed Central

    Liu, Yan; DeBoer, Kathleen; de Kretser, David M.; O’Donnell, Liza; O’Connor, Anne E.; Merriner, D. Jo; Okuda, Hidenobu; Whittle, Belinda; Jans, David A.; Efthymiadis, Athina; McLachlan, Robert I.; Ormandy, Christopher J.; Goodnow, Chris C.; Jamsai, Duangporn; O’Bryan, Moira K.

    2015-01-01

    Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT). For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line. PMID:25781171

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

    PubMed

    Schneider, Jutta M; Lesmono, Kristiani

    2009-09-01

    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. PMID:19515667

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

    PubMed Central

    Schneider, Jutta M.; Lesmono, Kristiani

    2009-01-01

    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. PMID:19515667

  14. 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

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

    PubMed

    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

  16. 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

  17. [Study of male mating behavior in some Drosophila melanogaster strains in experiments with fertilized females].

    PubMed

    Subocheva, E A; Romanova, N I; Kim, A I

    2004-07-01

    Male courtship ritual is among the main behavioral characteristics of Drosophila. This is a complex, genetically determined process consisting of four general stages: orientation, vibration, licking, and attempts at copulation (or successful copulation). Several genes are known that control some stages of this behavior. Most of them have pleiotropic effects and are involved in other biological processes. Earlier, we have shown that a mutation in locus flamenco (20A1-3), which controls transposition and infectivity of retrotransposon gypsy (MDG4), is involved in the genetic control of behavior. In strains mutant for this locus, the male mating activity is decreased and the structure of courtship ritual is changed. To understand the mechanisms of these changes, it is important to study all behavioral stages in genetically identical strains. For this purpose, the normal allele of gene flamenco from the X chromosome of the wild-type strain (stock) Canton S was introduced into strain SS carrying flamMS. This offers new opportunities in studying the role of gene flamenco in the control of mating behavior in Drosophila. PMID:15458200

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

    PubMed

    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

  19. Sox8 is a critical regulator of adult Sertoli cell function and male fertility.

    PubMed

    O'Bryan, Moira K; Takada, Shuji; Kennedy, Claire L; Scott, Greg; Harada, Shun-ichi; Ray, Manas K; Dai, Qunsheng; Wilhelm, Dagmar; de Kretser, David M; Eddy, E Mitch; Koopman, Peter; Mishina, Yuji

    2008-04-15

    Sox8 encodes a high-mobility group transcription factor that is widely expressed during development. Sox8, -9 and -10 form group E of the Sox gene family which has been implicated in several human developmental disorders. In contrast to other SoxE genes, the role of Sox8 is unclear and Sox8 mouse mutants reportedly showed only idiopathic weight loss and reduced bone density. The careful analysis of our Sox8 null mice, however, revealed a progressive male infertility phenotype. Sox8 null males only sporadically produced litters of reduced size at young ages. We have shown that SOX8 protein is a product of adult Sertoli cells and its elimination results in an age-dependent deregulation of spermatogenesis, characterized by sloughing of spermatocytes and round spermatids, spermiation failure and a progressive disorganization of the spermatogenic cycle, which resulted in the inappropriate placement and juxtaposition of germ cell types within the epithelium. Those sperm that did enter the epididymides displayed abnormal motility. These data show that SOX8 is a critical regulator of adult Sertoli cell function and is required for both its cytoarchitectural and paracrine interactions with germ cells. PMID:18342849

  20. Epidermal jasmonate perception is sufficient for all aspects of jasmonate-mediated male fertility in Arabidopsis.

    PubMed

    Jewell, Jeremy B; Browse, John

    2016-03-01

    Jasmonate (JA) signaling is essential for several environmental responses and reproductive development in many plant species. In Arabidopsis thaliana, the most obvious phenotype of JA biosynthetic and perception mutants is profound sporophytic male sterility characterized by failure of stamen filament elongation, severe delay of anther dehiscence and pollen inviability. The site of action of JA in the context of reproductive development has been discussed, but the ideas have not been tested experimentally. To this end we used targeted expression of a COI1-YFP transgene in the coi1-1 mutant background. As COI1 is an essential component of the JA co-receptor complex, the null coi1-1 mutant is male sterile due to lack of JA perception. We show that expression of COI1-YFP in the epidermis of the stamen filament and anther in coi1 mutant plants is sufficient to rescue filament elongation, anther dehiscence and pollen viability. In contrast, filament expression alone or expression in the tapetum do not restore dehiscence and pollen viability. These results demonstrate that epidermal JA perception is sufficient for anther function and pollen viability, and suggest the presence of a JA-dependent non-autonomous signal produced in the anther epidermis to synchronize both anther dehiscence and pollen maturation. PMID:26833563

  1. Regulation of male fertility by the bone-derived hormone osteocalcin

    PubMed Central

    KARSENTY, Gerard; OURY, Franck

    2013-01-01

    Traditionally, bone has been viewed as a relatively static tissue only fulfilling mechanical and scaffolding function. In the past decade however, this classical view of the bone has considerably evolved towards a more complex picture. It is now clear that the skeleton is not only a recipient for hormonal input but it is also an endocrine organ itself. Through the secretion of an osteoblast-derived molecule, osteocalcin, the skeleton regulates glucose homeostasis and male reproductive functions. When undercarboxylated, osteocalcin acts following its binding to a G-coupled receptor, GPRC6A, on pancreatic β cells to increase insulin secretion, on muscle and white adipose tissue to promote glucose homeostasis and on Leydig cells of the testis to favor testosterone biosynthesis. More recently, it was also shown that osteocalcin acts via a pancreas-bone-testis axis that regulates, independently of and in parallel to the hypothalamus-pituitary-testis axis, male reproductive functions by promoting testosterone biosynthesis. Lastly, in trying to expand the biological relevance of osteocalcin from mouse to human, it was shown that GPRC6A is a potential new susceptibility locus for primary testicular failure in humans. Altogether, these results shed new light on the importance of the endocrine role of the skeleton and also provide credence to the search for additional endocrine functions of this organ. PMID:24145129

  2. Sperm mobility: mechanisms of fertilizing efficiency, genetic variation and phenotypic relationship with male status in the domestic fowl, Gallus gallus domesticus.

    PubMed Central

    Froman, David P; Pizzari, Tommaso; Feltmann, Allen J; Castillo-Juarez, Hector; Birkhead, Tim R

    2002-01-01

    When females are sexually promiscuous, sexual selection continues after insemination through sperm competition and cryptic female choice, and male traits conveying an advantage in competitive fertilization are selected for. Although individual male and ejaculate traits are known to influence paternity in a competitive scenario, multiple mechanisms co-occur and interact to determine paternity. The way in which different traits interact with each other and the mechanisms through which their heritability is maintained despite selection remain unresolved. In the promiscuous fowl, paternity is determined by the number of sperm inseminated into a female, which is mediated by male social dominance, and by the quality of the sperm inseminated, measured as sperm mobility. Here we show that: (i) the number of sperm inseminated determines how many sperm reach the female sperm-storage sites, and that sperm mobility mediates the fertilizing efficiency of inseminated sperm, mainly by determining the rate at which sperm are released from the female storage sites, (ii) like social status, sperm mobility is heritable, and (iii) subdominant males are significantly more likely to have higher sperm mobility than dominant males. This study indicates that although the functions of social status and sperm mobility are highly interdependent, the lack of phenotypic integration of these traits may maintain the variability of male fitness and heritability of fertilizing efficiency. PMID:11916477

  3. 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

  4. Critical Roles of Vacuolar Invertase in Floral Organ Development and Male and Female Fertilities Are Revealed through Characterization of GhVIN1-RNAi Cotton Plants.

    PubMed

    Wang, Lu; Ruan, Yong-Ling

    2016-05-01

    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

  5. 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

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

    PubMed Central

    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. PMID:25316062

  7. The endocannabinoid system: an ancient signaling involved in the control of male fertility.

    PubMed

    Fasano, Silvia; Meccariello, Rosaria; Cobellis, Gilda; Chianese, Rosanna; Cacciola, Giovanna; Chioccarelli, Teresa; Pierantoni, Riccardo

    2009-04-01

    The effects of cannabinoids on human health have been known since the antiquities when the extract of the plant Cannabis sativa was used because of its psychoactivity. The scientific story of the cannabinoids started in the 1960s with the isolation and characterization of the active component of the plant. After the synthesis of cannabinoid analogues, the analysis of structure-effect relationships was implemented, and this had a similar effect to a positive "Pandora's box" opening. To date, numerous roles have been ascribed to the "endocannabinoid system." Here we describe its involvement in the control of male reproduction, taking into consideration possible evolutionary speculations. Indeed, the endocannabinoid system is a very ancient signaling system, being clearly present from the divergence of the protostomian/deuterostomian. PMID:19456333

  8. 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

  9. Melatonin alters the glycolytic profile of Sertoli cells: implications for male fertility.

    PubMed

    Rocha, Cátia S; Martins, Ana D; Rato, Luís; Silva, Branca M; Oliveira, Pedro F; Alves, Marco G

    2014-11-01

    Melatonin co-operates with insulin in the regulation of glucose homeostasis. Within the testis, glucose metabolism in the somatic Sertoli cells (SCs) is pivotal for spermatogenesis. Since the effects of melatonin on male reproductive physiology remain largely unknown, we hypothesized that melatonin may affect spermatogenesis by modulating SC metabolism, interacting with insulin. To test our hypothesis, rat SCs were maintained in culture for 24 h in the presence of insulin, melatonin or both and metabolite production/consumption was determined by proton nuclear magnetic resonance ((1)H-NMR). Protein levels of glucose transporters (GLUT1 and GLUT3), phosphofructokinase 1, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 were determined by western blot. LDH activity was also assessed. SCs treated with melatonin showed an increase in glucose consumption via modulation of GLUT1 levels, but decreased LDH protein expression and activity, which resulted in lower lactate production. Moreover, SCs exposed to melatonin produced and accumulated less acetate than insulin-exposed cells. The combined treatment (insulin plus melatonin) increased acetate production by SCs, but intracellular acetate content remained lower than in insulin exposed cells. Finally, the intracellular redox state, as reflected by intracellular lactate/alanine ratio, was maintained at control levels in SCs by melatonin exposure (i.e. melatonin, alone or with insulin, increased the lactate/alanine ratio versus cells treated with insulin). Furthermore, SCs exposed to insulin plus melatonin produced more lactate and maintained the protein levels of some glycolysis-related enzymes and transporters at control levels. These findings illustrate that melatonin regulates SCs metabolism, and thus may affect spermatogenesis. Since lactate produced by SCs provides nutritional support and has an anti-apoptotic effect in developing germ cells, melatonin supplementation may be an effective therapy for

  10. 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

  11. Observations as to male fertility in the Flemish environment and health studies.

    PubMed

    Dhooge, W; Stuyvaert, S; Kaufman, J M; Koppe, G; Nele, V; Schoeters, G; van Larebeke, N; Comhaire, F

    2001-01-01

    We report the observations made on 101 healthy non-smoking men aged 21-40 (50 from two industrial suburbs of the big city of Antwerp and 51 from Peer, a predominantly rural municipality with 14,622 inhabitants, 70 km east of Antwerp, chosen as the "control" area in spite of its intensive agriculture). Persons with known occupational exposures, persons working in a region with characteristics clearly different from the area of residence, and people commuting over long distances were excluded from the study. Sperm morphology was significantly worse in Peer than in Antwerp. Serum testosterone levels were significantly lower in Peer than in Antwerp. The proportions of men with very low and low serum testosterone levels, of men with very low and low spermatozoa concentrations and of men with very low and low percentages of spermatozoa with normal morphology, were all higher in Peer than in Antwerp. We speculate that both the lower testosterone concentrations and the poorer sperm quality are due to disturbance of the hypothalamic-pituitary-testicular function by hormone disrupters. Our data suggest that exposure to levels of environmental pollution which are widespread in developed nations, can have unfavourable effects on endocrine equilibrium and may disturb male fertiline disrupters. PMID:11820620

  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. PMID:26362961

  13. Expression of the oestrogen receptor GPER by testicular peritubular cells is linked to sexual maturation and male fertility.

    PubMed

    Sandner, F; Welter, H; Schwarzer, J U; Köhn, F M; Urbanski, H F; Mayerhofer, A

    2014-09-01

    Besides the two nuclear oestrogen receptors (ESR1/ESR2), the G protein-coupled oestrogen receptor (GPER) was described in the human testis but little is known about testicular GPER during development or male infertility. We performed an immunohistochemical analysis using human and rhesus monkey testicular samples. The results obtained in adult primate testes showed GPER in interstitial and vascular cells as well as in smooth muscle-like peritubular cells, which build the wall of seminiferous tubules. Expression of GPER was also found in cultured human testicular peritubular cells (HPTCs) by Western blotting and RT-PCR/sequencing. Furthermore, as seen in time-lapse videos of cultured cells, addition of a specific GPER agonist (G1) significantly reduced the numbers of HTPCs within 24 h. A GPER antagonist (G15) prevented this action, implying a role for GPER related to the control of cell proliferation or cell death of peritubular cells. Peritubular cell functions and their phenotype change, for example, during post-natal development and in the cases of male infertility. The study of non-human primate samples revealed that GPER in peritubular cells was detectable only from the time of puberty onwards, while in samples from infantile and prepubertal monkeys only interstitial cells showed immunopositive staining. In testicular biopsies of men with mixed atrophy, a reduction or loss of immunoreactive GPER was found in peritubular cells surrounding those tubules, in which spermatogenesis was impaired. In other cases of impaired spermatogenesis, namely when the tubular wall was fibrotically remodelled, a complete loss of GPER was seen. Thus, the observed inverse relation between the state of fertility and GPER expression by peritubular cells implies that the regulation of primate testicular peritubular cells by oestrogens is mediated by GPER in both, health and disease. PMID:25052196

  14. 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. PMID:27052434

  15. Production of fertile unreduced sperm by hybrid males of the Rutilus alburnoides complex (Teleostei, cyprinidae). An alternative route to genome tetraploidization in unisexuals.

    PubMed Central

    Alves, M J; Coelho, M M; Próspero, M I; Collares-Pereira, M J

    1999-01-01

    The hybrid minnow Rutilus alburnoides comprises diploid and polyploid females and males. Previous studies revealed that diploid and triploid females exhibit altered oogenesis that does not involve random segregation and recombination of the genomes of the two ancestors, constituting unisexual lineages. In the present study, we investigated the reproductive mode of hybrid males from the Tejo basin, using experimental crosses and flow cytometric analysis of blood and sperm. The results suggest that diploid hybrids produced fertile unreduced sperm, transmitting their hybrid genome intact to offspring. Triploid hybrids also produced unreduced sperm, but it was not possible to obtain data concerning their fertility. Finally, tetraploid hybrids produced fertile diploid sperm, which exhibited Mendelian segregation. Tetraploid R. alburnoides may reestablish biparental reproduction, as individuals of both sexes with the appropriate constitution for normal meiosis (two haploid genomes from each parental species) are likely to occur in natural populations. Tetraploids probably have arisen from syngamy of diploid eggs and diploid sperm produced by diploid hybrid males. Diploid hybrid males may therefore play a significant role in the dynamics of the complex, starting the evolutionary process that may ultimately lead to a new sexually reproducing species. PMID:9872966

  16. Endpoints of resuscitation.

    PubMed

    Cestero, Ramon F; Dent, Daniel L

    2015-04-01

    Despite the multiple causes of the shock state, all causes possess the common abnormality of oxygen supply not meeting tissue metabolic demands. Compensatory mechanisms may mask the severity of hypoxemia and hypoperfusion, since catecholamines and extracellular fluid shifts initially compensate for the physiologic derangements associated with patients in shock. Despite the achievement of normal physiologic parameters after resuscitation, significant metabolic acidosis may continue to be present in the tissues, as evidenced by increased lactate levels and metabolic acidosis. This review discusses the major endpoints of resuscitation in clinical use. PMID:25814109

  17. 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. PMID:26031622

  18. Oestrogenic markers and reduced population fertile egg production in a sand goby partial life-cycle test.

    PubMed

    Robinson, Craig D; Craft, John A; Moffat, Colin F; Davies, Ian M; Brown, Elaine S; Megginson, Colin

    2004-01-01

    Understanding the ecological significance of oestrogenic biomarker responses, seen in field surveys of some UK estuarine fish, requires a suitable model to link biochemical and reproductive effects. The sand goby (Pomatoschistus minutus) is a common inshore fish that has been successfully bred in laboratory aquaria. Juvenile sand goby were continuously exposed to 17beta-oestradiol (E2) during gonadal maturation, and their subsequent reproductive success investigated. Exposure endpoints included hepatic vitellogenin (VTG) mRNA expression and maturation (male nuptial colouration, sperm duct gland- and gonado-somatic indices (SDGSI, GSI)). Reproductive endpoints included spawning behaviour, brood size, fertility and population-level fertile egg production. Measured E2 exposure concentrations were <5 (controls), 17, 71 and 530 ngl(-1). Male maturation decreased with increasing E2 concentration. VTG mRNA expression increased with E2 concentration, but not with duration of exposure. Reproductive endpoints showed progressive impairment with increasing E2 concentration. For most endpoints, the lowest observed effect concentration (LOEC) was 71 ngl(-1), and EC50s were in the range 87-165 ngl(-1). Pre-breeding male colouration, VTG expression and SDGSI were good predictors of subsequent population-level fertile egg production, but GSI was not. The sensitivity of oestrogenic markers in sand goby are comparable to those used in other species, and feral fish populations exhibiting such oestrogenic responses at molecular and organ levels are likely to have reduced fertile egg production. PMID:15178026

  19. Optimizing Male Fertility

    MedlinePlus

    ... information about the amount, movement, and shape of sperm. If the sperm count is normal and the sperm are of normal shape and moving normally, the ... likely normal. If the results are abnormal, the sperm should be examined. Illness or medications three months ...

  20. Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility.

    PubMed

    Turner, K J; Morley, M; Atanassova, N; Swanston, I D; Sharpe, R M

    2000-02-01

    The aim of the present study was to evaluate the effects of the administration of a potent non-steroidal aromatase inhibitor, anastrozole, on male reproductive function in adult rats. As anastrozole was to be administered via the drinking water, a preliminary study was undertaken in female rats and showed that this route of administration was effective in causing a major decrease in uterine weight (P<0.02). In an initial study in male adult rats, anastrozole (100 mg/l or 400 mg/l) was administered via the drinking water for a period of 9 weeks. Treatment with either dose resulted in a significant increase ( approximately 10%) in testis weight and increase in plasma FSH concentrations (P<0.01) throughout the 9 weeks. Mating was altered in both groups of anastrozole-treated rats, as they failed to produce copulatory plugs. Histological evaluation of the testes from anastrozole-treated rats revealed that spermatogenesis was grossly normal. In a more detailed study, adult rats were treated with 200 mg/l anastrozole via the drinking water for periods ranging from 2 weeks to 1 year. Plasma FSH and testosterone concentrations were increased significantly (P<0.001) during the first 19 weeks of treatment. However, LH concentrations were increased only at 19 weeks (P<0.001) in anastrozole-treated rats, and this coincided with a further increase in circulating and intratesticular testosterone concentrations (P<0.05). No consistent change in inhibin-B concentrations was observed during the study. Suppression of plasma oestradiol concentrations could not be demonstrated in anastrozole-treated animals, but oestradiol concentrations in testicular interstitial fluid were reduced by 18% (P<0.01). Mating was again inhibited by anastrozole treatment, but could be restored by s.c. injection of oestrogen, enabling demonstration that rats treated for 10 weeks or 9 months were still fertile. Testis weight was increased by 19% and 6% after treatment for 19 weeks and 1 year, respectively

  1. 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

  2. Effects of abamectin exposure on male fertility in rats: potential role of oxidative stress-mediated poly(ADP-ribose) polymerase (PARP) activation.

    PubMed

    Celik-Ozenci, Ciler; Tasatargil, Arda; Tekcan, Merih; Sati, Leyla; Gungor, Ece; Isbir, Mehmet; Demir, Ramazan

    2011-12-01

    Despite the known adverse effects of abamectin pesticide, little is known about its action on male fertility. To explore the effects of exposure to abamectin on male fertility and its mechanism, low (1mg/kg/day) and high dose (4 mg/kg/day) abamectin were applied to male rats by oral gavage for 1week and for 6weeks. Weight of testes, serum reproductive hormone levels, sperm dynamics and histopathology of testes were used to evaluate the reproductive efficiency of abamectin-exposed rats. Abamectin level was determined at high concentrations in plasma and testicular tissues of male rats exposed to this pesticide. The testes weights of animals and serum testosterone concentrations did not show any significant changes after abamectin exposure. Abamectin administration was associated with decreased sperm count and motility and increased seminiferous tubule damage. In addition, significant elevations in the 4-hydroxy-2-nonenal (4-HNE)-modified proteins and poly(ADP-ribose) (PAR) expression, as markers for oxidative stress and poly(ADP-ribose) polymerase (PARP) activation, were observed in testes of rats exposed to abamectin. These results showed that abamectin exposure induces testicular damage and affects sperm dynamics. Oxidative stress-mediated PARP activation might be one of the possible mechanism(s) underlying testicular damage induced by abamectin. PMID:21945325

  3. 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

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

    PubMed Central

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

    2013-01-01

    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. PMID:23525049

  5. Genetically-induced Estrogen Receptor Alpha mRNA (Esr1) Overexpression Does Not Adversely Affect Fertility or Penile Development in Male Mice

    PubMed Central

    Heath, John; Abdelmageed, Yazeed; Braden, Tim D.; Williams, Carol S.; Williams, John W.; Paulose, Tessie; Hernandez-Ochoa, Isabel; Gupta, Rupesh; Flaws, Jodi A.; Goyal, Hari O.

