Heritable determinants of male fertilization success in the nematode Caenorhabditis elegans

PubMed Central

2011-01-01

Background Sperm competition is a driving force in the evolution of male sperm characteristics in many species. In the nematode Caenorhabditis elegans, larger male sperm evolve under experimentally increased sperm competition and larger male sperm outcompete smaller hermaphrodite sperm for fertilization within the hermaphrodite reproductive tract. To further elucidate the relative importance of sperm-related traits that contribute to differential reproductive success among males, we quantified within- and among-strain variation in sperm traits (size, rate of production, number transferred, competitive ability) for seven male genetic backgrounds known previously to differ with respect to some sperm traits. We also quantified male mating ability in assays for rates of courtship and successful copulation, and then assessed the roles of these pre- and post-mating traits in first- and second-male fertilization success. Results We document significant variation in courtship ability, mating ability, sperm size and sperm production rate. Sperm size and production rate were strong indicators of early fertilization success for males that mated second, but male genetic backgrounds conferring faster sperm production make smaller sperm, despite virgin males of all genetic backgrounds transferring indistinguishable numbers of sperm to mating partners. Conclusions We have demonstrated that sperm size and the rate of sperm production represent dominant factors in determining male fertilization success and that C. elegans harbors substantial heritable variation for traits contributing to male reproductive success. C. elegans provides a powerful, tractable system for studying sexual selection and for dissecting the genetic basis and evolution of reproduction-related traits. PMID:21492473

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-cancer-therapies.

Decrease in male mouse fertility by hydrogen sulfide and/or ammonia can Be inheritable.

PubMed

Zhang, Weidong; Zhao, Yong; Zhang, Pengfei; Hao, Yanan; Yu, Shuai; Min, Lingjiang; Li, Lan; Ma, Dongxue; Chen, Liang; Yi, Bao; Tang, Xiangfang; Meng, Qingshi; Liu, Lei; Wang, Shukun; Shen, Wei; Zhang, Hongfu

2018-03-01

Numerous epidemiological studies suggest that air pollutants cause a decline in the quality of human spermatozoa and thus a reduction in fertility. However, the exact cause of infertility remains unknown. Air pollution gases, such as NH 3 and H 2 S are either free or bound to airborne particular materials (PM) and are abundant and reactive. The aim of this current investigation was to explore the impacts of NH 3 and/or H 2 S on male fertility and the underlying mechanisms. Male mouse exposed to H 2 S and/or NH 3 and after two generations were used to evaluate the impacts on fertility. The fertility, and spermatozoa quality parameters and proteins involved in spermatogenesis were investigated. Our current investigation demonstrates: i) H 2 S and/or NH 3 decrease male fertility by 20-30%, reduce the spermatozoa concentration about 20-40%, decrease 10-20%, increase around 30%; ii) the reduction in male fertility by H 2 S and/or NH 3 can be inheritable; iii) H 2 S and/or NH 3 can diminish male fertility through the disruption of spermatogenesis without affecting other body parameters such as body weight and organ index. One component of air pollutants, for example NH 3 , does not have a severe impact; however, two or more pollutants such as H 2 S and NH 3 combined can cause serious health problems, especially with regard to male fertility. We suggest that greater attention should be paid to these air pollutants to improve human health and fertility. Copyright © 2017 Elsevier Ltd. All rights reserved.

The epididymis, cytoplasmic droplets and male fertility.

PubMed

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.

Male fertility preservation before gonadotoxic therapies.

PubMed

Wyns, C

2010-01-01

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. Relevant studies were identified by an extensive Medline search of English and French language articles. 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. 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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, Irv R.; Skillman, Ann D.; Nicolas, Jean-Marc

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 themore » 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.« less

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

PubMed

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

2003-06-01

The synthetic estrogen 17 alpha-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 17 alpha, 20 beta-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.

Semen evaluation and fertility assessment in a purebred dog breeding facility.

PubMed

Hesser, Andrea; Darr, Christa; Gonzales, Kris; Power, Heather; Scanlan, Tawny; Thompson, James; Love, Charles; Christensen, Bruce; Meyers, Stuart

2017-01-01

Semen quality in dogs has not been assessed in a longitudinal study that includes endpoints of female fertility and pregnancy. Although use of artificial insemination with chilled semen is increasingly used in canine reproduction, the resultant level of predictability and odds of fertile matings for dogs is still not fully understood. This research provides, for the first time, comprehensive semen evaluation in a large population of dogs in which fertility has been tracked. Duplicate ejaculates were obtained from 39 Labrador retriever males of the Guide Dogs for the Blind (San Rafael, CA, USA) breeding program. Sperm endpoints were determined in fresh semen and extended chilled semen at 48 hour after collection. Evaluation included total and progressive motility, average path velocity, morphology, membrane lipid peroxidation, presence of sperm reactive oxygen species, sperm chromatin structure, and mitochondrial DNA copy number. Male age ranged from 1 to 10 years and were grouped as young (Y; 1-3 years, n = 21), middle aged (M; 4-6 years, n = 13), and senior (S; 7 years or greater, n = 5) for analysis. The effects of age and sperm state (fresh vs. chilled) on the above sperm endpoints were determined using a linear mixed effects model. Semen endpoint values for all parameters were established for this group of fertile males. Progressive motility was only lower in the senior male chilled samples compared to all other groups, fresh and chilled (P < 0.05). Velocity decreased with increasing age and was lower overall in chilled samples (P < 0.05). Percent morphologically normal sperm was lower in senior dogs compared with the other age groups (P < 0.05). The presence of reactive oxygen species was lower in chilled samples compared with fresh (P < 0.05). For sperm chromatin structure, the senior-aged group had a higher %COMPα t than the middle-aged group (P < 0.05). Bayesian analysis determined that no differences were seen in total motility, membrane

An intact Pms2 ATPase domain is not essential for male fertility

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-03-01

The DNA mismatch repair (MMR) machinery in mammals plays critical roles in both mutation avoidance and spermatogenesis. Meiotic analysis of knockout mice of two different MMR genes, Mlh1 and Mlh3, revealed both male and female infertility associated with a defect in meiotic crossing over. In contrast, another MMR gene knockout, Pms2 (Pms2(ko/ko)), which contained a deletion of a portion of the ATPase domain, produced animals that were male sterile but female fertile. However, the meiotic phenotype of Pms2(ko/ko) males was less clear-cut than for Mlh1- or Mlh3-deficient meiosis. More recently, we generated a different Pms2 mutant allele (Pms2(cre)), which results in deletion of the same portion of the ATPase domain. Surprisingly, Pms2(cre/cre) male mice were completely fertile, suggesting that the ATPase domain of Pms2 is not required for male fertility. To explore the difference in male fertility, we examined the Pms2 RNA and found that alternative splicing of the Pms2(cre) allele results in a predicted Pms2 containing the C-terminus, which contains the Mlh1-interaction domain, a possible candidate for stabilizing Mlh1 levels. To study further the basis of male fertility, we examined Mlh1 levels in testes and found that whereas Pms2 loss in Pms2(ko/ko) mice results in severely reduced levels of Mlh1 expression in the testes, Mlh1 levels in Pms2(cre/cre) testes were reduced to a lesser extent. Thus, we propose that a primary function of Pms2 during spermatogenesis is to stabilize Mlh1 levels prior to its critical crossing over function with Mlh3. Copyright © 2015 Elsevier B.V. All rights reserved.

Hepatitis B virus infection on male partner has negative impact on in-vitro fertilization

NASA Astrophysics Data System (ADS)

Lubis, H. P.; Halim, B.; Adenin, I.; Rusda, M.; Prasetiawan, E.

2018-03-01

It is common to see HBV-infected couple seeking for fertility treatment in reproductive medical centers. The effect of hepatitis B virus (HBV) infection on pregnancy outcome after In Vitro Fertilization (IVF) treatment has been a controversy. The study aims this was to evaluate the outcome of in vitro fertilization in couples with the male partner being HBsAg-seropositive. A retrospective analytic study was in HBV-infected and non-HBV infected male partner groups who have been treated with in vitro fertilization (IVF) from October 2016 until May 2017 in HFC IVF Center. From 101 couples, 17 (16.83%) male partners were HBV seropositive. They had similar semen parameters compared to thenon-HBV infected group. Couples with the male partner being HBsAg-seropositive had significantly lower fertilized oocytes and cleaved embryos compared to thenon-HBV infected group. We also found lower clinical pregnancy rate in infected male partner group compared to control group (23.52% vs 51% respectively). Statistically, there was a significant difference in clinical pregnancy rate between HBV-infected group and control group (p<0.05). An hbv-infected male partner may lower the clinical pregnancy rate in couple undergoing IVF treatment. Therefore, the mechanism of impact of HBV infection on IVF outcome needs further exploration.

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

Levels of Leydig cell autophagy regulate the fertility of male naked mole-rats.

PubMed

Yang, Wenjing; Li, Li; Huang, Xiaofeng; Kan, Guanghan; Lin, Lifang; Cheng, Jishuai; Xu, Chen; Sun, Wei; Cong, Wei; Zhao, Shanmin; Cui, Shufang

2017-11-17

Fertility is abolished in nonbreeding males in colonies of natal naked mole-rats (NMRs). Although spermatogenesis occurs in both breeding and nonbreeding male NMRs, the mechanisms underlying the differences in fertility between breeders and nonbreeders remain unexplored. In this study, a significant decrease in autophagy was observed in Leydig cells of the testis from nonbreeding male NMRs. This alteration was visualised as a significant decrease in the levels of autophagy-related gene 7 (Atg7), Atg5, microtubule-associated protein 1A/B light chain 3 (LC3-II/I) and the number of autophagosomes and an increase in P62 levels using Western blotting analyses. Furthermore, monodansylcadaverine (MDC) staining and Western blot analyses revealed that testosterone production decreased in nonbreeding male NMR Leydig cells, this decrease was associated with a reduction in autophagy. Primary Leydig cells from breeding and nonbreeding male NMRs were processed to investigate the effect of an autophagy inhibitor (3-MA, 3-methyladenine) or an autophagy activator (rapamycin) on testosterone production. Rapamycin induced an increase in testosterone production in NMR Leydig cells, whereas 3-MA had the opposite effect. Consequently, spermatogenesis, the weight of the testis, and androgen levels were dramatically reduced in nonbreeding male NMRs. While rapamycin treatment restored the fertility of nonbreeding male NMRs. Based on these results, inadequate autophagy correlates with a decrease in steroid production in nonbreeding male NMR Leydig cells, which may ultimately influence the spermatogenesis and fertilities of these animals.

Body Size Correlates with Fertilization Success but not Gonad Size in Grass Goby Territorial Males

PubMed Central

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

2012-01-01

In fish species with alternative male mating tactics, sperm competition typically occurs when small males that are unsuccessful in direct contests steal fertilization opportunities from large dominant males. In the grass goby Zosterisessor ophiocephalus, large territorial males defend and court females from nest sites, while small sneaker males obtain matings by sneaking into nests. Parentage assignment of 688 eggs from 8 different nests sampled in the 2003–2004 breeding season revealed a high level of sperm competition. Fertilization success of territorial males was very high but in all nests sneakers also contributed to the progeny. In territorial males, fertilization success correlated positively with male body size. Gonadal investment was explored in a sample of 126 grass gobies collected during the period 1995–1996 in the same area (61 territorial males and 65 sneakers). Correlation between body weight and testis weight was positive and significant for sneaker males, while correlation was virtually equal to zero in territorial males. That body size in territorial males is correlated with fertilization success but not gonad size suggests that males allocate much more energy into growth and relatively little into sperm production once the needed size to become territorial is attained. The increased paternity of larger territorial males might be due to a more effective defense of the nest in comparison with smaller territorial males. PMID:23056415

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

PubMed

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

2012-01-01

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

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

PubMed

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

2016-01-01

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. 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. 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. 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.

Assessment of environmental factors affecting male fertility

PubMed Central

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

1979-01-01

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. ImagesFIGURE 6.FIGURE 9. PMID:446458

Fertility: purinergic receptors and the male contraceptive pill.

PubMed

Dunn, P M

2000-04-20

Knockout mice lacking the P2X(1) receptor appear normal, but fail to breed. Analysis of these mutant mice clearly shows that purinergic co-transmission has a physiological role in the was deferens. These findings also raise the possibility of developing non-hormonal ways of regulating male fertility.

Job strain and male fertility.

PubMed

Hjollund, Niels Henrik I; Bonde, Jens Peter E; Henriksen, Tine Brink; Giwercman, Aleksander; Olsen, Jørn

2004-01-01

Job strain, defined as high job demands and low job control, has not previously been explored as a possible determinant of male fertility. We collected prospective data on job strain among men, and describe the associations with semen quality and probability of conceiving a clinical pregnancy during a menstrual cycle. Danish couples (N = 399) who were trying to become pregnant for the first time were followed for up to 6 menstrual periods. All men collected semen samples, and a blood sample was drawn from both partners. Job demand and job control were measured by a self-administered questionnaire at entry, and in each cycle the participants recorded changes in job control or job demand during the previous 30 days. In adjusted analyses, no associations were found between any semen characteristic or sexual hormones and any job strain variable. The odds for pregnancy were not associated with job strain. Psychologic job strain encountered in normal jobs in Denmark does not seem to affect male reproductive function.

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

Identification Male Fertility Through Abnormalities Sperm Based Morphology (Teratospermia) using Invariant Moment Method

NASA Astrophysics Data System (ADS)

Syahputra, M. F.; Chairani, R.; Seniman; Rahmat, R. F.; Abdullah, D.; Napitupulu, D.; Setiawan, M. I.; Albra, W.; Erliana, C. I.; Andayani, U.

2018-03-01

Sperm morphology is still a standard laboratory analysis in diagnosing infertility in men. Manually identification of sperm form is still not accurate, the difficulty in seeing the form of the invisible sperm from the digital microscope image is often a weakness in the process of identification and takes a long time. Therefore, male fertility identification application system is needed Through sperm abnormalities based on sperm morphology (teratospermia). The method used is invariant moment method. This study uses 15 data testing and 20 data training sperm image. That the process of male fertility identification through sperm abnormalities based on sperm morphology (teratospermia) has an accuracy rate of 80.77%. Use of time to process Identification of male fertility through sperm abnormalities Based on sperm morphology (teratospermia) during 0.4369 seconds.

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

PubMed

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

2005-08-01

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

Male Fertility Issues

Cancer.gov

Fertility issues are common in boys and men getting cancer treatment. Fertility preservation options include sperm banking, testicular shielding, testicular sperm extraction (TESE), and testicular tissue freezing. Support and clinical trials are listed.

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

PubMed

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

2016-04-05

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. 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. 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 < 0.05, respectively). SKRBT had no adverse

In vitro fertilization/intracytoplasmic sperm injection for male infertility

PubMed Central

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

2011-01-01

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

Sphingomyelin Synthase 1 Is Essential for Male Fertility in Mice

PubMed Central

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

2016-01-01

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

Actin-related protein 2/3 complex-based actin polymerization is critical for male fertility.

PubMed

Lee, J S; Kwon, W S; Rahman, M S; Yoon, S J; Park, Y J; Pang, M G

2015-09-01

The actin-related protein 2/3 (Arp2/3) complex is critical for regulation of actin polymerization, which is associated with sperm motility and capacitation status. However, the function of the Arp2/3 complex in male fertility has not yet been fully elucidated. Therefore, this study was designed to investigate the role of the Arp2/3 complex in different processes in spermatozoa and its consequences on fertilization and early embryonic development. In this in vitro study, mouse spermatozoa were incubated with different concentrations (10, 100, and 500 μm) of CK-636, an Arp2/3 complex antagonist. Our results demonstrated that inhibition of the Arp2/3 complex by high concentrations (100 and 500 μm) of CK-636 induced hyper-activated motility and acrosomal reaction, whereas intracellular calcium and tyrosine phosphorylation levels in spermatozoa were inhibited. Moreover, exposure of spermatozoa to the highest concentration of CK-636 reduced fertilization and embryo development. Interestingly, fertilization was significantly increased after treatment with 100 μm CK-636, whereas embryonic development was significantly decreased. Therefore, we conclude that the Arp2/3 complex plays a decisive role in regulation of sperm function and male fertility via actin polymerization. We anticipate that the Arp2/3 complex may have clinical application as marker for male fertility and male contraceptive targeting. © 2015 American Society of Andrology and European Academy of Andrology.

Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice.

PubMed

Chen, Yongmei; Wang, Huizhen; Qi, Nan; Wu, Hui; Xiong, Weipeng; Ma, Jing; Lu, Qingxian; Han, Daishu

2009-10-01

Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM(-/-)) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYRO3. TAM(-/-) testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM(-/-) mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM(-/-) Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM(-/-) mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility.

Effects of psychological stress on male fertility.

PubMed

Nargund, Vinod H

2015-07-01

Psychological stress can be defined as any uncomfortable 'emotional experience' accompanied by predictable biochemical, physiological and behavioural changes or responses. Many clinical studies looking at the effects of psychological stress on male fertility have shown that stress is associated with reduced paternity and abnormal semen parameters. Enough scientific evidence exists to suggest that psychological stress could severely affect spermatogenesis, mainly as a result of varying testosterone secretion. The hypothalamic-pituitary-adrenal axis has a direct inhibitory action on the hypothalamic-pituitary-gonadal (HPG) axis and Leydig cells in the testes. The newly discovered hormone, gonadotropin-inhibitory hormone (GnIH), also has an inhibitory effect on the HPG axis. Inhibition of the HPG axis results in a fall in testosterone levels, which causes changes in Sertoli cells and the blood-testis barrier, leading to the arrest of spermatogenesis. Germ cells also become vulnerable to gonadotoxins and oxidation. However, the extent and severity of the effects of psychological stress on human testes is difficult to study and data mostly come from animal models. Despite this limitation, stress as a causative factor in male infertility cannot be ignored and patients should be made aware of its effects on testicular function and fertility and helped to manage them.

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

PubMed

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

2010-11-22

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

Paper-Based Quantification of Male Fertility Potential.

PubMed

Nosrati, Reza; Gong, Max M; San Gabriel, Maria C; Pedraza, Claudio E; Zini, Armand; Sinton, David

2016-03-01

More than 70 million couples worldwide are affected by infertility, with male-factor infertility accounting for about half of the cases. Semen analysis is critical for determining male fertility potential, but conventional testing is costly and complex. Here, we demonstrate a paper-based microfluidic approach to quantify male fertility potential, simultaneously measuring 3 critical semen parameters in 10 min: live and motile sperm concentrations and sperm motility. The device measures the colorimetric change of yellow tetrazolium dye to purple formazan by the diaphorase flavoprotein enzyme present in metabolically active human sperm to quantify live and motile sperm concentration. Sperm motility was determined as the ratio of motile to live sperm. We assessed the performance of the device by use of clinical semen samples, in parallel with standard clinical approaches. Detection limits of 8.46 and 15.18 million/mL were achieved for live and motile sperm concentrations, respectively. The live and motile sperm concentrations and motility values from our device correlated with those of the standard clinical approaches (R(2) ≥ 0.84). In all cases, our device provided 100% agreement in terms of clinical outcome. The device was also robust and could tolerate conditions of high absolute humidity (22.8 g/m(3)) up to 16 weeks when packaged with desiccant. Our device outperforms existing commercial paper-based assays by quantitatively measuring live and motile sperm concentrations and motility, in only 10 min. This approach is applicable to current clinical practices as well as self-diagnostic applications. © 2015 American Association for Clinical Chemistry.

Evaluation of the effect of using mobile phones on male fertility.

PubMed

Wdowiak, Artur; Wdowiak, Leszek; Wiktor, Henryk

2007-01-01

The problem of the lack of offspring is a phenomenon concerning approximately 15% of married couples in Poland. Infertility is defined as inability to conceive after a year of sexual intercourses without the use of contraceptives. In half of the cases the causative factor is the male. Males are exposed to the effect of various environmental factors, which may decrease their reproductive capabilities. A decrease in male fertility is a phenomenon which occurs within years, which may suggest that one of the reasons for the decrease in semen parameters is the effect of the development of techniques in the surrounding environment. A hazardous effect on male fertility may be manifested by a decrease in the amount of sperm cells, disorders in their mobility, as well as structure. The causative agents may be chemical substances, ionizing radiation, stress, as well as electromagnetic waves. The objective of the study was the determination of the effect of the usage of cellular phones on the fertility of males subjected to marital infertility therapy. The following groups were selected from among 304 males covered by the study: Group A: 99 patients who did not use mobile phones, Group B: 157 males who have used GSM equipment sporadically for the period of 1-2 years, and Group C: 48 people who have been regularly using mobile phone for more than 2 years. In the analysis of the effect of GSM equipment on the semen it was noted that an increase in the percentage of sperm cells of abnormal morphology is associated with the duration of exposure to the waves emitted by the GSM phone. It was also confirmed that a decrease in the percentage of sperm cells in vital progressing motility in the semen is correlated with the frequency of using mobile phones.

Male caffeine and alcohol intake in relation to semen parameters and in vitro fertilization outcomes among fertility patients.

PubMed

Karmon, A E; Toth, T L; Chiu, Y-H; Gaskins, A J; Tanrikut, C; Wright, D L; Hauser, R; Chavarro, J E

2017-03-01

Much of the literature on the impact of male caffeine and alcohol intake on reproductive outcomes has utilized semen quality as a proxy for male fertility, although semen parameters have a limited predictive value for spontaneous pregnancy. The objective of this study was to investigate whether male caffeine and alcohol intakes are associated with semen parameters and assisted reproductive technology outcome. The Environment and Reproductive Health Study, an ongoing prospective cohort study, enrolls subfertile couples presenting for treatment at an academic fertility center (2007-2012). A total of 171 men with 338 semen analyses and 205 assisted reproductive technology cycles were included in this analysis. Diet was assessed using a 131-item food frequency questionnaire. Mixed models adjusting for potential confounders were used to evaluate the relationships of male caffeine and alcohol intakes with semen parameters and assisted reproductive technology outcomes. There was no association between male caffeine and alcohol intake and semen quality. Male caffeine intake was negatively related to live birth after assisted reproductive technologies (p-trend < 0.01), and male alcohol intake was positively related to live birth after assisted reproductive technologies (p-trend = 0.04). Adjusted live birth rate among couples with a male partner in the highest quartile of caffeine intake (≥272 mg/day) compared to couples with a male partner in the lowest quartile of intake (<99 mg/day) was 19% vs. 55%, respectively, p < 0.01. In terms of alcohol intake, adjusted live birth rate among couples with a male partner in the highest quartile of alcohol intake (≥22 g/day) compared to couples with a male partner in the lowest quartile of intake (<3 g/day) was 61% vs. 28%, respectively, p = 0.05. In conclusion, male pre-treatment caffeine and alcohol intakes were associated with live birth after assisted reproductive technologies, but not with semen parameters, among

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

PubMed Central

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

2010-01-01

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

Pre-pubertal diet restriction reduces reactive oxygen species and restores fertility in male WNIN/Obese rat.