    2011-01-01

    Previously, we reported that estrogen receptor alpha mRNA (Esr1) or protein (ESR1) overexpression resulting from neonatal exposure to estrogens in rats was associated with infertility and mal-developed penis characterized by reduced length and weight and abnormal accumulation of fat cells. The objective of this study was to determine if mutant male mice overexpressing Esr1 are naturally infertile or have reduced fertility and/or develop abnormal penis. The fertility parameters, including fertility and fecundity indices, numbers of days from the day of cohabitation to the day of delivery, and numbers of pups per female, were not altered from controls, as a result of Esr1 overexpression. Likewise, penile morphology, including the length, weight, and diameter and os penis development, was not altered from controls. Conversely, weights of the seminal vesicles and bulbospongiosus and levator ani (BS/LA) muscles were significantly (P < 0.05) lower as compared to controls; however, the weight of the testis, the morphology of the testis and epididymis, and the plasma and testicular testosterone concentration were not different from controls. Hence, the genetically-induced Esr1 overexpression alone, without an exogenous estrogen exposure during the neonatal period, is unable to adversely affect the development of the penis as well as other male reproductive organs, except limited, but significant, reductions in weights of the seminal vesicles and BS/LA muscles. PMID:20930192

  6. Pollen Semi-Sterility1 Encodes a Kinesin-1–Like Protein Important for Male Meiosis, Anther Dehiscence, and Fertility in Rice[W

    PubMed Central

    Zhou, Shirong; Wang, Yang; Li, Wanchang; Zhao, Zhigang; Ren, Yulong; Wang, Yong; Gu, Suhai; Lin, Qibing; Wang, Dan; Jiang, Ling; Su, Ning; Zhang, Xin; Liu, Linglong; Cheng, Zhijun; Lei, Cailin; Wang, Jiulin; Guo, Xiuping; Wu, Fuqing; Ikehashi, Hiroshi; Wang, Haiyang; Wan, Jianmin

    2011-01-01

    In flowering plants, male meiosis produces four microspores, which develop into pollen grains and are released by anther dehiscence to pollinate female gametophytes. The molecular and cellular mechanisms regulating male meiosis in rice (Oryza sativa) remain poorly understood. Here, we describe a rice pollen semi-sterility1 (pss1) mutant, which displays reduced spikelet fertility (~40%) primarily caused by reduced pollen viability (~50% viable), and defective anther dehiscence. Map-based molecular cloning revealed that PSS1 encodes a kinesin-1–like protein. PSS1 is broadly expressed in various organs, with highest expression in panicles. Furthermore, PSS1 expression is significantly upregulated during anther development and peaks during male meiosis. The PSS1–green fluorescent protein fusion is predominantly localized in the cytoplasm of rice protoplasts. Substitution of a conserved Arg (Arg-289) to His in the PSS1 motor domain nearly abolishes its microtubule-stimulated ATPase activity. Consistent with this, lagging chromosomes and chromosomal bridges were found at anaphase I and anaphase II of male meiosis in the pss1 mutant. Together, our results suggest that PSS1 defines a novel member of the kinesin-1 family essential for male meiotic chromosomal dynamics, male gametogenesis, and anther dehiscence in rice. PMID:21282525

  7. Comparative Transcript Profiling of a Male Sterile Cybrid Pummelo and Its Fertile Type Revealed Altered Gene Expression Related to Flower Development

    PubMed Central

    Zheng, Bei-Bei; Wu, Xiao-Meng; Ge, Xiao-Xia; Deng, Xiu-Xin; Grosser, Jude W.; Guo, Wen-Wu

    2012-01-01

    Male sterile and seedless characters are highly desired for citrus cultivar improvement. In our breeding program, a male sterile cybrid pummelo, which could be considered as a variant of male fertile pummelo, was produced by protoplast fusion. Herein, ecotopic stamen primordia initiation and development were detected in this male sterile cybrid pummelo. Histological studies revealed that the cybrid showed reduced petal development in size and width, and retarded stamen primordia development. Additionally, disorganized cell proliferation was also detected in stamen-like structures (fused to petals and/or carpel). To gain new insight into the underlying mechanism, we compared, by RNA-Seq analysis, the nuclear gene expression profiles of floral buds of the cybrid with that of fertile pummelo. Gene expression profiles which identified a large number of differentially expressed genes (DEGs) between the two lines were captured at both petal primordia and stamen primordia distinguishable stages. For example, nuclear genes involved in nucleic acid binding and response to hormone synthesis and metabolism, genes required for floral bud identification and expressed in particular floral whorls. Furthermore, in accordance with flower morphology of the cybrid, expression of PISTILLATA (PI) was reduced in stamen-like structures, even though it was restricted to correct floral whorls. Down-regulated expression of APETALA3 (AP3) coincided with that of PI. These finding indicated that, due to their whorl specific effects in flower development, citrus class-B MADS-box genes likely constituted ‘perfect targets’ for CMS retrograde signaling, and that dysfunctional mitochondria seemed to cause male sterile phenotype in the cybrid pummelo. PMID:22952758

  8. Rhox8 Ablation in the Sertoli Cells Using a Tissue-Specific RNAi Approach Results in Impaired Male Fertility in Mice.

    PubMed

    Welborn, Joshua P; Davis, Matthew G; Ebers, Steven D; Stodden, Genna R; Hayashi, Kanako; Cheatwood, Joseph L; Rao, Manjeet K; MacLean, James A

    2015-07-01

    The reproductive homeobox X-linked, Rhox, genes encode transcription factors that are selectively expressed in reproductive tissues. While there are 33 Rhox genes in mice, only Rhox and Rhox8 are expressed in Sertoli cells, suggesting that they may regulate the expression of somatic-cell gene products crucial for germ cell development. We previously characterized Rhox5-null mice, which are subfertile, exhibiting excessive germ cell apoptosis and compromised sperm motility. To assess the role of Rhox8 in Sertoli cells, we used a tissue-specific RNAi approach to knockdown RHOX8 in vivo, in which the Rhox5 promoter was used to drive Rhox8-siRNA transgene expression in the postnatal Sertoli cells. Western and immunohistochemical analysis confirmed Sertoli-specific knockdown of RHOX8. However, other Sertoli markers, Gata1 and Rhox5, maintained normal expression patterns, suggesting that the knockdown was specific. Interestingly, male RHOX8-knockdown animals showed significantly reduced spermatogenic output, increased germ cell apoptosis, and compromised sperm motility, leading to impaired fertility. Importantly, our results revealed that while some RHOX5-dependent factors were also misregulated in Sertoli cells of RHOX8-knockdown animals, the majority were not, and novel putative RHOX8-regulated genes were identified. This suggests that while reduction in levels of RHOX5 and RHOX8 in Sertoli cells elicits similar phenotypes, these genes are not entirely redundant. Taken together, our study underscores the importance of Rhox genes in male fertility and suggests that Sertoli cell-specific expression of Rhox5 and Rhox8 is critical for complete male fertility. PMID:25972016

  9. Rhox8 Ablation in the Sertoli Cells Using a Tissue-Specific RNAi Approach Results in Impaired Male Fertility in Mice1

    PubMed Central

    Welborn, Joshua P.; Davis, Matthew G.; Ebers, Steven D.; Stodden, Genna R.; Hayashi, Kanako; Cheatwood, Joseph L.; Rao, Manjeet K.; MacLean, James A.

    2015-01-01

    The reproductive homeobox X-linked, Rhox, genes encode transcription factors that are selectively expressed in reproductive tissues. While there are 33 Rhox genes in mice, only Rhox and Rhox8 are expressed in Sertoli cells, suggesting that they may regulate the expression of somatic-cell gene products crucial for germ cell development. We previously characterized Rhox5-null mice, which are subfertile, exhibiting excessive germ cell apoptosis and compromised sperm motility. To assess the role of Rhox8 in Sertoli cells, we used a tissue-specific RNAi approach to knockdown RHOX8 in vivo, in which the Rhox5 promoter was used to drive Rhox8-siRNA transgene expression in the postnatal Sertoli cells. Western and immunohistochemical analysis confirmed Sertoli-specific knockdown of RHOX8. However, other Sertoli markers, Gata1 and Rhox5, maintained normal expression patterns, suggesting that the knockdown was specific. Interestingly, male RHOX8-knockdown animals showed significantly reduced spermatogenic output, increased germ cell apoptosis, and compromised sperm motility, leading to impaired fertility. Importantly, our results revealed that while some RHOX5-dependent factors were also misregulated in Sertoli cells of RHOX8-knockdown animals, the majority were not, and novel putative RHOX8-regulated genes were identified. This suggests that while reduction in levels of RHOX5 and RHOX8 in Sertoli cells elicits similar phenotypes, these genes are not entirely redundant. Taken together, our study underscores the importance of Rhox genes in male fertility and suggests that Sertoli cell-specific expression of Rhox5 and Rhox8 is critical for complete male fertility. PMID:25972016

  10. Molecular detection of potential sexually transmitted pathogens in semen and urine specimens of infertile and fertile males.

    PubMed

    Abusarah, Eman A; Awwad, Ziad M; Charvalos, Ekatherina; Shehabi, Asem A

    2013-12-01

    A total of 93 infertile and 70 fertile men attending various urology and gynecology clinics in Jordan were investigated in this prospective study. First void urine and the corresponding semen specimens were collected from 96% of the patients. Presence of Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), and Mycoplasma genitalium (MG) DNA in specimen was detected using polymerase chain reaction. The distribution of NG, CT, UU, and MG in semen and FVU specimens among infertile versus fertile men was 6.5% versus 0%, 4.3% versus 1.4%, 10.8% versus 5.7%, and 3.2% versus 1.4%, respectively. Two of infertile and 1 of fertile men harbored mixed pathogens. The highest number of positive potential pathogens was found among young men aged 20-29 years old. The present study found a very high concordance between the detection of CT, UU, and MG DNA in semen and the corresponding FVU specimens, while NG DNA found only in semen and not in the corresponding FVU specimens. This study also revealed that Ureaplasma parvum species is more prevalent than Ureaplasma urealyticum in specimens of infertile men (90%). The study demonstrates that infertile men have higher prevalence of NG, CT, UU, and MG compared with fertile men and NG as significantly associated with infertile men. PMID:24079950

  11. 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...

  12. The alpha-N-acetyl-glucosaminidase gene is transcriptionally activated in male and female gametes prior to fertilization and is essential for seed development in Arabidopsis.

    PubMed

    Ronceret, Arnaud; Gadea-Vacas, Jose; Guilleminot, Jocelyne; Devic, Martine

    2008-01-01

    Sugar residues in proteoglycan complexes carry important signalling and regulatory functions in biology. In humans, heparan sulphate is an example of such a complex polymer containing glucosamine and N-acetyl-glucosamine residues and is present in the extracellular matrix. Although heparan sulphate has not been found in plants, the At5g13690 gene encoding the alpha-N-acetyl-glucosaminidase (NAGLU), an enzyme involved in its catabolism, is present in the Arabidopsis genome. Among our collection of embryo-defective lines, a plant was identified in which the T-DNA had inserted into the AtNAGLU gene. The phenotype of atnaglu is an early arrest of seed development without apparent male or female gametophytic effects. These data demonstrated the essential function in Arabidopsis consistent with the contribution of NAGLU to the Sanfilippo syndrome in human. Expression of AtNAGLU in plants was shown to be prevalent during reproductive development. The presence of AtNAGLU mRNA was observed during early and late male gametogenesis and in each cell of the embryo sac at the time of fertilization. After fertilization, AtNAGLU was expressed in the embryo, suspensor, and endosperm until the cotyledonary stage embryo. This precise pattern of expression identifies the cells and tissues where a remodelling of the N-acetyl-glucosamine residues of proteoglycan complexes is occurring. This work provides original evidence of the important role of N-acetyl-glucosamines in plant reproductive development. PMID:18782908

  13. 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. PMID:24424320

  14. Nucleoside triphosphate diphosphohydrolase-1 ectonucleotidase is required for normal vas deferens contraction and male fertility through maintaining P2X1 receptor function.

    PubMed

    Kauffenstein, Gilles; Pelletier, Julie; Lavoie, Elise G; Kukulski, Filip; Martín-Satué, Mireia; Dufresne, Sébastien S; Frenette, Jérôme; Ribas Fürstenau, Cristina; Sereda, Michal J; Toutain, Bertrand; Henrion, Daniel; Sullivan, Robert; Vial, Catherine; Sévigny, Jean

    2014-10-10

    In this work, we report that Entpd1(-/-) mice, deficient for the ectonucleotidase nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), produce smaller litters (27% reduction) compared with wild-type C57BL6 animals. This deficit is linked to reduced in vivo oocyte fertilization by Entpd1(-/-) males (61 ± 11% versus 88 ± 7% for Entpd1(+/+)). Normal epididymal sperm count, spermatozoa morphology, capacitation, and motility and reduced ejaculated sperm number (2.4 ± 0.5 versus 3.7 ± 0.4 million for Entpd1(+/+)) pointed to vas deferens dysfunction. NTPDase1 was localized by immunofluorescence in the tunica muscularis of the vas deferens. Its absence resulted in a major ATP hydrolysis deficiency, as observed in situ by histochemistry and in primary smooth muscle cell cultures. In vitro, Entpd1(-/-) vas deferens displayed an exacerbated contraction to ATP, a diminished response to its non-hydrolysable analog αβMeATP, and a reduced contraction to electrical field stimulation, suggesting altered P2X1 receptor function with a propensity to desensitize. This functional alteration was accompanied by a 3-fold decrease in P2X1 protein expression in Entpd1(-/-) vas deferens with no variation in mRNA levels. Accordingly, exogenous nucleotidase activity was required to fully preserve P2X1 receptor activation by ATP in vitro. Our study demonstrates that NTPDase1 is required to maintain normal P2X1 receptor functionality in the vas deferens and that its absence leads to impaired peristalsis, reduced spermatozoa concentration in the semen, and, eventually, reduced fertility. This suggests that alteration of NTPDase1 activity affects ejaculation efficacy and male fertility. This work may contribute to unveil a cause of infertility and open new therapeutic potentials. PMID:25160621

  15. Four hours of daily contact with sexually active males is sufficient to induce fertile ovulation in anestrous goats.

    PubMed

    Bedos, M; Flores, J A; Fitz-Rodríguez, G; Keller, M; Malpaux, B; Poindron, P; Delgadillo, J A

    2010-08-01

    The study was conducted on two consecutive years to determine whether ovulatory activity can be induced in anovulatory goats by exposing them to sexually active bucks for 4, 8, 12 or 16 h per day during 15 consecutive days. In experiment 1, females remained continuously in the experimental pens where they were in contact with males. One group remained isolated from males (controls) and four other groups were exposed to sexually active males for 4, 8, 12 or 16 h per day. In experiment 2, females were taken away to "resting" pens free of male odours between the periods of contact with bucks. They were allocated to 5 groups as in experiment 1. Ovulations were determined by progesterone plasma levels and transrectal ultrasonography. Pregnancy was determined by abdominal ultrasonography. In both experiments, more than 90% of females exposed to the bucks had at least one ovulation during the whole experiment whereas only 11 or 0% (experiments 1 and 2, respectively) did so in the control group (P<0.001). Furthermore, the proportion of females ovulating did not differ among groups depending on duration of contact with bucks (P>0.05). In both experiments, pregnancy rates were not affected by the daily duration of contact with males (P>0.05). To conclude, 4h of daily contact with sexually active males is sufficient to stimulate ovulatory activity in anovulatory goats and this effect is not due to the presence of olfactory cues from the males remaining in the pens. PMID:20457159

  16. Efficient plant male fertility depends on vegetative nuclear movement mediated by two families of plant outer nuclear membrane proteins

    PubMed Central

    Zhou, Xiao; Meier, Iris

    2014-01-01

    Increasing evidence suggests that nuclear migration is important for eukaryotic development. Although nuclear migration is conserved in plants, its importance for plant development has not yet been established. The most extraordinary plant nuclear migration events involve plant fertilization, which is starkly different from that of animals. Instead of evolving self-propelled sperm cells (SCs), plants use pollen tubes to deliver SCs, in which the pollen vegetative nucleus (VN) and the SCs migrate as a unit toward the ovules, a fundamental but barely understood process. Here, we report that WPP domain-interacting proteins (WIPs) and their binding partners the WPP domain-interacting tail-anchored proteins (WITs) are essential for pollen nuclear migration. Loss-of-function mutations in WIT and/or WIP gene families resulted in impaired VN movement, inefficient SC delivery, and defects in pollen tube reception. WIPs are Klarsicht/ANC-1/Syne-1 Homology (KASH) analogs in plants. KASH proteins are key players in animal nuclear migration. Thus, this study not only reveals an important nuclear migration mechanism in plant fertilization but also, suggests that similar nuclear migration machinery is conserved between plants and animals. PMID:25074908

  17. The impact of sperm protamine deficiency and sperm DNA damage on human male fertility: a systematic review and meta-analysis.

    PubMed

    Ni, K; Spiess, A-N; Schuppe, H-C; Steger, K

    2016-09-01

    Existing literature suggests evidence that protamine deficiency is related to DNA damage and male fertility. In this meta-analysis, we analyzed the relationship between the ratio of protamine-1 and protamine-2 with male fertility and the association of protamine deficiency with sperm DNA damage. Quality of available cohort studies was evaluated using the Newcastle-Ottawa Scale checklist. Summary effect estimates with 95% confidence intervals (CI) were derived using a random effects model. The effect of the protamine ratio on male fertility was analyzed in nine studies demonstrating a significantly higher value of the protamine ratio in subfertile men (n = 633) when compared with controls (n = 453, SMD = 0.46, 95% CI 0.25-0.66, Z = 4.42, p < 0.00001). Both protamine mRNA (SMD = 0.45, 95% CI 0.11-0.79, Z = 2.63, p = 0.009) and protein ratio (SMD = 0.46, 95% CI 0.25-0.68, Z = 4.22, p < 0.0001) showed significantly increased values in subfertile patients. The association between protamine deficiency and DNA damage was analyzed in 12 studies (n = 845) exhibiting a combined overall correlation coefficient (COR) of 0.53 (95% CI 0.28-0.71, Z = 3.87, p < 0.001). Protamine deficiency measured by CMA3 staining was significantly associated with sperm DNA damage (COR = 0.71, 95% CI 0.48-0.85, Z = 4.87, p < 0.001), whereas the P1/P2 ratio was not (COR = 0.17, 95% CI -0.16 to 0.46, Z = 0.99, p = 0.33). It is concluded that the protamine ratio represents a suitable biomarker for the assessment of sperm quality and protamine deficiency is closely related with sperm DNA damage. PMID:27231200

  18. 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

  19. 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. PMID:24783196

  20. Male and Couple Fertility Impairment due to HPV-DNA Sperm Infection: Update on Molecular Mechanism and Clinical Impact—Systematic Review

    PubMed Central

    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. PMID:24783196

  1. 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

  2. The shorter zinc finger protein ZNF230 gene message is transcribed in fertile male testes and may be related to human spermatogenesis.

    PubMed Central

    Zhang, S; Qiu, W; Wu, H; Zhang, G; Huang, M; Xiao, C; Yang, J; Kamp, C; Huang, X; Huellen, K; Yue, Y; Pan, A; Lebo, R; Milunsky, A; Vogt, P H

    2001-01-01

    The zinc finger gene family represents one of the largest in the mammalian genome, with several of these genes reported to be involved in spermatogenesis. A newly discovered gene has been identified that is expressed abundantly in the testicular tissue of fertile men as determined by mRNA differential display. The gene encodes a C(3)HC(4)-type zinc finger protein motif (ring finger motif) consistent with a role in pre-meiotic or post-meiotic sperm development. The gene was named ZNF230 and mapped to the short arm of chromosome 11 (11p15). ZNF230 has two transcripts, of 1 kb and 4.4 kb in length. The shorter 1 kb transcript was only detected in testicular tissue whereas the longer 4.4 kb transcript was not detected in testis but was found in several other tissues. The lack of detectable ZNF230 expression in azoospermic patients by reverse transcriptase-mediated PCR analysis is interpreted to mean that this gene is involved in maintaining normal human male fertility. PMID:11672448

  3. ATP-binding cassette transporter G26 is required for male fertility and pollen exine formation in Arabidopsis.

    PubMed

    Quilichini, Teagen D; Friedmann, Michael C; Samuels, A Lacey; Douglas, Carl J

    2010-10-01

    The highly resistant biopolymer, sporopollenin, gives the outer wall (exine) of spores and pollen grains their unparalleled strength, shielding these structures from terrestrial stresses. Despite a limited understanding of the composition of sporopollenin, it appears that the synthesis of sporopollenin occurs in the tapetum and requires the transport of one or more sporopollenin constituents to the surface of developing microspores. Here, we describe ABCG26, a member of the ATP-binding cassette (ABC) transporter superfamily, which is required for pollen exine formation in Arabidopsis (Arabidopsis thaliana). abcg26 mutants are severely reduced in fertility, with most siliques failing to produce seeds by self-fertilization and mature anthers failing to release pollen. Transmission electron microscopy analyses revealed an absence of an exine wall on abcg26-1 mutant microspores. Phenotypic abnormalities in pollen wall formation were first apparent in early uninucleate microspores as a lack of exine formation and sporopollenin deposition. Additionally, the highest levels of ABCG26 mRNA were in the tapetum, during early pollen wall formation, sporopollenin biosynthesis, and sporopollenin deposition. Accumulations resembling the trilamellar lipidic coils in the abcg11 and abcg12 mutants defective in cuticular wax export were observed in the anther locules of abcg26 mutants. A yellow fluorescent protein-ABCG26 protein was localized to the endoplasmic reticulum and plasma membrane. Our results show that ABCG26 plays a critical role in exine formation and pollen development and are consistent with a model by which ABCG26 transports sporopollenin precursors across the tapetum plasma membrane into the locule for polymerization on developing microspore walls. PMID:20732973

  4. Antibiotic treatment based on seminal cultures from asymptomatic male partners in in-vitro fertilization is unnecessary and may be detrimental.

    PubMed

    Liversedge, N H; Jenkins, J M; Keay, S D; McLaughlin, E A; Al-Sufyan, H; Maile, L A; Joels, L A; Hull, M G

    1996-06-01

    We questioned the policy of routine microbiological culture of semen prior to in-vitro fertilization (IVF) with a view to prescribing antibiotics to reduce the risk of introducing seminal infection into the embryo culture system. An initial retrospective study examined serum microbiology reports of 449 couples undergoing IVF or gamete intra-Fallopian transfer (GIFT). In semen samples taking >/=1 days to reach the microbiology laboratory compared with same-day delivery there was increased frequency of significant culture of enterococci (27 versus 15%, P < 0.01). In samples taking >/=2 days there was increased frequency of significant culture of Gram-negative bacilli (31 versus 12%, P < 0.01) and of overall culture of other potentially pathogenic organisms (26 versus 14%, P < 0.01). We questioned diagnostic accuracy and relevance. Therefore, in a prospective study, semen and high vaginal swabs obtained on the day of oocyte collection were cultured from 100 couples having IVF or GIFT, of whom 52 male partners had been treated with antibiotics following positive pre-IVF semen culture. The presence of bacteria in semen samples used only for IVF (n = 90) did not reduce fertilization rates nor lead to infection of the embryo culture system. However, there was an increased incidence of significant culture of vaginal Gram-negative bacilli in patients with treated partners compared with untreated partners [15/52 (29%) versus 5/48 (10%), P < 0.05]. Thus antibiotic therapy in the male partner may increase the likelihood of inoculation of antibiotic-resistant pathogenic bacteria from the vagina into the embryo culture system during vaginal oocyte collection. In asymptomatic patients, microbiological screening of semen samples prior to IVF treatment and subsequent treatment with antibiotic therapy in those with positive cultures appears to be unnecessary and may be detrimental to IVF outcome. PMID:8671429

  5. 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…

  6. 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

  7. Effect of noise stress on male rat fertility, and the protective effect of vitamins C and E on its potential effect

    PubMed Central

    Fathollahi, Ali; Jasemi, Majid; Saki, Ghasem

    2013-01-01

    Objective To evaluate the effect of noise on the fertility of male rats, and to assess the effect of vitamins C and E on its potential effect. Materials and methods Forty adult male rats were randomly divided into five equal groups. Group 1 (control) was not exposed to noise. Groups 2–5 were exposed to noise of 90–130 dB and 300–350 Hz from 19.00 to 07.00 h every day for 50 days; group 2 received vitamin C and group 3 received vitamin E. Group 4 received vitamins C and E concomitantly and group 5 received no vitamins. After 50 days, the serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH) and testosterone were measured. Each rat was then left for 1 week with three female rats, for mating. Pregnant females were killed humanely after 19 days of pregnancy and evaluated for the presence and number of viable, dead and absorbed fetuses. Results The mean serum FSH level was statistically significantly different between the control and groups 2 (P < 0.05) and 5 (P < 0.001). The mean serum LH level differed significantly between the control and groups 2 (P = 0.05), 3 (P < 0.05) and 5 (P < 0.001). The mean serum testosterone level was significantly different between the control and group 5 (P < 0.001). Serum FSH, LH and testosterone levels in group 5 were significantly different from all the others (P < 0.001). The pregnancy rates in females mated with groups 1 and 5 were statistically different (P < 0.05). Comparing groups 1–4, there was no difference in the occurrence of abnormal pregnancy (P > 0.05), but group 5 values were significantly different from the others (P < 0.001). Conclusion These data strongly suggest that noise stress has a significant effect on the fertility of male rats. PMID:26579254

  8. 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. PMID:11725334

  9. 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.

  10. 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...

  11. Efficacy of an anti-fertility vaccine based on mammalian gonadotrophin releasing hormone (GnRH-I)--a histological comparison in male animals.

    PubMed

    Ferro, V A; Khan, M A H; McAdam, D; Colston, A; Aughey, E; Mullen, A B; Waterston, M M; Harvey, M J A

    2004-09-01

    A N-terminal modified gonadotrophin releasing hormone (GnRH-I, tetanus toxoid-CHWSYGLRPG-NH2) conjugate was evaluated histologically in a number of male animal species (mice, dogs and sheep). The immunogen has previously been shown to be highly effective in rats, by suppressing both steroidogenesis and spermatogenesis. However, cross-species efficacy of peptide vaccines is known to be highly variable. Therefore, a comparative evaluation of reproductive tissues from animals immunized against this immunogen adsorbed onto an alum-based adjuvant was made. The sheep and dogs were chosen, as use of anti-fertility vaccines in these species is important in farming and veterinary practice. Changes in testicular size were measured during the immunization period and the greatest alteration (attributed to gonadal atrophy) was observed in the rat. Following euthanasia, the testicular tissue was evaluated for spermatogenesis. The most susceptible species to GnRH-I ablation was the rat, which showed significant (P < 0.0001) arrest in spermatogenesis compared with untreated controls. Testicular sections taken from treated animals were completely devoid of spermatozoa or spermatids, in comparison with 94% of the untreated controls showing evidence of spermatogenesis. The immunized mice and rams also showed significant arrest (P < 0.0001). There was a 30-45% decrease in spermatogenesis and total azoospermia was not apparent. However, the least responsive were the dogs, which showed little significant variation compared to untreated animals and only a 5% decrease in activity. A comparison of the specific IgG response to GnRH-I indicated that in sheep and dogs the response was not maintained, unlike in rodents, suggesting that suppression of fertility may be due to differences in immune responses in different animal species. PMID:15261694

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

    PubMed

    Mei, Shiyong; Liu, Touming; Wang, Zhiwei

    2016-01-01

    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

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

    PubMed Central

    Mei, Shiyong; Liu, Touming; Wang, Zhiwei

    2016-01-01

    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. Pathophysiological Progression Model for Selected Toxicological Endpoints

    EPA Science Inventory

    The existing continuum paradigms are effective models to organize toxicological data associated with endpoints used in human health assessments. A compendium of endpoints characterized along a pathophysiological continuum would serve to: weigh the relative importance of effects o...

  15. Role of Inhibitors of Apoptosis Proteins in Testicular Function and Male Fertility: Effects of Polydeoxyribonucleotide Administration in Experimental Varicocele.

    PubMed

    Minutoli, Letteria; Arena, Salvatore; Antonuccio, Pietro; Romeo, Carmelo; Bitto, Alessandra; Magno, Carlo; Rinaldi, Mariagrazia; Micali, Antonio; Irrera, Natasha; Pizzino, Gabriele; Galfo, Federica; Squadrito, Francesco; Altavilla, Domenica; Marini, Herbert

    2015-01-01

    Neuronal apoptosis inhibitory protein (NAIP) and survivin might play an important role in testicular function. We investigated the effect of PDRN, an agonist of adenosine A2A receptor, on testicular NAIP and survivin expression in an experimental model of varicocele. After the creation of experimental varicocele (28 days), adolescent male Sprague-Dawley rats were randomized to one of the following treatments lasting 21 days: vehicle, PDRN (8 mg/kg i.p., daily), PDRN + 3,7-dimethyl-propargylxanthine (DMPX, a specific adenosine A2A-receptor antagonist, 0.1 mg/kg i.p., daily), varicocelectomy, and varicocelectomy + PDRN (8 mg/kg i.p., daily). Sham-operated animals were used as controls. Animals were then euthanized and testis expression of NAIP and survivin was evaluated through qRT-PCR, western blot, and immunohistochemical analysis. Spermatogenetic activity was also assessed. NAIP and survivin expressions were significantly reduced following varicocele induction when compared to sham animals whereas PDRN-treated rats showed an increase in NAIP and survivin levels. Immunohistochemistry revealed an enhanced expression of NAIP and survivin with a characteristic pattern of cellular localization following PDRN treatment. Moreover, administration of PDRN significantly restored spermatogenic function in varicocele rats. PDRN may represent a rational therapeutic option for accelerating recovery from depressed testicular function through a strategic modulation of apoptosis in experimental varicocele. PMID:26347229

  16. Cosuppression of a Plasma Membrane H+-ATPase Isoform Impairs Sucrose Translocation, Stomatal Opening, Plant Growth, and Male Fertility

    PubMed Central

    Zhao, Rongmin; Dielen, Vincent; Kinet, Jean-Marie; Boutry, Marc

    2000-01-01

    The plasma membrane H+-ATPase builds up a pH and potential gradient across the plasma membrane, thus activating a series of secondary ion and metabolite transporters. pma4 (for plasma membrane H+-ATPase 4), the most widely expressed H+-ATPase isogene in Nicotiana plumbaginifolia, was overexpressed in tobacco. Plants that overexpressed PMA4 showed no major changes in plant growth under normal conditions. However, two transformants were identified by their stunted growth, slow leaf initiation, delayed stem bolting and flowering, and male sterility. Protein gel blot analysis showed that expression of the endogenous and transgenic pma4 was cosuppressed. Cosuppression was developmentally regulated because PMA4 was still present in developing leaves but was not detected in mature leaves. The glucose and fructose content increased threefold, whereas the sucrose content remained unchanged. The rate of sucrose exudation from mature leaves was reduced threefold and the sugar content of apical buds was reduced twofold, suggesting failure of sucrose loading and translocation to the sink tissues. Cosuppression of PMA4 also affected the guard cells, stomatal opening, and photosynthesis in mature leaves. These results show that a single H+-ATPase isoform plays a major role in several transport-dependent physiological processes. PMID:10760242

  17. PiggyBac Transposon-Mediated Mutagenesis in Rats Reveals a Crucial Role of Bbx in Growth and Male Fertility.

    PubMed

    Wang, Chieh-Ying; Tang, Ming-Chu; Chang, Wen-Chi; Furushima, Kenryo; Jang, Chuan-Wei; Behringer, Richard R; Chen, Chun-Ming

    2016-09-01

    Bobby sox homolog (Bbx) is an evolutionally conserved gene, but its biological function remains elusive. Here, we characterized defects of Bbx mutant rats that were created by PiggyBac-mediated insertional mutagenesis. Smaller body size and male infertility were the two major phenotypes of homozygous Bbx mutants. Bbx expression profile analysis showed that Bbx was more highly expressed in the testis and pituitary gland than in other organs. Histology and hormonal gene expression analysis of control and Bbx-null pituitary glands showed that loss of Bbx appeared to be dispensable for pituitary histogenesis and the expression of major hormones. BBX was localized in the nuclei of postmeiotic spermatids and Sertoli cells in wild-type testes, but absent in mutant testes. An increased presence of aberrant multinuclear giant cells and apoptotic cells was observed in mutant seminiferous tubules. TUNEL-positive cells costained with CREM (round spermatid marker), but not PLZF (spermatogonia marker), gammaH2Ax (meiotic spermatocyte marker), or GATA4 (Sertoli cell marker). Finally, there were drastically reduced numbers and motility of epididymal sperm from Bbx-null rats. These results suggest that loss of BBX induces apoptosis of postmeiotic spermatids and results in spermiogenesis defects and infertility. PMID:27465138

  18. Role of Inhibitors of Apoptosis Proteins in Testicular Function and Male Fertility: Effects of Polydeoxyribonucleotide Administration in Experimental Varicocele

    PubMed Central

    Minutoli, Letteria; Arena, Salvatore; Antonuccio, Pietro; Romeo, Carmelo; Bitto, Alessandra; Magno, Carlo; Rinaldi, Mariagrazia; Micali, Antonio; Irrera, Natasha; Pizzino, Gabriele; Galfo, Federica; Squadrito, Francesco; Altavilla, Domenica; Marini, Herbert

    2015-01-01

    Neuronal apoptosis inhibitory protein (NAIP) and survivin might play an important role in testicular function. We investigated the effect of PDRN, an agonist of adenosine A2A receptor, on testicular NAIP and survivin expression in an experimental model of varicocele. After the creation of experimental varicocele (28 days), adolescent male Sprague-Dawley rats were randomized to one of the following treatments lasting 21 days: vehicle, PDRN (8 mg/kg i.p., daily), PDRN + 3,7-dimethyl-propargylxanthine (DMPX, a specific adenosine A2A-receptor antagonist, 0.1 mg/kg i.p., daily), varicocelectomy, and varicocelectomy + PDRN (8 mg/kg i.p., daily). Sham-operated animals were used as controls. Animals were then euthanized and testis expression of NAIP and survivin was evaluated through qRT-PCR, western blot, and immunohistochemical analysis. Spermatogenetic activity was also assessed. NAIP and survivin expressions were significantly reduced following varicocele induction when compared to sham animals whereas PDRN-treated rats showed an increase in NAIP and survivin levels. Immunohistochemistry revealed an enhanced expression of NAIP and survivin with a characteristic pattern of cellular localization following PDRN treatment. Moreover, administration of PDRN significantly restored spermatogenic function in varicocele rats. PDRN may represent a rational therapeutic option for accelerating recovery from depressed testicular function through a strategic modulation of apoptosis in experimental varicocele. PMID:26347229

  19. Neofunctionalization of Duplicated Tic40 Genes Caused a Gain-of-Function Variation Related to Male Fertility in Brassica oleracea Lineages1[W][OPEN

    PubMed Central

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

    2014-01-01

    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. PMID:25185122

  20. What Is Fertility Preservation?

    MedlinePlus

    ... endometriosis Have uterine fibroids Have polycystic ovarian syndrome (PCOS) Have been treated for cancer Have been treated ... male fertility, NIH study suggests Some women with PCOS may have adrenal disorder, NIH researchers suggest Weight ...

  1. The PTK7-Related Transmembrane Proteins Off-track and Off-track 2 Are Co-receptors for Drosophila Wnt2 Required for Male Fertility

    PubMed Central

    Honemann-Capito, Mona; Brechtel-Curth, Katja; Hedderich, Marie; Wodarz, Andreas

    2014-01-01

    Wnt proteins regulate many developmental processes and are required for tissue homeostasis in adult animals. The cellular responses to Wnts are manifold and are determined by the respective Wnt ligand and its specific receptor complex in the plasma membrane. Wnt receptor complexes contain a member of the Frizzled family of serpentine receptors and a co-receptor, which commonly is a single-pass transmembrane protein. Vertebrate protein tyrosine kinase 7 (PTK7) was identified as a Wnt co-receptor required for control of planar cell polarity (PCP) in frogs and mice. We found that flies homozygous for a complete knock-out of the Drosophila PTK7 homolog off track (otk) are viable and fertile and do not show PCP phenotypes. We discovered an otk paralog (otk2, CG8964), which is co-expressed with otk throughout embryonic and larval development. Otk and Otk2 bind to each other and form complexes with Frizzled, Frizzled2 and Wnt2, pointing to a function as Wnt co-receptors. Flies lacking both otk and otk2 are viable but male sterile due to defective morphogenesis of the ejaculatory duct. Overexpression of Otk causes female sterility due to malformation of the oviduct, indicating that Otk and Otk2 are specifically involved in the sexually dimorphic development of the genital tract. PMID:25010066

  2. Increased Progesterone Production in Cumulus–Oocyte Complexes of Female Mice Sired by Males With the Y-Chromosome Long Arm Deletion and its Potential Influence on Fertilization Efficiency

    PubMed Central

    Galas, Jerzy; Przybyło, Małgorzata; Bilińska, Barbara; Styrna, Józefa

    2015-01-01

    It was revealed previously that B10.BR(Ydel) females sired by males with the Y-chromosome long arm deletion differ from genetically identical B10.BR females sired by males with the intact Y chromosome. This is interpreted as a result of different epigenetic information which females of both groups inherit from their fathers. In the following study, we show that cumulus–oocyte complexes ovulated by B10.BR(Ydel) females synthesize increased amounts of progesterone, which is important sperm stimulator. Because their extracellular matrix is excessively firm, the increased progesterone secretion belongs presumably to factors that compensate this feature enabling unchanged fertilization ratios. Described compensatory mechanism can act only on sperm of high quality, presenting proper receptors. Indeed, low proportion of sperm of Ydel males that poorly fertilize B10.BR(Ydel) oocytes demonstrates positive staining of membrane progesterone receptors. This proportion is significantly higher for sperm of control males that fertilize B10.BR(Ydel) and B10.BR oocytes with the same efficiency. PMID:24899473

  3. Increased progesterone production in cumulus-oocyte complexes of female mice sired by males with the Y-chromosome long arm deletion and its potential influence on fertilization efficiency.

    PubMed

    Kotarska, Katarzyna; Galas, Jerzy; Przybyło, Małgorzata; Bilińska, Barbara; Styrna, Józefa

    2015-02-01

    It was revealed previously that B10.BR(Y(del)) females sired by males with the Y-chromosome long arm deletion differ from genetically identical B10.BR females sired by males with the intact Y chromosome. This is interpreted as a result of different epigenetic information which females of both groups inherit from their fathers. In the following study, we show that cumulus-oocyte complexes ovulated by B10.BR(Y(del)) females synthesize increased amounts of progesterone, which is important sperm stimulator. Because their extracellular matrix is excessively firm, the increased progesterone secretion belongs presumably to factors that compensate this feature enabling unchanged fertilization ratios. Described compensatory mechanism can act only on sperm of high quality, presenting proper receptors. Indeed, low proportion of sperm of Y(del) males that poorly fertilize B10.BR(Y(del)) oocytes demonstrates positive staining of membrane progesterone receptors. This proportion is significantly higher for sperm of control males that fertilize B10.BR(Y(del)) and B10.BR oocytes with the same efficiency. PMID:24899473

  4. 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. PMID:24464649

  5. Endpoint matrix: a conceptual tool to promote consideration of the multiple dimensions of humane endpoints.

    PubMed

    Ashall, Vanessa; Millar, Kate

    2014-01-01

    This paper proposes a framework to support appropriate application of endpoints in animal experiments. It is recommended that unpredicted endpoints should be explicitly considered alongside scientific endpoints and justifiable endpoints as the three types of endpoint which comprise the "humane." We suggest there is a need for clear identification of each type of endpoint and an understanding of the interactions between these types. The use of an "endpoint matrix" during study planning is proposed to promote methodically sound and consistent definition, determination, and detection of unpredicted, scientific, and justifiable endpoints in animal experiments. It is claimed that the further development and use of this tool will support a more effective and harmonized practical application of humane endpoints for all animal use in line with best practice recommendations. PMID:24794004

  6. 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.

  7. Biomarkers and Surrogate Endpoints In Clinical Trials

    PubMed Central

    Fleming, Thomas R.; Powers, John H

    2012-01-01

    One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures and radiological tests, often are considered as replacement endpoints or “surrogates” for clinically meaningful endpoints. We discuss the definitions of clinically meaningful endpoints and surrogate endpoints, and provide examples from recent clinical trials. We provide insight into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. We also discuss the nature of evidence that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and provide insights into why this reliability is specific to the context of use of the biomarker. . PMID:22711298

  8. Exact relativistic {beta} decay endpoint spectrum

    SciTech Connect

    Masood, S. S.; Nasri, S.; Schechter, J.; Tortola, M. A.; Valle, J. W. F.

    2007-10-15

    The exact relativistic form for the {beta} decay endpoint spectrum is derived and presented in a simple factorized form. We show that our exact formula can be well approximated to yield the endpoint form used in the fit method of the KATRIN Collaboration. We also discuss the three-neutrino case and how information from neutrino oscillation experiments may be useful in analyzing future {beta} decay endpoint experiments.

  9. 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. PMID:21872922

  10. Discovery of human posterior head 20 (hPH20) and homo sapiens sperm acrosome associated 1 (hSPACA1) immunocontraceptive epitopes and their effects on fertility in male and female mice.

    PubMed

    Chen, Xuemei; Liu, Xiaodong; Ren, Xiuhua; Li, Xuewu; Wang, Li; Zang, Weidong

    2016-03-01

    The key goals of immunocontraception research are to obtain full contraceptive effects using vaccines administered to both males and females. Current research concerning human anti-sperm contraceptive vaccines is focused on delineating infertility-related epitopes to avoid autoimmune disease. We constructed phage-display peptide libraries to select epitope peptides derived from human posterior head 20 (hPH20) and homo sapiens sperm acrosome associated 1 (hSPACA1) using sera collected from infertile women harbouring anti-sperm antibodies. Following five rounds of selection, positive colonies were reconfirmed for reactivity with the immunoinfertile sera. We biopanned and analysed the chemical properties of four epitope peptides, named P82, Sa6, Sa37 and Sa76. Synthetic peptides were made and coupled to either bovine serum albumin (BSA) or ovalbumin. We used the BSA-conjugated peptides to immunise BALB/c mice and examined the effects on fertility in female and male mice. The synthetic peptides generated a sperm-specific antibody response in female and male mice that caused a contraceptive state. The immunocontraceptive effect was reversible and, with the disappearance of peptide-specific antibodies, there was complete restoration of fertility. Vaccinations using P82, Sa6 and Sa76 peptides resulted in no apparent side effects. Thus, it is efficient and practical to identify epitope peptide candidates by phage display. These peptides may find clinical application in the specific diagnosis and treatment of male and female infertility and contraceptive vaccine development. PMID:25209425

  11. [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. PMID:26887309

  12. 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

  13. Fallback tests for co-primary endpoints.

    PubMed

    Ristl, Robin; Frommlet, Florian; Koch, Armin; Posch, Martin

    2016-07-20

    When efficacy of a treatment is measured by co-primary endpoints, efficacy is claimed only if for each endpoint an individual statistical test is significant at level α. While such a strategy controls the family-wise type I error rate (FWER), it is often strictly conservative and allows for no inference if not all null hypotheses can be rejected. In this paper, we investigate fallback tests, which are defined as uniform improvements of the classical test for co-primary endpoints. They reject whenever the classical test rejects but allow for inference also in settings where only a subset of endpoints show a significant effect. Similarly to the fallback tests for hierarchical testing procedures, these fallback tests for co-primary endpoints allow one to continue testing even if the primary objective of the trial was not met. We propose examples of fallback tests for two and three co-primary endpoints that control the FWER in the strong sense under the assumption of multivariate normal test statistics with arbitrary correlation matrix and investigate their power in a simulation study. The fallback procedures for co-primary endpoints are illustrated with a clinical trial in a rare disease and a diagnostic trial. © 2016 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:26919166

  14. Fertility and developmental toxicity assessment in rats and rabbits with LY500307, a selective estrogen receptor beta (ERβ) agonist.