PubMed

Dinesh Yadav, D M; Muralidhar, M N; Prasad, S M V K; Rajender Rao, K

2018-03-01

Obesity is a multifactorial disorder associated with increased body adiposity, chronic oxidative stress which contributes to impaired fertility in males. Diet restriction and anti-oxidant supplementations are known to protect obese subjects from oxidative stress and improves fertility. However, the role of oxidative stress and the age of intervention in restoring male fertility are poorly understood. This study was aimed to assess the effect of diet restriction on fertility with respect to the age of intervention, body composition and oxidative stress using WNIN/Ob obese mutant rat strain. Unlike lean and carrier phenotypes, obese rats are hyperphagic, hyperlipaemic and infertile. Male obese rats aged for 35, 60 and 90 days were fed either ad libitum or diet restricted for 6 weeks. Upon diet restriction mean body weight, total body fat percentage, circulatory lipids and oxidative stress markers were significantly reduced and it follows the order as 35 < 60 < 90 days. Diet-restricted males of the three age groups were allowed to mate with female carrier rats, and fertility was restored only in 35-day group. Diet restriction in male obese WNIN/Ob rats lowered the rate of body weight gain, with reduced oxidative stress overall and fertility restoration in groups intervened at pre-pubertal stages. © 2017 Blackwell Verlag GmbH.

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

PubMed

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

2011-12-01

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

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

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

PubMed

Rogers, David W; Denniff, Matthew; Chapman, Tracey; Fowler, Kevin; Pomiankowski, Andrew

2008-08-18

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. 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. 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 other substances per ejaculate. The

ERK Signaling in the Pituitary Is Required for Female But Not Male Fertility

PubMed Central

Bliss, Stuart P.; Miller, Andrew; Navratil, Amy M.; Xie, JianJun; McDonough, Sean P.; Fisher, Patricia J.; Landreth, Gary E.; Roberson, Mark S.

2009-01-01

Males and females require different patterns of pituitary gonadotropin secretion for fertility. The mechanisms underlying these gender-specific profiles of pituitary hormone production are unknown; however, they are fundamental to understanding the sexually dimorphic control of reproductive function at the molecular level. Several studies suggest that ERK1 and -2 are essential modulators of hypothalamic GnRH-mediated regulation of pituitary gonadotropin production and fertility. To test this hypothesis, we generated mice with a pituitary-specific depletion of ERK1 and 2 and examined a range of physiological parameters including fertility. We find that ERK signaling is required in females for ovulation and fertility, whereas male reproductive function is unaffected by this signaling deficiency. The effects of ERK pathway ablation on LH biosynthesis underlie this gender-specific phenotype, and the molecular mechanism involves a requirement for ERK-dependent up-regulation of the transcription factor Egr1, which is necessary for LHβ expression. Together, these findings represent a significant advance in elucidating the molecular basis of gender-specific regulation of the hypothalamic-pituitary-gonadal axis and sexually dimorphic control of fertility. PMID:19372235

Dandelion (Taraxacum officinale) decreases male rat fertility in vivo.

PubMed

Tahtamouni, Lubna H; Alqurna, Noor M; Al-Hudhud, Mariam Y; Al-Hajj, Hameed A

2011-04-26

Taraxacum officinale (L.) Weber ex F.H. Wigg. is commonly used in Jordan folk medicine for the treatment of panophthalmitis, chronic constipation, and diabetes. In addition, herbalists prescribe the aqueous extract of Taraxacum officinale to enhance male's fertility. The current work was undertaken to investigate the validity and/or invalidity of the aqueous extract of Taraxacum officinale on enhancing the reproductive activity in male rat. Thirty three adult male rats were divided into three groups. Experimental groups received the aqueous extract of Taraxacum officinale orally for 60 days in two different sublethal doses; 1/10 LD(50) as high dose and 1/20 LD(50) as low dose, whereas the control group received distilled water. The administration of the aqueous extract of Taraxacum officinale resulted in a significant decrease in testis weight in the two experimental groups in comparison to the control group but had no effect on body or organ weight. The extract of this plant caused a decrease of the following in the two experimental groups, compared to the control group: sperm count, motility and normal morphology, pregnancy rate and diameter and wall thickness of seminiferous tubules. Also, distortion of morphology of the seminiferous tubules and arrest in spermatogenesis was observed in the experimental groups. In addition, the percentage of sperm with damaged chromatin integrity was significantly higher in the two experimental groups. From the present study, we can conclude that the aqueous extract of Taraxacum officinale acts as an anti-fertility agent rather than a fertility booster as prescribed by Jordanian herbalists. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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.

Environmental risk factors and male fertility and reproduction.

PubMed

Petrelli, Grazia; Mantovani, Alberto

2002-04-01

Several environmental substances and pesticides exert a direct, cytotoxic effect on male germ cells. However, an increasing concern has been raised by compounds that may act through more subtle mechanisms, for example, specific pesticides that are potentially capable of modulating or disrupting the endocrine system. Overall, exposure to pesticides with endocrine-disrupting potential raise a particular concern for male fertility because of the possible occurrence of both effects at low concentrations and additive interactions with other environmental risk factors. Delayed reproductive problems deserve special attention, since experimental data consistently indicate a high vulnerability in the developing male reproductive system. Epidemiologic studies have confirmed an increased risk of conception delay associated with occupational exposure to pesticides. Moreover, an increased risk of spontaneous abortion has been noted among wives of exposed workers.

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. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Effects of Anethum graveolens L. on fertility in male rats.

PubMed

Monsefi, Malihezaman; Zahmati, Maryam; Masoudi, Mojtaba; Javidnia, Katayoun

2011-12-01

The effects of Anethum graveolens seed extract on fertility of male rats were investigated. Male Wistar rats were divided into five groups according to the treatment they received during 42 days: control, low dose (0.5 g/kg) and high dose (5 g/kg) of aqueous extracts, and low dose (0.045 g/kg) and high dose (0.45 g/kg) of ethanol extracts of Anethum graveolens seed. Sperm count and motility and testosterone concentration were measured. Sections of the testes, epididymis, and seminal vesicles were stained with peroxidase-conjugated lectins of Ulex europaeus agglutinin, peanut agglutinin, Dolichos biflorus agglutinin, soy bean agglutinin and concanavalin A. The treated male rats were mated with females and the crown-rump lengths and weights of their newborn pups were measured. No significant differences in sperm count, sperm motility or testosterone concentration were observed in the experimental groups. However, female rats did not become pregnant after mating with rats given the high dose of the ethanol extract. The distribution of terminal sugars on the epithelial surface of the reproductive structures decreased in the experimental groups. Anethum graveolens extract decreased fertility rate by modifying some terminal sugars on the cell surface of male reproductive organs involved in sperm maturation, capacitation and oocyte recognition.

Organizational differences between cytoplasmic male sterile and male fertile Brassica mitochondrial genomes are confined to a single transposed locus.

PubMed Central

L'Homme, Y; Brown, G G

1993-01-01

Comparison of the physical maps of male fertile (cam) and male sterile (pol) mitochondrial genomes of Brassica napus indicates that structural differences between the two mtDNAs are confined to a region immediately upstream of the atp6 gene. Relative to cam mtDNA, pol mtDNA possesses a 4.5 kb segment at this locus that includes a chimeric gene that is cotranscribed with atp6 and lacks an approximately 1kb region located upstream of the cam atp6 gene. The 4.5 kb pol segment is present and similarly organized in the mitochondrial genome of the common nap B.napus cytoplasm; however, the nap and pol DNA regions flanking this segment are different and the nap sequences are not expressed. The 4.5 kb CMS-associated pol segment has thus apparently undergone transposition during the evolution of the nap and pol cytoplasms and has been lost in the cam genome subsequent to the pol-cam divergence. This 4.5 kb segment comprises the single DNA region that is expressed differently in fertile, pol CMS and fertility restored pol cytoplasm plants. The finding that this locus is part of the single mtDNA region organized differently in the fertile and male sterile mitochondrial genomes provides strong support for the view that it specifies the pol CMS trait. Images PMID:8388101

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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, whenmore » 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.« less

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

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

PubMed

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

2015-06-15

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

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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed

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

2013-04-01

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

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

Walnut leaf extract acts as a fertility agent in male Wistar albino rats - A search for herbal male fertility enhancer.

PubMed

Akomolafe, Seun F; Oboh, Ganiyu

2017-11-17

Background Walnut leaf is one of the many medicinal plants used in folklore as male fertility enhancers. The present work was therefore undertaken with an aim to scientifically validate this claim. As such, we evaluated the effect of the aqueous extract from walnut leaves on biomolecules related to fertility in adult male rats and its mode of action as fertility-enhancing agent. Methods Twenty-five rats were randomly divided into five groups of five animals each; Group 1 served as control and received normal (0.9%) saline only; Groups II, III, IV received 50, 500, 1,000 mg/kg body weight (BW) of T. conophorum leaf extract orally, while Group V served as standard and was given suspension of clomiphene citrate orally at the dose of 1.04 mg/kg/ml BW. The extract and drug were given daily and the experiment lasted for 21 consecutive days. Results The testicular biochemical parameters in treated groups showed significant (p<0.05) increase in lactate dehydrogenase activity activity, Glucose-6-phosphate dehydrogenase (G-6PDH) activity, glycogen content, 3β and 17β hydroxysteroid dehydrogenase activities and testicular and epididymal Zn and Se contents with a significant decrease in cholesterol content. A significant increase in testis weight and epididymis weight were also observed. Also, a significant (p<0.05) increase in the level of serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone, sperm count, motility, viability and a decrease in sperm abnormality were observed in the various treated groups when compared with the control group. This increment was concentration dependent, while the extract at the highest concentration showed a more pronounced effect than the standard drug. Also, no sperm DNA fragmentation index was found in all the treatment groups. Photomicrographs from light and scanning electron microscopy showed large fenestrae of interstitial tissue, large fluid space and intact seminiferous epithelium layers fully packed with

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

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.

The impact of commonly prescribed drugs on male fertility.

PubMed

Hayashi, Tetsuo; Miyata, Akiomi; Yamada, Takumi

2008-09-01

To analyze the impact of commonly used drugs on male fertility, we assessed the clinical characteristics of patients with impaired semen quality while they were taking medication for chronic diseases and after switching therapies. Of 1768 infertile males, 201 patients were taking medications and had impaired semen quality without any seminal tract obstruction, spermatogenic abnormalities or hypogonadotropic hypogonadism. Of these 201 men, a total of 165 had no history of testicular diseases nor abnormalities in any examinations. Amongst them, H1 receptor antagonists were the most common medication taken, followed by antiepileptics and antibiotics. They were divided into two groups: an intervention group (73 patients), who could stop or switch their medications, and a control group (92 patients), who could not. In the intervention group, semen quality improvement rate and conception rate (93% and 85%, respectively) were much higher than those of the control group (12% and 10%, respectively). After switching therapies, the time interval before conception was 7.3 months, which was significantly shorter in asthenozoospermia than oligozoospermia. Our results confirm the potential fertility hazards of commonly used drugs and their reversibility. Moreover, after switching medication, drug-induced asthenozoospermia was cured more rapidly than oligozoospermia, suggesting that further delineation of such differences may help to elucidate mechanisms of spermatogenesis and might facilitate the development of non-hormonal male contraceptive agents.

Therapeutic and fertility restoration effects of Ionidium suffruticosum on sub-fertile male albino Wistar rats: effects on testis and caudal spermatozoa.

PubMed

Chenniappan, Kuppusamy; Murugan, Kadarkari

2017-12-01

Ionidium suffruticosum (L.) Ging (Violaceae) is an important medicinal plant widely used as a herbal traditional medicine in Ayurveda for the treatment of infertility. Currently, little pharmacological information is available on its male fertility properties following prolonged use. To investigate I. suffruticosum leaf extracts for male fertility parameters. The ethanol lyophilized fraction was administered orally on carbendazim-induced sub-fertility rats (250 mg/kg body weight for 28 days). The effects of fractions on rat's fertility parameters i.e., body and testes weight, sperm motility, sperm vitality, epididymal sperm counts, its morphology, enzyme and antioxidant stress and histopathology were studied and compared with clomiphene citrate. The sub-fertile male rats treated with I. suffruticosum leaf extract increased the body weight of 7 g, testis weight of 97 mg, increased cauda epididymal sperm counts of 34.2 × 10 6 sperm/mL, motility of sperm 46% and vitality 28% also increased and normal sperm morphology also improved up to 32%. The carbendazim-treated group showed loss in body weight of 33 g, testis weight of 851 mg, decreased epididymal sperm counts of 15 × 10 6 sperm/mL, with sluggish motility and a highly significant fall in the live sperms of about 57%. The leaf fraction of I. suffructicosum increased the testicular weight, spermatogenesis, sperm counts, lessened sperm agglutination, and increased testicular oxidative biomarkers, SOD, and CAT. This study therefore supports the usage of I. suffructicosum in traditional medicine for infertility.

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...

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

USDA-ARS?s Scientific Manuscript database

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

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

PubMed

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

2006-11-10

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

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

The impact of drugs on male fertility: a review.

PubMed

Semet, M; Paci, M; Saïas-Magnan, J; Metzler-Guillemain, C; Boissier, R; Lejeune, H; Perrin, J

2017-07-01

Beside cytotoxic drugs, other drugs can impact men's fertility through various mechanisms. Via the modification of the hypothalamic-pituitary-gonadal axis hormones or by non-hormonal mechanisms, drugs may directly and indirectly induce sexual dysfunction and spermatogenesis impairment and alteration of epididymal maturation. This systematic literature review summarizes existing data about the negative impact and associations of pharmacological treatments on male fertility (excluding cytotoxic drugs), with a view to making these data more readily available for medical staff. In most cases, these effects on spermatogenesis/sperm maturation/sexual function are reversible after the discontinuation of the drug. When a reprotoxic treatment cannot be stopped and/or when the impact on semen parameters/sperm DNA is potentially irreversible (Sulfasalazine Azathioprine, Mycophenolate mofetil and Methotrexate), the cryopreservation of spermatozoa before treatment must be proposed. Deleterious impacts on fertility of drugs with very good or good level of evidence (Testosterone, Sulfasalazine, Anabolic steroids, Cyproterone acetate, Opioids, Tramadol, GhRH analogues and Sartan) are developed. © 2017 American Society of Andrology and European Academy of Andrology.

Genome-wide ENU mutagenesis for the discovery of novel male fertility regulators.

PubMed

Jamsai, Duangporn; O'Bryan, Moira K

2010-06-01

The completion of genome sequencing projects has provided an extensive knowledge of the contents of the genomes of human, mouse, and many other organisms. Despite this, the function of most of the estimated 25,000 human genes remains largely unknown. Attention has now turned to elucidating gene function and identifying biological pathways that contribute to human diseases, including male infertility. Our understanding of the genetic regulation of male fertility has been accelerated through the use of genetically modified mouse models including knockout, knock-in, gene-trapped, and transgenic mice. Such reverse genetic approaches however, require some fore-knowledge of a gene's function and, as such, bias against the discovery of completely novel genes and biological pathways. To facilitate high throughput gene discovery, genome-wide mouse mutagenesis via the use of a potent chemical mutagen, N-ethyl-N-nitrosourea (ENU), has been developed over the past decade. This forward genetic, or phenotype-driven, approach relies upon observing a phenotype first, then subsequently defining the underlining genetic defect. Mutations are randomly introduced into the mouse genome via ENU exposure. Through a controlled breeding scheme, mutations causing a phenotype of interest (e.g., male infertility) are then identified by linkage analysis and candidate gene sequencing. This approach allows for the possibility of revealing comprehensive phenotype-genotype relationships for a range of genes and pathways i.e. in addition to null alleles, mice containing partial loss of function or gain-of-function mutations, can be recovered. Such point mutations are likely to be more reflective of those that occur within the human population. Many research groups have successfully used this approach to generate infertile mouse lines and some novel male fertility genes have been revealed. In this review, we focus on the utility of ENU mutagenesis for the discovery of novel male fertility regulators.

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

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.

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

PubMed

Mínguez-Alarcón, L; Afeiche, M C; Chiu, Y-H; Vanegas, J C; Williams, P L; Tanrikut, C; Toth, T L; Hauser, R; Chavarro, J E

2015-07-01

Male factor etiology may be a contributing factor in up to 60% of infertility cases. Dietary intake of phytoestrogens has been related to abnormal semen quality and hormone levels. However, its effect on couple fecundity is still unclear. Intake of soy products was assessed in 184 men from couples undergoing infertility treatment with in vitro fertilization. Couples were recruited between February 2007 and May 2014 and prospectively followed to document treatment outcomes including fertilization, implantation, clinical pregnancy and live birth. Multivariate generalized linear mixed models with random intercepts, binomial distribution and logit link function were used to examine this relation while accounting for repeated treatment cycles and adjusting for potential confounders. Male partner's intake of soy foods and soy isoflavones was unrelated to fertilization rates, the proportions of poor quality embryos, accelerated or slow embryo cleavage rate, and implantation, clinical pregnancy and live birth. The adjusted live birth rates per initiated cycle (95% CI) for partners of men in increasing categories of soy food intake were 0.36 (0.28-0.45), 0.42 (0.29-0.56), 0.36 (0.24-0.51), and 0.37 (0.24-0.52), respectively. Soy food intake in men was not related to clinical outcomes among couples presenting at an infertility clinic. Data on the relation between phytoestrogens and male reproductive potential remain scarce and additional research is required to clarify its role in human reproduction. © 2015 American Society of Andrology and European Academy of Andrology.

[Genetics of fertility restoration in the isocytoplasm allonuclear C-group of cytoplasmic male sterility in maize].

PubMed

Zhao, Zhuo Fan; Huang, Ling; Liu, Yong Ming; Zhang, Peng; Wei, Gui; Cao, Mo Ju

2018-05-20

Maize is one of the first crops to produce hybrids using cytoplasmic male sterile lines. The C-type cytoplasmic male sterile (CMS-C) line is vital for hybrid seed production, and the fertility-restoration reaction along with its stability has a direct bearing on its applications. However, fertility restoration mechanism of CMS-C is complex and is still not clear so far. To further explore the factors affecting the fertility restoration of maize CMS, a series of test crosses were carried out by pollinating the isocytoplasm allonuclear CMS-C lines C48-2, Chuangzaosi and C478 with the test lines 18 bai, zi 330, 5022 and the restorer line A619, respectively. Four F 2 populations and six double-cross combinations were obtained from the self-cross of fertility restored F 1 and pollinating male-sterility-maintained F 1 with the male-fertility-restored F 1 , respectively. Meanwhile, we developed the incomplete diallel-cross combinations using the isocytoplasm allonuclear male sterile lines as maternal parents and their respective maintainer lines 48-2, huangzaosi and 478 as paternal parents. All the F 1 , F 2 and double-cross populations were planted at distinct locations in different years, and the fertility-restoration reaction was scored by field investigation and pollen staining with I 2 -IK. The results were as follows: 1) The same test line could restore the CMS-C line at a certain genetic background, but failed to restore the CMS-C line at the other genetic backgrounds, suggesting that the genetic background of CMS-C lines plays an important role in the fertility restoration. 2) The fertile-to-sterile segregation ratio of (C48-2×A619) F 2 population planted in both Sichuan and Yunnan fited well to 15:1 by the χ 2 test. However, the fertility level of individuals in Yunnan mainly belonged to the 3 and 4grades, but which in Sichuan mainly belonged to the 5 grade, indicating the environmental factors had effect on the fertility-restoration reaction of (C48-2×A619) F

Calcium Influx and Male Fertility in the Context of the Sperm Proteome: An Update

PubMed Central

Rahman, Md Saidur; Kwon, Woo-Sung; Pang, Myung-Geol

2014-01-01

Freshly ejaculated spermatozoa are incapable or poorly capable of fertilizing an oocyte. The fertilization aptness of spermatozoa depends on the appropriate and time-dependent acquisition of hyperactivation, chemotaxis, capacitation, and the acrosome reaction, where calcium (Ca2+) is extensively involved in almost every step. A literature review showed that several ion channel proteins are likely responsible for regulation of the Ca2+ uptake in spermatozoa. Therefore, manipulation of the functions of channel proteins is closely related to Ca2+ influx, ultimately affecting male fertility. Recently, it has been shown that, together with different physiological stimuli, protein-protein interaction also modifies the Ca2+ influx mechanism in spermatozoa. Modern proteomic analyses have identified several sperm proteins, and, therefore, these findings might provide further insight into understanding the Ca2+ influx, protein functions, and regulation of fertility. The objective of this review was to synthesize the published findings on the Ca2+ influx mechanism in mammalian spermatozoa and its implications for the regulation of male fertility in the context of sperm proteins. Finally, Pathway Studio (9.0) was used to catalog the sperm proteins that regulate the Ca2+ influx signaling by using the information available from the PubMed database following a MedScan Reader (5.0) search. PMID:24877140

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

PubMed

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.

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.

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

PubMed

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

2012-06-08

Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10(-4) for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values < 0.05 and seven with p values < 0.01 in the validation study. On the basis of 5,000 permutations of our data, the probabilities of observing this many or more small p values were 0.0014 and 5.6 × 10(-4), respectively. Among the nine associated loci, outstanding candidates for male fertility genes include USP8, an essential deubiquitinating enzyme that has a role in acrosome assembly; UBD and EPSTI1, which have potential roles in innate immunity; and LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2012-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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...

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...

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

2015-03-07

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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

[Thermo-sensitive period and critical temperature of fertility transition of thermo-photo-sensitive genic male sterile wheat].

PubMed

Zhang, Jiankui; Feng, Li; He, Liren; Yu, Guodong

2003-01-01

The thermo-sensitive period and the critical temperature of fertility transition of C49S, a principal thermo-photosensitive genic male sterile line in two-line hybrid wheat, was studied in the growth chambers for controlling temperature and photoperiod. The seeds were sown on different time for some years. The results showed that the thermo-sensitive period in fertility expression of C49S was from PMC formation stage to mature pollen stage, and there were two most sensitive stages to temperature on fertility expression. One was the PMC meiosis stage, and the other was the middle microspore stage. The critical temperatures evoking a complete male sterility were the mean minimum temperature at PMC meiosis stage (Tmin1), the mean temperature at microspore stage (T2) and the mean minimum temperature at microspore stage (Tmin2) lower than 8.5 degrees C, 13.5 degrees C and 10.5 degrees C, respectively. The critical temperatures keeping a nearly normal male fertility Tmin1 and T2 and Tmin2 were higher than 11.5 degrees C, 15.0 degrees C and 12.5 degrees C, respectively. The value as well as the conditions and the risks of thermo-photo-sensitive genic male sterile line of wheat applied to hybrid wheat were evaluated in this paper.

Prostasomes--their effects on human male reproduction and fertility.

PubMed

Burden, H P; Holmes, C H; Persad, R; Whittington, K

2006-01-01

The prostate is a glandular male accessory sex organ vital for normal fertility. It provides the prostatic component of seminal plasma which nourishes and protects sperm following ejaculation. Prostasomes are small (40-500 nm) membrane-bound vesicles produced by epithelial cells lining the prostate acini and are a component of prostatic secretions. Although the existence of these particles has been known for many years, their full function and relevance to reproductive health are largely unknown. Proteomic studies have shown a wide range of proteins (enzymes, structural proteins and novel, unannotated proteins) present in or on the surface of prostasomes providing them with a diverse nature. Interestingly prostasomes are able to fuse with sperm, this event and the associated transfer of proteins lies at the heart of many of their proposed functions. Sperm motility is increased by the presence of prostasomes and their fusion prevents premature acrosome reactions. Prostasomes have been shown to aid protection of sperm within the female reproductive tract because of immunosuppressive, antioxidant and antibacterial properties. Clinically these functions imply a role for prostasomes in male factor infertility. However, the very functions that promote fertility may have negative connotations in later life; recent work has suggested that prostasomes are involved in prostate cancer. Clearly more work is needed to clarify the role of these novel particles and their impact on men's health.

Two bHLH-type transcription factors, JA-ASSOCIATED MYC2-LIKE2 and JAM3, are transcriptional repressors and affect male fertility

PubMed Central

Nakata, Masaru; Ohme-Takagi, Masaru

2013-01-01

The jasmonate (JA) plant hormones regulate responses to biotic and abiotic stress and aspects of plant development, including male fertility in Arabidopsis thaliana. The bHLH-type transcription factor JA-ASSOCIATED MYC2-LIKE1 (JAM1) negatively regulates JA signaling and gain-of-function JAM1 transgenic plants have impaired JA-mediated male fertility. Here we report that JAM2 and JAM3, 2 bHLHs closely related to JAM1, also act as transcriptional repressors. Moreover, overexpression of JAM2 and JAM3 also results in reduced male fertility. These results suggest that JAM1, JAM2, and JAM3 act redundantly as negative regulators of JA-mediated male fertility. PMID:24056034

Evolvement of transgenic male-sterility and fertility-restoration system in rice for production of hybrid varieties.

PubMed

Rao, Gundra Sivakrishna; Deveshwar, Priyanka; Sharma, Malini; Kapoor, Sanjay; Rao, Khareedu Venkateswara

2018-01-01

We have developed a unique male-sterility and fertility-restoration system in rice by combining Brassica napus cysteine-protease gene (BnCysP1) with anther-specific P12 promoter of rice for facilitating production of hybrid varieties. In diverse crop plants, male-sterility has been exploited as a useful approach for production of hybrid varieties to harness the benefits of hybrid vigour. The promoter region of Os12bglu38 gene of rice has been isolated from the developing panicles and was designated as P12. The promoter was fused with gusA reporter gene and was expressed in Arabidopsis and rice systems. Transgenic plants exhibited GUS activity in tapetal cells and pollen of the developing anthers indicating anther/pollen-specific expression of the promoter. For engineering nuclear male sterility, the coding region of Brassica napus cysteine protease1 (BnCysP1) was isolated from developing seeds and fused to P12 promoter. Transgenic rice plants obtained with P12-BnCysP1 failed to produce functional pollen grains. The F 1 seeds obtained from BnCysP1 male-sterile plants and untransformed controls showed 1:1 (tolerant:sensitive) ratio when germinated on the MS medium supplemented with phosphinothricin (5 mg/l), confirming that the male sterility has been successfully engineered in rice. For male fertility restoration, transgenic rice plants carrying BnCysP1Si silencing system were developed. The pollination of BnCysP1 male-sterile (female-fertile) plants with BnCysP1Si pollen resulted in normal grain filling. The F 1 seeds of BnCysP1 × BnCysP1Si when germinated on the MS basal medium containing PPT (5 mg/l) and hygromycin (70 mg/l) exhibited 1:1 (tolerant:sensitive) ratio and the tolerant plants invariably showed normal grain filling. The overall results clearly suggest that the customized male-sterility & fertility-restoration system can be exploited for quality hybrid seed production in various crops.

Effects of intermediate frequency magnetic fields on male fertility indicators in mice.

PubMed

Kumari, K; Capstick, M; Cassara, A M; Herrala, M; Koivisto, H; Naarala, J; Tanila, H; Viluksela, M; Juutilainen, J

2017-08-01

Human exposure to intermediate frequency (IF) fields is increasing due to new applications such as electronic article surveillance systems, wireless power transfer and induction heating cookers. However, limited data is available on effects of IF magnetic fields (MF) on male fertility function. This study was conducted to assess possible effects on fertility indicators from exposure to IF MF. Male C57BL/6J mice were exposed continuously for 5 weeks to 7.5kHz MF at 12 and 120μT. Sperm cells from cauda epididymis were analysed for motility, total sperm counts, and head abnormalities. Motile sperm cells were classified as progressive or non-progressive. Testicular spermatid heads were counted as well. The body weight development and reproductive tissue weights were not affected. No exposure-related differences were observed in sperm counts or sperm head abnormalities. Proportion of non-motile cells was significantly decreased in the 120µT group, and a corresponding increase was seen in the percentage of motile cells (significant in non-progressive motile cells). In conclusion, no adverse effects on fertility indicators were observed. Increased sperm motility is an interesting finding that needs to be confirmed in further studies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A new insight into male fertility preservation for patients with completely immotile spermatozoa.

PubMed

Chen, Huanhua; Feng, Guixue; Zhang, Bo; Zhou, Hong; Wang, Caizhu; Shu, Jinhui; Gan, Xianyou; Lin, Ruoyun; Huang, Dongmei; Huang, Yingqin

2017-09-18

Sperm cryopreservation is the most effective method to preserve male fertility but this is normally used for motile spermatozoa. Thus, only motile spermatozoa are used for cryopreservation in most reproductive medicine centers worldwide. The immotile spermatozoa from some problematic patients are usually discarded, resulting in a missed opportunity of sterility cryopreservation for future assisted reproductive treatments. Many studies have shown that successful fertilization can be obtained after selection of viable sperm from the completely immotile spermatozoa before ICSI. Whether the completely immotile spermatozoa are worth of freezing has not been realized The aim of this study is to explore the clinical value of cryopreservation of immotile spermatozoa. Completely immotile spermatozoa were collected and frozen, and subsequently viable but immotile frozen-thawed spermatozoa were selected by laser plus for ICSI. Main outcomes included spermatozoa survival index, fertilization rate and good quality embryo rate. After identification by laser, the fresh samples of spermatozoa presented with a mean survival rate of 54.86% and 26.05%, and this was reduced to 44.13% and 18.13% in frozen-thawed spermatozoa samples, which showed a frozen-thawed spermatozoa survival index of 0.80 and 0.70 in the testicular and ejaculate sperm, respectively. There were no statistically differences in fertilization rate (80% vs80.51%, 75.00% vs 81.48%), cleavage rate (95.45% vs 98.95%, 100.00% vs 95.45%) and good quality embryo rate (40.48% vs 52.13%, 33.33%vs38.10%) between the frozen-thawed immotile spermatozoa group and the routine fresh immotile spermatozoa ICSI group in both testicular and ejaculate sperm, respectively. The results of the study show that completely immotile spermatozoa can be frozen in order to preserve male fertility as long as viable spermatozoa are present. This procedure provides a further possibility for fertility preservation for patients with completely

Obesity-Induced Infertility in Male Mice Is Associated With Disruption of Crisp4 Expression and Sperm Fertilization Capacity.

PubMed

Borges, Beatriz C; Garcia-Galiano, David; da Silveira Cruz-Machado, Sanseray; Han, Xingfa; Gavrilina, Galina B; Saunders, Thomas L; Auchus, Richard J; Hammoud, Saher S; Smith, Gary D; Elias, Carol F

2017-09-01

Approximately 15% of human couples of reproductive age have impaired fertility, and the male component accounts for about half of these cases. The etiology is usually unknown, but high correlation with the increase in obesity rates is documented. In this study, we show that diet-induced and genetically obese mice display copulatory behavior comparable to controls, but the number of females impregnated by obese males is remarkably low. Screening for changes in gene expression in the male reproductive tract showed decreased Crisp4 expression in testis and epididymis of obese mice. Lack of CRISP4 in the luminal membrane of epididymal cells indicated inadequate secretion. Consistent with CRISP4 action in acrosome reaction, sperm from mice fed a high-fat diet (HFD) had decreased fertilization capacity. CRISP4 treatment of sperm from HFD mice prior to in vitro fertilization improved fertilization rate. In leptin-deficient obese and infertile mice, leptin's effect to restore CRISP4 expression and function required gonadal hormones. Our findings indicate that the obesity-induced decline in sperm motility and fertilization capacity results in part from the disruption of epididymal CRISP4 expression and secretion. Copyright © 2017 Endocrine Society.

Fertility as a priority among at-risk adolescent males newly diagnosed with cancer and their parents.

PubMed

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

2015-02-01

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. 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. "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 third among adolescents, fourth among fathers, and fifth among mothers. Future health was ranked the top priority across groups, distinct from all other goals (ps < 0.001), and fertility ranked higher than home ownership and wealth for all groups (ps < 0.001). For adolescents, low/moderate fertility risk perception was associated with higher fertility rankings than no/high risk perceptions (p = 0.01). 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.

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

DO BODY WEIGHT CHANGES IMPACT AGE OF PUBERTY AND REPRODUCTIVE ENDPOINTS IN THE EDSP TIER 1 MALE AND FEMALE PUBERTAL PROTOCOLS?

EPA Science Inventory

DO BODY WEIGHT CHANGES IMPACT AGE OF PUBERTY AND REPRODUCTIVE ENDPOINTS IN THE EDSP TIER 1 MALE AND FEMALE PUBERTAL PROTOCOLS? T.E. Stoker, K. McElroy, J. Ferrell, K. Bremser, R. Cooper and S.C. Laws. Endocrinology Branch, RTD, NHEERL, ORD, USEPA, RTP, NC.

The relations...

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

Optimizing Male Fertility

MedlinePlus

... Videos State Infertility Insurance Laws Protect Your Fertility Campaign Find a Health Professional ABOUT ASRM Vision of ASRM ASRM's Mission Statement Site Endowment ASRM Board of Directors ASRM Office of Public Affiars Social Media Contact Us Donate ASRM Cookie Policy Donate ASRM ...

Brown adipose tissue transplantation ameliorates male fertility impairment caused by diet-induced obesity.

PubMed

Liu, Hui; Liu, Xiaomeng; Wang, Li; Sheng, Nan

Populations with obesity or overweight have a high incidence of infertility. We hypothesised that brown adipose tissue (BAT) transplantation can attenuate the impairment of male fertility caused by diet-induced obesity. BATs were transplanted from male donor mice into age and sex matched recipient mice fed high-fat diets (HFD). Sperm motility experiment was conducted after surgical procedure. X-ray computed tomography scanning, biochemical assay, real-time PCR and western blot analysis were performed. BAT transplantation reduced body fat and epididymal fat mass, as well as triglycerides (TG) content in testis and epididymis and total cholesterol (TCHO) contents in epididymis compared with the HFD group. Sperm motility and progressiveness were recovered and mRNA and protein levels of genes related to sperm motility such as cullin 3 (Cul3), peroxisome proliferator activated receptor alpha (PPARα) and its down-stream genes were significantly down-regulated post BAT transplantation. BAT transplantation partially ameliorated impairment of male fertility caused by diet-induced obesity. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Male fertility following occupational exposure to dichlorodiphenyltrichloroethane (DDT).

PubMed

Campagna, Marcello; Satta, Giannina; Fadda, Domenica; Pili, Sergio; Cocco, Pierluigi

2015-04-01

The inconsistent epidemiological results of the endocrine disrupting effects of DDT fuel a harsh debate on its global ban. We tested the hypothesis that occupational exposure to dichloro-diphenyl-trichloroethane (DDT) causes impairment in male fertility in a cohort of DDT exposed workers, in Sardinia, Italy. We accessed official records on date of marriage and date of birth of the first child to estimate time to pregnancy (TTP) in the spouses of 1223 workers employed in a 1946-1950 anti-malarial campaign. The TTP calculation was censored at the 13th month after date of marriage. We used a modified Cox's proportional hazard model to calculate the fecundability ratio (FR) by job, by cumulative exposure to DDT, and by time window in relation to the anti-malarial operations, adjusting by paternal age at marriage. Among the spouses of DDT applicators, fecundability did not vary during DDT use (FR=1.22, 95% CI 0.84-1.77) nor in the following decade (FR=1.01, 95% CI 0.67-1.50) with reference to the prior years. A significant increase occurred among the unexposed and the less exposed sub-cohorts, which generated a non-significantly reduced FR among the DDT applicator sub-cohort with reference to the unexposed following exposure. We did not find evidence of an impairment in male fertility following heavy occupational exposure to DDT. However, although fecundability was highest among the spouses of the DDT applicators in the years prior to the anti-malarial campaign, we cannot exclude that DDT exposure prevented an increase parallel to that observed among the unexposed and the less exposed sub-cohorts. Copyright © 2015. Published by Elsevier Ltd.

Assessment of sublethal endpoints after chronic exposure of the nematode Caenorhabditis elegans to palladium, platinum and rhodium.

PubMed

Schertzinger, Gerhard; Zimmermann, Sonja; Grabner, Daniel; Sures, Bernd

2017-11-01

The aim of this study was to investigate chronic effects of the platinum-group elements (PGE) palladium (Pd), platinum (Pt) and rhodium (Rh) on the nematode Caenorhabditis elegans. Aquatic toxicity testing was carried out according to ISO 10872 by determining 96 h EC 50 values for sublethal endpoints, including growth, fertility and reproduction. Single PGE standard solutions were used as metal source. Based on the EC 50 values for Pt, reproduction (96 h EC 50  = 497 μg/L) was the most sensitive endpoint followed by fertility (96 h EC 50  = 726 μg/L) and growth (96 h EC 50  = 808 μg/L). For Pd, no precise EC 50 values could be calculated due to bell-shaped concentration response curves, but the 96 h EC 50 for reproduction ranged between 10 and 100 μg/L. Pd and Pt had effects on all endpoints. With raising element concentrations reproduction was inhibited first. At a certain concentration, fertility was also affected, which in turn had an additional effect on reproduction. Growth inhibition can also lead to a loss of fertility if the worms do not reach an appropriate body size to become fertile. Rhodium showed no inhibition of any endpoint between concentrations of 100 to 10,000 μg Rh/L. The results of this study allow the following order of PGE with respect to decreasing toxicity to C. elegans: Pd > Pt » Rh. Copyright © 2017 Elsevier Ltd. All rights reserved.

Men's knowledge of their own fertility: a population-based survey examining the awareness of factors that are associated with male infertility.

PubMed

Daumler, D; Chan, P; Lo, K C; Takefman, J; Zelkowitz, P

2016-12-01

How knowledgeable are men about the medical, environmental and psychological factors that are associated with male infertility? Men, across most demographic groups, have limited knowledge of the various factors that are associated with male infertility. Few surveys have focused on men's knowledge of their own fertility. Studies of both men and women have found that men are comparatively less knowledgeable about issues of fertility and reproductive health. A regionally representative sample of Canadian men completed a web-based survey of male fertility and reproductive health, over a 2-month period in 2015. Men, aged 18-50 years, were recruited for the study. There were 701 male participants, with a mean age of 34.1 years. Each participant was asked to identify factors associated with male infertility; fertility knowledge was assessed through two open-ended questions and a comprehensive list of risk factors and attendant health issues. Men were only able to identify 51% of the risk factors and 45% of the health issues associated with male infertility. Men were most aware of the modifiable risk factors for infertility (e.g. sexually transmitted infections, smoking cigarettes), relative to their knowledge of fixed risk factors (e.g. delayed puberty, size of testicles) and the attendant health issues (e.g. cardiovascular disease, diabetes). The overall level of fertility knowledge did not vary by most demographic characteristics (e.g. age, education, employment, income), though men from ethnic minority groups displayed moderately greater awareness. Additionally, younger men, those with lower incomes and those who had no desire to have future biological children were more likely to identify themselves as unaware of associations with infertility in the open-ended questions. Self-reported knowledge was significantly associated with higher overall knowledge scores. More than half of the sample expressed an interest in obtaining information about male fertility and

Men's knowledge of their own fertility: a population-based survey examining the awareness of factors that are associated with male infertility

PubMed Central

Daumler, D.; Chan, P.; Lo, K.C.; Takefman, J.; Zelkowitz, P.

2016-01-01

STUDY QUESTION How knowledgeable are men about the medical, environmental and psychological factors that are associated with male infertility? SUMMARY ANSWER Men, across most demographic groups, have limited knowledge of the various factors that are associated with male infertility. WHAT IS KNOWN ALREADY Few surveys have focused on men's knowledge of their own fertility. Studies of both men and women have found that men are comparatively less knowledgeable about issues of fertility and reproductive health. STUDY DESIGN, SIZE, DURATION A regionally representative sample of Canadian men completed a web-based survey of male fertility and reproductive health, over a 2-month period in 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS Men, aged 18–50 years, were recruited for the study. There were 701 male participants, with a mean age of 34.1 years. Each participant was asked to identify factors associated with male infertility; fertility knowledge was assessed through two open-ended questions and a comprehensive list of risk factors and attendant health issues. MAIN RESULTS AND THE ROLE OF CHANCE Men were only able to identify 51% of the risk factors and 45% of the health issues associated with male infertility. Men were most aware of the modifiable risk factors for infertility (e.g. sexually transmitted infections, smoking cigarettes), relative to their knowledge of fixed risk factors (e.g. delayed puberty, size of testicles) and the attendant health issues (e.g. cardiovascular disease, diabetes). The overall level of fertility knowledge did not vary by most demographic characteristics (e.g. age, education, employment, income), though men from ethnic minority groups displayed moderately greater awareness. Additionally, younger men, those with lower incomes and those who had no desire to have future biological children were more likely to identify themselves as unaware of associations with infertility in the open-ended questions. Self-reported knowledge was

The Influence of Methotrexate Treatment on Male Fertility and Pregnancy Outcome After Paternal Exposure.

PubMed

Grosen, Anne; Kelsen, Jens; Hvas, Christian Lodberg; Bellaguarda, Emanuelle; Hanauer, Stephen B

2017-04-01

Inflammatory bowel disease incidence peaks during the reproductive years. Methotrexate (MTX) is frequently used for inflammatory bowel disease, but its use during pregnancy is contraindicated in women because of teratogenic effects. The aim of this review is to investigate the influence of MTX on male fertility and pregnancy outcomes after paternal MTX exposure. A systematic literature search was performed by applying 2 focus areas, "methotrexate" and "male fertility or pregnancy outcome." Terms and keywords were used both as MeSH terms and free-text searches. Pertinent articles were searched for additional relevant references. In animal studies, MTX induces aberrations in sperm DNA that have not been identified in humans. The effects of MTX on human sperm quality have only been described in case reports. A transient adverse effect on sperm quality with low-dose MTX has been reported, but several other cases have not found harmful effects of MTX. MTX has not been measured in human sperm ejaculates; yet, the risk of a direct toxic effect on the fetus through MTX-contaminated seminal plasma seems negligible. Until now, 284 pregnancies with paternal MTX exposure have been reported. The outcomes were 248 live births and a total of 13 malformations, with no overt indication of MTX embryopathy. This review reveals the lack of studies on the safety of MTX with regard to male reproduction. It is not clear whether MTX transiently influences male fertility and sperm DNA integrity, and more studies are needed. Comparative cohort studies found no increased risk of adverse pregnancy outcomes.

Endocrine approaches to male fertility control.

PubMed

Knuth, U A; Nieschlag, E

1987-02-01

As in the female, gametogenesis in the male is under the control of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Their suppression should inhibit spermatogenesis. If a non-androgenic substance is used to suppress gonadotrophins, androgens must be supplemented to maintain virility, potency and metabolic processes. To avoid administration of several substances, testosterone and its esters were used to develop a male antifertility agent. Although azoospermia can be induced in a high proportion of men with administration of testosterone esters alone, this effect is not uniform. Even frequent injections with testosterone enanthate at weekly intervals fail to inhibit spermatogenesis in all participants. Combinations of gestagenic compounds with testosterone esters show a somewhat better effect, but again azoospermia is only achieved in around 50% of participants. LHRH analogues, although considered by many to offer a realistic potential for male fertility regulation, have not been proven to be successful for this purpose so far. Animal studies in monkeys and preliminary clinical trials demonstrate that agonistic analogues of LHRH have to be given continuously by pump or implant to achieve a pronounced effect on spermatogenesis. But even under these provisions, results in clinical trials have been worse than effects achieved with testosterone/gestagen combinations. Whether new antagonistic compounds offer a better potential awaits clinical trials. Studies in non-human primates demonstrate that testosterone by itself can maintain and initiate spermatogenesis. Based on these findings one could postulate an attenuating effect of high serum androgen levels after supplementation with available testosterone esters. Trials of alternative androgenic substances with slow-release characteristics and without high serum levels after single injections, like 19-nortestosterone hexyloxyphenylpropionate (19NT-HPP), tend to support this theory. With slow

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.