    PubMed

    Hilbish, Kim G; Breslin, William J; Johnson, Jason T; Sloter, Eddie D

    2013-10-01

    LY500307 is a selective estrogen receptor beta (ERβ) agonist that was developed for the treatment of benign prostatic hyperplasia. The in vitro functional selectivity of LY500307 for ERβ agonist activity is 32-fold above the activity at the alpha receptor (ERα). LY500307 was evaluated in a series of male (M) and female (F) rat fertility and rat and rabbit embryo-fetal development (EFD) studies, using 20 or 25 animals/group. LY500307 was administered daily by oral gavage starting 2 weeks (F) or 10 weeks (M) before mating, during cohabitation, until necropsy (M) or through gestation day (GD) 6 (F) in the fertility studies and from GD 6 to 17 (rats) or GD 7 to 19 (rabbits) in the EFD studies. Dosage levels of LY500307 ranged from 0.03 to 10 mg/kg/day for rats and from 1 to 25 mg/kg/day for rabbits. Fertility, estrous, maternal reproductive endpoints, conceptus viability, sperm parameters, organ weights, and histopathology were evaluated in the fertility studies. Maternal reproductive endpoints and fetal viability, weight, and morphology were evaluated in the EFD studies. Toxicokinetics were assessed in satellite animals. At 10 mg/kg/day in the male fertility study, findings included decreased body weight (BW); food consumption (FC); fertility, mating, and conception indices; sperm concentration; and reproductive tissue weight (associated with atrophic histologic changes). In the female fertility study, effects included decreased BW and FC at ≥0.3 mg/kg/day and persistent diestrus, delayed mating, and reduced fertility/conception indices at 3 mg/kg/day. In the rat EFD study, findings included decreased maternal BW and FC and increased incidences of adverse clinical signs, abortion, maternal mortality/moribundity, postimplantation loss, and fetal skeletal variations at 3 mg/kg/day. Effects in the rabbit EFD study were limited to decreases in maternal BW and FC at 25 mg/kg/day. In general, systemic maternal exposure increased proportionally with dosage in rats, but

  15. 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

  16. 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...

  17. Epididymal protein markers and fertility.

    PubMed

    Dacheux, Jean-Louis; Dacheux, Françoise; Druart, Xavier

    2016-06-01

    The last stages of male gamete differentiation occur outside the gonad in a specific environment controlled by the epididymal epithelium. All the fundamental characteristics of a fertile spermatozoon are acquired sequentially during transit through the epididymal tubule. Full understanding of the mechanisms involved in these gamete modifications is a key to understanding and controlling such important stages in male fertility. With the development of new large scale technologies, large amounts of information give hope of identifying the fundamental elements involved in such cellular events and of being able to obtain some markers predictive of male fertility that would be valuable both in human and/or animal reproduction. PMID:26963046

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Hispanic Adolescent Fertility.

    ERIC Educational Resources Information Center

    Darabi, Katherine F.; And Others

    1986-01-01

    Discusses fertility of Hispanic adolescents in the United States. Summarizes what is known about sexuality, contraception, pregnancy, and childbearing among male and female Hispanics of various countries of origin. Indicates Hispanic adolescent birthrates fall between those of non-Hispanic Whites and Blacks, but there is considerable within-group…

  3. Enabling communication concurrency through flexible MPI endpoints

    DOE PAGESBeta

    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 thatmore » contrasts current multithreaded communication performance with the need for high degrees of communication concurrency to achieve peak communication performance.« less

  4. 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.

  5. [QUANTITATIVE DNA EVALUATION OF THE HIGH CARCINOGENIC RISK OF HUMAN PAPILLOMA VIRUSES AND HUMAN HERPES VIRUSES IN MALES WITH FERTILITY DISORDERS].

    PubMed

    Evdokimov, V V; Naumenko, V A; Tulenev, Yu A; Kurilo, L F; Kovalyk, V P; Sorokina, T M; Lebedeva, A L; Gomberg, M A; Kushch, A A

    2016-01-01

    Infertility is an actual medical and social problem. In 50% of couples it is associated with the male factor and in more than 50% of cases the etiology of the infertility remains insufficiently understood. The goal of this work was to study the prevalence and to perform quantitative analysis of the human herpes viruses (HHV) and high carcinogenic risk papilloma viruses (HR HPV) in males with infertility, as well as to assess the impact of these infections on sperm parameters. Ejaculate samples obtained from 196 males fall into 3 groups. Group 1 included men with the infertility of unknown etiology (n = 112); group 2, patients who had female partners with the history of spontaneous abortion (n = 63); group 3 (control), healthy men (n = 21). HHV and HR HPV DNA in the ejaculates were detected in a total of 42/196 (21.4%) males: in 31 and 11 patients in groups 1 and 2, respectively (p > 0.05) and in none of healthy males. HHV were detected in 24/42; HR HPV, in 18/42 males (p > 0.05) without significant difference between the groups. Among HR HPV genotypes of the clade A9 in ejaculate were more frequent (14/18, p = 0.04). Comparative analysis of the sperm parameters showed that in the ejaculates of the infected patients sperm motility as well as the number of morphologically normal cells were significantly reduced compared with the healthy men. The quantification of the viral DNA revealed that in 31% of the male ejaculates the viral load was high: > 3 Ig10/100000 cells. Conclusion. The detection of HHV and HR HPV in the ejaculate is associated with male infertility. Quantification of the viral DNA in the ejaculate is a useful indicator for monitoring viral infections in infertility and for decision to start therapy. PMID:27451497

  6. LIFE CYCLE IMPACT ASSESSMENT - MIDPOINTS VS. ENDPOINTS

    EPA Science Inventory

    The question of whether to use midpoints or endpoints or both in an LCIA framework is often dependent upon the goal and scope and the decision that is being supported by the LCIA. LCIAs for Enlightenment may not require an aggregation of impact categories and may be most useful ...

  7. IPF clinical trial design and endpoints

    PubMed Central

    Nathan, Steven D.; Meyer, Keith C.

    2014-01-01

    Purpose of review There remains a dire need for therapies that impact the clinical course of patients with idiopathic pulmonary fibrosis (IPF). Indeed, there is a surge of interest in IPF therapeutics, with many candidate agents in various stages of development. Optimal design and implementation of the appropriate prospective clinical trials are essential to demonstrate clinical efficacy of promising drugs for the treatment of IPF. A key element in the success of such clinical trials is the choice of the best endpoint(s) to match the design of the study. Recent findings Although the results of many IPF clinical trials have been disappointing, these trials have provided valuable insights into the epidemiology and natural history of the disease and have sparked debate into the best clinical trial designs and endpoints. Summary This review will discuss the various clinical trial endpoints that have been used or proposed with a focus on their potential utility, as well as possible pitfalls that investigators should consider in the design of such studies. Video abstract http://links.lww.com/COPM/A13 PMID:25022315

  8. A search for immunocontraceptive agent from marine sources--role of antispermatheca globulin of Telescopium telescopium on fertility regulation in male rat.

    PubMed

    Pakrashi, A; Datta, U; Choudhury, A

    1992-11-01

    Polyclonal antisera were developed in rabbits against 'spermatheca', the reproductive gland of T. telescopium, a marine mollusc. The gland contains spermatozoa. Antisera and its IgG fraction (ASTG) indicated common antigenic determinants by immunodiffusion and had titer values 81920 and 1280 against crude antigen extract. Cycling female rats when exposed to passively immunized male rats with different doses of ASTG, had reduction in implantation sites and litter size. Females had pseudopregnancy when exposed to higher doses of immunized males and had normal cycle after 20 days in average. ASTG in male rats caused decrease in weight of the reproductive glands, alteration in sperm concentration, motility and morphology, formation of multinucleated giant cells and vacuoles leading to arrest of spermatogenesis and reduction in seminiferous tubular diameter. The effects were dose dependent with reversible infertility. The results indicate presence of a common antigenic determinants which cross-react with vertebrates and existence of common relation through phylogenetic evolution and their immune responses. PMID:1284054

  9. Germinal vesicle materials are requisite for male pronucleus formation but not for change in the activities of CDK1 and MAP kinase during maturation and fertilization of pig oocytes.

    PubMed

    Ogushi, Sugako; Fulka, Josef; Miyano, Takashi

    2005-10-01

    In amphibian oocytes, it is known that germinal vesicle (GV) materials are essential for sperm head decondensation but not for activation of MPF (CDK1 and cyclin B). However, in large animals, the role of GV materials in maturation and fertilization is not defined. In this study, we prepared enucleated pig oocytes at the GV stage and cultured them to examine the activation and inactivation of CDK1 and MAP kinase during maturation and after electro-activation. Moreover, enucleated GV-oocytes after maturation culture were inseminated or injected intracytoplasmically with spermatozoa to examine their ability to decondense the sperm chromatin. Enucleated oocytes showed similar activation/inactivation patterns of CDK1 and MAP kinase as sham-operated oocytes during maturation and after electro-stimulation or intracytoplasmic sperm injection. During the time corresponding to MI/MII transition of sham-operated oocytes, enucleated oocytes inactivated CDK1. However, penetrating sperm heads in enucleated oocytes did not decondense enough to form male pronuclei. To determine whether the factor(s) involved in sperm head decondensation remains associated with the chromatin after GV breakdown (GVBD), we did enucleation soon after GVBD (corresponding to pro-metaphase I, pMI) to remove only chromosomes. The injected sperm heads in pMI-enucleated oocytes decondensed and formed the male pronuclei. These results suggest that in pig oocytes, GV materials are not required for activation/inactivation of CDK1 and MAP kinase, but they are essential for male pronucleus formation. PMID:16153631

  10. 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.

  11. 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

  12. 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...

  13. Prediction of bull fertility.

    PubMed

    Utt, Matthew D

    2016-06-01

    Prediction of male fertility is an often sought-after endeavor for many species of domestic animals. This review will primarily focus on providing some examples of dependent and independent variables to stimulate thought about the approach and methodology of identifying the most appropriate of those variables to predict bull (bovine) fertility. Although the list of variables will continue to grow with advancements in science, the principles behind making predictions will likely not change significantly. The basic principle of prediction requires identifying a dependent variable that is an estimate of fertility and an independent variable or variables that may be useful in predicting the fertility estimate. Fertility estimates vary in which parts of the process leading to conception that they infer about and the amount of variation that influences the estimate and the uncertainty thereof. The list of potential independent variables can be divided into competence of sperm based on their performance in bioassays or direct measurement of sperm attributes. A good prediction will use a sample population of bulls that is representative of the population to which an inference will be made. Both dependent and independent variables should have a dynamic range in their values. Careful selection of independent variables includes reasonable measurement repeatability and minimal correlation among variables. Proper estimation and having an appreciation of the degree of uncertainty of dependent and independent variables are crucial for using predictions to make decisions regarding bull fertility. PMID:26791329

  14. ATP-Binding Cassette Transporter G26 Is Required for Male Fertility and Pollen Exine Formation in Arabidopsis1[W][OA

    PubMed Central

    Quilichini, Teagen D.; Friedmann, Michael C.; Samuels, A. Lacey; Douglas, Carl J.

    2010-01-01

    The highly resistant biopolymer, sporopollenin, gives the outer wall (exine) of spores and pollen grains their unparalleled strength, shielding these structures from terrestrial stresses. Despite a limited understanding of the composition of sporopollenin, it appears that the synthesis of sporopollenin occurs in the tapetum and requires the transport of one or more sporopollenin constituents to the surface of developing microspores. Here, we describe ABCG26, a member of the ATP-binding cassette (ABC) transporter superfamily, which is required for pollen exine formation in Arabidopsis (Arabidopsis thaliana). abcg26 mutants are severely reduced in fertility, with most siliques failing to produce seeds by self-fertilization and mature anthers failing to release pollen. Transmission electron microscopy analyses revealed an absence of an exine wall on abcg26-1 mutant microspores. Phenotypic abnormalities in pollen wall formation were first apparent in early uninucleate microspores as a lack of exine formation and sporopollenin deposition. Additionally, the highest levels of ABCG26 mRNA were in the tapetum, during early pollen wall formation, sporopollenin biosynthesis, and sporopollenin deposition. Accumulations resembling the trilamellar lipidic coils in the abcg11 and abcg12 mutants defective in cuticular wax export were observed in the anther locules of abcg26 mutants. A yellow fluorescent protein-ABCG26 protein was localized to the endoplasmic reticulum and plasma membrane. Our results show that ABCG26 plays a critical role in exine formation and pollen development and are consistent with a model by which ABCG26 transports sporopollenin precursors across the tapetum plasma membrane into the locule for polymerization on developing microspore walls. PMID:20732973

  15. 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. PMID:27627110

  16. 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

  17. 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.

  18. Biomarkers and correlative endpoints for immunotherapy trials.

    PubMed

    Morse, Michael A; Osada, Takuya; Hobeika, Amy; Patel, Sandip; Lyerly, H Kim

    2013-01-01

    Immunotherapies for lung cancer are reaching phase III clinical trial, but the ultimate success likely will depend on developing biomarkers to guide development and choosing patient populations most likely to benefit. Because the immune response to cancer involves multiple cell types and cytokines, some spatially and temporally separated, it is likely that multiple biomarkers will be required to fully characterize efficacy of the vaccine and predict eventual benefit. Peripheral blood markers of response, such as the ELISPOT assay and cytokine flow cytometry analyses of peripheral blood mononuclear cells following immunotherapy, remain the standard approach, but it is increasingly important to obtain tissue to study the immune response at the site of the tumor. Earlier clinical endpoints such as response rate and progression-free survival do not correlate with overall survival demonstrated for some immunotherapies, suggesting the need to develop other intermediary clinical endpoints. Insofar as all these biomarkers and surrogate endpoints are relevant in multiple malignancies, it may be possible to extrapolate findings to immunotherapy of lung cancer. PMID:23714525

  19. 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…

  20. Some Endpoint Results for β-Generalized Weak Contractive Multifunctions

    PubMed Central

    Alikhani, H.; Gopal, D.; Miandaragh, M. A.; Rezapour, Sh.; Shahzad, N.

    2013-01-01

    We introduce β-generalized weak contractive multifunctions and give some results about endpoints of the multifunctions. Also, we give some results about role of a point in the existence of endpoints. PMID:24348197

  1. 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...

  2. 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

  3. Mammalian Sperm Fertility Related Proteins

    PubMed Central

    Ashrafzadeh, Ali; Karsani, Saiful Anuar; Nathan, Sheila

    2013-01-01

    Infertility is an important aspect of human and animal reproduction and still presents with much etiological ambiguity. As fifty percent of infertility is related to the male partner, molecular investigations on sperm and seminal plasma can lead to new knowledge on male infertility. Several comparisons between fertile and infertile human and other species sperm proteome have shown the existence of potential fertility markers. These proteins have been categorized into energy related, structural and other functional proteins which play a major role in sperm motility, capacitation and sperm-oocyte binding. The data from these studies show the impact of sperm proteome studies on identifying different valuable markers for fertility screening. In this article, we review recent development in unraveling sperm fertility related proteins. PMID:24151436

  4. Reversible antifertility effect of aqueous leaf extract of Allamanda cathartica L. in male laboratory mice.

    PubMed

    Singh, A; Singh, S K

    2008-12-01

    The efficacy of oral administration of aqueous leaf extract of Allamanda cathartica (150 mg kg(-1) body weight day(-1) for 14, 28 and 42 days) in inducing infertility and changes in various male reproductive endpoints was evaluated in Parkes strain mice. The effect of the treatment on organ weight, histopathology, sperm parameters, testosterone level, haematology, serum biochemistry and on fertility indices was assessed. Histologically, testes in extract-treated mice showed nonuniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same sections. The treatment also had adverse effects on motility, viability, morphology and on number of spermatozoa in the cauda epididymidis. Serum levels of testosterone, alanine aminotransferase, aspartate aminotransferase and creatinine, haematological parameters and liver and kidney histoarchitecture were, however, not affected by the treatment. Fertility of the extract-treated males was also suppressed, although the libido remained unaffected. By 56 days of treatment withdrawal, however, the above parameters recovered to control levels. Our results thus suggest that A. cathartica treatment causes reversible suppression of fertility in male mice, without causing detectable toxic effects. PMID:19032682

  5. The Role of Ecological Endpoints in Watershed Management

    EPA Science Inventory

    Landscape change and pollution in watersheds affect ecological endpoints in receiving water bodies. Therefore, these endpoints are useful in watershed management. Fish and benthic macro invertebrates are often used as endpoints, since they are easily measured in the field and int...

  6. Kin recognition and cannibalistic behaviours by adult male fathead minnows ( Pimephales promelas)

    NASA Astrophysics Data System (ADS)

    Green, Warren W.; Mirza, Reehan S.; Pyle, Greg G.

    2008-03-01

    Parental care is an energetically demanding activity that ensures genes are efficiently passed from one generation to the next. According to evolutionary theory, the greatest energetic investment should be directed towards offspring that are most closely related to the parent. Male fathead minnows, Pimephales promelas, provide this parental investment to developing embryos but not newly hatched larvae. Therefore, selection should favour recognition of embryonic kin to ensure energetic expenditure is optimally invested. In this study, adult male fathead minnows were tested using behavioural assays, with egg cannibalism as an endpoint, to determine whether adult males could discriminate between related and unrelated embryos. Egg cannibalism was highest when adult male fathead minnows were presented with unrelated eggs and lowest when presented with eggs fertilized by the test subject (related eggs). The degree of cannibalism was also a function of breeding status. Unrelated males in breeding condition showed an intermediate response between the low cannibalism demonstrated by related males and the high cannibalism demonstrated by unrelated males in a nonbreeding condition. These results suggest that although male fathead minnows can discriminate between unrelated and related embryos, at least some component of parental investment is a simple function of breeding status.

  7. Fertility Awareness

    MedlinePlus

    ... planning, periodic abstinence, and the rhythm method. How Does It Work? If a couple doesn't have ... get pregnant should not have sex. How Well Does It Work? Fertility awareness is not a reliable ...

  8. Helicopter EMS: Research Endpoints and Potential Benefits

    PubMed Central

    Thomas, Stephen H.; Arthur, Annette O.

    2012-01-01

    Patients, EMS systems, and healthcare regions benefit from Helicopter EMS (HEMS) utilization. This article discusses these benefits in terms of specific endpoints utilized in research projects. The endpoint of interest, be it primary, secondary, or surrogate, is important to understand in the deployment of HEMS resources or in planning further HEMS outcomes research. The most important outcomes are those which show potential benefits to the patients, such as functional survival, pain relief, and earlier ALS care. Case reports are also important “outcomes” publications. The benefits of HEMS in the rural setting is the ability to provide timely access to Level I or Level II trauma centers and in nontrauma, interfacility transport of cardiac, stroke, and even sepsis patients. Many HEMS crews have pharmacologic and procedural capabilities that bring a different level of care to a trauma scene or small referring hospital, especially in the rural setting. Regional healthcare and EMS system's benefit from HEMS by their capability to extend the advanced level of care throughout a region, provide a “backup” for areas with limited ALS coverage, minimize transport times, make available direct transport to specialized centers, and offer flexibility of transport in overloaded hospital systems. PMID:22203905

  9. 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

  10. 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.

  11. 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

  12. 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

  13. End-Point Detection With Laser Interferometry

    NASA Astrophysics Data System (ADS)

    Busta, Heinz H.

    1981-04-01

    A laser interferometric method was developed to detect end-of-etching of materials such as doped and undoped polysilicon, Si3N4, Si02 and metals used during different stages of IC and thin film device processing. For metal etching, a detector trace of constant magnitude is obtained until the underlying layers are exposed. At this point, a step change in re-flectivity occurs, signaling the end-point. For the other above mentioned films, a sinu-soidal waveform is obtained which changes its frequency once the film of interest is etched and the underlying layers become exposed. The method is applicable to all of the dry etch-ing processes and will be illustrated in some detail for polysilicon and silicon nitride etching applications using a barrel-type plasma reactor.

  14. [Is the LHRH Agonist Recommended for Fertility Preservation ?].

    PubMed

    Kimura, Kosei; Iwamoto, Mitsuhiko; Tanaka, Satoru; Watanabe, Toru; Aihara, Tomohiko; Sugimoto, Takeki; Miyara, Kyuichiro; Hayashi, Mitsuhiro; Kouno, Tsutomu; Baba, Shinichi; Kawashima, Hiroaki; Hashimoto, Naoki; Uchiyama, Kazuhisa

    2015-08-01

    The POEMS reportedan effect of goserelin for fertility preservation. The Clinical Practice Guideline for Breast Cancer by The Japanese Breast Cancer Society indicates that the use of the LHRH agonist (LHRHa) for preventing chemotherapy-induced early menopause is a grade C-1 recommendation, and its use for fertility preservation is a grade C-2 recommendation. Results from previous studies on the effects of LHRHa for fertility preservation have varied owing to differences in chemotherapy regimens, definitions of ovarian failure, and dosages of tamoxifen. In the POEMS, the primary endpoint of ovarian failure at 2 years was significantly lower, and the secondary endpoint of pregnancy outcomes was better in the combination group; however, precise interpretation is difficult because many cases were excluded. Currently, it is not necessary to revise The Clinical Practice Guideline; however, desirable results from future studies may allow the recommendation of a specific dosage of LHRHa for fertility preservation. PMID:26321722

  15. MedlinePlus: Male Infertility

    MedlinePlus

    ... Male Infertility? (National Institute of Child Health and Human Development) Living With How a Man's Diet Affects Fertility Too (Academy of Nutrition and Dietetics) Related Issues Finasteride (Propecia/Proscar) and ...