Treatment of severe male infertility by micromanipulation-assisted fertilization: an update.

PubMed

Tesarik, Jan; Mendoza, Carmen

2007-01-01

In the past 5-10 years the evolution of micromanipulation-assisted fertilization for the treatment of severe male infertility was marked by the introduction of new technical support, refinement of diagnostic methods for the evaluation of sperm developmental potential, and development of new treatment regimens for the newly discovered abnormalities. The new technical support involves the use of non-contact laser technology to assist micromanipulation for fertilization, the evolution of polarized microscopy-based optical systems to non-invasively detect the position of the meiotic spindle in living human oocytes, and the development of high-magnification optical systems for a better morphological selection of spermatozoa to be used for fertilization. Diagnostic approaches were enriched by commercial availability of kits for the analysis of sperm DNA integrity, leading to the definition of sperm nuclear DNA damage as a distinct cause of male infertility, and by the development of tests, based on heterologous ICSI, for detection of sperm failure to activate oocytes. Several treatment options for these conditions have been proposed and are currently being tested in larger-scale trials. Some technical improvement was also achieved in the field of in vitro maturation of germ cells from men with in vivo maturation arrest, but only a modest clinical improvement resulted from their application. As to the risk for the offspring, recent data are rather reassuring. Except for the risk of transmission of genetically based infertility, no straightforward evidence for a health risk derived from these techniques has been provided. Nevertheless, caution is necessary, particularly concerning the eventual increase in genomic-imprinting abnormalities.

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.

Effects of nicotine on sperm characteristics and fertility profile in adult male rats: a possible role of cessation.

PubMed

Oyeyipo, Ibukun Peter; Raji, Yinusa; Emikpe, Benjamin Obukowho; Bolarinwa, Adeyombo Folashade

2011-07-01

Infertility is common among couples of child-bearing age and approximately half of known causes of primary infertility are attributable to male factor. It is still unclear whether the injurious effects of cigarette smoking on sperm characteristics and infertility are due to nicotine. Therefore, the present study investtigated the effects of orally administered of nicotine on sperm characteristics and libido in adult male albino rats. The study also sought nicotine effects on fertility rate, litter size and weight in female animals cohabited with nicotine treated male rats. Forty male and twenty-five female rats were used for the study. The male rats were divided into five groups and were treated for a period of 30 days with nicotine 0.5 mg/kg (low dose) and 1.0 mg/kg (high dose) per body weight while the control rats received 0.2 ml/kg normal saline. The fourth and fifth groups were gavaged with 0.5 mg/kg and 1.0 mg/kg body weight of nicotine but were left untreated for another 30 days. These groups served as the recovery groups. At the end of each experimental period, sperm analysis, fertility study, litter weight and size were determined. Sperm motility and count significantly decreased (P < 0.05) while the percentage of abnormality significantly increased (P < 0.05) in both treatment groups. However, there was an insignificant decrease (P > 0.05) in the viability and semen volume of the treated groups. Fertility studies revealed that nicotine reduced libido in male rats, litter weight and number delivered by the untreated female during the experiments. The present study showed that nicotine has a dose-dependent deleterious effect on the sperm characteristics and that fertility is ameliorated by nicotine cessation in male rats.

Protective effects of Lycium barbarum polysaccharide on male sexual dysfunction and fertility impairments by activating hypothalamic pituitary gonadal axis in streptozotocin-induced type-1 diabetic male mice.

PubMed

Shi, Guang-Jiang; Zheng, Jie; Wu, Jing; Qiao, Hai-Qi; Chang, Qing; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

2017-09-30

Diabetes-associated male sexual dysfunction and fertility impairments are both common clinical complications with limited therapeutic options; hence it seriously affects the quality of life of the patients, in particular, the patients of reproductive age. Lycium barbarum polysaccharide (LBP) has long being believed to maintain and to promote reproductive functions in the traditional medical practice in China. The current study was to investigate if LBP may contribute to recovery of male sexual dysfunction and fertility impairments in diabetic individuals. The effects of LBP on sexual behaviors and histological changes of testis were studied in the type-1 diabetes male mice induced by intra-peritoneal (i.p.) injection of streptozotocin (STZ). After oral administration of LBP (10, 20 or 40 mg/kg), sildenafil citrate (SC, 5 mg/kg) or saline for 62 consecutive days, the typical abnormal changes in the sperm parameters, in relative weight of reproductive organs and in morphology of testis were observed in diabetic mice. LBP treatment of the diabetic mice considerably reversed those changes and Johnsen's testicular score, serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) level were also increased to different degrees. Moreover, our data have also shown that a marked improvement in sexual behavior and fertility level after administration of LBP (40 mg/kg) compared to the diabetic group. These results suggested that LBP can exert functional recovery of male sexual dysfunction and fertility damages induced by diabetes in male mice, which is likely to be mediated through regulating the hypothalamus- pituitary-gonadal axis endocrine activity.

Male Fertility Defect Associated with Disrupted BRCA1-PALB2 Interaction in Mice*

PubMed Central

Simhadri, Srilatha; Peterson, Shaun; Patel, Dharm S.; Huo, Yanying; Cai, Hong; Bowman-Colin, Christian; Miller, Shoreh; Ludwig, Thomas; Ganesan, Shridar; Bhaumik, Mantu; Bunting, Samuel F.; Jasin, Maria; Xia, Bing

2014-01-01

PALB2 links BRCA1 and BRCA2 in homologous recombinational repair of DNA double strand breaks (DSBs). Mono-allelic mutations in PALB2 increase the risk of breast, pancreatic, and other cancers, and biallelic mutations cause Fanconi anemia (FA). Like Brca1 and Brca2, systemic knock-out of Palb2 in mice results in embryonic lethality. In this study, we generated a hypomorphic Palb2 allele expressing a mutant PALB2 protein unable to bind BRCA1. Consistent with an FA-like phenotype, cells from the mutant mice showed hypersensitivity and chromosomal breakage when treated with mitomycin C, a DNA interstrand crosslinker. Moreover, mutant males showed reduced fertility due to impaired meiosis and increased apoptosis in germ cells. Interestingly, mutant meiocytes showed a significant defect in sex chromosome synapsis, which likely contributed to the germ cell loss and fertility defect. Our results underscore the in vivo importance of the PALB2-BRCA1 complex formation in DSB repair and male meiosis. PMID:25016020

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

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.

Evaluation of a two-generation reproduction toxicity study adding endpoints to detect endocrine disrupting activity using vinclozolin.

PubMed

Matsuura, Ikuo; Saitoh, Tetsuji; Ashina, Michiko; Wako, Yumi; Iwata, Hiroshi; Toyota, Naoto; Ishizuka, Yoshihito; Namiki, Masato; Hoshino, Nobuhito; Tsuchitani, Minoru

2005-12-01

A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using vinclozolin by dietary administration at 0, 40, 200, and 1000 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed changes due to vinclozolin in the AGD, nipple development, sexual maturation, sex organ weights, and blood sex hormone concentrations in males of both parental animals and offspring, even at the lowest dose of 40 ppm, confirmed by results for the classical endpoints of histopathological examination at 200 ppm and mating at 1000 ppm. The effects on parental males included increased pituitary and testis weights, and decreased epididymis weights at 1000 ppm in both generations, and decreased prostate and epididymis weights at 200 and 1000 ppm and seminal vesicle weights at 1000 ppm in F1 males. Histopathological examination revealed hypertrophy of the basophilic cells in the pituitary at these two doses, and diffuse hyperplasia of the testicular interstitial cells and atrophy of the seminal vesicle mucosa at 1000 ppm in F0 and F1 males. In addition, F1 males demonstrated decrease in prostate fluid at 200 and 1000 ppm. Blood hormone analysis revealed increases in LH, FSH, testosterone, and DHT in F0 and F1 males at 1000 ppm. General toxicological effects included suppressed body weight gain in F0 and F1 females and in F1 males, and reduced food consumption in F0 and F1 females at 1000 ppm. Histopathological examination revealed centrilobular hepatocellular hypertrophy in males at 200 and 1000 ppm and in females at 1000 ppm, increased lipid droplets in the adrenal zona fasciculata and zona glomerulosa in

[Hormone regulation of male fertility].

PubMed

Anselmo, J G

1975-01-01

An innocuous, sure, reversible means of male fertility control which does not disturb the libido is being sought. 20 healthy volunteers from ages 20 to 36 participated, using a 2nd form of protection when necessary. 10 received implants of 60 mg testosterone equally divided into 3 tubes, and began oral ingestion of 100 mg weekly, divided into daily doses, of R2323 (13-ethyl-17-hydroxy-gonen 4,9,11, trien-3-one) until the sperm became ineffective. Then oral doses were given according to personal requirements from 50 to 25 mg. The 2nd series of 10 received no testosterone implants, but followed the same scheme for oral ingestion. All patients but 1 reduced their sperm count and 80% were low enough to consider the sperm inactive. For those who used the hormone treatment as the only protection against pregnancy, no pregnancy occurred. Of the 1st group, 2 had excessive weight gain, 3 felt their libido reduced, and 1 had pain in the nipples and 1 had pain in the hepatic region. Recuperation of normal sperm characteristics was slow, especially motility and vitality. The spermogram is so altered during treatment that any accidental pregnancy could result in a defective egg and serious complications. It should definitely be avoided.

Effects of age on male fertility.

PubMed

Zitzmann, Michael

2013-08-01

Later parenting is considered by many to have advantages, parents-to-be may feel themselves more stable to rear children. In addition, many men start a second family later in life. Thus, paternal age becomes an emerging issue. Aging affects male fertility by a scope of factors, which are not fully understood to date. Generally, the amount of produced sperm cells as well as their motility decreases with age, as testicular histological architecture deteriorates. Decreased fecundity and an increased risk for disturbed pregnancies occur with advancing paternal age. Some rare autosomal dominant pathologies are clearly related to paternal age. Altered patterns of epigenetics/gene expression in aging sperm seem to affect a range of neurocognitive disorders and also metabolic dyshomeostasis across generations. Such effects refer to men older than 40 years and may have impact on socio-economic issues. Nevertheless, councelling of older men seeking paternity should be patient-oriented and weigh statistical probabilities against the right for individual life-planning. Copyright © 2013 Elsevier Ltd. All rights reserved.

Do extra-group fertilizations increase the potential for sexual selection in male mammals?

PubMed

Isvaran, Kavita; Sankaran, Sumithra

2017-10-01

Fertilizations by males outside the social breeding group (extra-group paternity, EGP) are widespread in birds and mammals. EGP is generally proposed to increase male reproductive skew and thereby increase the potential for sexual selection, but the generality of this relationship is unclear. We extracted data from 27 mammals in seven orders and used phylogenetic comparative methods to investigate the influence of EGP and social mating system on measures of inequality in male fertilization success, which are indices of the potential for sexual selection. We find that EGP and social mating system can predict the potential for sexual selection in mammalian populations, but only when considered jointly and not individually. EGP appears to increase the potential for sexual selection but only when the degree of social polygyny is relatively low. When social polygyny is high, EGP appears to result in a more uniform distribution of reproduction and a decrease in the potential for sexual selection. A possible explanation to be investigated is that the phenotype of extra-group fathers differs systematically across social mating systems. Our findings have implications for the use of EGP and social mating system as indices of sexual selection in comparative analyses of trait evolution under sexual selection. © 2017 The Author(s).

Effect of aqueous leaf extract of Dalbergia sissoo Roxb. on spermatogenesis and fertility in male mice.

PubMed

Verma, Hari Prakash; Singh, Shio Kumar

2014-12-01

Antifertility effects of Dalbergia sissoo in male mice were investigated. Adult Parkes strain male mice were orally administered aqueous leaf extract of Dalbergia sissoo (50 and 100 mg/kg body weight/day) or distilled water or no treatment (controls) for 35 days (n = 5/group). Motility, viability and number of spermatozoa in the cauda epididymidis; testis histology; serum level of testosterone; and toxicological parameters were evaluated. To assess reversibility, more mice were treated with 100 mg/kg body weight of Dalbergia sissoo or distilled water (n = 5/group) for 35 days and sacrificed 56 days later. Fertility was also assessed separately. Histologically, testes of Dalbergia-treated mice showed dissimilar degenerative changes in the seminiferous tubules. Significant reductions were noted (i) in epididymal sperm motility, viability and number, and (ii) in serum level of testosterone in Dalbergia-treated mice compared to controls. However, serum levels of alanine aminotransferase, aspartate aminotransferase and creatinine, and haematological parameters were not affected. Also libido of Dalbergia-treated males showed no change, but their fertility was markedly suppressed. By 56 days of treatment withdrawal, alterations induced in the above parameters returned to control levels. Dalbergia sissoo treatment caused reversible suppression of spermatogenesis and fertility in P mice, without eliciting detectable toxic effects.

A novel test of the phenotype-linked fertility hypothesis reveals independent components of fertility.

PubMed Central

Pizzari, Tommaso; Jensen, Per; Cornwallis, Charles K.

2004-01-01

The phenotype-linked fertility hypothesis predicts that male sexual ornaments signal fertilizing efficiency and that the coevolution of male ornaments and female preference for such ornaments is driven by female pursuit of fertility benefits. In addition, directional testicular asymmetry frequently observed in birds has been suggested to reflect fertilizing efficiency and to covary with ornament expression. However, the idea of a phenotypic relationship between male ornaments and fertilizing efficiency is often tested in populations where environmental effects mask the underlying genetic associations between ornaments and fertilizing efficiency implied by this idea. Here, we adopt a novel design, which increases genetic diversity through the crossing of two divergent populations while controlling for environmental effects, to test: (i) the phenotypic relationship between male ornaments and both, gonadal (testicular mass) and gametic (sperm quality) components of fertilizing efficiency; and (ii) the extent to which these components are phenotypically integrated in the fowl, Gallus gallus. We show that consistent with theory, the testosterone-dependent expression of a male ornament, the comb, predicted testicular mass. However, despite their functional inter-dependence, testicular mass and sperm quality were not phenotypically integrated. Consistent with this result, males of one parental population invested more in testicular and comb mass, whereas males of the other parental population had higher sperm quality. We found no evidence that directional testicular asymmetry covaried with ornament expression. These results shed new light on the evolutionary relationship between male fertilizing efficiency and ornaments. Although testosterone-dependent ornaments may covary with testicular mass and thus reflect sperm production rate, the lack of phenotypic integration between gonadal and gametic traits reveals that the expression of an ornament is unlikely to reflect the

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

PubMed

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

2015-10-01

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

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

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. Copyright © 2015, American Association for the Advancement of Science.

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

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

PubMed

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

2015-06-30

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

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.

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

USDA-ARS?s Scientific Manuscript database

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...

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. © 2016 Blackwell Verlag GmbH.

Suppression and restoration of male fertility using a transcription factor.

PubMed

Li, Song Feng; Iacuone, Sylvana; Parish, Roger W

2007-03-01

The Arabidopsis AtMYB103 gene codes for an R2R3 MYB domain protein whose expression is restricted to the tapetum of developing anthers and to trichomes. Down-regulation of expression using anti-sense leads to abnormal tapetum and pollen development, although seed setting still occurs (Higginson, T., Li, S.F. and Parish, R.W. (2003) AtMYB103 regulates tapetum and trichome development in Arabidopsis thaliana. Plant J. 35, 177-192). In this study, we show that blocking the function of the AtMYB103 gene, employing either an insertion mutant or an AtMYB103EAR chimeric repressor construct under the control of the AtMYB103 promoter, results in complete male sterility and failure to set seed. These plants exhibit similar abnormalities in tapetum and pollen development, with the tapetum becoming highly vacuolated at early stages and degenerating prematurely. No exine is deposited on to the pollen wall. The degeneration of pollen grains commences prior to pollen mitosis, the pollen collapsing and largely lacking cytoplasmic content. A restorer containing the AtMYB103 gene under the control of a stronger anther-specific promoter was introduced into pollen donor plants and crossed into the male sterile plants transgenic for the repressor. The male fertility of F1 plants was restored. The chimeric repressor and the restorer constitute a reversible male sterility system which could be adapted for hybrid seed production. This is the first reversible male sterility system targeting a transcription factor essential for pollen development. Strategies for generating inducible male sterility and maintainable male sterility for the production of hybrid crops are discussed.

New Markers for Predicting Fertility of the Male Gametes in the Post Genomic Age.

PubMed

Dipresa, Savina; De Toni, Luca; Foresta, Carlo; Garolla, Andrea

2018-04-18

A number of test have been proposed to assess male fertility potential, ranging from routine testing by light microscopic method for evaluating semen samples, to screening test for DNA integrity aimed to look at sperm chromatin abnormalities. Spermatozoa are an extremely differentiated cell, they have critical functions for embryo development and heredity, in addiction to delivering a haploid paternal genome to the oocyte. Towards this goal certain requirements must always be met. The ability of spermatozoa to perform its reproductive function taking place in the spermatogenesis, a highly specialized process depending on multiple factors with effect on male fertility. In the past 30 years, large-scale analyses of transcriptomic and genome expression in mammals have generated a large amount of informations on numberless biomolecules involved in spermatogenesis and male germ cell reproductive function. Sperm proteome represents the protein content that spermatozoa needs to survive and work correctly and modifications of sperm proteome play a role in determining functional changes leading to a decrease of reproductive competence into affected spermatozoa. The post-genomic approach consists of different methodologies for concurrently testicular transcriptome studies, protein compositional analysis and metabolomics findings of the spermatozoa in humans. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male fertility: a study using adipose triglyceride lipase deficient mice.

PubMed

Masaki, Hidetake; Kim, Namhyo; Nakamura, Hitomi; Kumasawa, Keiichi; Kamata, Eriko; Hirano, Ken-Ichi; Kimura, Tadashi

2017-07-01

Does the deletion of adipose triglyceride lipase (Atgl) gene impair male fertility? The deletion of Atgl gene impaired male fertility but the effect was partially reversed by a low long-chain triglyceride (TG) diet. ATGL specifically hydrolyses long-chain fatty acid TG to diacylglycerol and a high level of expression of ATGL in testes has been reported. However, the role of ATGL in male fertility is unknown. To investigate the effect of deletion of Atgl gene on male fertility, cauda epididymides and testes were collected from wild-type, heterozygous and homozygous Atgl-deficient mice at 10 weeks of age and epididymal sperm analysis and histological analysis of the testes were performed. To investigate whether a medium-chain triglycerides (MCTs) replacement diet mitigated the impaired male fertility by deletion of Atgl gene, homozygous Atgl-deficient mice were fed a MCT replacement diet, or a standard diet including long-chain triglycerides (LCTs) in a control group, for 6 weeks from 5 weeks of age (n = 22). The systematic and local effects of the MCT replacement diet on spermatogenesis and sperm maturation in the epididymis were analyzed at 10 weeks of age. Hematoxylin and eosin staining in paraffin-embedded sections of testes and Oil Red O staining in frozen sections of testes were performed. The epididymal sperm concentrations were analyzed. Statistical analyses were performed using the Student's t-test or Mann-Whitney U test with Shapiro-Wilk Normality test. Although heterozygous mice were fertile and showed a similar number of epididymal total and motile sperm concentrations to wild-type mice, the deletion of Atgl gene in homozygous mice led to accumulation of TG deposits in testes and impaired spermatogenesis. The deletion of Atgl gene also impaired the sperm maturation process required for sperm to acquire the ability to move forward in the epididymis. The MCT replacement diet for 6 weeks increased the plasma level of non-esterified fatty acid (NEFA) (1

De novo-based transcriptome profiling of male-sterile and fertile watermelon lines

PubMed Central

Seo, Minseok; Jang, Yoon Jeong; Sim, Tae Yong; Cho, Seoae; Han, Sang-Wook

2017-01-01

The whole-genome sequence of watermelon (Citrullus lanatus (Thunb.) Matsum. & Nakai), a valuable horticultural crop worldwide, was released in 2013. Here, we compared a de novo-based approach (DBA) to a reference-based approach (RBA) using RNA-seq data, to aid in efforts to improve the annotation of the watermelon reference genome and to obtain biological insight into male-sterility in watermelon. We applied these techniques to available data from two watermelon lines: the male-sterile line DAH3615-MS and the male-fertile line DAH3615. Using DBA, we newly annotated 855 watermelon transcripts, and found gene functional clusters predicted to be related to stimulus responses, nucleic acid binding, transmembrane transport, homeostasis, and Golgi/vesicles. Among the DBA-annotated transcripts, 138 de novo-exclusive differentially-expressed genes (DEDEGs) related to male sterility were detected. Out of 33 randomly selected newly annotated transcripts and DEDEGs, 32 were validated by RT-qPCR. This study demonstrates the usefulness and reliability of the de novo transcriptome assembly in watermelon, and provides new insights for researchers exploring transcriptional blueprints with regard to the male sterility. PMID:29095876

Female sexual behavior and sexual swelling size as potential cues for males to discern the female fertile phase in free-ranging Barbary macaques (Macaca sylvanus) of Gibraltar.

PubMed

Brauch, Katrin; Pfefferle, Dana; Hodges, Keith; Möhle, Ulrike; Fischer, Julia; Heistermann, Michael

2007-09-01

Although female catarrhine primates show cyclic changes in sexual behavior and sexual swellings, the value of these sexual signals in providing information to males about timing of the fertile phase is largely unclear. Recently, we have shown that in Barbary macaques, males receive information from females which enables them to discern the fertile phase and to focus their reproductive effort accordingly. Here, we investigate the nature of the cues being used by examining female sexual behavior and the size of sexual swelling as potential indicators of the fertile phase. We collected behavioral data and quantified swelling size using digital images of 11 females of the Gibraltar Barbary macaque population and related the data to the time of ovulation and the fertile phase as determined from fecal hormone analysis. We found that rates of female sexual behaviors were not correlated with female estrogen levels and did not significantly differ between the fertile and non-fertile phases of the cycle. In contrast, swelling size was significantly correlated with female estrogen levels and increased predictably towards ovulation with size being maximal during the fertile phase. Moreover, frequencies of male ejaculatory copulations showed a strong positive correlation with swelling size and highest rates were found during maximum swelling. Our data provide strong evidence that female Barbary macaques honestly signal the probability of fertility through sexual swelling and that males apparently use this information to time their mating activities. Honest advertising of the fertile phase might be part of a female strategy to manipulate male mating behavior for their own advantage, such as ensure fertilization with high quality sperm or influence paternity outcome.

Insulin Rescues Impaired Spermatogenesis via the Hypothalamic-Pituitary-Gonadal Axis in Akita Diabetic Mice and Restores Male Fertility

PubMed Central

Schoeller, Erica L.; Albanna, Gabriella; Frolova, Antonina I.; Moley, Kelle H.

2012-01-01

The mechanism responsible for poor reproductive outcomes in type 1 diabetic males is not well understood. In light of new evidence that the Sertoli cells of the testis secrete insulin, it is currently unclear whether diabetic subfertility is the result of deficiency of pancreatic insulin, testicular insulin, or both. In this study, the Akita mouse diabetic model, which expresses a mutant, nonfunctional form of ins2 in testes and pancreas, was used to distinguish between systemic and local effects of insulin deficiency on the process of spermatogenesis and fertility. We determined that Akita homozygous male mice are infertile and have reduced testis size and abnormal morphology. Spermatogonial germ cells are still present but are unable to mature into spermatocytes and spermatids. Exogenous insulin treatment regenerates testes and restores fertility, but this plasma insulin cannot pass through the blood-testis barrier. We conclude that insulin does not rescue fertility through direct interaction with the testis; instead, it restores function of the hypothalamic-pituitary-gonadal axis and, thus, normalizes hormone levels of luteinizing hormone and testosterone. Although we show that the Sertoli cells of the testis secrete insulin protein, this insulin does not appear to be critical for fertility. PMID:22522616

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

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

DOE PAGES

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

2017-02-23

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

Reproductive and fertility effects of an extract of Andrographis paniculata in male Wistar rats.

PubMed

Allan, J Joshua; Pore, Mukul P; Deepak, M; Murali, B; Mayachari, Anand S; Agarwal, Amit

2009-01-01

The possible effect of extract of Andrographis paniculata Nees (A paniculata) standardized to >or=10% andrographolide, the main bioactive component, on male fertility in albino Wistar rats was evaluated, by orally administering 0, 20, 200, and 1000 mg/kg of body weight per day, for 65 days prior to mating and 21 days during mating. The treated groups showed no signs of dose-dependent toxicity. The body weight gain and feed consumption were not affected at any of the dose levels. The testosterone levels and fertility indices in treatment groups were found to be comparable with that of the control indicating no effect on fertility. Total sperm count and sperm motility were not affected. The testes and epididymides did not show any gross and histopathological changes. Based on these findings, it can be concluded that the no-observed adverse effect level of extract of A paniculata (>or=10% andrographolide) was found to be more than 1000 mg/kg per day.

Application of a ready-to-use calcium ionophore increases rates of fertilization and pregnancy in severe male factor infertility.

PubMed

Ebner, Thomas; Köster, Maria; Shebl, Omar; Moser, Marianne; Van der Ven, Hans; Tews, Gernot; Montag, Markus

2012-12-01

To analyze whether a ready-to-use calcium ionophore improves outcomes, from fertilization to live birth, in patients with severe male factor infertility. Artificial oocyte activation offered to applicable patients over a 20-month period. Specialized in vitro fertilization (IVF) centers in Austria and Germany. Twenty-nine azoospermic and 37 cryptozoospermic men. Mature oocytes treated with a ready-to-use Ca(2+)-ionophore (GM508 Cult-Active) immediately after intracytoplasmic sperm injection (ICSI). Rates of fertilization, implantation, clinical pregnancy, and live birth. Patients had had 88 previous cycles without artificial activation that resulted in a fertilization rate of 34.7%, 79 transfers (89.8%), and 5 pregnancies, which all spontaneously aborted except one. After artificial oocyte activation, the fertilization rate was 56.9%. In terms of fertilization rate, both azoospermic (64.4%) and cryptozoospermic (48.4%) men statistically significantly benefited from use of the ionophore. In 73 transfer cycles, positive β-human chorionic gonadotropin levels were observed in 34 cases (46.6%) and 29 cycles (39.7%) that ended with a clinical pregnancy. The corresponding implantation rate was 33.3%. Four spontaneous abortions occurred (11.8%), and 32 healthy children were born. This is the first prospective multicenter study on artificial oocyte activation in severe male factor infertility. Present data indicate that a ready-to-use calcium ionophore can yield high fertilization and pregnancy rates for this particular subgroup. In addition to fertilization failure after ICSI, severe male factor infertility is an additional area for application of artificial oocyte activation. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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...

Maturational changes in the survivability and fertility of fowl sperm during their passage through the male reproductive tract.

PubMed

Ahammad, Muslah U; Nishino, C; Tatemoto, H; Okura, N; Kawamoto, Y; Okamoto, S; Nakada, T

2011-10-01

The objective of this study was to examine whether domestic fowl (Gallus domesticus) sperm undergo maturation in their capacity for survival and fertilization in the male reproductive tract. Sperm collected from the testis, epididymis and the proximal, middle and distal vas deferens were simultaneously stored in vitro in minimum essential medium (MEM) at 39°C for 0, 3 and 6h, and at 4°C for 24 and 48h. Sperm membrane integrity was measured using the dual fluorescent stain SYBR-14/propidium iodide (PI). Aliquots of sperm from the various sites were subjected to artificial insemination (AI) into the uteri of hens to assess the duration of sperm survival in the oviduct and to determine the fertility status of the sperm. Testicular sperm exhibited a very low capacity to survive under in vitro liquid storage conditions, irrespective of the storage temperature used, and in the oviduct, and they had a low ability to fertilize the ovum. On the contrary, sperm from the distal vas deferens had a higher survival rate during in vitro storage periods, a longer life span in the oviduct, and high fertility. Survival and fertilizing capacity of the sperm recovered from the testes increased gradually (P<0.05) from the testes to the distal vas deferens. In conclusion, we suggest that fowl sperm may undergo functional maturation through a process of gradual changes in their survival and fertilization capacities during their passage through the successive parts of the male reproductive tract. Copyright © 2011 Elsevier B.V. All rights reserved.

Fertility of Male Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

PubMed Central

Green, Daniel M.; Kawashima, Toana; Stovall, Marilyn; Leisenring, Wendy; Sklar, Charles A.; Mertens, Ann C.; Donaldson, Sarah S.; Byrne, Julianne; Robison, Leslie L.

2010-01-01

Purpose This study was undertaken to determine the effect of treatment for childhood cancer on male fertility. Patients and Methods We reviewed the fertility of male Childhood Cancer Survivor Study survivor and sibling cohorts who completed a questionnaire. We abstracted the chemotherapeutic agents administered, the cumulative dose of drug administered for selected drugs, and the doses and volumes of all radiation therapy from medical records. Risk factors for siring a pregnancy were evaluated using Cox proportional hazards models. Results The 6,224 survivors age 15 to 44 years who were not surgically sterile were less likely to sire a pregnancy than siblings (hazard ratio [HR], 0.56; 95% CI, −0.49 to 0.63). Among survivors, the HR of siring a pregnancy was decreased by radiation therapy of more than 7.5 Gy to the testes (HR, 0.12; 95% CI, −0.02 to 0.64), higher cumulative alkylating agent dose (AAD) score or treatment with cyclophosphamide (third tertile HR, 0.42; 95% CI, −0.31 to 0.57) or procarbazine (second tertile HR, 0.48; 95% CI, −0.26 to 0.87; third tertile HR, 0.17; 95% CI, −0.07 to 0.41). Compared with siblings, the HR for ever siring a pregnancy for survivors who had an AAD score = 0, a hypothalamic/pituitary radiation dose = 0 Gy, and a testes radiation dose = 0 Gy was 0.91 (95% CI, 0.73 to 1.14; P = .41). Conclusion This large study identified risk factors for decreased fertility that may be used for counseling male cancer patients. PMID:19949008

Practical evolution and application of direct intracytoplasmic sperm injection for male factor and idiopathic fertilization failure infertilities.

PubMed

Tucker, M J; Wright, G; Morton, P C; Mayer, M P; Ingargiola, P E; Jones, A E

1995-04-01

To analyze the introduction of a new assisted fertilization technique for the treatment of severe male factor and idiopathic fertilization failure infertilities. Retrospective analysis of 16-month clinical application of IVF-ET where insemination was performed solely by direct intracytoplasmic sperm injection. Clinical IVF-ET program. Ninety-two couples undergoing 105 cycles of sperm injection. One hundred embryo transfers yielded 28 viable pregnancies (28%) from which eight normal deliveries have occurred to date. Complete cleavage arrest or fertilization failure occurred in four cycles, and one couple had all embryos cryopreserved. One thousand one hundred forty-three eggs were injected of which 173 (15%) degenerated. Four hundred seventy-nine of the surviving 970 eggs became normally fertilized (49%), and 381 of these zygotes (79.5%) developed suitably for cryopreservation or for transfer. Thirty-four of 310 embryos transferred implanted, yielding an implantation rate of 11%. Both testicular and epididymal sperm were used successfully to achieve fertilization and pregnancies, as was sperm retrieved by electroejaculation. Older women and couples suffering from prior idiopathic fertilization failure had a markedly poorer outcome. These results confirm that the intracytoplasmic sperm injection technique is a successful form of assisted fertilization that can be applied to a wide range of couples at significant risk from fertilization failure.

Fertility of male rats treated with 15(S)-15-methyl prostaglandin F2 alpha methyl ester-containing silastic implants.

PubMed

Kimball, F A; Frielink, R D; Porteus, S E

1978-01-01

Male Spraque-Dawley rats receiving implants of silicone rubber discs containing 1% or 2% 15(S)-15-methyl prostaglandin F2 alpha methyl ester (15-Me-PGF 2 alpha) or no prostaglandin were tested in successive breeding trials for potency and fertility. One week after implantation, discs containing 1% 15-Me-PGF2 alpha reduced potency and fertility, which returned 2 weeks after implantation. Animals receiving implants of the 2% discs were apparently impotent the 1st week following implantation; potency returned before full fertility returned 11 weeks after implantation.

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

Gq activity- and β-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility

PubMed Central

Lin, Hui; Li, Rui-Rui; Liang, Zong-Lai; Gao, Yuan; Yang, Zhao; He, Dong-Fang; Lin, Amy; Mo, Hui; Lu, Yu-Jing; Li, Meng-Jing; Kong, Wei; Chung, Ka Young; Yi, Fan; Li, Jian-Yuan; Qin, Ying-Ying; Li, Jingxin; Thomsen, Alex R B; Kahsai, Alem W; Chen, Zi-Jiang; Xu, Zhi-Gang; Liu, Mingyao

2018-01-01

Luminal fluid reabsorption plays a fundamental role in male fertility. We demonstrated that the ubiquitous GPCR signaling proteins Gq and β-arrestin-1 are essential for fluid reabsorption because they mediate coupling between an orphan receptor ADGRG2 (GPR64) and the ion channel CFTR. A reduction in protein level or deficiency of ADGRG2, Gq or β-arrestin-1 in a mouse model led to an imbalance in pH homeostasis in the efferent ductules due to decreased constitutive CFTR currents. Efferent ductule dysfunction was rescued by the specific activation of another GPCR, AGTR2. Further mechanistic analysis revealed that β-arrestin-1 acts as a scaffold for ADGRG2/CFTR complex formation in apical membranes, whereas specific residues of ADGRG2 confer coupling specificity for different G protein subtypes, this specificity is critical for male fertility. Therefore, manipulation of the signaling components of the ADGRG2-Gq/β-arrestin-1/CFTR complex by small molecules may be an effective therapeutic strategy for male infertility. PMID:29393851

Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility.

PubMed

Blomqvist, Sandra Rodrigo; Vidarsson, Hilmar; Söder, Olle; Enerbäck, Sven

2006-09-06

An essential aspect of male reproductive capacity is the immediate availability of fertilization-ready spermatozoa. To ensure this, most mammals rely on post-testicular sperm maturation. In epididymis, germ cells are matured and stored in a quiescent state that readily can be altered to produce active spermatozoa. This depends on active proton secretion into the epididymal lumen. We have identified Foxi1 as an important regulator of gene expression in narrow and clear cells-the major proton secretory cells of epididymal epithelia. Foxi1 appears to be required for the expression of the B1-subunit of the vacuolar H+ -ATPase proton pump and for carbonic anhydrase II as well as the chloride/bicarbonate transporter pendrin. Using transfection experiments, we have identified a Foxi1 binding cis-element in the ATP6V1B1 (encoding the B1-subunit) promoter that is critical for reporter gene activation. When this site is mutated to eliminate Foxi1 binding, activation is also abolished. As a consequence of defect Foxi1-dependent epididymal sperm maturation, we demonstrate that spermatozoa from Foxi1 null males fail to reach the female genital tract in sufficient number to allow fertilization.

Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility

PubMed Central

Blomqvist, Sandra Rodrigo; Vidarsson, Hilmar; Söder, Olle; Enerbäck, Sven

2006-01-01

An essential aspect of male reproductive capacity is the immediate availability of fertilization-ready spermatozoa. To ensure this, most mammals rely on post-testicular sperm maturation. In epididymis, germ cells are matured and stored in a quiescent state that readily can be altered to produce active spermatozoa. This depends on active proton secretion into the epididymal lumen. We have identified Foxi1 as an important regulator of gene expression in narrow and clear cells—the major proton secretory cells of epididymal epithelia. Foxi1 appears to be required for the expression of the B1-subunit of the vacuolar H+-ATPase proton pump and for carbonic anhydrase II as well as the chloride/bicarbonate transporter pendrin. Using transfection experiments, we have identified a Foxi1 binding cis-element in the ATP6V1B1 (encoding the B1-subunit) promoter that is critical for reporter gene activation. When this site is mutated to eliminate Foxi1 binding, activation is also abolished. As a consequence of defect Foxi1-dependent epididymal sperm maturation, we demonstrate that spermatozoa from Foxi1 null males fail to reach the female genital tract in sufficient number to allow fertilization. PMID:16932748

Synthesis and assessment of fertility-regulating potential of 2-(2''-chloroacetamidobenzyl)-3-(3'-indolyl) quinoline in adult rats as a male contraceptive agent.

PubMed

Bhowal, Sujit K; Lala, Sanchita; Hazra, Abhijit; Paira, Priyankar; Banerjee, Sukdeb; Mondal, Nirup B; Chakraborty, Smritinath

2008-03-01

The purpose of this study was to investigate the fertility-regulating potential of the compound 2-(2''-chloroacetamidobenzyl)-3-(3'-indolyl) quinoline in male rats. Rats of proven fertility were treated with the compound by oral gavage for 1 to 8 consecutive weeks. Functional fertility, testicular, epididymal and seminal vesicular weight, epididymal sperm count and spermatogenesis were quantitated. Reproductive hormones and some biochemical parameters were measured. Functional fertility was reduced significantly as revealed by a fall in fertility and pregnancy rate. The weight of the reproductive organs was reduced significantly. A reduction of sperm count and number of different types of testicular cells was observed. The treatment with the compound resulted in decline of testosterone and an increase of FSH hormone levels. The compound effectively reduced testicular protein, glycogen and epididymal glyceryl phosphorylcholine. Increase in testicular alkaline phosphatase and cholesterol was also observed. Fertility and other effects were regained gradually after cessation of treatment. The results revealed from the study indicate that the compound has reversible antifertility activity and can be explored as male contraceptive agent.

Collaboration between industry and academia--prospects for male fertility control.

PubMed

Stock, G; Habenicht, U F

1999-12-01

Drug development within the pharmaceutical industry is probably the field with the highest level of regulations. Due to the complexity of the different components of drug development and drug surveillance the need for a sophisticated organization and infrastructure is obvious. In addition, there is a necessity for sufficient resources and long-term commitment as well as logistic and long-term knowledge management. In order to secure high professional standards at all levels of this highly complex value creating chain, the number of cooperative arrangements in the pharmaceutical industry are increasing. The identification of new targets in the drug finding process calls in particular for outside partners. At the same time the preparedness of non-industrial researchers to cooperate with industry has also increased significantly. The area of fertility control, especially male fertility control, provides an excellent example for this kind of cooperation between industrial and non-industrial partners. Here a cooperative network is described which probably meets practically all relevant criteria for both the non-industrial but also the industrial partner. Some principles for the management of such a cooperative network are discussed. We believe that this kind of network can serve as a model for similar networks in other fields.

Restoring pollen fertility in transgenic male-sterile eggplant by Cre/loxp-mediated site-specific recombination system.

PubMed

Cao, Bihao; Huang, Zhiyin; Chen, Guoju; Lei, Jianjun

2010-04-01

This study was designed to control plant fertility by cell lethal gene Barnase expressing at specific developmental stage and in specific tissue of male organ under the control of Cre/loxP system, for heterosis breeding, producing hybrid seed of eggplant. The Barnase-coding region was flanked by loxP recognition sites for Cre-recombinase. The eggplant inbred/pure line ('E-38') was transformed with Cre gene and the inbred/pure line ('E-8') was transformed with the Barnase gene situated between loxp. The experiments were done separately, by means of Agrobacterium co-culture. Four T(0) -plants with the Barnase gene were obtained, all proved to be male-sterile and incapable of producing viable pollen. Flowers stamens were shorter, but the vegetative phenotype was similar to wild-type. Five T (0) -plants with the Cre gene developed well, blossomed out and set fruit normally. The crossing of male-sterile Barnase-plants with Cre expression transgenic eggplants resulted in site-specific excision with the male-sterile plants producing normal fruits. With the Barnase was excised, pollen fertility was fully restored in the hybrids. The phenotype of these restored plants was the same as that of the wild-type. Thus, the Barnase and Cre genes were capable of stable inheritance and expression in progenies of transgenic plants.

CDC14A phosphatase is essential for hearing and male fertility in mouse and human.

PubMed

Imtiaz, Ayesha; Belyantseva, Inna A; Beirl, Alisha J; Fenollar-Ferrer, Cristina; Bashir, Rasheeda; Bukhari, Ihtisham; Bouzid, Amal; Shaukat, Uzma; Azaiez, Hela; Booth, Kevin T; Kahrizi, Kimia; Najmabadi, Hossein; Maqsood, Azra; Wilson, Elizabeth A; Fitzgerald, Tracy S; Tlili, Abdelaziz; Olszewski, Rafal; Lund, Merete; Chaudhry, Taimur; Rehman, Atteeq U; Starost, Matthew F; Waryah, Ali M; Hoa, Michael; Dong, Lijin; Morell, Robert J; Smith, Richard J H; Riazuddin, Sheikh; Masmoudi, Saber; Kindt, Katie S; Naz, Sadaf; Friedman, Thomas B

2018-03-01

The Cell Division-Cycle-14 gene encodes a dual-specificity phosphatase necessary in yeast for exit from mitosis. Numerous disparate roles of vertebrate Cell Division-Cycle-14 (CDC14A) have been proposed largely based on studies of cultured cancer cells in vitro. The in vivo functions of vertebrate CDC14A are largely unknown. We generated and analyzed mutations of zebrafish and mouse CDC14A, developed a computational structural model of human CDC14A protein and report four novel truncating and three missense alleles of CDC14A in human families segregating progressive, moderate-to-profound deafness. In five of these families segregating pathogenic variants of CDC14A, deaf males are infertile, while deaf females are fertile. Several recessive mutations of mouse Cdc14a, including a CRISPR/Cas9-edited phosphatase-dead p.C278S substitution, result in substantial perinatal lethality, but survivors recapitulate the human phenotype of deafness and male infertility. CDC14A protein localizes to inner ear hair cell kinocilia, basal bodies and sound-transducing stereocilia. Auditory hair cells of postnatal Cdc14a mutants develop normally, but subsequently degenerate causing deafness. Kinocilia of germ-line mutants of mouse and zebrafish have normal lengths, which does not recapitulate the published cdc14aa knockdown morphant phenotype of short kinocilia. In mutant male mice, degeneration of seminiferous tubules and spermiation defects result in low sperm count, and abnormal sperm motility and morphology. These findings for the first time define a new monogenic syndrome of deafness and male infertility revealing an absolute requirement in vivo of vertebrate CDC14A phosphatase activity for hearing and male fertility.

Long term impact of the endocrine disruptor tributyltin on male fertility following a single acute exposure.

PubMed

Mitra, Sumonto; Srivastava, Ankit; Khandelwal, Shashi

2017-10-01

Declining rate of human fertility is a growing concern, where lifestyle and environmental factors play an important role. We recently demonstrated that tributyltin (TBT), an omnipresent endocrine disruptor, affects testicular cells in vitro. In this study, male Wistar rats were gavaged a single dose of 10, 20, and 30 mg/kg TBT-chloride (TBTC) (to mimic accidental exposure in vivo) and sacrificed on day 3 and day 7, respectively. TBT bioavailability was evaluated by estimating total tin content, and essential metal levels were analyzed along with redox molecules (ROS and GSH/GSSG) to understand the effect on physiological conditions. Blood-testicular barrier (BTB) disruption, levels of associated proteins and activity of proteolytic enzymes were evaluated to understand the effect on BTB. Histological analysis of tissue architecture and effect on protein expression of steroidogenic, stress and apoptotic markers were also evaluated. Widespread TBTC pollution can be an eventual threat to male fertility worldwide. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2006-10-01

A hermaphrodite fish, Kryptolebias marmoratus, is the only known vertebrate that reproduces by self-fertilization. In nature, males have been rarely observed. Low-temperature treatment during late embryonic stages is known to induce males but its efficacy is variable. Here we report that 17alpha-methyltestosterone (MT) treatment of the embryos converted most of the fish to males. We examined a time course of this male induction with histological and marker gene expression analyses. Oogenesis started in the gonads of the control embryo at hatching; spermatogenesis did not start until two months after hatching. In the MT-treated fish, oogenesis started initially as in the control but stopped completely within one month after hatching. Instead, spermatogonial proliferation started earlier than in the control fish and progressed to full spermatogenesis. Expression profiles of the sex-specific marker genes corresponded well with histological observations. From one month after hatching, expression of an oocyte-specific marker, figalpha, and a testicular somatic cell marker, dmrt1, started to increase in the control and in the MT-treated fish, respectively. (c) 2006 Wiley-Liss, Inc.

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

PubMed

Jesus, Tito T; Oliveira, Pedro F; Sousa, Mário; Cheng, C Yan; Alves, Marco G

2017-06-01

Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermatogenesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

PubMed Central

Jesus, Tito T.; Oliveira, Pedro F.; Sousa, M ario; Cheng, C. Yan; Alves, Marco G.