  16. REGULATION OF SPERM NUCLEAR REACTIVATION DURING FERTILIZATION

    EPA Science Inventory

    Upon fusion of sperm and oocyte at fertilization, a series of events is initiated whereby the highly compacted sperm nucleus expands and is transformed into a male pronucleus capable of DNA synthesis. The regulation of these early post-fusion fertilization events has been studied...

  17. Age-Related Factors That Influence Fertility

    MedlinePlus

    ... pressure Diabetes Thyroid disease Infection in the uterus PCOS Antiphospholipid syndrome, an autoimmune disorder caused when immune ... male fertility, NIH study suggests Some women with PCOS may have adrenal disorder, NIH researchers suggest Weight ...

  18. 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. PMID:26925808

  19. 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.

  20. 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

  1. Predicting the endpoints of earthquake ruptures.

    PubMed

    Wesnousky, Steven G

    2006-11-16

    The active fault traces on which earthquakes occur are generally not continuous, and are commonly composed of segments that are separated by discontinuities that appear as steps in map-view. Stress concentrations resulting from slip at such discontinuities may slow or stop rupture propagation and hence play a controlling role in limiting the length of earthquake rupture. Here I examine the mapped surface rupture traces of 22 historical strike-slip earthquakes with rupture lengths ranging between 10 and 420 km. I show that about two-thirds of the endpoints of strike-slip earthquake ruptures are associated with fault steps or the termini of active fault traces, and that there exists a limiting dimension of fault step (3-4 km) above which earthquake ruptures do not propagate and below which rupture propagation ceases only about 40 per cent of the time. The results are of practical importance to seismic hazard analysis where effort is spent attempting to place limits on the probable length of future earthquakes on mapped active faults. Physical insight to the dynamics of the earthquake rupture process is further gained with the observation that the limiting dimension appears to be largely independent of the earthquake rupture length. It follows that the magnitude of stress changes and the volume affected by those stress changes at the driving edge of laterally propagating ruptures are largely similar and invariable during the rupture process regardless of the distance an event has propagated or will propagate. PMID:17108963

  2. Endpoint distinctiveness facilitates analogical mapping in pigeons.

    PubMed

    Hagmann, Carl Erick; Cook, Robert G

    2015-03-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due to endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal mapping of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons' capacity for more advanced types of analogical reasoning. This article is part of a Special Issue entitled: Tribute to Tom Zentall. PMID:25447511

  3. Endpoint Distinctiveness Facilitates Analogical Mapping in Pigeons

    PubMed Central

    Hagmann, Carl Erick; Cook, Robert G.

    2015-01-01

    Analogical thinking necessitates mapping shared relations across two separate domains. We investigated whether pigeons could learn faster with ordinal mapping of relations across two physical dimensions (circle size & choice spatial position) relative to random mapping of these relations. Pigeons were trained to relate six circular samples of different sizes to horizontally positioned choice locations in a six alternative matching-to-sample task. Three pigeons were trained in a mapped condition in which circle size mapped directly onto choice spatial position. Three other pigeons were trained in a random condition in which the relations between size and choice position were arbitrarily assigned. The mapped group showed an advantage over the random group in acquiring this task. In a subsequent second phase, reassignment, relations between the dimensions were ordinally reversed for the mapped group and re-randomized for the random group. There was no difference in how quickly matching accuracy re-emerged in the two groups, although the mapped group eventually performed more accurately. Analyses suggested this mapped advantage was likely due endpoint distinctiveness and the benefits of proximity errors during choice responding rather than a conceptual or relational advantage attributable to the common or ordinal map of the two dimensions. This potential difficulty in mapping relations across dimensions may limit the pigeons’ capacity for more advanced types of analogical reasoning. PMID:25447511

  4. Holographic endpoint of spatially modulated phase transition

    SciTech Connect

    Ooguri, Hirosi; Park, Chang-Soon

    2010-12-15

    In a previous paper [S. Nakamura, H. Ooguri, and C. S. Park, Phys. Rev. D 81, 044018 (2010)], we showed that the Reissner-Nordstroem black hole in the five-dimensional anti-de Sitter space coupled to the Maxwell theory with the Chern-Simons term is unstable when the Chern-Simons coupling is sufficiently large. In the dual conformal field theory, the instability suggests a spatially modulated phase transition. In this paper, we construct and analyze nonlinear solutions which describe the endpoint of this phase transition. In the limit where the Chern-Simons coupling is large, we find that the phase transition is of the second order with the mean field critical exponent. However, the dispersion relation with the Van Hove singularity enhances quantum corrections in the bulk, and we argue that this changes the order of the phase transition from the second to the first. We compute linear response functions in the nonlinear solution and find an infinite off-diagonal DC conductivity in the new phase.

  5. Identification of miRNAs and their targets using high-throughput sequencing and degradome analysis in cytoplasmic male-sterile and its maintainer fertile lines of brassica juncea

    PubMed Central

    2013-01-01

    Background Regulatory network of cytoplasmic male sterility (CMS) occurrence is still largely unknown in plants, although numerous researches have been attempted to isolate genes involved in CMS. Here, we employed high-throughput sequencing and degradome analysis to identify microRNAs and their targets using high-throughput sequencing in CMS and its maintainer fertile (MF) lines of Brassica juncea. Results We identified 197 known and 78 new candidate microRNAs during reproductive development of B. juncea. A total of 47 differentially expressed microRNAs between CMS and its MF lines were discovered, according to their sequencing reads number. Different expression levels of selected microRNAs were confirmed by using real-time quantitative PCR between CMS and MF lines. Furthermore, we observed that the transcriptional patterns of these microRNAs could be mimicked by artificially inhibiting mitochondrial F1F0-ATPase activity and its function in MF line by using treatment with oligomycin. Targeted genes of the microRNAs were identified by high-throughput sequencing and degradome approaches, including auxin response factor, NAC (No Apical Meristem) domain transcription factor, GRAS family transcription factor, MYB transcription factor, squamosa promoter binding protein, AP2-type transcription factor, homeobox/homeobox-leucine zipper family and TCP family transcription factors, which were observed to be differentially expressed between CMS and MF. Conclusion Taken together, from these findings we suggested microRNA might participate in the regulatory network of CMS by tuning fork in gene expressions in CMS B. juncea. The differential expression of miRNAs observed between CMS and MF lines suggested that biogenesis of miRNAs could be influenced in the CMS. PMID:23324572

  6. Translating Cancer Trial Endpoints Into the Language of Managed Care

    PubMed Central

    KOGAN, ALLAN JAY; HAREN, MELINDA

    2008-01-01

    Oncology endpoints are an essential component of cancer trials, but often they are confusing, making it difficult to evaluate cancer therapies based on trial data. As more oncology agents hit the market and as indications expand for existing products, familiarity with these endpoints is critical for payers when making coverage decisions. PMID:22478698

  7. 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. PMID:23512871

  8. Antisperm antibodies and in vitro fertilization.

    PubMed

    Janssen, H J; Bastiaans, B A; Goverde, H J; Hollanders, H M; Wetzels, A A; Schellekens, L A

    1992-08-01

    The purpose of this study was to investigate the influence of antisperm antibodies in the male, the female, or both partners on the outcome of in vitro fertilization treatment. The results in terms of ongoing pregnancies in the male and female antibody-positive group were the same as in the antibody-negative group. In the double antibody-positive group two of the three patients became pregnant. When high levels of antisperm antibodies were present on the spermatozoa, the fertilization rate was significantly reduced. In the female positive group no clear relationship between the antibody titer and the fertilization percentage could be detected. Abnormal semen quality was responsible for a much lower fertilization rate than the presence of antibodies. The conclusion of this study is that in vitro fertilization provides an equal change of conception in couples with antisperm antibodies in comparison with couples with no antibodies if the other semen parameters are normal. PMID:1472812

  9. Semen collection and fertility in naturally fertile sandhill cranes

    USGS Publications Warehouse

    Chen, G.; Gee, G.F.; Nicolich, J.M.; Taylor, J.A.

    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. 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.

  11. AB008. Management of fertility post cancer

    PubMed Central

    Smith, James

    2016-01-01

    The successful treatment of males with cancer has led to increasing numbers of men and boys interested in life after cancer. One of the top priorities for many of these males is the opportunity to have a family. Most cancer treatments used for common malignancies in men and boys are associated with impaired fertility; for patients receiving alkylating agents or total body irradiation, severe fertility impairment occurs in most patients. While sperm banking for males, even those as young as 12, facing sterilizing cancer treatment can be effective, this approach requires subsequent use of reproductive procedures such as in vitro fertilization (IVF) or intrauterine insemination to achieve a pregnancy. Most males would prefer to restore their natural ability to father children and avoid these expensive and invasive approaches. No proven method for human male fertility restoration has yet been demonstrated; however, work in many mammalian species and recently in primates has demonstrated that autologous testicular cell transplant (TCT) can restore spermatogenesis after cancer treatment. Promising work in non-primate species has demonstrated the feasibility of in vitro development of mature sperm from neonatal testicular tissue. The safety and efficacy of either approach has not been established in humans. The objective of this lecture is to explore current and future fertility preservation and restoration techniques for males at risk of sterility from medical and surgical treatment.

  12. Exactly solvable model for the QCD tricritical endpoint

    SciTech Connect

    Bugaev, K. A.

    2008-09-15

    An inclusion of temperature and chemical-potential-dependent surface-tension in the gas of quark-gluon bags model resolves a long-standing problem of a unified description of the first-and second-order phase transition with the crossover. The suggested model has an exact analytical solution and allows one to rigorously study the vicinity of the critical endpoint of the deconfinement phase transition. It is found that, at the curve of a zero surface-tension coefficient, there must exist the surface-induced phase transition of the seond or higher order. The present model predicts that the critical endpoint of quantum chromodynamics is the tricritical endpoint.

  13. 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 effect on a clinical endpoint other than survival or irreversible morbidity. 601.41 Section 601.41 Food... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

  14. 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... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

  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, 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 effect on a clinical endpoint other than survival or irreversible morbidity. 601.41 Section 601.41 Food... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

  16. 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 effect on a clinical endpoint other than survival or irreversible morbidity. 601.41 Section 601.41 Food... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

  17. Endpoint behavior of high-energy scattering cross sections

    SciTech Connect

    Chay, Junegone; Kim, Chul

    2010-11-01

    In high-energy processes near the endpoint, there emerge new contributions associated with spectator interactions. Away from the endpoint region, these new contributions are suppressed compared to the leading contribution, but the leading contribution becomes suppressed as we approach the endpoint and the new contributions become comparable. We present how the new contributions scale as we reach the endpoint and show that they are comparable to the suppressed leading contributions in deep inelastic scattering by employing a power-counting analysis. The hadronic tensor in deep inelastic scattering is shown to factorize including the spectator interactions, and it can be expressed in terms of the light cone distribution amplitudes of initial hadrons. We also consider the contribution of the spectator contributions in Drell-Yan processes. Here the spectator interactions are suppressed compared to double parton annihilation according to the power counting.

  18. Determination of 50% endpoint titer using a simple formula.

    PubMed

    Ramakrishnan, Muthannan Andavar

    2016-05-12

    Two commonly used methods for calculating 50% endpoint using serial dilutions are Spearman-Karber method and Reed and Muench method. To understand/apply the above formulas, moderate statistical/mathematical skills are necessary. In this paper, a simple formula/method for calculating 50% endpoints has been proposed. The formula yields essentially similar results as those of the Spearman-Karber method. The formula has been rigorously evaluated with several samples. PMID:27175354

  19. Determination of 50% endpoint titer using a simple formula

    PubMed Central

    Ramakrishnan, Muthannan Andavar

    2016-01-01

    Two commonly used methods for calculating 50% endpoint using serial dilutions are Spearman-Karber method and Reed and Muench method. To understand/apply the above formulas, moderate statistical/mathematical skills are necessary. In this paper, a simple formula/method for calculating 50% endpoints has been proposed. The formula yields essentially similar results as those of the Spearman-Karber method. The formula has been rigorously evaluated with several samples. PMID:27175354

  20. Motor contagion: the contribution of trajectory and end-points.

    PubMed

    Roberts, James W; Hayes, Spencer J; Uji, Makoto; Bennett, Simon J

    2015-07-01

    Increased involuntary arm movement deviation when observing an incongruent human arm movement has been interpreted as a strong indicator of motor contagion. Here, we examined the contribution of trajectory and end-point information on motor contagion by altering congruence between the stimulus and arm movement. Participants performed cyclical horizontal arm movements whilst simultaneously observing a stimulus representing human arm movement. The stimuli comprised congruent horizontal movements or vertical movements featuring incongruent trajectory and end-points. A novel, third, stimulus comprised curvilinear movements featuring congruent end-points, but an incongruent trajectory. In Experiment 1, our dependent variables indicated increased motor contagion when observing the vertical compared to horizontal movement stimulus. There was even greater motor contagion in the curvilinear stimulus condition indicating an additive effect of an incongruent trajectory comprising congruent end-points. In Experiment 2, this additive effect was also present when facing perpendicular to the display, and thus with end-points represented as a product of the movement rather than an external spatial reference. Together, these findings support the theory of event coding (Hommel et al., Behav Brain Sci 24:849-878, 2001), and the prediction that increased motor contagion takes place when observed and executed actions share common features (i.e., movement end-points). PMID:24947759

  1. 77 FR 46444 - Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics (GREAT); Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-03

    ... HUMAN SERVICES Food and Drug Administration Gastroenterology Regulatory Endpoints and the Advancement of... announcing a 4-day public workshop entitled ``Gastroenterology Regulatory Endpoints and the Advancement of... endpoints that can support drug development in the following disease areas: Eosinophilic...

  2. [Fertility and HIV: equal opportunity for everyone].

    PubMed

    Kedem, Eynat; Shahar, Eduardo; Hassoun, Gammal; Pollack, Shimon

    2013-04-01

    Highly active antiretroviral treatment (HAART), the increase in life expectancy and improved HIV viral detection methods, have all led to a change in attitude towards fertility in people living with HIV. There is now acknowledgment of the fundamental rights of HIV patients to parenthood and growing implementation of assisted fertility in this group. The aims of fertility treatment are prevention of infection in HIV-discordant couples, and treatment for fertility problems, identical to the general population. We review the influence of HIV on the reproduction systems of males and females, conditions requiring fertility intervention, various methods that are possible and describe the optional treatment existing in Israel for patients with viral infection, and specifically HIV. PMID:23844527

  3. 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

  4. Sperm chemotaxis promotes individual fertilization success in sea urchins.

    PubMed

    Hussain, Yasmeen H; Guasto, Jeffrey S; Zimmer, Richard K; Stocker, Roman; Riffell, Jeffrey A

    2016-05-15

    Reproductive success fundamentally shapes an organism's ecology and evolution, and gamete traits mediate fertilization, which is a critical juncture in reproduction. Individual male fertilization success is dependent on the ability of sperm from one male to outcompete the sperm of other males when searching for a conspecific egg. Sperm chemotaxis, the ability of sperm to navigate towards eggs using chemical signals, has been studied for over a century, but such studies have long assumed that this phenomenon improves individual male fitness without explicit evidence to support this claim. Here, we assessed fertilization changes in the presence of a chemoattractant-digesting peptidase and used a microfluidic device coupled with a fertilization assay to determine the effect of sperm chemotaxis on individual male fertilization success in the sea urchin Lytechinus pictus We show that removing chemoattractant from the gametic environment decreases fertilization success. We further found that individual male differences in chemotaxis to a well-defined gradient of attractant correlate with individual male differences in fertilization success. These results demonstrate that sperm chemotaxis is an important contributor to individual reproductive success. PMID:26994183

  5. Testosterone and Male Infertility.

    PubMed

    Ohlander, Samuel J; Lindgren, Mark C; Lipshultz, Larry I

    2016-05-01

    Hypogonadism and its therapies have a significant impact on male fertility potential. It is necessary to determine the etiology to treat and counsel the patient appropriately on therapeutic options. For the hypogonadal male on exogenous testosterone, management should begin with cessation of the exogenous testosterone and supplemental subcutaneous human chorionic gonadotropin and an oral follicle-stimulating hormone (FSH)-inducing agent to allow reestablishment of the hypothalamic-pituitary-gonadal axis and spermatogenesis. Further supplemental therapy with recombinant FSH in some patients may be necessary to achieve optimal semen parameters. PMID:27132576

  6. Intermediate markers as surrogate endpoints in cancer research.

    PubMed

    Schatzkin, A

    2000-08-01

    Because studies with surrogate cancer endpoints can be smaller, faster, and substantially less expensive than those with frank cancer outcomes, the use of surrogate endpoints is undeniably attractive. This attractiveness is likely to grow in coming years as the rapidly advancing discoveries in cell and molecular biology generate new therapies requiring testing and new markers that could plausibly serve as surrogates for cancer. Surrogate endpoint studies can certainly be suggestive. They continue to play a legitimate role in phase II studies, and they may give the right answers about intervention effects on or exposure associations with cancer. The problem is the uncertainty attached to most potential surrogates. Except for those few surrogates that are both necessary for and developmentally relatively close to cancer, the existence of plausible alternative pathways makes inferences about cancer from many surrogates problematic. Merely being on the causal pathway to cancer does not in itself constitute surrogate validity. It is the totality of causal connections that is critical. There is, unfortunately, a fairly extensive history of quite plausible surrogate markers giving the wrong answer about various chronic disease therapies. There is no reason to believe that cancer surrogacy is immune to such inferential difficulties. This article is, in part, an invitation, even a plea, for researchers to carry out the investigations necessary to evaluate potential surrogates, particularly surrogate-cancer studies and intervention or exposure-surrogate-cancer mediation analyses. Such studies are needed to generalize from surrogate endpoint findings to cancer. There is, however, an implicit and perhaps unavoidable irony here: the large, long, expensive studies required to evaluate potential surrogates fully are precisely the studies that surrogates were designed to replace. The exposure dependence alluded to earlier complicates matters further: establishing validity for a

  7. Endpoints for Comparative Effectiveness Research in Heart Failure

    PubMed Central

    Allen, Larry A.; Spertus, John A.

    2012-01-01

    With the increasing availability of therapeutic strategies (drugs, devices, disease management systems) and the growing complexity of health care delivery, there is an attendant need for objective evidence of the tangible benefits of different approaches to care. This is particularly true for patients with heart failure, a common, morbid, and resource-intensive disease. There are few well-proven therapies for patients with acute decompensation or for patients with normal LVEF. Comparative effectiveness research (CER) offers an important avenue for making progress in the field. However, CER, like any well-designed research program, requires the explicit articulation of clinically important outcomes to be compared. For patients with heart failure, there is a need to develop endpoint measures that capture the totality of potential benefits and risks for alternative therapeutic approaches. Ultimately, for one therapeutic approach to be considered superior to another, it must improve one of three relevant endpoints: make patients live longer, make them feel better, or save money without adversely affecting the other two goals. Importantly, these outcomes must be measured directly and surrogates should be avoided, even if such surrogates appear to be associated with clinically meaningful, patient-centered outcomes. In this review, we discuss the available CER endpoint domains from both a clinical and a statistical perspective, summarize the wide variety of endpoints used in CER studies, and suggest steps for greater standardization of endpoints across CER studies of patients with heart failure. PMID:23168314

  8. Ovarian fluid allows directional cryptic female choice despite external fertilization.

    PubMed

    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

  9. 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

  10. Semiparametric inference for surrogate endpoints with bivariate censored data.

    PubMed

    Ghosh, Debashis

    2008-03-01

    Considerable attention has been recently paid to the use of surrogate endpoints in clinical research. We deal with the situation where the two endpoints are both right censored. While proportional hazards analyses are typically used for this setting, their use leads to several complications. In this article, we propose the use of the accelerated failure time model for analysis of surrogate endpoints. Based on the model, we then describe estimation and inference procedures for several measures of surrogacy. A complication is that potentially both the independent and dependent variable are subject to censoring. We adapt the Theil-Sen estimator to this problem, develop the associated asymptotic results, and propose a novel resampling-based technique for calculating the variances of the proposed estimators. The finite-sample properties of the estimation methodology are assessed using simulation studies, and the proposed procedures are applied to data from an acute myelogenous leukemia clinical trial. PMID:17651457

  11. Continuous Speech Recognition without End-point Detection

    NASA Astrophysics Data System (ADS)

    Segawa, Osamu; Takeda, Kazuya; Itakura, Fumitada

    A new continuous speech recognition method that does not need the explicit speech end-point detection is proposed. A one-pass decoding algorithm is modified to decode the input speech of infinite length so that, with appropriate non-speech models for silence and ambient noises, continuous speech recognition can be executed without the explicit end-point detection. The basic algorithm 1) decodes a processing block of the predetermined length, 2) tracebacks and finds the boundaries of the processing blocks where the word history in the preceding processing block is merged into one, and 3) restarts decoding from the boundary frame with the merged word history. The effectiveness of the method is verified by the spoken dialogue transcription experiments. With a 5-minute dialogue in a moving car, the proposed method gives better results in word accuracy than the results using the explicit end-point detection method and the conventional one-pass decoder.

  12. Origin of electrical signals for plasma etching endpoint detection

    SciTech Connect

    Sobolewski, Mark A.