2017-01-01

Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermato-genesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system. PMID:28124577

Ethical, moral, and theological insights into advances in male pediatric and adolescent fertility preservation.

PubMed

Ramstein, J J; Halpern, J; Gadzinski, A J; Brannigan, R E; Smith, J F

2017-07-01

The successful treatment of boys with cancer has led to increasing attention to preserving their quality of life after completing cancer therapy. One of the top priorities for living a full life is keeping open the opportunity to have children. While sperm banking for males facing sterilizing cancer treatment can be effective, this approach requires subsequent use of reproductive procedures such as in vitro fertilization (IVF) or intrauterine insemination (IUI) to achieve a pregnancy. Advances in fertility preservation techniques may allow pre-pubertal boys to conceive using advanced stem cell technologies and stem cell transplantation in the future. This review summarizes the ethical positions of leading medical societies and explores the religious and moral stances of major religious institutions regarding these options. © 2017 American Society of Andrology and European Academy of Andrology.

Endpoints and surrogate endpoints in colorectal cancer: a review of recent developments.

PubMed

Piedbois, Pascal; Buyse, Marc

2008-07-01

The purpose of this review is to discuss recently published work on endpoints for early and advanced colorectal cancer, as well as the statistical approaches used to validate surrogate endpoints. Most attempts to validate surrogate endpoints have estimated the correlation between the surrogate and the true endpoint, and between the treatment effects on these endpoints. The correlation approach has made it possible to validate disease-free survival and progression-free survival as acceptable surrogates for overall survival in early and advanced disease, respectively. The search for surrogate endpoints will intensify over the coming years. In parallel, efforts to either standardize or extend the endpoints or both will improve the reliability and relevance of clinical trial results.

The transformer2 gene of the pumpkin fruit fly, Bactrocera tau (Walker), functions in sex determination, male fertility and testis development.

PubMed

Thongsaiklaing, Thanaset; Nipitwattanaphon, Mingkwan; Ngernsiri, Lertluk

2018-06-22

The insect transformer2 (tra2) gene has a prevalent role in cooperating with the sex determining gene transformer (tra) to direct female differentiation. Here, we report the identification and characterization of Btau-tra2, the tra2 ortholog of the pumpkin fruit fly, Bactrocera tau, an invasive agricultural pest. The Btau-tra2 gene produces three transcript variants. However, only two transcripts can be examined; one is present at all developmental stages in the soma and germline of both sexes and the other one is specific to embryo and the germline. Knocking down the function of Btau-tra2 produced a male biased sex ratio and some intersexes. Consistent with a role in sex determination, the obtained intersexual and male sterility phenotypes express a mix of male and female splice variants of the tra and doublesex (dsx) orthologs, indicating that Btau-tra2 has a conserved splicing regulatory function and acts together/upstream of tra and dsx. In addition, some males obtained from the knock down are fertile but their fertilities are extremely reduced. Moreover, almost all surviving RNAi males harbor testes having some defects in their external morphologies. Most notably, the body size of a few surviving RNAi flies was two to three folds increased with respect to the normal size. Our findings suggest that Btua-tra2 is involved in male fertility and may also have an unprecedented role in body size control besides its conserved role in sex determination. This article is protected by copyright. All rights reserved. © 2018 The Royal Entomological Society.

Localization patterns of the ganglioside GM1 in human sperm are indicative of male fertility and independent of traditional semen measures

PubMed Central

Cardona, Cristina; Neri, Queenie V.; Simpson, Alana J.; Moody, Melissa A.; Ostermeier, G. Charles; Seaman, Eric K.; Paniza, Theodore; Rosenwaks, Zev; Palermo, Gianpiero D.

2017-01-01

Semen analysis lacks a functional component and best identifies extreme cases of infertility. The ganglioside GM1 is known to have functional roles during capacitation and acrosome exocytosis. Here, we assessed whether GM1 localization patterns (Cap‐Score™) correspond with male fertility in different settings: Study 1 involved couples pursuing assisted reproduction in a tertiary care fertility clinic, while Study 2 involved men with known fertility versus those questioning their fertility at a local urology center. In Study 1, we examined various thresholds versus clinical history for 42 patients; 13 had Cap‐Scores ≥39.5%, with 12 of these (92.3%) achieving clinical pregnancy by natural conception or ≤3 intrauterine insemination cycles. Of the 29 patients scoring <39.5%, only six (20.7%) attained clinical pregnancy by natural conception or ≤3 intrauterine insemination cycles. In Study 2, Cap‐Scores were obtained from 76 fertile men (Cohort 1, pregnant partner or recent father) and compared to 122 men seeking fertility assessment (Cohort 2). Cap‐Score values were normally distributed in Cohort 1, with 13.2% having Cap‐Scores more than one standard deviation below the mean (35.3 ± 7.7%). Significantly, more men in Cohort 2 had Cap‐Scores greater than one standard deviation below the normal mean (33.6%; p = 0.001). Minimal/no relationship was found between Cap‐Score and sperm concentration, morphology, or motility. Together, these data demonstrate that Cap‐Score provides novel, clinically relevant insights into sperm function and male fertility that complement traditional semen analysis. Furthermore, the data provide normal reference ranges for fertile men that can help clinicians counsel couples toward the most appropriate fertility treatment. PMID:28418610

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

PubMed

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

2016-09-01

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

Diet-Induced Obesity in Male C57BL/6 Mice Decreases Fertility as a Consequence of Disrupted Blood-Testis Barrier

PubMed Central

Fan, Yong; Liu, Yue; Xue, Ke; Gu, Guobao; Fan, Weimin; Xu, Yali; Ding, Zhide

2015-01-01

Obesity is a complex metabolic disease that is a serious detriment to both children and adult health, which induces a variety of diseases, such as cardiovascular disease, type II diabetes, hypertension and cancer. Although adverse effects of obesity on female reproduction or oocyte development have been well recognized, its harmfulness to male fertility is still unclear because of reported conflicting results. The aim of this study was to determine whether diet-induced obesity impairs male fertility and furthermore to uncover its underlying mechanisms. Thus, male C57BL/6 mice fed a high-fat diet (HFD) for 10 weeks served as a model of diet-induced obesity. The results clearly show that the percentage of sperm motility and progressive motility significantly decreased, whereas the proportion of teratozoospermia dramatically increased in HFD mice compared to those in normal diet fed controls. Besides, the sperm acrosome reaction fell accompanied by a decline in testosterone level and an increase in estradiol level in the HFD group. This alteration of sperm function parameters strongly indicated that the fertility of HFD mice was indeed impaired, which was also validated by a low pregnancy rate in their mated normal female. Moreover, testicular morphological analyses revealed that seminiferous epithelia were severely atrophic, and cell adhesions between spermatogenic cells and Sertoli cells were loosely arranged in HFD mice. Meanwhile, the integrity of the blood-testis barrier was severely interrupted consistent with declines in the tight junction related proteins, occludin, ZO-1 and androgen receptor, but instead endocytic vesicle-associated protein, clathrin rose. Taken together, obesity can impair male fertility through declines in the sperm function parameters, sex hormone level, whereas during spermatogenesis damage to the blood-testis barrier (BTB) integrity may be one of the crucial underlying factors accounting for this change. PMID:25886196

Diet-induced obesity in male C57BL/6 mice decreases fertility as a consequence of disrupted blood-testis barrier.

PubMed

Fan, Yong; Liu, Yue; Xue, Ke; Gu, Guobao; Fan, Weimin; Xu, Yali; Ding, Zhide

2015-01-01

Obesity is a complex metabolic disease that is a serious detriment to both children and adult health, which induces a variety of diseases, such as cardiovascular disease, type II diabetes, hypertension and cancer. Although adverse effects of obesity on female reproduction or oocyte development have been well recognized, its harmfulness to male fertility is still unclear because of reported conflicting results. The aim of this study was to determine whether diet-induced obesity impairs male fertility and furthermore to uncover its underlying mechanisms. Thus, male C57BL/6 mice fed a high-fat diet (HFD) for 10 weeks served as a model of diet-induced obesity. The results clearly show that the percentage of sperm motility and progressive motility significantly decreased, whereas the proportion of teratozoospermia dramatically increased in HFD mice compared to those in normal diet fed controls. Besides, the sperm acrosome reaction fell accompanied by a decline in testosterone level and an increase in estradiol level in the HFD group. This alteration of sperm function parameters strongly indicated that the fertility of HFD mice was indeed impaired, which was also validated by a low pregnancy rate in their mated normal female. Moreover, testicular morphological analyses revealed that seminiferous epithelia were severely atrophic, and cell adhesions between spermatogenic cells and Sertoli cells were loosely arranged in HFD mice. Meanwhile, the integrity of the blood-testis barrier was severely interrupted consistent with declines in the tight junction related proteins, occludin, ZO-1 and androgen receptor, but instead endocytic vesicle-associated protein, clathrin rose. Taken together, obesity can impair male fertility through declines in the sperm function parameters, sex hormone level, whereas during spermatogenesis damage to the blood-testis barrier (BTB) integrity may be one of the crucial underlying factors accounting for this change.

Factors affecting aggressive behaviour of spawning migratory males towards mature male parr in masu salmon Oncorhynchus masou.

PubMed

Watanabe, M; Maekawa, K

2010-07-01

This study examined whether dominant migratory males (adopting fighter tactics) of the masu salmon Oncorhynchus masou would more aggressively attack large mature male parr (adopting sneaker tactics) as large mature male parr are expected to have the potential to cause a greater decrease in fertilization success. The frequency of aggressive behaviour was not related to the body size of males, and it increased with the frequency of interactions with mature male parr. The fertilization success of mature male parr was much lower than migratory males, and no relationship was observed between fertilization success and aggressive behaviour. The low fertilization success of mature male parr, despite infrequent aggressive behaviour by migratory males, indicates that there might be little benefit for migratory males to attack mature male parr more aggressively according to their body size.

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. © 2016. Published by The Company of Biologists Ltd.

Sexual maturation and fertility of male Nigerian Dwarf goat (Capra hircus) clones produced by somatic cell nuclear transfer.

PubMed

Gauthier, M; Pierson, J; Drolet, M; Bhatia, B; Baldassarre, H; Keefer, C L

2001-01-01

Three, genetically identical, Nigerian Dwarf bucks produced by somatic cell nuclear transfer (NT) of fetal fibroblasts were monitored for sexual maturation and fertility. Starting at four months of age, these male clones were trained to serve an artificial vagina (AV). Average age of the NT-derived bucks at first semen collection was 20 weeks, which was not different from that of other young bucks of this breed (average age at first collection = 20 weeks). Average sperm production at 5 months of age for the NT-derived bucks was 5.0 x 10(8) spermatozoa, which was comparable to that of dwarf bucks of similar age (3.4 x 10(8) spermatozoa). At seven months of age, semen collected from two NT-derived bucks was used to artificially inseminate six females (three does per buck). Five does were confirmed pregnant by ultrasound at day 42. Nine healthy kids, four males and five females, were born in March and April 2000. Viable spermatozoa were collected from one of the F1 males at 28 weeks of age. These results demonstrated that NT-derived bucks and one of their male offspring developed sexually within the normal timeframe for their breed and that the clones were fertile.

Comparison of in vitro fertilization/intracytoplasmic sperm injection outcomes in male factor infertility patients with and without spinal cord injuries.

PubMed

Kathiresan, Anupama S Q; Ibrahim, Emad; Aballa, Teodoro C; Attia, George R; Ory, Steven J; Hoffman, David I; Maxson, Wayne S; Barrionuevo, Marcelo J; Lynne, Charles M; Brackett, Nancy L

2011-09-01

To determine if outcomes after in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) using sperm from men with spinal cord injury (SCI group) differ from those of other etiologies of male factor infertility (non-SCI group). In men with SCI, to determine if IVF/ICSI outcomes differ with sperm obtained by penile vibratory stimulation (PVS group) versus electroejaculation (EEJ group). Retrospective analysis. University medical center and major infertility center. Couples with male factor infertility due to SCI versus other etiologies. PVS, EEJ, surgical sperm retrieval, and IVF/ICSI. Rates of fertilization, pregnancy, and live birth. A total of 31 couples in the SCI group underwent 48 cycles of IVF/ICSI, and a total of 297 couples in the non-SCI group underwent 443 cycles of IVF/ICSI. The SCI group had lower fertilization rates but similar pregnancy and live birth rates compared with the non-SCI group. These rates, however, did not differ significantly when the PVS group was compared with the EEJ group. IVF/ICSI of sperm from men with SCI yield lower fertilization rates but similar pregnancy and live birth outcomes as IVF/ICSI of sperm from men with other etiologies of male factor infertility. Sperm collected by PVS versus EEJ in men with SCI appear to result in similar IVF/ICSI success rates. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Protect Your Fertility

MedlinePlus

... your teens and early twenties can affect your fertility for years to come. This prevention guide was written by ... loss of testic- ulor size, see your doctor. Fertility is something that you ... approximately 40 percent of infertile couples, the male partner is ...

Mumps orchitis in the non-immune postpubertal male: a resurgent threat to male fertility?

PubMed

Philip, Joe; Selvan, David; Desmond, Anthony D

2006-01-01

To report clinical findings associated with an increased incidence of mumps orchitis in Liverpool, UK, as in the last 2 years there has been a four-fold increase in the number of notified viral mumps cases in the UK. In the 8 months before April 2005, patients presenting to the Accident and Emergency/Urology Departments of the Royal Liverpool University Hospital with a diagnosis of epididymo-orchitis were identified from the emergency urological admission database. Of 195 males presenting with an acute history of testicular pain and swelling, 25 gave a history of mumps parotitis 4-11 days earlier. Three had bilateral orchitis and two needed scrotal exploration to exclude torsion. Scrotal ultrasonography findings varied from increased vascularity to abnormal testicular echo texture. Treatment included analgesia, scrotal support, re-hydration and broad-spectrum antibiotics. Of the 10 patients followed-up to date, four had testicular abnormalities; one had persistent testicular pain, one a change in testicular consistency, one a noticeably reduced size of one testis, and one significant testicular atrophy. As postpubertal mumps in males is associated with a 40% incidence of orchitis, parents should be made aware that failing to immunize their children threatens the future fertility of their sons. Young men not immunized as children should be counselled and offered urgent vaccination. Clinicians should be aware that epididymo-orchitis may be secondary to mumps infection even with no history or clinical evidence of parotitis.

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.

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

Analysis of semen parameters in male referrals: impact of reference limits, stratification by fertility categories, predictors of change, and comparison of normal semen parameters in subfertile couples.

PubMed

Baker, Karen; Li, Jianbo; Sabanegh, Edmund

2015-01-01

To [1] determine the impact of semen reference limits on referrals for male fertility evaluations, [2] analyze the stratification of subjects based on published "normal" thresholds, [3] analyze the odds of changing fertility categories during serial tests and thereby the potential impact of inherent variability of semen parameters on referrals, and [4] determine variable(s) predictive of change. Retrospective chart review. Academic referral center for male fertility. New encounters in a male fertility clinic over a 5-year period that straddles the publication of World Health Organization (WHO) 2010 reference values. None. Demographic and clinical variables, semen values, and fertility categories as follows: BE (below WHO 2010 criteria), BTWN (above WHO 2010 but below WHO 1999 criteria), and N (above WHO 1999 criteria). A total of 82.3% of initial semen tests were categorized as BE, and the predominance of this category was unchanged by publication of the WHO 2010 criteria. Men with initial semen analysis categorized as BTWN or N represented 16.2% and 1.5% of the referral population, respectively. Subjects initially categorized as BTWN were more likely to change fertility categories, and overwhelmingly this migration was downward. Analysis of normal individual semen parameters revealed statistically worse mean concentration and motility when at least one other parameter fell below the WHO 2010 criteria. Men with semen results above reference criteria are underrepresented, indicating that reference limits influence referral patterns for male fertility evaluations. Normal mean concentration and motility were lower in men with at least one other individual semen parameter below the 2010 criteria, suggesting global dysfunction in spermatogenesis. Published by Elsevier Inc.

Surrogate endpoints and emerging surrogate endpoints for risk reduction of cardiovascular disease.

PubMed

Rasnake, Crystal M; Trumbo, Paula R; Heinonen, Therese M

2008-02-01

This article reviews surrogate endpoints and emerging biomarkers that were discussed at the annual "Cardiovascular Biomarkers and Surrogate Endpoints" symposium cosponsored by the US Food and Drug Administration (FDA) and the Montreal Heart Institute. The FDA's Center for Food Safety and Applied Nutrition (CFSAN) uses surrogate endpoints in its scientific review of a substance/disease relationship for a health claim. CFSAN currently recognizes three validated surrogate endpoints: blood pressure, blood total cholesterol, and blood low-density lipoprotein (LDL) concentration in its review of a health claim for cardiovascular disease (CVD). Numerous potential surrogate endpoints of CVD are being evaluated as the pathophysiology of heart disease is becoming better understood. However, these emerging biomarkers need to be validated as surrogate endpoints before they are used by CFSAN in the evaluation of a CVD health claim.

Artocarpus heterophyllus seeds inhibits sexual competence but not fertility of male rats.

PubMed

Ratnasooriya, W D; Jayakody, J R A C

2002-03-01

According to Ayurvedic literature of Sri Lanka, roasted seeds of Artocarpus heterophyllus Lam. (Family: Moraceae) has aphrodisiac activity. However, some reproductively active young men in rural areas of Sri Lanka claim that consumption of these seeds few hours prior to coitus disrupts sexual function. Because of these two conflicting claims, it was thought useful to scientifically investigate the effects of A. heterophyllus seeds on male sexual function and fertility. This was done using a seed suspension in 1% methylcellulose (SS) in rats. In a sexual behaviour study using receptive female rats, an oral administration of 500 mg/kg dose of SS markedly inhibited libido, sexual arousal, sexual vigour and sexual performance within 2 hr. Further, the treatment induced a mild erectile dysfunction. These antimasculine effects on sexual function was not evident 6 hr post treatment indicating rapid onset and offset of action. Further, these actions on the sexual behaviour was not due to general toxicity, liver toxicity, stress or reduction in blood testosterone level but due to marked sedative activity. In a mating study, SS failed to alter ejaculating competence and fertility. These results suggest that A. heterophyllous seeds do not have aphrodisiac action, at least, in rats.

Challenge of surrogate endpoints.

PubMed

Furgerson, James L; Hannah, William N; Thompson, Jennifer C

2012-03-01

Surrogate endpoints are biomarkers that are intended to substitute for clinical endpoints. They have been used to find novel therapeutic targets, improve the statistical power and shorten the duration of clinical trials, and control the cost of conducting research studies. The more generalized use of surrogate endpoints in clinical decision making can be hazardous and should be undertaken with great caution. This article reviews prior work with surrogate endpoints and highlights caveats and lessons learned from studies using surrogate endpoints.

Seminal fluid enhances competitiveness of territorial males' sperm in a fish with alternative male reproductive tactics.

PubMed

Poli, Federica; Locatello, Lisa; Rasotto, Maria B

2018-05-29

The most common adaptation to sperm competition in males is represented by an increase in the sperm number and/or quality released at mating, to raise their probability of egg fertilization. However, rapidly mounting evidence highlights that seminal fluid may directly influence the competitive fertilization success of a male by affecting either own and/or rival sperm performances. In the black goby, Gobius niger , an external fertilizer with guard-sneaker mating tactics and high sperm competition level, sneaker males' ejaculates contain less seminal fluid and more sperm, that are also of better quality, than those of territorial males. However, territorial males, gain a higher paternity success inside natural nests. Here, we ask whether the seminal fluid can contribute to territorial males' reproductive success by enhancing their sperm performances and/or by decreasing those of sneaker males. Using sperm and seminal fluid manipulation and in vitro fertilization tests, we found that own seminal fluid influences the velocity and fertilization ability of sperm only in territorial males, making them as faster as those of sneakers and with similar fertilization rate. Moreover, both sneaker and territorial males' sperm remain unaffected by the seminal fluid of rival males. Thus, black goby males respond to the different level of sperm competition faced by differently allocating in sperm and non-sperm components of the ejaculate, with sneakers primarily investing in sperm of intrinsic high quality and territorial males relying on the effect of seminal fluid to increase the lower intrinsic quality of their sperm. © 2018. Published by The Company of Biologists Ltd.

Obesity: modern man's fertility nemesis.

PubMed

Cabler, Stephanie; Agarwal, Ashok; Flint, Margot; du Plessis, Stefan S

2010-07-01

The obesity pandemic has grown to concerning proportions in recent years, not only in the Western World, but in developing countries as well. The corresponding decrease in male fertility and fecundity may be explained in parallel to obesity, and obesity should be considered as an etiology of male fertility. Studies show that obesity contributes to infertility by reducing semen quality, changing sperm proteomes, contributing to erectile dysfunction, and inducing other physical problems related to obesity. Mechanisms for explaining the effect of obesity on male infertility include abnormal reproductive hormone levels, an increased release of adipose-derived hormones and adipokines associated with obesity, and other physical problems including sleep apnea and increased scrotal temperatures. Recently, genetic factors and markers for an obesity-related infertility have been discovered and may explain the difference between fertile obese and infertile obese men. Treatments are available for not only infertility related to obesity, but also as a treatment for the other comorbidities arising from obesity. Natural weight loss, as well as bariatric surgery are options for obese patients and have shown promising results in restoring fertility and normal hormonal profiles. Therapeutic interventions including aromatase inhibitors, exogenous testosterone replacement therapy and maintenance and regulation of adipose-derived hormones, particularly leptin, may also be able to restore fertility in obese males. Because of the relative unawareness and lack of research in this area, controlled studies should be undertaken and more focus should be given to obesity as an etiolgy of male infertility.

Tubulin cytoskeleton during microsporogenesis in the male-sterile genotype of Allium sativum and fertile Allium ampeloprasum L.

PubMed

Tchórzewska, Dorota; Deryło, Kamil; Błaszczyk, Lidia; Winiarczyk, Krystyna

2015-12-01

Microsporogenesis in garlic. The male-sterile Allium sativum (garlic) reproduces exclusively in the vegetative mode, and anthropogenic factors seem to be the cause of the loss of sexual reproduction capability. There are many different hypotheses concerning the causes of male sterility in A.sativum; however, the mechanisms underlying this phenomenon have not been comprehensively elucidated.Numerous attempts have been undertaken to understand the causes of male sterility, but the tubulin cytoskeleton in meiotically dividing cells during microsporogenesis has never been investigated in this species. Using sterile A.sativum genotype L13 and its fertile close relative A. ampeloprasum (leek), we have analysed the distribution of the tubulin cytoskeleton during microsporogenesis. We observed that during karyokinesis and cytokinesis, in both meiotic divisions I and II, the microtubular cytoskeleton in garlic L13 formed configurations that resembled tubulin arrangement typical of monocots. However, the tubulin cytoskeleton in garlic was distinctly poorer (composed of a few MT filaments) compared with that found in meiotically dividing cells in A. ampeloprasum. These differences did not affect the course of karyogenesis, chondriokinesis, and cytokinesis, which contributed to completion of microsporogenesis, but there was no further development of the male gametophyte. At the very beginning of the successive stage of development of fertile pollen grains, i.e. gametogenesis, there were disorders involving the absence of a normal cortical cytoskeleton and dramatically progressive degeneration of the cytoplasm in garlic. Therefore,we suggest that, due to disturbances in cortical cytoskeleton formation at the very beginning of gametogenesis, the intracellular transport governed by the cytoskeleton might be perturbed, leading to microspore decay in the male-sterile garlic genotype.

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

Chirault, Marlène; Lucas, Christophe; Goubault, Marlène; Chevrier, Claude; Bressac, Christophe; Lécureuil, Charlotte

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.

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.

Transgenic expression of an unedited mitochondrial orfB gene product from wild abortive (WA) cytoplasm of rice (Oryza sativa L.) generates male sterility in fertile rice lines.

PubMed

Chakraborty, Anirban; Mitra, Joy; Bhattacharyya, Jagannath; Pradhan, Subrata; Sikdar, Narattam; Das, Srirupa; Chakraborty, Saikat; Kumar, Sachin; Lakhanpaul, Suman; Sen, Soumitra K

2015-06-01

Over-expression of the unedited mitochondrial orfB gene product generates male sterility in fertile indica rice lines in a dose-dependent manner. Cytoplasmic male sterility (CMS) and nuclear-controlled fertility restoration are widespread developmental features in plant reproductive systems. In self-pollinated crop plants, these processes often provide useful tools to exploit hybrid vigour. The wild abortive CMS has been employed in the majority of the "three-line" hybrid rice production since 1970s. In the present study, we provide experimental evidence for a positive functional relationship between the 1.1-kb unedited orfB gene transcript, and its translated product in the mitochondria with male sterility. The generation of the 1.1-kb unedited orfB gene transcripts increased during flowering, resulting in low ATP synthase activity in sterile plants. Following insertion of the unedited orfB gene into the genome of male-fertile plants, the plants became male sterile in a dose-dependent manner with concomitant reduction of ATPase activity of F1F0-ATP synthase (complex V). Fertility of the transgenic lines and normal activity of ATP synthase were restored by down-regulation of the unedited orfB gene expression through RNAi-mediated silencing. The genetic elements deciphered in this study could further be tested for their use in hybrid rice development.

[Environment and lifestyle: Impacts on male fertility?

PubMed

Bendayan, M; Alter, L; Swierkowski-Blanchard, N; Caceres-Sanchez, L; Selva, J; Robin, G; Boitrelle, F

2018-01-01

In this last century, an increase of men infertility has been registered. It has been suggested that environmental factors could a negative impact over sperm quality. Among these factors, impact of environmental toxicant has been spread by media. In this review of scientific literature, we identify several environmental factors that could impact men fertility in a negative way. These factors are tobacco, marijuana, weight, body mass index, heat, nutritional state, electromagnetic waves and altitude. For each of these factors, the impact over men fertility, their mechanism, as well their influence over the use of Assisted Reproductive Technics are reported. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2014-03-01

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. 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. 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. 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.

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

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. © 2013 The Population Council, Inc.

Awareness, knowledge, and perceptions of infertility, fertility assessment, and assisted reproductive technologies in the era of oocyte freezing among female and male university students.

PubMed

Meissner, C; Schippert, C; von Versen-Höynck, Frauke

2016-06-01

The aims of our study were to analyze university student's knowledge and attitude towards parenthood, female fertility, fertility assessment, and oocyte freezing and to explore associations between these aspects and the participant's sex or degree program they were registered for. The study was designed as an online-based cross-sectional survey. A total of 1144 participants answered 27 questions. The data were analyzed using descriptive statistics. Linear regression models were employed to explore associations between sex or university program and attitude towards parenthood, fertility assessment, and oocyte freezing. Female students and students of non-medical degree programs were more likely to plan to have children earlier than male students or students of medical degree programs. Female sex or medical degree program was associated with an overall better knowledge about women's fertility. The better the participant's knowledge about fertility, the more likely the students would consider assisted reproductive technology (ART) treatments as an option to become pregnant when ovarian reserve is low. The majority of students knew the principal of oocyte freezing but would not consider using it. However, in the case of a low ovarian reserve, oocyte freezing would be accepted as an option. Students planned to have children at an age when women's fertility is already declining. Gaps in knowledge about female fertility and the potential of ART were more pronounced in male students and students of non-medical degree programs suggesting an increase of fertility awareness is necessary in these groups to prevent them from infertility and unwanted childlessness.

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.

A general description of additive and nonadditive elements of sperm competitiveness and their relation to male fertilization success.

PubMed

Engqvist, Leif

2013-05-01

A complete understanding of male reproductive success, and thus sexual selection, often requires an insight into male success in sperm competition. Genuine conclusions on male sperm competitiveness can only be made in real competitive situations. However, statistical analyses of sperm competitiveness from fertilization success data have been shown to be problematic. Here, I first outline a comprehensive general description of the different additive and nonadditive elements relevant for the outcome of sperm competition staged between two males. Based on this description, I will highlight two main problems that are frequently encountered in experiments aiming at estimating sperm competitiveness. First, I focus on potential problems when using standardized competitors versus random mating trials, because trials with standardized competitors do not allow generalization if male-male interactions are important. Second, I illustrate the necessity to analyze data on the logit scale rather than on raw proportions, because only the logit scale allows a clean separation of additive and nonadditive effects (i.e., male × male and female × male interactions). © 2012 The Author(s). Evolution © 2012 The Society for the Study of Evolution.

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. © 2016 American Society of Plant Biologists. All Rights Reserved.

Reproductive performance and fertility testing in strain 13 and Hartley guinea pigs.

PubMed

Doyle, R E; Sharp, G C; Irvin, W S; Berck, K

1976-08-01

A study to test the effects of certain experimental manipulation on the reproductive capacity of male guinea pigs required verifying the fertility of the male guinea pigs before and after manipulation. Methods of testing fertility were evaluated, and normal reproductive data from preexperimental and control groups were tabulated and analyzed. No data from the actual experiments were included. Virgin and proven fertile males were mated with 1 (1:1) or 2 (2:1) virgin or proven fertile females. Inbred (13/N Umm) and conventional (Mfi:CFDH-ML (DH) ) guinea pigs were used. Ninety-five percent of both groups of males were fertile. Eighty-four percent of both groups of females were fertile. Male guinea pigs previously proven fertile had the same subsequent fertility rate as virgin males. Over one-third of the conceptions did not take place during the first estrus cycle (16 da) during which the males and females were mated. Strain 13 and Hartley females had litters of approximately the same size (3.1 vs 3.0), but the neonatal mortality was statistically lower (P less than 0.001) in the Hartley stock (9.3%) than in the Strain 13 guinea pigs (28.4%).

Urinary paraben concentrations and in vitro fertilization outcomes among women from a fertility clinic.

PubMed

Mínguez-Alarcón, Lidia; Chiu, Yu-Han; Messerlian, Carmen; Williams, Paige L; Sabatini, Mary E; Toth, Thomas L; Ford, Jennifer B; Calafat, Antonia M; Hauser, Russ

2016-03-01

To explore the relationship between urinary paraben concentrations and IVF outcomes among women attending an academic fertility center. Prospective cohort study. Fertility clinic in a hospital setting. A total of 245 women contributing 356 IVF cycles. None. Quantification of urinary concentrations of parabens by isotope-dilution tandem mass spectrometry, and assessment of clinical endpoints of IVF treatments abstracted from electronic medical records at the academic fertility center. Total and mature oocyte counts, proportion of high-quality embryos, fertilization rates, and rates of implantation, clinical pregnancy, and live births. The geometric means of the urinary concentrations of methylparaben, propylparaben, and butylparaben in our study population were 133, 24, and 1.5 μg/L, respectively. In models adjusted for age, body mass index, race/ethnicity, smoking status, and primary infertility diagnosis, urinary methylparaben, propylparaben, and butylparaben concentrations were not associated with IVF outcomes, specifically total and mature oocyte counts, proportion of high embryo quality, and fertilization rates. Moreover, no significant associations were found between urinary paraben concentrations and rates of implantation, clinical pregnancy, and live births. Urinary paraben concentrations were not associated with IVF outcomes among women undergoing infertility treatments. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

Comprehensive proteomic analysis of bovine spermatozoa of varying fertility rates and identification of biomarkers associated with fertility.

PubMed

Peddinti, Divyaswetha; Nanduri, Bindu; Kaya, Abdullah; Feugang, Jean M; Burgess, Shane C; Memili, Erdogan

2008-02-22

Male infertility is a major problem for mammalian reproduction. However, molecular details including the underlying mechanisms of male fertility are still not known. A thorough understanding of these mechanisms is essential for obtaining consistently high reproductive efficiency and to ensure lower cost and time-loss by breeder. Using high and low fertility bull spermatozoa, here we employed differential detergent fractionation multidimensional protein identification technology (DDF-Mud PIT) and identified 125 putative biomarkers of fertility. We next used quantitative Systems Biology modeling and canonical protein interaction pathways and networks to show that high fertility spermatozoa differ from low fertility spermatozoa in four main ways. Compared to sperm from low fertility bulls, sperm from high fertility bulls have higher expression of proteins involved in: energy metabolism, cell communication, spermatogenesis, and cell motility. Our data also suggests a hypothesis that low fertility sperm DNA integrity may be compromised because cell cycle: G2/M DNA damage checkpoint regulation was most significant signaling pathway identified in low fertility spermatozoa. This is the first comprehensive description of the bovine spermatozoa proteome. Comparative proteomic analysis of high fertility and low fertility bulls, in the context of protein interaction networks identified putative molecular markers associated with high fertility phenotype.

Comprehensive proteomic analysis of bovine spermatozoa of varying fertility rates and identification of biomarkers associated with fertility

PubMed Central

Peddinti, Divyaswetha; Nanduri, Bindu; Kaya, Abdullah; Feugang, Jean M; Burgess, Shane C; Memili, Erdogan

2008-01-01

Background Male infertility is a major problem for mammalian reproduction. However, molecular details including the underlying mechanisms of male fertility are still not known. A thorough understanding of these mechanisms is essential for obtaining consistently high reproductive efficiency and to ensure lower cost and time-loss by breeder. Results Using high and low fertility bull spermatozoa, here we employed differential detergent fractionation multidimensional protein identification technology (DDF-Mud PIT) and identified 125 putative biomarkers of fertility. We next used quantitative Systems Biology modeling and canonical protein interaction pathways and networks to show that high fertility spermatozoa differ from low fertility spermatozoa in four main ways. Compared to sperm from low fertility bulls, sperm from high fertility bulls have higher expression of proteins involved in: energy metabolism, cell communication, spermatogenesis, and cell motility. Our data also suggests a hypothesis that low fertility sperm DNA integrity may be compromised because cell cycle: G2/M DNA damage checkpoint regulation was most significant signaling pathway identified in low fertility spermatozoa. Conclusion This is the first comprehensive description of the bovine spermatozoa proteome. Comparative proteomic analysis of high fertility and low fertility bulls, in the context of protein interaction networks identified putative molecular markers associated with high fertility phenotype. PMID:18294385

Sex and Fertility After SCI

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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. © The Author(s) 2014.

A unique mechanism of successful fertilization in a domestic bird.

PubMed

Sasanami, Tomohiro; Izumi, Shunsuke; Sakurai, Naoki; Hirata, Toshifumi; Mizushima, Shusei; Matsuzaki, Mei; Hiyama, Gen; Yorinaga, Eriko; Yoshimura, Takashi; Ukena, Kazuyoshi; Tsutsui, Kazuyoshi

2015-01-09

Fertilization is an indispensable step for formation of a zygote in sexual reproduction, leading to species survival. When mating occurs, sperm is transported to the female reproductive tracts via the seminal plasma (SP). SP is derived from male accessory sex glands and it plays pivotal roles for fertilization in animals. However, molecular mechanisms of SP or a fluid derived from male accessory sex glands for successful fertilization remain unclear. Here, we report that in male quail the cloacal gland (CG) produces prostaglandin F2α (PGF2α) that contributes to successful fertilization. PGF2α, as well as the secretion of CG (CGS), induced vaginal contractions and caused the opening of the entrance of the sperm storage tubules, the structures responsible for the long-term sperm storage and fertilization. The removal of CGS from the male before mating reduced the fertility, but the supplementation of CGS or PGF2α rescued the subfertility. We further showed that male CG contains glucose that is utilized as energy source for the intrinsic sperm mobility after transportation to female vagina. This mechanism, in concert with the excitatory effects of PGF2α enables successful fertilization in the domestic bird.

Effect of heat stress on the fertility of male mice in vivo and in vitro.

PubMed

Yaeram, J; Setchell, B P; Maddocks, S

2006-01-01

A study was conducted to determine whether following exposure of male mice to high temperatures, the ability of their spermatozoa to fertilise ova was reduced, especially during the period before the males became completely infertile. Male mice placed in a microclimate chamber at 36 degrees C for two periods, each of 12 h on successive days, were less able to fertilise control females in vivo when mated and, even in those females that became pregnant, litter size was reduced. However, these effects were associated with falls in testis weight and numbers of spermatozoa in the testis and epididymis. To determine whether the effect on fertility was a result of the decreased spermatozoa numbers, spermatozoa were collected from the epididymides of heated and control males. Equal numbers of motile spermatozoa from an unselected sample or those subjected to a swim-up procedure to separate those that were motile from the immotile ones in the sample were then mixed in vitro with oocytes from superovulated normal females. Similar numbers of spermatozoa from both control and heated males bound to the zona pellucida but smaller percentages of the oocytes were fertilised by spermatozoa from the heated males and fewer of these spermatozoa penetrated the ova. The effects were first seen 7 days after the heat exposure and became more obvious after 10 or 14 days.

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

Short amplexus duration in a territorial anuran: a possible adaptation in response to male-male competition.

PubMed

Chuang, Ming-Feng; Bee, Mark A; Kam, Yeong-Choy

2013-01-01

Mating duration is a reproductive behaviour that can impact fertilization efficiency and offspring number. Previous studies of factors influencing the evolution of mating duration have focused on the potential role of internal sperm competition as an underlying source of selection; most of these studies have been on invertebrates. For vertebrates with external fertilization, such as fishes and frogs, the sources of selection acting on mating duration remain largely unknown due, in part, to the difficulty of observing complete mating behaviours in natural conditions. In this field study, we monitored breeding activity in a population of the territorial olive frog, Rana adenopleura, to identify factors that affect the duration of amplexus. Compared with most other frogs, amplexus was short, lasting less than 11 min on average, which included about 8 min of pre-oviposition activity followed by 3 min of oviposition. We evaluated the relationship between amplexus duration and seven variables: male body size, male condition, operational sex ratio (OSR), population size, clutch size, territory size, and the coverage of submerged vegetation in a male's territory. We also investigated the influence of these same variables, along with amplexus duration, on fertilization rate. Amplexus duration was positively related with clutch size and the degree of male-bias in the nightly OSR. Fertilization rate was directly related to male body size and inversely related to amplexus duration. Agonistic interactions between males in amplexus and intruding, unpaired males were frequent. These interactions often resulted in mating failure, prolonged amplexus duration, and reduced fertilization rates. Together, the pattern of our findings indicates short amplexus duration in this species may be an adaptive reproductive strategy whereby males attempt to reduce the risks of mating and fertilization failures and territory loss resulting from male-male competition.

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

PubMed Central

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

2016-01-01

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

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

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

PubMed

Dattilo, Maurizio; Cornet, Dominique; Amar, Edouard; Cohen, Marc; Menezo, Yves

2014-07-29

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. 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. 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). 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 effect on their fertility potential.

Impaired fertilizing ability of superoxide dismutase 1-deficient mouse sperm during in vitro fertilization.

PubMed

Tsunoda, Satoshi; Kawano, Natsuko; Miyado, Kenji; Kimura, Naoko; Fujii, Junichi

2012-11-01

The oxidative modification of gametes by a reactive oxygen species is a major deleterious factor that decreases the successful rate of in vitro fertilization. Superoxide dismutase 1 (SOD1) plays a pivotal role in antioxidation by scavenging the superoxide anion, and its deficiency causes infertility in female mice, but the significance of the enzyme in male mice remains unclear. In the present study, we characterized Sod1(-/-) (Sod1-KO) male reproductive organs and compiled the first report of the impaired fertilizing ability of Sod1-KO sperm in in vitro fertilization. Insemination of wild-type oocytes with Sod1-KO sperm exhibited lower rates of fertility compared with insemination by wild-type sperm. The low fertilizing ability found for Sod1-KO sperm was partially rescued by reductant 2-mercaptoethanol, which suggested the oxidative modification of sperm components. The numbers of motile and progressive sperm decreased during the in vitro fertilization process, and a decline in ATP content and elevation in lipid peroxidation occurred in the Sod1-KO sperm in an incubation time-dependent manner. Tyrosine phosphorylation, which is a hallmark for sperm capacitation, was also impaired in the Sod1-KO sperm. These results collectively suggest that machinery involved in sperm capacitation and motility are vulnerable to oxidative damage during the in vitro fertilization process, which could increase the rate of inefficient fertilization.

The effects of chronic administration of pyrimethamine on spermatogenesis and fertility in male rats.

PubMed

Awoniyi, C A; Chandrashekar, V; Hurst, B S; Kim, W K; Schlaff, W D

1993-01-01

The present study examines whether the antifertility effects of pyrimethamine (PYR), an inhibitor of dihydrofolate reductase, are mediated by a reduction in intratesticular testosterone (T) concentrations or whether PYR exerts its effect by a cytotoxic insult to spermatogenic cells that is independent of intratesticular testosterone. Adult male rats were treated daily with 100 mg/kg (n = 16) or 400 mg/kg (n = 16) of PYR in honey for 8 weeks. Control rats (n = 16) received honey without PYR. Eight weeks after treatment, five rats from each PYR-treated group and five control rats were mated with normal cycling female rats, and fertility was assessed. These rats were euthanized after the fertility trial; testis weight, testicular sperm, and epididymal sperm counts were determined, and serum levels of T, LH, FSH, and seminiferous tubule fluid T (STF-T) concentrations were measured by RIA. Testes from three rats per group were perfusion-fixed for histological evaluation. PYR was discontinued in the remaining rats for 8 weeks and similar parameters were evaluated after 8 weeks of recovery. PYR (100 mg/kg/day) treatment for 8 weeks did not have any effects on organ weights, testicular and epididymal sperm counts, and hormone levels when compared to controls. In contrast, PYR (400 mg/kg/day) treatment significantly reduced testis and epididymis weights, testicular and epididymal sperm counts, and fertility. Despite these effects, serum T, LH, FSH, and STF-T concentrations were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

[Molecular aspects of the impact of the Speroton complex on the male fertility in idiopathic infertility].

PubMed

Galimov, Sh N; Akhmetov, R M; Galimova, E F; Bairamgulov, F M; Bikkulova, L R

2017-06-01

To characterize the effect of the Speroton complex on the free radical homeostasis in the ejaculate of males of infertile couples and the likelihood of pregnancy in partners. The study group comprised 30 men aged between 26 and 43 years (mean 33 +/- 4.8 years) with idiopathic infertility. All patients received Speroton one sachet once daily during meals for 3 months. The comparison group consisted of 29 men of fertile age having 1 to 3 healthy children. In infertile men, standard semen parameters including the ejaculate volume, sperm concentration, total count and proportion of abnormal forms were within the normal range. Markers of oxidative damage to ejaculate macromolecules were determined using standard diagnostic testing systems. The patients with idiopathic infertility were found to have statistically significant changes in the degree of chemical modification of ejaculate biopolymers. The level of lipid hydroperoxides in infertile men was significantly higher than in fertile participants. Taking Speroton resulted in the decrease of lipid hydroperoxides to the level that did not differ from that in the control group. Using Speroton was also accompanied by a decrease in the level of the oxidative damage DNA biomarker 8-oxodGu and a tendency toward normalization of the carbonyl modification of the ejaculate proteins. Five married couples in the treatment group reported achieving pregnancy. Taking Speroton was associated with the normalization of the balance of pro- and antioxidant processes in the ejaculate, as indicated by a decrease in the oxidative destruction of sperm biopolymers. The revealed molecular mechanism of the drug action is the basis for restoring the fertilizing ability and increasing the likelihood of pregnancy. The treatment effectiveness was 16.7%. Speroton is a promising drug that improves the functional sperm characteristics and contributes to achieving pregnancy in couples with a male infertility factor.

Sneaker “jack” males outcompete dominant “hooknose” males under sperm competition in Chinook salmon (Oncorhynchus tshawytscha)

PubMed Central

Young, Brent; Conti, David V; Dean, Matthew D

2013-01-01

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

Evaluating the anti-fertility potential of α-chlorohydrin on testis and spermatozoa in the adult male wild Indian house rat (Rattus rattus).