    2011-11-14

    Electrical signals are used for endpoint detection in plasma etching, but the origin of the electrical changes observed at endpoint is not known. They may be caused by changes in the gas-phase densities of etch products and reactants or by changes in substrate surface properties such as photoemitted or ion-induced electron yield. To investigate these effects, experiments were performed in an inductively coupled, rf-biased reactor, during CF{sub 4}/Ar etches of SiO{sub 2} films on Si wafers. The rf bias impedance was measured vs. time during etching, simultaneous with Langmuir probe measurements. At endpoint, a decrease in impedance coincided with increases in ion current and electron energy. The data, analyzed by a numerical model of the discharge, indicate that changes in electron emission yield were relatively insignificant or entirely absent. Thus the impedance change is not a surface effect but is, instead, predominantly or entirely a gas-phase phenomenon.

  13. 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.

  14. The Roberge-Weiss phase transition and its endpoint

    NASA Astrophysics Data System (ADS)

    Kouno, Hiroaki; Sakai, Yuji; Kashiwa, Kouji; Yahiro, Masanobu

    2009-11-01

    The Roberge-Weiss (RW) phase transition in the imaginary chemical potential region is analyzed by the Polyakov-loop extended Nambu-Jona-Lasinio (PNJL) model. In the RW phase transition, the charge-conjugation symmetry is spontaneously broken, while the extended {\\mathbb Z}_{3} symmetry (the RW periodicity) is preserved. The RW transition is of second order at the endpoint. At the zero chemical potential, a crossover deconfinement transition appears as a remnant of the second-order RW phase transition at the endpoint, while the charge-conjugation symmetry is always preserved.

  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, 2010 CFR

    2010-04-01

    ... effect on a clinical endpoint other than survival or irreversible morbidity. 601.41 Section 601.41 Food... 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

    ... 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 Food... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect...

  17. 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 effect on a clinical endpoint other than survival or irreversible morbidity. 314.510 Section 314.510 Food... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect...

  18. 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 effect on a clinical endpoint other than survival or irreversible morbidity. 314.510 Section 314.510 Food... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect...

  19. 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 effect on a clinical endpoint other than survival or irreversible morbidity. 314.510 Section 314.510 Food... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect...

  20. Barriers to Managing Fertility: Findings From the Understanding Fertility Management in Contemporary Australia Facebook Discussion Group

    PubMed Central

    Rowe, Heather

    2016-01-01

    Background As part of research investigating the complexities of managing fertility in Australia, public opinions about how Australians manage their fertility were sought from women and men. Objective To identify public opinion about sexual and reproductive health in Australia. Methods To ensure access to a diverse group of people throughout Australia, an online group was advertised and convened on Facebook from October through December 2013. In a closed-group moderated discussion, participants responded to questions about how people in Australia attempt to manage three aspects of fertility: avoiding pregnancy, achieving pregnancy, and difficulties conceiving. Nonidentifiable demographic information was sought; no personal accounts of fertility management were requested. The discussion transcript was analyzed thematically. Results There were 61 female and 2 male Facebook users aged 18 to 50 years living in Australia participating in the study. Four main themes about fertility management were identified: access, geographical location, knowledge, and cost. Participants reported that young people and people from rural areas face barriers accessing contraception and fertility services. Limited knowledge about sex and reproduction and the cost of fertility services and contraception were also said to impede effective fertility management. Conclusions Reasons for inequalities in effective fertility management that are amenable to change were identified. Facebook is an effective method for gaining insights into public opinion about sexual and reproductive health. PMID:26878865

  1. 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...

  2. 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...

  3. Defining response in migraine: which endpoints are important?

    PubMed

    Edmeads, John

    2005-01-01

    The primary endpoint traditionally measured in clinical trials of triptans for acute migraine therapy has been 2-hour pain relief, a decrease in pain intensity from moderate/severe to mild/none. Although harder to achieve, endpoints such as 2-hour pain free and the composite measure sustained pain free are now preferred as they better reflect what patients desire from medication, namely rapid onset of action, and complete and lasting relief of pain. A comprehensive meta-analysis has shown that oral triptans differ in their ability to achieve these endpoints, with almotriptan 12.5 mg, eletriptan 80 mg and rizatriptan 10 mg providing the highest likelihood of success. Although all triptans have simple and consistent pharmacokinetic features, they also have specific differences that may play a part in their differing clinical attributes. Incorporating tolerability to generate a more stringent endpoint, sustained pain free with no adverse events (SNAE), may provide an even better representation of patients' expectations. Comparison of SNAE rates using data from the meta-analysis of oral triptans indicates that almotriptan 12.5 mg has the best balance of high efficacy and good tolerability. PMID:15920334

  4. 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…

  5. Immediate skin responses to laser and light treatments: Therapeutic endpoints: How to obtain efficacy.

    PubMed

    Wanner, Molly; Sakamoto, Fernanda H; Avram, Mathew M; Chan, Henry H; Alam, Murad; Tannous, Zeina; Anderson, R Rox

    2016-05-01

    Clinical endpoints are immediate or early tissue reactions that occur during laser treatment. They can guide the laser surgeon in delivering safe and effective laser treatment. Some endpoints act as warning signs of injury to the skin; others can indicate a therapeutic response. The first article in this series reviewed undesirable and warning endpoints, and this article focuses on desirable and therapeutic endpoints and their underlying mechanisms in laser surgery. We will also review treatments without clinical endpoints. PMID:27085228

  6. Treatment of male infertility.

    PubMed

    Palermo, Gianpiero D; Kocent, Justin; Monahan, Devin; Neri, Queenie V; Rosenwaks, Zev

    2014-01-01

    Major difficulties exist in the accurate and meaningful diagnosis of male reproductive dysfunction, and our understanding of the epidemiology and etiology of male infertility has proven quite complex.The numerous spermatozoa produced in mammals and other species provides some degree of protection against adverse environmental conditions represented by physical and chemical factors that can reduce reproductive function and increase gonadal damage even resulting in testicular cancer or congenital malformations. The wide fluctuations of sperm production in men, both geographical and temporal, may reflect disparate environmental exposures, occurring on differing genetic backgrounds, in varying psychosocial conditions, and leading to the diversified observed outcomes.Sperm analysis is still the cornerstone in diagnosis of male factor infertility, indeed, individually compromised semen paramaters while adequately address therapeutic practices is progressively flanked by additional tests. Administration of drugs, IUI, correction of varicocele, and, to a certain extent, IVF although they may not be capable of restoring fertility itself often result in childbearing. PMID:24782020

  7. 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. PMID:26003938

  8. Segmentation of endpoint trajectories does not imply segmented control.

    PubMed

    Sternad, D; Schaal, S

    1999-01-01

    While it is generally assumed that complex movements consist of a sequence of simpler units, the quest to define these units of action, or movement primitives, remains an open question. In this context, two hypotheses of movement segmentation of endpoint trajectories in three-dimensional human drawing movements are reexamined: (1) the stroke-based segmentation hypothesis based on the results that the proportionality coefficient of the two-thirds power law changes discontinuously with each new "stroke," and (2) the segmentation hypothesis inferred from the observation of piecewise planar endpoint trajectories of three-dimensional drawing movements. In two experiments human subjects performed a set of elliptical and figure eight patterns of different sizes and orientations using their whole arm in three dimensions. The kinematic characteristics of the endpoint trajectories and the seven joint angles of the arm were analyzed. While the endpoint trajectories produced similar segmentation features to those reported in the literature, analyses of the joint angles show no obvious segmentation but rather continuous oscillatory patterns. By approximating the joint angle data of human subjects with sinusoidal trajectories, and by implementing this model on a 7-degree-of-freedom (DOF) anthropomorphic robot arm, it is shown that such a continuous movement strategy can produce exactly the same features as observed by the above segmentation hypotheses. The origin of this apparent segmentation of endpoint trajectories is traced back to the nonlinear transformations of the forward kinematics of human arms. The presented results demonstrate that principles of discrete movement generation may not be reconciled with those of rhythmic movement as easily as has been previously suggested, while the generalization of nonlinear pattern generators to arm movements can offer an interesting alternative to approach the question of units of action. PMID:9928796

  9. Hormone-Based Treatments in Subfertile Males.

    PubMed

    Patel, Darshan P; Chandrapal, Jason C; Hotaling, James M

    2016-08-01

    Subfertility is defined as the condition of being less than normally fertile though still capable of effecting fertilization. When these subfertile couples seek assistance for conception, a thorough evaluation of male endocrine function is often overlooked. Spermatogenesis is a complex process where even subtle alterations in this process can lead to subfertility or infertility. Male endocrine abnormalities may suggest a specific diagnosis contributing to subfertility; however, in many patients, the underlying etiology is still unknown. Optimizing underlying endocrine abnormalities may improve spermatogenesis and fertility. This manuscript reviews reproductive endocrine abnormalities and hormone-based treatments. PMID:27292256

  10. Integration of Mutation and Chromosomal Damage Endpoints into 28-Day Repeat Dose Toxicology Studies

    PubMed Central

    Dertinger, Stephen D.; Phonethepswath, Souk; Franklin, Dean; Weller, Pamela; Torous, Dorothea K.; Bryce, Steven M.; Avlasevich, Svetlana; Bemis, Jeffrey C.; Hyrien, Ollivier; Palis, James; MacGregor, James T.

    2010-01-01

    Two endpoints of genetic toxicity, mutation at the X-linked Pig-a gene and chromosomal damage in the form of micronucleated reticulocytes (MN-RETs), were evaluated in blood samples obtained from 28-day repeat-dosing studies typical of those employed in toxicity evaluations. Male Wistar Han rats were treated at 24-h intervals on days 1 through 28 with one of five prototypical genotoxicants: N-ethyl-N-nitrosourea, 7,12-dimethyl-12-benz[a]anthracene, 4-nitroquinoline-1-oxide (4NQO), benzo(a)pyrene, and N-methyl-N-nitrosourea. Flow cytometric scoring of CD59-negative erythrocytes (indicative of glycosylphosphatidylinositol anchor deficiency and hence Pig-a mutation) was performed using blood specimens obtained on days −1, 15, 29, and 56. Blood specimens collected on days 4 and 29 were evaluated for MN-RET frequency using flow cytometry–based MicroFlow Kits. With the exception of 4NQO, each chemical induced significant increases in the frequency of MN-RETs on days 4 and 29. All five agents increased the frequency of mutant phenotype (CD59 negative) reticulocytes (RETs) and erythrocytes. Mutation responses in RETs occurred earlier than in erythrocytes and tended to peak, or nearly peak, at day 29. In contrast, the mutant phenotype erythrocyte responses were modest on day 29 and required additional time to reach their maximal value. The observed kinetics were expected based on the known turnover of RETs and erythrocytes. The data show that RETs can serve as an appropriate indicator cell population for 28-day studies. Collectively, these data suggest that blood-based genotoxicity endpoints can be effectively incorporated into routine toxicology studies, a strategy that would reduce animal usage while providing valuable genetic toxicity information within the context of other toxicological endpoints. PMID:20202993

  11. Fertility Clinic Success Rates

    MedlinePlus

    ... 2013 Assisted Reproductive Technology Fertility Clinic Success Rates Report Recommend on Facebook Tweet Share Compartir 2013 ART Fertility Clinic Success Rates Report [PDF - 1MB] Bookmarks and thumbnails are available within ...

  12. 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. ...

  13. Commercial Fertilizers 1994

    SciTech Connect

    Berry, J.T.

    1994-12-01

    This document presents a compilation of annual data about fertilizer use in the USA, including statistics about various kinds of fertilizer, how much and where they are used, chemical composition, etc.

  14. 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. PMID:24455130

  15. 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...

  16. 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...

  17. 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. PMID:8014629

  18. Genetic evaluation of beef carcass data using different endpoint adjustments.

    PubMed

    Rumph, J M; Shafer, W R; Crews, D H; Enns, R M; Lipsey, R J; Quaas, R L; Pollak, E J

    2007-05-01

    Carcass data from 6,795 Simmental-sired animals born from 1992 to 2001 were used to determine whether adjustment to a constant age, back-fat, HCW, or marbling score would result in differences in heritability of the carcass traits and, correspondingly, if EPD calculated using those variance components and adjustments would result in sire reranking. The endpoints were age (EPA), backfat (EPF), HCW (EPC), or marbling (EPM). The traits analyzed were 12th-rib backfat (FAT), HCW, marbling (MRB), LM area (LMA), and percentage retail cuts (PRC). The data were analyzed using an animal model, where contemporary group was included as a fixed effect and was composed of slaughter date, sex, and herd. Random effects included in the model were direct genetic and residual. Estimates of heritability ranged from 0.12 to 0.14, 0.32 to 0.34, and 0.26 to 0.27 for FAT, HCW, and LMA, respectively, for the corresponding endpoints. Heritability for MRB was estimated to be 0.27 at all endpoints. For PRC, estimates of heritability were more variable, with estimates of 0.23 +/- 0.05, 0.32 +/- 0.05, 0.21 +/- 0.05, and 0.20 +/- 0.04 for EPA, EPF, EPC, and EPM, respectively. However, because the EPF and EPC adjustments adjust for a component trait of PRC (FAT and HCW, respectively), they may be altering the trait to one different from PRC. Spearman rank correlations between EPD within a trait using EPA compared with the other endpoints were >0.90 (P < 0.01) for FAT, HCW, MRB, and LMA. For PRC, Spearman rank correlations with EPA EPD were 0.73 (P < 0.01), 0.93 (P < 0.01), and 0.95 (P < 0.01) for EPF, EPC, and EPM, respectively. For most traits and endpoints, there was little reranking among sires when alternative endpoints were used. However, adjusting PRC to EPF appears to result in a greater heritability and substantial re-ranking of sires, potentially due to the adjustment changing the trait to one other than PRC. PMID:17224467

  19. 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. PMID:25459976

  20. Roberge-Weiss endpoint in Nf=2 QCD

    NASA Astrophysics Data System (ADS)

    Bonati, Claudio; Cossu, Guido; D'Elia, Massimo; Sanfilippo, Francesco

    2011-03-01

    We present the results of extensive simulations regarding the critical behavior at the endpoint of the Roberge-Weiss transition for Nf=2 QCD. We confirm early evidence, presented in Ref. [M. D’Elia and F. Sanfilippo, Phys. Rev. DPRVDAQ1550-799810.1103/PhysRevD.80.111501 80, 111501(R) (2009).], according to which the Roberge-Weiss endpoint is first order in the limit of large or small quark masses, and second order for intermediate masses. A systematic study of the transition strength as a function of the quark mass in the first order regions, permits us to estimate the tricritical values of the quark mass separating the second order region from the first order ones.

  1. 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

  2. Cervical cancer chemoprevention, vaccines, and surrogate endpoint biomarkers.

    PubMed

    Follen, Michele; Meyskens, Frank L; Alvarez, Ronald D; Walker, Joan L; Bell, Maria C; Storthz, Karen Adler; Sastry, Jagannadha; Roy, Krishnendu; Richards-Kortum, Rebecca; Cornelison, Terri L

    2003-11-01

    At the Second International Conference on Cervical Cancer, held April 11-14, 2002, experts in cervical cancer prevention, detection, and treatment reviewed the need for more research in chemoprevention, including prophylactic and therapeutic vaccines, immunomodulators, peptides, and surrogate endpoint biomarkers. Investigators and clinicians noted the need for more rigorous Phase I randomized clinical trials, more attention to the risk factors that can affect study results in this patient population, and validation of optical technologies that will provide valuable quantitative information in real time regarding disease regression and progression. They discussed the role of the human papillomavirus (HPV) in cervical cancer development and the importance of developing strategies to suppress HPV persistence and progression. Results in Phase I randomized clinical trials have been disappointing because few have demonstrated statistically significant regression attributable to the agent tested. Researchers recommended using a transgenic mouse model to test and validate new compounds, initiating vaccine and immunomodulator trials, and developing immunologic surrogate endpoint biomarkers. PMID:14603541

  3. Commercial fertilizers 1992

    SciTech Connect

    Berry, J.T.; Montgomery, M.H.

    1992-12-01

    Fertilizer consumption information in the USA for 1992 submitted by state regulatory officials is presented. This includes total sales or shipments for farm and non-farm use. Liming materials were excluded. Materials used for manufacture or blending of reported fertilizers or for use in other fertilizers are excluded to avoid double-counting. The consumption of multiple-nutrient and single-nutrient fertilizers is listed. Dry bulk, fluid, and bagged classes are given. Typical fertilizers include: anhydrous ammonia, aqua ammonia, nitrogen solutions, urea, ammonium nitrates, ammonium sulfates, phosphoric acid, superphosphates, potassium chlorides, and potassium sulfates.

  4. Multi-criteria decision analysis of test endpoints for detecting the effects of endocrine active substances in fish full life cycle tests.

    PubMed

    Crane, Mark; Gross, Melanie; Matthiessen, Peter; Ankley, Gerald T; Axford, Stephen; Bjerregaard, Poul; Brown, Ross; Chapman, Peter; Dorgeloh, Michael; Galay-Burgos, Malyka; Green, John; Hazlerigg, Charles; Janssen, John; Lorenzen, Kai; Parrott, Joanne; Rufli, Hans; Schäfers, Christoph; Seki, Masanori; Stolzenberg, Hans-Christian; van der Hoeven, Nelly; Vethaak, Dick; Winfield, Ian J; Zok, Sabine; Wheeler, James

    2010-07-01

    Fish full life cycle (FFLC) tests are increasingly required in the ecotoxicological assessment of endocrine active substances. However, FFLC tests have not been internationally standardized or validated, and it is currently unclear how such tests should best be designed to provide statistically sound and ecologically relevant results. This study describes how the technique of multi-criteria decision analysis (MCDA) was used to elicit the views of fish ecologists, aquatic ecotoxicologists and statisticians on optimal experimental designs for assessing the effects of endocrine active chemicals on fish. In MCDA qualitative criteria (that can be valued, but not quantified) and quantitative criteria can be used in a structured decision-making process. The aim of the present application of MCDA is to present a logical means of collating both data and expert opinions on the best way to focus FFLC tests on endocrine active substances. The analyses are presented to demonstrate how MCDA can be used in this context. Each of 3 workgroups focused on 1 of 3 species: fathead minnow (Pimephales promelas), Japanese medaka (Oryzias latipes), and zebrafish (Danio rerio). Test endpoints (e.g., fecundity, growth, gonadal histopathology) were scored for each species for various desirable features such as statistical power and ecological relevance, with the importance of these features determined by assigning weights to them, using a swing weighting procedure. The endpoint F1 fertilization success consistently emerged as a preferred option for all species. In addition, some endpoints scored highly in particular species, such as development of secondary sexual characteristics (fathead minnow) and sex ratio (zebrafish). Other endpoints such as hatching success ranked relatively highly and should be considered as useful endpoints to measure in tests with any of the fish species. MCDA also indicated relatively less preferred endpoints in fish life cycle tests. For example, intensive

  5. Digit mechanics in relation to endpoint compliance during precision pinch

    PubMed Central

    Nataraj, Raviraj; Audu, Musa L.; Li, Zong-Ming

    2015-01-01

    This study investigates the mechanics of the thumb and index finger in relation to compliant endpoint forces during precision pinch. The objective was to gain insight into how individuals modulate motor output at the digit endpoints and joints according to compliance-related sensory feedback across the digits. Thirteen able-bodied subjects performed precision pinch upon elastic resistance bands of a customized apparatus instrumented with six degree-of-freedom load-cells. Compliance levels were discretely adjusted according to the number of bands connected. Subjects were provided visual feedback to control the rate of force application. Fifteen repetitions of low-to-moderate force (<20 N) pinches were analyzed at each of five compliance levels, during which force and motion data were collected. Joint angles and moments normalized by pinch force magnitude were computed. Second-order polynomials were used to characterize joint mechanics as a function of compliance. The joint degrees-of-freedom (DOFs) at the finger showed greater dependence on compliance for angular position while the thumb joint DOFs demonstrated greater dependence for normalized joint moment. The digits also adjusted coordination of their endpoint forces according to compliance. Overall, the finger may be altering its position to increase load to the joints of the thumb with changing compliance. These findings describe naturally emergent changes in digit mechanics for compliant precision pinch, which involves motor execution in response to endpoint sensory feedback. Identifying and understanding these motor patterns may provide theoretical basis for restoring and rehabilitating sensorimotor pathologies of the hand. PMID:25596633

  6. Second critical endpoints and their bearing on subduction zone magmatism

    NASA Astrophysics Data System (ADS)

    Mibe, K.

    2011-12-01

    Understanding the phase relations in silicate-H2O systems is fundamental for clarifying the physical and chemical evolution of the Earth, because H2O affects melting temperature of rocks, composition of magmas generated, and rheology of rocks. Under high pressure and high temperature conditions, it is known that the solubility of both water in silicate melt and silicate in aqueous fluid increases with increasing pressure. As a result, silicate melt and aqueous fluid in the Earth's interior is expected to become supercritical fluid and the hydrous solidus of the system can no longer be defined beyond a certain critical condition. This condition is called the second critical endpoint and is the point of intersection between the critical curve and hydrous solidus. In recent years, the second critical endpoints in the systems peridotite-H2O and basalt-H2O have been determined using high-pressure and high-temperature X-ray radiography technique [Mibe et al., 2007, JGR; 2011, PNAS]. In these studies, it was concluded that the second critical endpoints in the systems peridotite-H2O and basalt-H2O occurred at around 3.8 and 3.4 GPa, respectively. These results suggest that the aqueous fluid and silicate melt becomes indistinguishable at the depths deeper than ~120 km in the mantle wedge peridotite and ~100 km in the subducting basaltic oceanic crust in subduction zones. The melting temperature of the subducting oceanic crust can no longer be defined beyond this critical condition. The fluid released from subducting oceanic crust at depths deeper than 100 km under volcanic arcs are supercritical fluid rather than aqueous fluid and/or hydrous melts. It is suggested that the position of the second critical endpoint explains why there is a limitation of slab depth (~90 km) where Adakitic magmas are produced and also explains the origin of across-arc geochemical variations of trace elements in volcanic rocks in subduction zones.

  7. Visual information throughout a reach determines endpoint precision.

    PubMed

    Ma-Wyatt, Anna; McKee, Suzanne P

    2007-05-01

    People make rapid, goal-directed movements to interact with their environment. Because these movements have consequences, it is important to be able to control them with a high level of precision and accuracy. Our hypothesis is that vision guides rapid hand movements, thereby enhancing their accuracy and precision. To test this idea, we asked observers to point to a briefly presented target (110 ms). We measured the impact of visual information on endpoint precision by using a shutter to close off view of the hand 50, 110 and 250 ms into the reach. We found that precision was degraded if the view of the hand was restricted at any time during the reach, despite the fact that the target disappeared long before the reach was completed. We therefore conclude that vision keeps the hand on the planned trajectory. We then investigated the effects of a perturbation of target position during the reach. For these experiments, the target remained visible until the reach was completed. The target position was shifted at 110, 180 or 250 ms into the reach. Early shifts in target position were easily compensated for, but late shifts led to a shift in the mean position of the endpoints; observers pointed to the center of the two locations, as a kind of best bet on the position of the target. Visual information is used to guide the hand throughout a reach and has a significant impact on endpoint precision. PMID:17109109

  8. 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

  9. Challenges assessing clinical endpoints in early Huntington disease.

    PubMed

    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

    2010-11-15

    The basic 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. As the advent of genetic testing for HD, it is possible to identify gene carriers before 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 multinational, 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

  10. [Advances in fertility regulation].

    PubMed

    Harper, M J

    1984-02-01

    The author summarizes some crucial research projects in the field of contraception and fertility control which are going on from now to the end of this century. In the next 20 years, numerous new methods and devices for birth control will be used. Among them are some completely new developments and inventions. Certain research items suffered setbecks in the process of development because of poor effectiveness, the nature of toxicity, or strong side effects. Through constant studies and adequate financial support, most of these research projects have become successful. The results have been made possible because of close cooperation among theoretical researchers, toxicity specialists, pathologists, clinical doctors, and technicians. In addition, support from international societies has also contributed to their success. Because of limited financial resources, it is impossible to support all research projects at the same time. Some research projects have been selected as priorities to receive financial support, and these projects include the ones on IUDs, contraceptive vaccines, prediction of ovulation periods, male contraceptives, and others. These research projects are extremely significant for the development of birth control techniques for the next generation. PMID:12339566

  11. The determinants of fertility among Australian Aborigines.

    PubMed

    Cowlishaw, G

    1981-06-01

    This paper concerns the determinants of fertility of precontact Australian Aborigine women. Emphasis is placed on social organization as well as the physical environment and considerations of adaptation. The key to understanding the fertility of Australian Aborigines is the structural tension evident in male-female relations. Ethnographic data on hunter-gatherers fertility indicate a low fertility rate, e.g. 4.7-5.2 live births/woman for the Kung. Traditional Aboriginal physiological fertility was also low if infant mortality is separated from infertility. Past studies of population and transition theory in pre-contact situations have attributed increase in population to reduction in mortality. This paper suggests that there must have been an increase in the birth rate. Factors affecting ovulation, conception, and parturition are examined for traditional Aboriginal populations. Ovulation is affected by nutrition, lactation, and introcision. Lack of body fat in women causes anovulation due to insufficent energy reserves. Increased fertility appears to be a greatly reduced energy expenditure and an increased carbohydrate intake leading to a build up of body weight. Pre-contact Aboriginal fertility was low because of a low caloric intake and a high energy expenditure. Prolonged lactation does not seem to cause birth spacing. The actual length of time after parturition appears to be an independent cause of reduced prolactin, and of reestablishment of ovulation. Stress and anxiety are factors which could reduce fertility by causing anovulation in women and/or reduced sperm counts in men. Contraception is affected by coital frequency and male fertility. Aboriginal coital frequency may have been affected by the lack of privacy and competition of a co-wife. Gestation is affected by spontaneous abortion, sterility, and foetal wastage. Harsh conditions of traditional Aborigines may have affected their ability to conceive. Voluntary controls on fertility for Aborigines

  12. Thyroid, spermatogenesis, and male infertility.

    PubMed

    Rajender, Singh; Monica, Marie Gray; Walter, Lee; Agarwal, Ashok

    2011-01-01

    Since the identification of thyroid hormone receptors on the testes, thyroid has been suggested to have a significant impact on the male reproductive tract, spermatogenesis, and male fertility. Several research articles on the role of thyroid in spermatogenesis or male infertility have been published in the last three decades. We conducted an exhaustive literature search was conducted in order to create an up-to-date review of literature. This review aims to discuss the impact of thyroid on testicular development, spermatogenesis, hypo- or hyper- thyroidism and male infertility, and the management of thyroid related abnormal semen profile. The literature revealed that thyroid significantly impacts testicular development and that abnormal thyroid profile affects semen quality and male fertility by compromising testicular size, sperm motility and ejaculate volume. A clear link exists between thyroid hormones, testicular development and spermatogenesis. Thyroid disease negatively affects spermatogenesis and consequently may cause male infertility. In such cases, infertility is reversible, but more studies need to be conducted, especially in post-pubertal males to cement the current findings. PMID:21622096

  13. Wolbachia infection lowers fertile sperm transfer in a moth

    PubMed Central

    Lewis, Z.; Champion de Crespigny, F. E.; Sait, S. M.; Tregenza, T.; Wedell, N.

    2011-01-01

    The endosymbiotic bacterium Wolbachia pipientis manipulates host reproduction by rendering infected males reproductively incompatible with uninfected females (cytoplasmic incompatibility; CI). CI is believed to occur as a result of Wolbachia-induced modifications to sperm during maturation, which prevent infected sperm from initiating successful zygote development when fertilizing uninfected females' eggs. However, the mechanism by which CI occurs has been little studied outside the genus Drosophila. Here, we show that in the sperm heteromorphic Mediterranean flour moth, Ephestia kuehniella, infected males transfer fewer fertile sperm at mating than uninfected males. In contrast, non-fertile apyrene sperm are not affected. This indicates that Wolbachia may only affect fertile sperm production and highlights the potential of the Lepidoptera as a model for examining the mechanism by which Wolbachia induces CI in insects. PMID:20880864

  14. 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. PMID:27080628

  15. 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.

  16. 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.

  17. High-fertility phenotypes: two outbred mouse models exhibit substantially different molecular and physiological strategies warranting improved fertility.

    PubMed

    Langhammer, Martina; Michaelis, Marten; Hoeflich, Andreas; Sobczak, Alexander; Schoen, Jennifer; Weitzel, Joachim M

    2014-01-01

    Animal models are valuable tools in fertility research. Worldwide, there are more than 400 transgenic or knockout mouse models available showing a reproductive phenotype; almost all of them exhibit an infertile or at least subfertile phenotype. By contrast, animal models revealing an improved fertility phenotype are barely described. This article summarizes data on two outbred mouse models exhibiting a 'high-fertility' phenotype. These mouse lines were generated via selection over a time period of more than 40 years and 161 generations. During this selection period, the number of offspring per litter and the total birth weight of the entire litter nearly doubled. Concomitantly with the increased fertility phenotype, several endocrine parameters (e.g. serum testosterone concentrations in male animals), physiological parameters (e.g. body weight, accelerated puberty, and life expectancy), and behavioral parameters (e.g. behavior in an open field and endurance fitness on a treadmill) were altered. We demonstrate that the two independently bred high-fertility mouse lines warranted their improved fertility phenotype using different molecular and physiological strategies. The fertility lines display female- as well as male-specific characteristics. These genetically heterogeneous mouse models provide new insights into molecular and cellular mechanisms that enhance fertility. In view of decreasing fertility in men, these models will therefore be a precious information source for human reproductive medicine. Translated abstract A German translation of abstract is freely available at http://www.reproduction-online.org/content/147/4/427/suppl/DC1. PMID:24248751

  18. The effects of semen collection on fertility in captive, naturally fertile, sandhill cranes

    USGS Publications Warehouse

    Chen, G.; Gee, G.F.; Nicolich, J.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.

  19. 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. PMID:12307194

  20. Fertility Issues in Disorders of Sex Development.

    PubMed

    Guercio, Gabriela; Costanzo, Mariana; Grinspon, Romina P; Rey, Rodolfo A

    2015-12-01

    Fertility potential should be considered by the multidisciplinary team when addressing gender assignment, surgical management, and patient and family counselling of individuals with disorders of sex development. In 46,XY individuals, defects of gonadal differentiation or androgen or anti-Müllerian hormone synthesis or action result in incomplete or absent masculinization. In severe forms, raised as females, motherhood is possible with oocyte donation if Müllerian ducts have developed. In milder forms, raised as males, azoospermia or oligospermia are frequently found, however paternity has been reported. Most 46,XX patients with normal ovarian organogenesis are raised as females, and fertility might be possible after treatment. PMID:26568498

  1. 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

  2. Challenges in translating endpoints from trials to observational cohort studies in oncology

    PubMed Central

    Ording, Anne Gulbech; Cronin-Fenton, Deirdre; Ehrenstein, Vera; Lash, Timothy L; Acquavella, John; Rørth, Mikael; Sørensen, Henrik Toft

    2016-01-01

    Clinical trials are considered the gold standard for examining drug efficacy and for approval of new drugs. Medical databases and population surveillance registries are valuable resources for post-approval observational research, which are increasingly used in studies of benefits and risk of new cancer drugs. Here, we address the challenges in translating endpoints from oncology trials to observational studies. Registry-based cohort studies can investigate real-world safety issues – including previously unrecognized concerns – by examining rare endpoints or multiple endpoints at once. In contrast to clinical trials, observational cohort studies typically do not exclude real-world patients from clinical practice, such as old and frail patients with comorbidity. The observational cohort study complements the clinical trial by examining the effectiveness of interventions applied in clinical practice and by providing evidence on long-term clinical outcomes, which are often not feasible to study in a clinical trial. Various endpoints can be included in clinical trials, such as hard endpoints, soft endpoints, surrogate endpoints, and patient-reported endpoints. Each endpoint has it strengths and limitations for use in research studies. Endpoints used in oncology trials are often not applicable in observational cohort studies which are limited by the setting of standard clinical practice and by non-standardized endpoint determination. Observational studies can be more helpful moving research forward if they restrict focus to appropriate and valid endpoints. PMID:27354827

  3. INDIVIDUALS VERSUS ORGANISMS VERSUS POPULATIONS IN THE DEFINITION OF ECOLOGICAL ASSESSMENT ENDPOINTS

    EPA Science Inventory

    The choice of endpoints for ecological risk assessments can be controversial, and some ecologists dismiss endpoints below the population level as irrelevant. This paper attempts to clarify the concept of assessment endpoints and what is meant by organismal or population attri...

  4. 40 CFR Appendix A to Part 68 - Table of Toxic Endpoints

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 16 2013-07-01 2013-07-01 false Table of Toxic Endpoints A Appendix A to Part 68 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Endpoints CAS No. Chemical name Toxic endpoint (mg/L) 107-02-8 Acrolein 0.0011 107-13-1 Acrylonitrile...

  5. 40 CFR Appendix A to Part 68 - Table of Toxic Endpoints

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Table of Toxic Endpoints A Appendix A to Part 68 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Endpoints CAS No. Chemical name Toxic endpoint (mg/L) 107-02-8 Acrolein 0.0011 107-13-1 Acrylonitrile...

  6. 40 CFR Appendix A to Part 68 - Table of Toxic Endpoints

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 16 2012-07-01 2012-07-01 false Table of Toxic Endpoints A Appendix A to Part 68 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Endpoints CAS No. Chemical name Toxic endpoint (mg/L) 107-02-8 Acrolein 0.0011 107-13-1 Acrylonitrile...

  7. 40 CFR Appendix A to Part 68 - Table of Toxic Endpoints

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 16 2014-07-01 2014-07-01 false Table of Toxic Endpoints A Appendix A to Part 68 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Endpoints CAS No. Chemical name Toxic endpoint (mg/L) 107-02-8 Acrolein 0.0011 107-13-1 Acrylonitrile...

  8. 78 FR 49530 - Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-14

    ... HUMAN SERVICES Food and Drug Administration Gastroenterology Regulatory Endpoints and the Advancement of... workshop entitled ``Gastroenterology Regulatory Endpoints and the Advancement of Therapeutics (GREAT II... Health. The purpose of this workshop is to provide a forum to consider issues related to endpoints...

  9. The roles played by mitochondrial DNA and nuclear genes in reversions to fertility in S-type male-sterile maize: Progress report, April 1, 1985 through November 30, 1986

    SciTech Connect

    Not Available

    1986-01-01

    Spontaneous cytoplasmic reversion to fertility of cms-S maize has been studied at the mitochondrial DNA (mtDNA) level in the three inbred line backgrounds M825, 38-11 and WF9. In the cases of M825 and 38-11, the free, linear plasmid-like molecules S1 and S2 are lost upon reversion. They are retained, however, upon reversion of cms-S in the WF9 nuclear background. Sequences homologous to S1 and S2 are found in the main mitochondrial genome of cms-S; thus they occur as both free and integrated versions. In M825 cytoplasmic revertants, the left end of the integrated S2 is always disrupted, as compared with the sterile progenitor, as evidenced by the loss of the left-most Pst-1 restriction site. In 38-11 revertants it is the left end of S1 that is disrupted. In the WF9 nuclear background, the integrated S1 and S2 sequences of revertants are not disrupted, but main mitochondrial regions flanking these integrated S sequences are rearranged. In all three inbred line backgrounds there is reorganization around the cytochrome oxidase I gene, while there is generally no rearrangement of the cytochrome oxidase II and apocytochrome B genes.

  10. 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.

  11. Benzo[a]pyrene Effects on Reproductive Endpoints in Fundulus heteroclitus

    PubMed Central

    Booc, Frank; Thornton, Cammi; Lister, Andrea; MacLatchy, Deborah; Willett, Kristine L.

    2014-01-01

    Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that has been implicated in modulating aromatase enzyme function with the potential to interrupt normal reproductive function. The aim of this study was to use a fish model, Fundulus heteroclitus, to assess whether BaP exposure adversely impacts reproduction. Adult fish were exposed to waterborne BaP nominal concentrations of (0, 1, or 10 μg/l) for 28 days. Males and females were combined for the second half of the exposure (days 14–28) in order to quantitate egg production and fertilization success. Egg fertilization and subsequent hatching success of F1 embryos was significantly decreased by the high dose of BaP. In males, both gonad weight and plasma testosterone concentrations were significantly reduced compared to controls by 10 μg/l BaP. Histopathological examination of testes including spermatogonia, spermatocyte and spermatid cyst areas, percentage of cysts per phase, and area of spermatozoa per seminiferous tubule were not significantly affected. Other biomarkers, including male liver weight, liver vitellogenin (vtg) mRNA expression and sperm concentrations, were also not affected. In females, estradiol concentrations were significantly reduced after BaP exposure, but egg production, gonad weight, liver weight, vtg expression and oocyte maturation were not altered. Steroid concentrations in Fundulus larvae from exposed parents at 1 and 3 weeks posthatch were not significantly changed. BaP exposure at these environmentally relevant concentrations caused negative alterations particularly in male fish to both biochemical and phenotypic biomarkers associated with reproduction and multigenerational embryo survival. PMID:24747980

  12. [Treatment of male infertility].

    PubMed

    Jardin, A

    1995-10-28

    Progress in medically assisted procreation has made it possible to obtain an embryon with a single spermatozoid or even a single spermatid. But such advanced technology must not overshadow the basic principles of patient management since there are many other medical or surgical possibilities for improving male fertility. Although the physiological mechanisms leading to azoospermia are relatively well understood, many questions remain as to the origin of oligo-asthenoteratospermia. Varicocela had been incriminated by many authors: in 25% of the cases, surgical care is followed by pregnancy. Other factors including autoimmunity, infection, environment and drugs also have an effect. Careful history taking can identify the main causes of male infertility before the problem of procreation occurs and in cases of definitive azoospermia the principles of management are relatively simple. The true problem is the fact that new techniques such as in vitro fertilization have acquired popularity in the general population but cannot be accepted as the gold standard by the medical community. It must not be forgotten that these artificial techniques cause a major psychological trauma to the couple and can lead to difficult situations (multiple pregnancies, extra embryos) with no totally satisfactory solution. PMID:8545356

  13. Dynamical realization of end-point memory in consolidated materials

    NASA Astrophysics Data System (ADS)

    Vakhnenko, Vyacheslav O.; Vakhnenko, Oleksiy O.; TenCate, James A.; Shankland, Thomas J.

    2006-05-01

    Starting with a soft-ratchet model of slow dynamics in nonlinear resonant response of sedimentary rocks we predict the dynamical realization of end-point memory in resonating bar experiments with a cyclic frequency protocol. The effect we describe and simulate is defined as the memory of previous maximum amplitude of alternating stress and manifested in the form of small hysteretic loops inside the big hysteretic loop on the resonance curve. It is most clearly pronounced in the vicinity of bar resonant frequency. These theoretical findings are confirmed experimentally.

  14. 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.

  15. ASPREE Cancer Endpoints Study | Division of Cancer Prevention

    Cancer.gov

    The ASPREE Cancer Endpoint Study (ACES), an ancillary study of the ASPirin in the Prevention of Events in the Elderly (ASPREE) Study, will allow for the examination of the effect of daily low-dose aspirin (100 mg) compared to placebo, on specific DNA biomarkers and selected specific incident and recurrent cancer and metastases. The establishment of this ACES biobank will allow for the exploration of DNA-related molecular mechanisms of aspirin's protective effect against cancer, cancer associated mortality and metastases, using blood or saliva DNA specimens, urine, and tumor tissue. |

  16. 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

  17. Condoms - male

    MedlinePlus

    ... Rubbers; Male condoms; Contraceptive - condom; Contraception - condom; Barrier method - condom ... infections.) Latex rubber Polyurethane Condoms are the only method of birth control for men that are not ...

  18. 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…

  19. 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. PMID:27085227

  20. Mapping and characterization of Rf5: A new gene conditioning pollen fertility restoration in A1 and A2 cytoplasm in sorghum (Sorghum bicolor (L.) Moench)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    With an aim to further characterize the cytoplasmic male sterility-fertility restoration system in sorghum, a major fertility restoration gene was mapped, along with a second locus capable of partial restoration of pollen fertility. The major fertility restoration gene, Rf5, was located on sorghum ...

  1. Fertility and pacification among the Mekranoti of Central Brazil.

    PubMed

    Werner, D

    1983-06-01

    Demographic data from 3 different historical periods of the Mekranoti-Kayapo Indians of Central Brazil were used to examine various explanations for historical changes in fertility among this group. The possible effects of warfare on Mekranoti fertility were also examined since warfare has had an important role in many preindustrial societies. The Mekranoti are a group of 285 relatively unacculturated Indians living in a single village in southern Para, Brazil. As in precontact days, their economy is based on slash and burn agriculture, hunting, and fishing. To assess Mekranoti fertility, pregnancy histories collected from all women 15 years or older as of December 1976 were used. In precontact years a woman who survived to age 50 could expect to give birth 6.5 times. During the contact years this average dropped to 5.6 and in the postcontact period it soared to almost 8.5. The drop in Mekranoti fertility from precontact to contact years corresponds with an increase in mortality. The direction of these changes would support a "health" argument about fertility, but the degrees of change do not. Whereas mortality increased markedly after 1955, fertility fell only slightly. The data are not consistent with the view that changes in lactation periods are responsible for fertility changes. The number of uses of contraceptives per reproductive woman year did not not vary much in the different historical periods and certainly could not account for differences in Mekranoti fertility. The data suggest that fertility changes over Mekranoti history may be due in part to sexual abstinence resulting either from postpartum sexual taboos or, more importantly, from a lack of husbands. Sex imbalances resulting from high male mortality in warfare and subsequent disruption of marriages by disease and death left many women without spouses for long periods of time. The findings are consistent with other studies that found lower fertility associated with male absence. The Mekranoti are

  2. Critical endpoint for deconfinement in matrix and other effective models

    NASA Astrophysics Data System (ADS)

    Kashiwa, Kouji; Pisarski, Robert D.; Skokov, Vladimir V.

    2012-06-01

    We consider the position of the deconfining critical endpoint, where the first order transition for deconfinement is washed out by the presence of massive, dynamical quarks. We use an effective matrix model, employed previously to analyze the transition in the pure glue theory. If the parameters of the pure glue theory are unaffected by the presence of dynamical quarks, and if the quarks only contribute perturbatively, then for three colors and three degenerate quark flavors this quark mass is very heavy, mde˜2.5GeV, while the critical temperature Tde barely changes, ˜1% below that in the pure glue theory. The location of the deconfining critical endpoint is a sensitive test to differentiate between effective models. For example, models with a logarithmic potential for the Polyakov loop give much smaller values of the quark mass, mde˜1GeV, and a large shift in Tde˜10% lower than that in the pure glue theory.

  3. Biomarkers and cognitive endpoints to optimize trials in Alzheimer's disease

    PubMed Central

    Insel, Philip S; Mattsson, Niklas; Mackin, R Scott; Kornak, John; Nosheny, Rachel; Tosun-Turgut, Duygu; Donohue, Michael C; Aisen, Paul S; Weiner, Michael W

    2015-01-01

    Objective To find the combination of candidate biomarkers and cognitive endpoints to maximize statistical power and minimize cost of clinical trials of healthy elders at risk for cognitive decline due to Alzheimer's disease. Methods Four-hundred and twelve cognitively normal participants were followed over 7 years. Nonlinear methods were used to estimate the longitudinal trajectories of several cognitive outcomes including delayed memory recall, executive function, processing speed, and several cognitive composites by subgroups selected on the basis of biomarkers, including APOE-ε4 allele carriers, cerebrospinal fluid biomarkers (Aβ42, total tau, and phosphorylated tau), and those with small hippocampi. Results Derived cognitive composites combining Alzheimer's Disease Assessment Scale (ADAS)-cog scores with additional delayed memory recall and executive function components captured decline more robustly across biomarker groups than any measure of a single cognitive domain or ADAS-cog alone. Substantial increases in power resulted when including only participants positive for three or more biomarkers in simulations of clinical trials. Interpretation Clinical trial power may be improved by selecting participants on the basis of amyloid and neurodegeneration biomarkers and carefully tailoring primary cognitive endpoints to reflect the expected decline specific to these individuals. PMID:26000325

  4. Population-scale assessment endpoints in ecological risk assessment. Part 1: Reflections of stakeholder values.

    PubMed

    Landis, Wayne G

    2006-01-01

    The selection of appropriate assessment endpoints is a basic element of an ecological risk assessment, especially at regional or watershed scales. Because ecological services often are tied to specific species, the risk to populations is a critical endpoint and feature of ecological risk assessments. The first item is a discussion of the replacement of population-level risk assessment with the construct of a population-scale assessment endpoint. Next, the criteria that are currently used for assessment endpoints are reviewed and evaluated for utility in an ecological risk assessment. Following this examination, assessment endpoints from a number of regional-scale ecological risk assessments are compared. The outcome of this evaluation is that population-scale assessment endpoints are important expressions of the valued components of ecological structures. Finally, a few recommendations for the selection of assessment endpoints at a population scale are listed. PMID:16640323

  5. Commercial fertilizers 1991

    SciTech Connect

    Hargett, N.L.; Berry, J.T.; Montgomery, M.H.

    1991-12-01

    This document contains consumption data for commercial fertilizers in the USA for 1991. Graphical information on the consumption by class is given for the nation. State by state data for consumption of several types of commercial fertilizers are presented. Only numerical data is included.

  6. 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

  7. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

    PubMed

    Koch, Amory; 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

  8. 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

    ... effect on a clinical endpoint other than survival or irreversible morbidity. 314.510 Section 314.510 Food... a clinical endpoint other than survival or irreversible morbidity. FDA may grant marketing approval for a new drug product on the basis of adequate and well-controlled clinical trials establishing...

  9. Advances in the management of male infertility.

    PubMed

    Haidl, Gerhard

    2009-01-01

    Male infertility can be treated by surgical procedures (e.g., varicocelectomy) or by administration of drugs if causal factors (e.g., seminal tract infections) are detected. In more severe cases, methods of assisted fertilization often have to be applied, but even these have only a limited success rate. Recent studies have demonstrated that disturbances of sperm DNA integrity (determined by the acridine orange test) can explain certain cases of fertilization failure and failure to achieve pregnancy following in vitro fertilisation with intracytoplasmic sperm injection. The evaluation of DNA integrity should be considered when diagnosing male infertility as it has been shown to be an independent factor and can be used as a supplement to standard semen analysis. Analysis of DNA integrity may, therefore, provide further information about altered male fertility and lead to administration of more appropriate therapy. PMID:20948685

  10. TVA fertilizer patents

    SciTech Connect

    Mackey, J.J.; Aldridge, J.W.

    1980-12-01

    Fertilizer research has been an important function of the Tennessee Valley Authority from the time it was established in 1933 to the present. During this period there have been extensive changes in the fertilizer industry. New and improved products have been developed and more efficient manufacturing methods have emerged. Products and processes developed by TVA are in widespread use today in the fertilizer industry. This bulletin is a collection of abstracts of patents granted to TVA on fertilizer technology and related topics over about 45 years. It contains 200 abstracts of patents. The abstracts have been divided into 13 major sections. Each section reflects the improved technology through this period of time. Abstracts of some of the patents issued to TVA since 1968 have already appeared in Fertilizer Abstracts, a journal published monthly since 1968. Inventor and subject indexes are provided in this bulletin.

  11. [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. PMID:12336394

  12. 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. PMID:27085935

  13. Social mobility and fertility.

    PubMed

    Kasarda, J D; Billy, J O

    1985-01-01

    This review examines 4 possible causal links between social mobility and fertility: 1) fertility affects social mobility; 2) social mobility affects fertility; 3) fertility and social mobility simultaneously affect each other; and 4) social mobility and fertility are unrelated. Due to the lack of systematic theory guiding the research, conceptualizations and measures of social mobility and fertility vary markedly from study to study, leading to inconsistent findings. The review focuses on theoretical perspectives underpinning the research, causal operators proposed to interpret observed associations, and analytical methods used. The selectivity perspective is based on the contention that a family must be small in order to rise on the social scale. This has found little support, however. In fact, studies suggest that children induce slightly higher levels of status achievement and family responsibilities may stimulate the energy and ambition of some so that they achieve more than they would have done without a family. Most studies have concerned the hypothesis that social mobility affects fertility. 4 theoretical perspectives have emerged: status enhancement; relative economic status; social isolation; and stress and disorientation. At any time in a couple's reproductive life cycle the decision or actual experience of either social mobility or fertility may influence the decision or actual experience of the other variable. Mobility-fertility research has defined an individual's or couple's position in terms of income, education, or occupation with occupation used most often as a single index of social class and indexes of social mobility developed by comparing persons' changes in occupational position. A common theme in much of the research literature is that the existence of an effect of social mobility on fertility depends on the societal conditions of a given population. Most studies through the mid-60s used a common measurement method to assess whether a

  14. Fluctuations in neighbourhood fertility generate variable signalling effort

    PubMed Central

    Taff, Conor C.; Patricelli, Gail L.; Freeman-Gallant, Corey R.

    2014-01-01

    Studies of sexual signalling generally focus on interactions between dyadic pairs, yet communication in natural populations often occurs in the context of complex social networks. The ability to survey social environments and adjust signal production appropriately should be a critical component of success in these systems, but has rarely been documented empirically. Here, we used autonomous recording devices to identify 118 472 songs produced by 26 male common yellowthroats (Geothlypis trichas) over two breeding seasons, coupled with detailed surveys of social conditions on each territory. We found strong evidence that common yellowthroat males adjusted their total song production in response to both changes in within-pair social context and changes in the fertility of neighbouring females up to 400 m away. Within the social pair, males drastically reduced their song production when mated, but the magnitude of this reduction depended on both the time of day and on the fertility status of the social mate. By contrast, when fertile females were present on nearby territories, males increased their song output, especially during daytime singing. At this time, it is unclear whether males actively gathered information on neighbouring female fertility or whether the patterns that we observed were driven by changes in social interactions that varied with neighbourhood fertility. Regardless of the mechanism employed, however, subtle changes in the social environment generated substantial variation in signalling effort. PMID:25339717

  15. Neoadjuvant endocrine therapy: Patient selection, treatment duration and surrogate endpoints.

    PubMed

    Yeo, Belinda; Dowsett, Mitch

    2015-11-01

    Neoadjuvant endocrine treatment has become of increasing interest for downstaging primary ER+ breast cancers as it has become clear that the pathologic complete response rate of luminal tumours to chemotherapy is much lower than that of non-luminal and differs little from that to endocrine therapy. There is much more experience in postmenopausal than premenopausal women. Aromatase inhibitors are generally the agent of choice. Responses are lower in those with the low levels of ER. While duration of endocrine treatment in clinical trials has usually been standardized at around three to four months it is clear that volume reductions continue to occur beyond that time in a large proportion of cases and routine clinical practice is often to treat to maximum response. This relatively slow emergence of downstaging relates to the absence of any increase in apoptosis with endocrine therapy and dependence of responses on the antiproliferative effects of oestrogen withdrawal: apoptosis occurs but at a slightly lower rate such that cell loss is attritional. The dependence of responses on the reduced proliferation underpins the value of Ki67 as an intermediate end-point for treatment benefit with multiple studies having found that relative effects on proliferation by different drugs in neoadjuvant trials match their relative impact on recurrence. While change in Ki67 is now accepted as a validated endpoint for comparing endocrine agents in the neoadjuvant scenario, on-treatment levels of Ki67 are related to long-term prognosis more closely than pretreatment Ki67. The Preoperative Endocrine Prognostic Index (PEPI) that combines residual Ki67 score with measures of on-treatment ER and other clinicopathologic factors has also found application in clinical trials. The potential to make longitudinal assessments of both clinical and biomarker responses has encouraged the development of novel clinical trial designs for assessing the impact of agents that aim to enhance response

  16. Sperm investment in male meadow voles is affected by the condition of the nearby male conspecifics

    PubMed Central

    delBarco-Trillo, Javier; Ferkin, Michael H.

    2008-01-01

    Sperm competition occurs when 2 or more males copulate with a particular female during the same reproductive cycle, and their sperm compete to fertilize the female's available eggs. One strategy that male voles use to assess the risk and intensity of sperm competition involves responding to the presence of scent marks of conspecific males found near a sexually receptive female. Previously, we have shown that if a male vole copulated with a female while he was in the presence of the odors of another male he increased his sperm investment relative to his investment if another male's odors were not present. The aim of the present study was to test the hypothesis that males assess differences in the relative quality of competing males and adjust their sperm investment accordingly. We did so by allowing males to copulate when they were exposed to the scent mark of a 24-h food-deprived male (low-quality male) or the scent mark of a male that was not food deprived (high-quality male). The data indicate that male meadow voles did not increase their sperm investment during copulation when exposed to the scent mark of a food-deprived male but did so when they were exposed to the scent mark of a male that was not food deprived. The results support the hypothesis that male voles are able to adjust sperm investment when they encounter the scent marks of males that differ in quality. PMID:19529815

  17. Fertility regulating agents from traditional Chinese medicines.

    PubMed

    Kong, Y C; Xie, J X; But, P P

    1986-01-01

    Chinese scientists have capitalized on the rich flora and the ethnomedical experience in China, in their pursuit of fertility regulating agents from natural products. Discoveries range from anti-implantation agents to abortifacient and pregnancy-terminating compounds, as well as a male contraceptive. Chemistry and bioactivity of these compounds and materials are reviewed in this paper, with the hope that further research and collaboration will take place to help solve the problem of population explosion. PMID:3520152

  18. 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. PMID:24419521

  19. Clinical guide to fertility preservation in hematopoietic cell transplant recipients

    PubMed Central

    Joshi, S; Savani, BN; Chow, EJ; Gilleece, MH; Halter, J; Jacobsohn, DA; Pidala, J; Quinn, GP; Cahn, J-Y; Jakubowski, AA; Kamani, NR; Lazarus, HM; Rizzo, JD; Schouten, HC; Socie, G; Stratton, P; Sorror, ML; Warwick, AB; Wingard, JR; Loren, AW; Majhail, NS

    2014-01-01

    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. PMID:24419521

  20. Use of behavioral endpoints in natural resource damage assessment

    SciTech Connect

    Lipton, J.; Marr, J.

    1994-12-31

    Behavioral effects caused by exposure to hazardous substances can play an important role in Natural Resource Damage Assessment (NRDA) cases. Behavioral avoidance has been recognized as a natural resource injury in the Department of Interior`s NRDA regulations. Behavioral avoidance may be particularly important as an NRDA endpoint because it can occur at exposure concentrations substantially less than lethal concentrations, and can result in the effective loss of aquatic habitat. For example, in a recent NRDA case, laboratory testing demonstrated behavioral avoidance at copper concentrations of 1.2 {micro}g/l and 6 {micro}g/l for rainbow and brown trout, respectively. Other behavioral effects may have similar adverse effects on populations in the wild and may merit inclusion in NRDA injury and restoration studies.

  1. [Endpoints in clinical trials and their relevance for patients].

    PubMed

    Faber, Ulrike

    2010-01-01

    Patient participation, which has been established since 2004, has brought more attention to patients' concerns in healthcare. More and more endpoints in clinical trials are defined with respect to their relevance for patients. But this development has still been found wanting. For important drugs, no evidence-based benefit has been demonstrated in the benefit assessment, which also has become possible since 2004. Furthermore, this assessment has arrived too late for patients who have been medicated for a long time. Healthcare policies, applicants and stakeholders have contributed a lot to the patients' scepticism towards benefit assessments, though, in principle, patients are interested in high evidence levels and reasonable pricing. New drugs are often licensed under less ambitious conditions. Whether this is in the patients' interest needs to be put up for a large-scale, and societal, discussion. PMID:20608257

  2. Condoms - male

    MedlinePlus

    ... PREGNANCY? If the sperm contained in a male's semen reach a woman's vagina, pregnancy may occur. Condoms ... receptacle) on the end of it (to collect semen), place the condom against the top of the ...

  3. 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

  4. Mouse handling limits the impact of stress on metabolic endpoints.

    PubMed

    Ghosal, Sriparna; Nunley, Amanda; Mahbod, Parinaz; Lewis, Alfor G; Smith, Eric P; Tong, Jenny; D'Alessio, David A; Herman, James P

    2015-10-15

    Studies focused on end-points that are confounded by stress are best performed under minimally stressful conditions. The objective of this study was to demonstrate the impact of handling designed to reduce animal stress on measurements of glucose tolerance. A cohort of mice (CD1.C57BL/6) naïve to any specific handling was subjected to either a previously described "cup" handling method, or a "tail-picked" method in which the animals were picked up by the tail (as is common for metabolic studies). Following training, an elevated plus maze (EPM) test was performed followed by measurement of blood glucose and plasma corticosterone. A second cohort (CD1.C57BL/6) was rendered obese by exposure to a high fat diet, handled with either the tail-picked or cup method and subjected to an intraperitoneal glucose tolerance test. A third cohort of C57BL/6 mice was exposed to a cup regimen that included a component of massage and was subjected to tests of anxiety-like behavior, glucose homeostasis, and corticosterone secretion. We found that the cup mice showed reduced anxiety-like behaviors in the EPM coupled with a reduction in blood glucose levels compared to mice handled by the tail-picked method. Additionally, cup mice on the high fat diet exhibited improved glucose tolerance compared to tail-picked controls. Finally, we found that the cup/massage group showed lower glucose levels following an overnight fast, and decreased anxiety-like behaviors associated with lower stress-induced plasma corticosterone concentration compared to tail-picked controls. These data demonstrate that application of handling methods that reduce anxiety-like behaviors in mice mitigates the confounding contribution of stress to interpretation of metabolic endpoints (such as glucose tolerance). PMID:26079207

  5. Novel Drug Therapies for Fertility Preservation in Men Undergoing Chemotherapy: Clinical Relevance of Protector Agents.

    PubMed

    Rabaça, A; Sousa, M; Alves, M G; Oliveira, P F; Sá, R

    2015-01-01

    Cancer has been affecting a growing number of children, adolescents and adult males in reproductive age. Male reproductive potential is adversely affected by chemotherapeutic drugs and patients are at risk for prolonged infertility. Fertility recovery is related to the chemotherapeutic agent and dosage used, being thus difficult to predict. As a result, there is a strong need to identify a natural or synthetic compound that is able to preserve male fertility without interfering with the efficacy of the chemotherapeutic regimen. New procedures, as well as several drugs, are being investigated to assess their efficiency in protecting male reproductive functions from the chemotherapy side-effects. This review provides an overview of the wide range of chemotherapeutic drugs regularly used in cancer treatment and their detrimental effects on male fertility. In addition, it also assesses the existing protector agents for male fertility and their usefulness in preserving and protecting male reproductive functions exposed to chemotherapeutics. Several protector agents for male fertility are being studied, and results are promising. Nonetheless, further research must be implemented to identify a supplemental therapy that addresses the multiple side effects of chemotherapy on male reproductive function. Until such therapy is discovered, it is fundamental that all fertility preservation options are discussed with patients, before treatment is initiated, to assure parenthood. PMID:26295467

  6. Fertility preservation for boys and adolescents facing sterilizing medical therapy

    PubMed Central

    Hussein, Ahmed A.; Tran, Nam D.

    2014-01-01

    Improvements in childhood cancer survival have allowed boys and their families to increasingly focus on quality of life after therapy, particularly their future ability to father children. Treatments should maintain comprehensive cancer care goals and consider the long-term quality of life of these children. While semen cryopreservation is a well-established method of fertility preservation for post-pubertal children, the use of cryopreserved pre-treatment testicular tissue represents a promising, yet experimental method of fertility preservation for prepubertal males facing sterilizing therapy. Healthcare providers should counsel families about the fertility risks of therapy, discuss or refer patients for standard fertility preservation options, and consider experimental approaches to fertility preservation while being mindful of the ethical questions these treatments raise. PMID:26816794

  7. Semen predictors of in vitro fertilization and embryo cleavage.

    PubMed

    Daya, S; Gunby, J; Kohut, J

    1989-11-01

    In vitro fertilization treatment for male infertility is not very successful because fertilization is known to be affected by semen quality. Information on fertilizing ability may provide prognostic information for couples contemplating such treatment. The purpose of this study was to identify semen variables that would predict fertilization and embryo cleavage. Sperm was prepared by the swim-up method before insemination of oocytes obtained by laparoscopy after ovulation induction. Routine semen analysis and the hypoosmotic swelling test for assessment of sperm membrane integrity were performed on aliquots of prepared sperm. Logistic regression and receiver-operator characteristic curve analyses were performed to determine the overall best-fitting model and discriminatory level of variables that would predict cleavage. The results indicate that after the swim-up procedure, at least 10 million sperm/ml, capable of undergoing swelling in hypoosmotic medium, are necessary to increase the likelihood of in vitro fertilization and cleavage. PMID:2589452

  8. 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.

  9. 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.

  10. [Fertility and cancer].

    PubMed

    Poirot, Catherine; Sitbon, Leslie; Fortin, Anne; Berthaut, Isabelle; Jaudi, Suha; Anastacio, Amandine; Prades, Marie

    2013-11-01

    Information about chemo and/or radiotherapy gonadotoxicity and about fertility preservation is essential. Sperm cryopreservation has to be systematically offered before gonadotoxic treatments. Efficiency of ovarian function preservation with GnRH agonists is still debated. A controlled ovarian stimulation is necessary before oocyte or embryo cryopreservation. It is only feasible if the treatment is not urgent and if the tumor is not hormone-sensitive. If the treatment is highly gonadotoxic, an ovarian tissue cryopreservation may be appropriate. It is the only fertility preservation technique feasible for prepubertal girls. It is now possible to preserve the fertility of prepubertal boys by cryopreservation of testicular tissue. It is essential to send patients and/or their parents to a specialized fertility preservation center. PMID:24184281

  11. Infertility and Fertility

    MedlinePlus

    ... NICHD Research Information Clinical Trials Resources and Publications Infertility and Fertility: Condition Information Skip sharing on social media links Share this: Page Content What is infertility? "Infertility" is a term that describes when a ...

  12. TCRC Fertility Page

    MedlinePlus

    ... and then use the sperm in conjunction with artificial insemination , IVF or ICSI . Fertility and Chemotherapy: The chemotherapy ... the high probability of an indefinite period of infertility following chemotherapy, we strongly recommend that men facing ...

  13. 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...

  14. Weight and Fertility

    MedlinePlus

    ... evidence that obesity lowers the success rates of in vitro fertilization (IVF). Studies have shown lower pregnancy rates and higher miscarriage rates in obese women. Obese women are at an increased ...

  15. Bioremediation with oleophilic fertilizer

    SciTech Connect

    Basseres, A.; Ladousse, A.

    1993-12-31

    To enhance hydrocarbon breakdown by indigenous microbial communities, a fertilizer formulation that would keep nutrients in contact with oil, was designed ten years ago by ELF AQUITAINE. The fertilizer known as INIPOL EAP 22 is an oil soluble additive but also an easily biodegradable carbon source (oleic acid). Numerous experiments, in both laboratory and field, have shown that the application of this fertilizer increases the number of hydrocarbon degrading organisms and the extent and rate of hydrocarbon biodegradation Laboratory experiments with radiolabelled hydrocarbons have shown that in addition to its physico chemical role, oleic acid acts as a biological starter, increasing the biomass and the rate of biodegradation. A large bioremediation project in ALASKA has shown that it its possible to enhance the biodegradation of oil through the application of such a fertilizer, on coarse sediments. Recently, on sandy sediments, the use of INIPOL EAP 22 shown a clear development in hydrocarbon specific bacteria, and an increase of the rate of biodegradation.

  16. Cryptorchidism and Fertility.

    PubMed

    Virtanen, Helena E; Toppari, Jorma

    2015-12-01

    Congenital cryptorchidism, that is, undescended testis, is one of the most common urogenital abnormalities observed in newborn boys. In addition to the congenital form, there is also acquired form of cryptorchidism. Fertility potential of patients with cryptorchidism has been evaluated by testicular histology and volume, semen quality, reproductive hormone levels, time to conception, and paternity rates. Cryptorchidism is associated with abnormalities in testicular development, and early treatment is recommended to optimize the fertility potential of the patients. PMID:26568490

  17. North American fertilizer capacity data

    SciTech Connect

    Not Available

    1991-12-01

    This listing of producers and their fertilizer production capacities was compiled in October 1991 with the cooperation of the US and Canadian fertilizer industry. Fertilizers production is reported or forecasted for the years 1987 through 1997. The fertilizers reported on are: ammonia, ammonium nitrate, nitrogen solutions, urea, phosphate rock, wet-process phosphoric acid, ammonium phosphates, concentrated superphosphates, and potash.

  18. End-point Region of the Electron Spectrum in Inclusive Semileptonic Heavy Quark Decay

    SciTech Connect

    Isgur, Nathan

    1992-01-01

    I examine the relationship between the inclusive and sum-over-exclusive-resonances pictures for the electron spectrum of semileptonic heavy quark decay. The analysis shown to that obtained from a free-quark-decay-type model with an endpoint adjusted to the physical endpoint. This conclusion removes the need for nonresonant contributions in the endpoint region and is consistent with arguments that free-quark-decay-type models are, in principle,

  19. 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.

  20. Long sperm fertilize more eggs in a bird.

    PubMed

    Bennison, Clair; Hemmings, Nicola; Slate, Jon; Birkhead, Tim

    2015-01-22

    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