PubMed

Madhu, Nithar Ranjan; Sarkar, Bhanumati; Biswas, Surjyo Jyoti; Behera, Biplab Kumar; Patra, Ashis

2011-01-01

To examine the effects of α-chlorohydrin on testis and cauda epididymis in the male house rat (Rattus rattus), 24 adult male rats were segregated into two groups. Group I rats were force-fed daily by intragastric intubation with α-chlorohydrin at a single dose of 1.0 mg/100 g body weight/d for 5, 15, and 45 days. Another group was fed with distilled water, which served as the control. The treated male rats were paired with 24 adult proestrus female rats for 5 days after the last oral treatment and fertility was tested. At the end of the experiments, all of the male rats were weighed and killed by cervical dislocation. The right testes were removed, weighed, and processed for ultrastructural changes of spermatozoa from the cauda epididymis and testis under scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The seminiferous tubular area, nuclear diameter of the Sertoli and Leydig cells, percentage of spermatogonia, primary spermatocytes, secondary spermatocytes, spermatids, spermatozoa, and Sertoli cells in each group were compared morphometrically. Our results showed that the percentages of primary spermatocytes steadily increased from 5 to 15 days, but primary and secondary spermatocytes decreased significantly at 45 days. There was a steady decline in the percentages of spermatozoa and spermatids at all fixation intervals in the treated animals, but the percentages of spermatogonia and Sertoli cells increased significantly at 15 and 45 days. Seminiferous tubular areas, nuclear diameter of Leydig and Sertoli cells, and fertility rates were reduced after 45 days of treatment. SEM and TEM studies revealed severe morphological abnormalities in the spermatozoa, including deglutination of the acrosomal part, loss of head capsules, and fragmentation of tail fibrils. There was an enhanced anti-fertility effect and a lower number of implantation sites in the rats treated for 5 days. Our results validate α-chlorohydrin as a successful anti-fertility

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

PubMed

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

2016-11-10

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

Impact of Imatinib on the Fertility of Male Patients with Chronic Myelogenous Leukaemia in the Chronic Phase.

PubMed

Chang, Xiaohui; Zhou, Lin; Chen, Xiaoxia; Xu, Baoli; Cheng, Yubin; Sun, Shujun; Fang, Meiyun; Xiang, Yang

2017-12-01

Imatinib is a first-line tyrosine kinase inhibitor for treating chronic myelogenous leukaemia (CML) and has greatly improved the prognosis of this disease. An increasing number of CML patients of reproductive age are diagnosed each year, and the impact of imatinib on fertility is a major concern. Providing useful advice to these patients regarding the choice of their therapeutic treatment is very important. This study examined the impact of imatinib on the fertility of male patients with CML in the chronic phase. We performed a study of 48 adult male CML patients in the chronic phase (CML-CP), 50 healthy control subjects, and 10 male patients with infertility. Imatinib levels in semen and plasma were measured using high-performance liquid chromatography/mass spectrometry. We examined the effects of imatinib on sperm parameters and the male reproductive system using a computer-assisted sperm assay and ultrasound, respectively. We analysed sex hormone levels in the sera of CML-CP patients using an enzyme-linked immunosorbent assay. Imatinib levels in semen were comparable to plasma levels in CML-CP patients. CML-CP patients treated with imatinib exhibited reduced sperm density, counts, survival rates, and activity. Ultrasound demonstrated that the shape and size of the testis and epididymis in CML-CP patients undergoing imatinib treatment were normal. However, 19 of these patients exhibited a hydrocele in their tunica vaginalis, with a large dark area of effusion (0.7-2.9 cm in width). Sex hormone levels in the sera of the CML-CP patients were normal. These results suggest that imatinib crosses the blood-testis barrier and reduces sperm density, sperm count, survival rates, and activity in CML-CP patients. However, imatinib did not affect the structure of reproductive organs or sex hormone levels.

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

Embryo yield after in vitro fertilization in women undergoing embryo banking for fertility preservation before chemotherapy.

PubMed

Robertson, Audra D; Missmer, Stacey A; Ginsburg, Elizabeth S

2011-02-01

To evaluate embryo yield after IVF in patients undergoing embryo banking before chemotherapy. A retrospective cohort study. Hospital-based academic medical center. Thirty-eight women diagnosed with cancer or autoimmune disease presenting for IVF cycles, with or without intracytoplasmic sperm injection (ICSI), for embryo cryopreservation before any therapy were compared with 921 presumably fertile women undergoing IVF for male factor infertility from January 2001 through October 2007. Standard IVF or ICSI protocol, embryo freezing, and ET. The number of 2 pronuclear (2PN) embryos created and suitable for cryopreservation or transfer. No statistically significant differences were observed between preservation and male factor groups for number of embryos, number of oocytes, or amount of gonadotropin needed to stimulate follicular development. Peak serum E(2) levels were significantly lower for women with disease-seeking fertility preservation. Women facing chemotherapy as treatment for cancer or systemic autoimmune disease infrequently undergo fertility preservation. If offered this potentially fertility-preserving option, these data suggest equivalent embryo yield compared with women with infertile male partners. Our data report no significant complications in subsequent births in those who sought fertility preservation, which is informative and encouraging for these women and their providers. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Understanding fertilization through intracytoplasmic sperm injection (ICSI).

PubMed

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

2014-01-01

Since the establishment of in vitro fertilization, it became evident that almost half of the couples failed to achieve fertilization and this phenomenon was attributed to a male gamete dysfunction. The adoption of assisted fertilization techniques particularly ICSI has been able to alleviate male factor infertility by granting the consistent ability of a viable spermatozoon to activate an oocyte. Single sperm injection, by pinpointing the beginning of fertilization, has been an invaluable tool in clarifying the different aspects of early fertilization and syngamy. However, even with ICSI some couples fail to fertilize due to ooplasmic dysmaturity in relation to the achieved nuclear maturation marked by the extrusion of the first polar body. More uncommon are cases where the spermatozoa partially or completely lack the specific oocyte activating factor. In this work, we review the most relevant aspects of fertilization and its failure through assisted reproductive technologies. Attempts at diagnosing and treating clinical fertilization failure are described. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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. © 2015 by the Society for the Study of Reproduction, Inc.

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

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.

[Comparison of seminal vitamin B12, folate, reactive oxygen species and various sperm parameters between fertile and infertile males].

PubMed

Chen, Q; Ng, V; Mei, J; Chia, S E

2001-03-01

Vitamin B12(VB12), folate and reactive oxygen species(ROS) in human semen from both fertile and infertile males, and their relationships with other parameters were observed. Semen samples from 44 infertile and 176 fentile control subjects were collected and measured based on the guidelines issued by WHO. The results showed that no significant differences on semen VB12 and folate were observed between fertile and infertile groups(P > 0.05). However, the levels of ROS in infertile group were significantly higher than those in fertile group(P < 0.01). The morphological defects and low motility of sperm in infertile group was significantly higher than those in fertile group(P < 0.01). A positive relation was observed between the levels of ROS production and the morphological defect of sperm(P < 0.01). There was a significant negative correlation between the levels of VB12, folate and ROS(P < 0.01) in semen. It is interesting to note that the values of ROS also show a significantly positive correlation with sperm motility (P < 0.01). A significant differences of ROS levels between fertile and infertile group with negative white blood cells in sperm was also observed. It is concluded that the increase of ROS on the morphological defect of sperm is one of the most important factors related to poor sperm quality and human infertility.

Hybrid male sterility and genome-wide misexpression of male reproductive proteases.

PubMed

Gomes, Suzanne; Civetta, Alberto

2015-07-06

Hybrid male sterility is a common barrier to gene flow between species. Previous studies have posited a link between misregulation of spermatogenesis genes in interspecies hybrids and sterility. However, in the absence of fully fertile control hybrids, it is impossible to differentiate between misregulation associated with sterility vs. fast male gene regulatory evolution. Here, we differentiate between these two possibilities using a D. pseudoobscura species pair that experiences unidirectional hybrid sterility. We identify genes uniquely misexpressed in sterile hybrid male reproductive tracts via RNA-seq. The sterile male hybrids had more misregulated and more over or under expressed genes relative to parental species than the fertile male hybrids. Proteases were the only gene ontology class overrepresented among uniquely misexpressed genes, with four located within a previously identified hybrid male sterility locus. This result highlights the potential role of a previously unexplored class of genes in interspecific hybrid male sterility and speciation.

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.

[Structural endpoints for glaucoma studies].

PubMed

Popa-Cherechenau, A; Schmidl, D; Garhöfer, G; Schmetterer, L

2018-03-06

Structural endpoints have been discussed as surrogate endpoints for the approval of neuroprotective drugs in glaucoma. Is the evidence strong enough to establish structural endpoints as surrogate endpoints? Review of current understanding between structure and function in glaucoma. The introduction of optical coherence tomography has revolutionized imaging in glaucoma patients. Clinically either the nerve fiber layer thickness can be measured along a circle centered in the optic nerve head or the ganglion cell layer thickness can be assessed in the macular region, the latter being quantified in combination with other inner retinal layers. On a microscopic level there is a strong correlation between structural and functional loss but this relation can only partially be described with currently available clinical methods. This is particularly true for longitudinal course of the disease in glaucoma patients. Novel imaging techniques that are not yet used clinically may have the potential to increase our understanding between structure and function in glaucoma but further research in this field is required. The current evidence does not allow the establishment of structural endpoints as surrogate endpoints for phase 3 studies in glaucoma. Neuroprotective drugs have to be approved on the basis of visual field data because this is the patient-relevant endpoint. Structural endpoints can, however, play an important role in phase 2 and proof of concept studies.

Female giant panda (Ailuropoda melanoleuca) chirps advertise the caller's fertile phase

PubMed Central

Charlton, Benjamin D.; Keating, Jennifer L.; Rengui, Li; Huang, Yan; Swaisgood, Ronald R.

2010-01-01

Although female mammal vocal behaviour is known to advertise fertility, to date, no non-human mammal study has shown that the acoustic structure of female calls varies significantly around their fertile period. Here, we used a combination of hormone measurements and acoustic analyses to determine whether female giant panda chirps have the potential to signal the caller's precise oestrous stage (fertile versus pre-fertile). We then used playback experiments to examine the response of male giant pandas to female chirps produced during fertile versus pre-fertile phases of the caller's reproductive cycle. Our results show that the acoustic structure of female giant panda chirps differs between fertile and pre-fertile callers and that male giant pandas can perceive differences in female chirps that allow them to determine the exact timing of the female's fertile phase. These findings indicate that male giant pandas could use vocal cues to preferentially associate and copulate with females at the optimum time for insemination and reveal the likely importance of female vocal signals for coordinating reproductive efforts in this critically endangered species. PMID:19955154

[Osteopontin and male reproduction].

PubMed

Liu, Qian; Xie, Qing-Zhen

2012-05-01

Osteopontin (OPN) is an extracellular matrix protein with multifunctions, expressed in various tissues and body fluids, involved in various physiological and pathological processes. It is also detected in the reproductive tract of both males and females, and participates in the implantation, development and differentiation of embryos. Recent studies have indicated that OPN is closely related with male fertility and may affect sperm quality and fertilization. An insight into the functions of OPN may help to explain the mechanisms of male infertility and improve the success rate of assisted reproductive technology.

Development and current applications of assisted fertilization.

PubMed

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

2012-02-01

Since the very early establishment of in vitro insemination, it became clear that one of the limiting steps is the achievement of fertilization. Among the different assisted fertilization methods, intracytoplasmic sperm injection emerged as the ultimate technique to allow fertilization with ejaculated, epididymal, and testicular spermatozoa. This work describes the early steps that brought forth the development of intracytoplasmic sperm injection and its role in assisted reproductive techniques. The current methods to select the preferential male gamete will be elucidated and the concerns related to the offspring of severe male factor couples will be discussed. Copyright © 2012. Published by Elsevier Inc.

Behavioural ecology: transient sexual mimicry leads to fertilization.

PubMed

Hanlon, Roger T; Naud, Marié-Jose; Shaw, Paul W; Havenhand, Jon N

2005-01-20

Sexual mimicry among animals is widespread, but does it impart a fertilization advantage in the widely accepted 'sneak-guard' model of sperm competition? Here we describe field results in which a dramatic facultative switch in sexual phenotype by sneaker-male cuttlefish leads to immediate fertilization success, even in the presence of the consort male. These results are surprising, given the high rate at which females reject copulation attempts by males, the strong mate-guarding behaviour of consort males, and the high level of sperm competition in this complex mating system.

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

Hybrid male sterility and genome-wide misexpression of male reproductive proteases

PubMed Central

Gomes, Suzanne; Civetta, Alberto

2015-01-01

Hybrid male sterility is a common barrier to gene flow between species. Previous studies have posited a link between misregulation of spermatogenesis genes in interspecies hybrids and sterility. However, in the absence of fully fertile control hybrids, it is impossible to differentiate between misregulation associated with sterility vs. fast male gene regulatory evolution. Here, we differentiate between these two possibilities using a D. pseudoobscura species pair that experiences unidirectional hybrid sterility. We identify genes uniquely misexpressed in sterile hybrid male reproductive tracts via RNA-seq. The sterile male hybrids had more misregulated and more over or under expressed genes relative to parental species than the fertile male hybrids. Proteases were the only gene ontology class overrepresented among uniquely misexpressed genes, with four located within a previously identified hybrid male sterility locus. This result highlights the potential role of a previously unexplored class of genes in interspecific hybrid male sterility and speciation. PMID:26146165

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

USGS Publications Warehouse

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

2001-01-01

We tested to see if semen collection interferes with fertility in naturally fertile pairs of cranes. We used 12 naturally fertile, Florida sandhill crane (Grus canadensis pratensis) pairs for this study, 6 control and 6 experimental. All pairs had previously produced fertile eggs. Semen was collected on Tuesday mornings and Friday afternoons from 26 February 1993 to 4 June 1993. We used standard artificial insemination methods to collect and to evaluate the semen and spermatozoa. Semen collection had minimal effect on semen quality and semen quantity. Semen volume, sperm density, sperm motility, sperm morphology, sperm viability, sperm number per collection, and male response to semen collection exhibited significant daily variation. Although semen collection began 13 days before the first egg in the experimental group, we did not observe differences in the date of first egg laid or in fertility between experimental and control groups. Also, we observed no statistically significant differences in the interval between clutches or in the percentage of broken eggs between experimental and control groups. However, 4 eggs were broken by adults during the disturbance associated with capturing birds for semen collection. We found that females with mates from which we consistently gathered better semen samples produced fewer fertile eggs than females with sires producing poorer semen samples (r = 0.60). We interpret these results to mean that males that were successfully breeding with their mates had little left at the time of our collection.

The evolution of polyandry: patterns of genotypic variation in female mating frequency, male fertilization success and a test of the sexy-sperm hypothesis.

PubMed

Simmons, L W

2003-07-01

The sexy-sperm hypothesis predicts that females obtain indirect benefits for their offspring via polyandy, in the form of increased fertilization success for their sons. I use a quantitative genetic approach to test the sexy-sperm hypothesis using the field cricket Teleogryllus oceanicus. Previous studies of this species have shown considerable phenotypic variation in fertilization success when two or more males compete. There were high broad-sense heritabilities for both paternity and polyandry. Patterns of genotypic variance were consistent with X-linked inheritance and/or maternal effects on these traits. The genetic architecture therefore precludes the evolution of polyandry via a sexy-sperm process. Thus the positive genetic correlation between paternity in sons and polyandry in daughters predicted by the sexy-sperm hypothesis was absent. There was significant heritable variation in the investment by females in ovaries and by males in the accessory gland. Surprisingly there was a very strong genetic correlation between these two traits. The significance of this genetic correlation for the coevolution of male seminal products and polyandry is discussed.

Identification of AFLP markers linked to fertility restorer genes for tournefortii cytoplasmic male-sterility system in Brassica napus.

PubMed

Janeja, H S; Banga, S S; Lakshmikumaran, M

2003-06-01

The tournefortii cytoplasmic male-sterility system is being used as a method of pollination control to develop hybrids in Brassica napus. Genetic analyses have indicated that two dominant genes, one major ( Rft1) and another minor ( Rft2), were required to achieve complete fertility restoration. Though the major gene ( Rft1) can cause complete fertility restoration on its own, its expression was significantly enhanced in the presence of the minor gene ( Rft2). In the absence of Rft1, Rft2 caused only partial fertility restoration. We used a pair of near-isogenic lines (NILs), differing for the presence/absence of Rf genes, to identify AFLP markers linked to fertility restorer genes. A total of 64 EcoRI/ MseI primer combinations were surveyed which produced 3,225 bands, of which 19 (0.006%) were polymorphic between parental NILs. Primer combinations which led to the identification of polymorphic bands present in fertile parental NILs were used for assaying a mapping population of 70 F(2) plants for determining the segregation pattern of markers. Initial screening resulted in the identification of five AFLP markers. The recombination analyses of these AFLP markers revealed that at least two (EACC/MCTT(105), EAAG/MCTC(80)) were present in the same linkage group along with the Rf loci. Marker EACC/MCTT(105) was separated from the major gene ( Rft1) by a distance of 18.1 cM, while it was 33.2 cM away from the minor fertility restorer gene ( Rft2). Another marker EAAG/MCTC(80) was also located adjacent to Rft1 at a distance of 18.1 cM, but on other side. Identification of flanking markers (EACC/MCTT(105), EAAG/MCTC(80)) for the major fertility restorer gene ( Rft1) provides a crucial component for marker-assisted selection and map-based cloning of the restorer genes, and can hence be used to construct elite restorer genotypes.

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

PubMed Central

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

2016-01-01

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

Cytokines in Male Fertility and Reproductive Pathologies: Immunoregulation and Beyond

PubMed Central

Loveland, Kate L.; Klein, Britta; Pueschl, Dana; Indumathy, Sivanjah; Bergmann, Martin; Loveland, Bruce E.; Hedger, Mark P.; Schuppe, Hans-Christian

2017-01-01

Germline development in vivo is dependent on the environment formed by somatic cells and the differentiation cues they provide; hence, the impact of local factors is highly relevant to the production of sperm. Knowledge of how somatic and germline cells interact is central to achieving biomedical goals relating to restoring, preserving or restricting fertility in humans. This review discusses the growing understanding of how cytokines contribute to testicular function and maintenance of male reproductive health, and to the pathologies associated with their abnormal activity in this organ. Here we consider both cytokines that signal through JAKs and are regulated by SOCS, and those utilizing other pathways, such as the MAP kinases and SMADs. The importance of cytokines in the establishment and maintenance of the testis as an immune-privilege site are described. Current research relating to the involvement of immune cells in testis development and disease is highlighted. This includes new data relating to testicular cancer which reinforce the understanding that tumorigenic cells shape their microenvironment through cytokine actions. Clinical implications in pathologies relating to local inflammation and to immunotherapies are discussed. PMID:29250030

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

Evaluation of a two-generation reproduction toxicity study adding endpoints to detect endocrine disrupting activity using lindane.

PubMed

Matsuura, Ikuo; Saitoh, Tetsuji; Tani, Einosuke; Wako, Yumi; Iwata, Hiroshi; Toyota, Naoto; Ishizuka, Yoshihito; Namiki, Masato; Hoshino, Nobuhito; Tsuchitani, Minoru; Ikeda, Yasuo

2005-12-01

A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using lindane by dietary administration at 0, 10, 60, and 300 ppm, for investigation of its utility. The extra endpoints included anogenital distance (AGD), nipple development, sexual maturation (vaginal opening and preputial separation), estrous cycle, spermatogenesis, sex organ weights, and blood hormone concentrations (thyroid and sex hormones). F1 offspring were examined for emotionality (open field test), motor coordination (rotarod test), as well as learning and memory (pole-climbing test). Hepatic drug-metabolizing enzyme activities were also measured. The results revealed general toxicological effects on parental animals, influence on reproductive function, and altered development of offspring; however, they did not demonstrate any distinct changes in the extra endpoints for detection of endocrine disrupting activity. Adult toxicity was observed in both F0 and F1 animals, including suppressed body weight gain and reduced food consumption in both sexes, and deaths of females at 300 ppm. Convulsions and irritability were observed during the perinatal period in pregnant F1 females given 300 ppm. Pathological examination revealed increased liver weights and centrilobular hepatocellular hypertrophy in both sexes and generations at 10 or 60 ppm and above; in addition, increased kidney weights and increased hyaline droplets in the proximal tubule epithelium, and basophilic renal tubules in males were noted at 10 ppm and above. Pituitary weights were decreased in F0 females and in F1 males and females and adrenal weights were increased in F1 males and females at 300 ppm; however, no histological changes were observed, and manifestations suggesting endocrine disrupting activity related to these changes were lacking. Hypertrophy of the thyroid follicular epithelium in F0 females at 300 ppm and in F1 males at 60 and 300 ppm, and decreases

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.

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

PubMed

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

2017-06-01

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

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

PubMed

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

2015-04-01

The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases. © 2014 Blackwell Verlag GmbH.

[Obesity and male infertility].

PubMed

Heráček, J; Sobotka, V; Urban, M

2012-10-01

The authors present a review on the effects of obesity on male fertility. Current scientific findings suggest an elevated risk of infertility among couples in which the male partner is obese. In obese men can be found reduced serum levels of androgens and SHBG and increased estrogen levels without compensatory increase in FSH. Among other impacts of male obesity that may contribute to increased risk of infertility are altered retention and metabolism of environmental toxins, lifestyle, sexual dysfunction, genetic factors, excessive secretion of hormones derived from adipose tissue, oxidative stress, sperm specific proteomic changes or elevated levels of cytokines. The increasing prevalence of obesity calls for greater clinical awareness of its impact on male fertility.

Semen collection and fertility in naturally fertile sandhill cranes

USGS Publications Warehouse

Chen, G.; Gee, G.F.; Nicolich, Jane M.; Taylor, J.A.; Urbanek, R.P.; Stahlecker, D.W.

1997-01-01

Aviculturists often ask if semen collection will interfere with fertility in naturally fertile pairs of cranes. We used 12 naturally fertile Florida sandhill crane (Grus canadensis pratensis) pairs for this study, 6 control and 6 experimental. All pairs had produced fertile eggs in previous years and were in out-of-doors pens scattered throughout different pen complexes, within auditory range but physically isolated. Semen was collected on Tuesday mornings and Friday afternoons from 26 February 1993 to 4 June 1993. We used standard artificial insemination methods to collect and to evaluate the semen and spermatozoa. Semen collection did not affect semen quality or quantity. Semen volume, sperm density, sperm motility, sperm morphology, sperm live, sperm number per collection, and male response to semen collection exhibited significant daily variation (P < 0.05). Although semen collection began 13 days before the first egg in the experimental group, we observed no differences in the date of first egg laid or in fertility between experimental and control groups. Also, we observed no differences in the interval between clutches or in the percentage of broken eggs between experimental and control groups. Sires consistently producing better semen samples produced fewer fertile eggs than sires producing poorer semen samples (r = 0.60).

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

Quantitative genetic models of sexual selection by male choice.

PubMed

Nakahashi, Wataru

2008-09-01

There are many examples of male mate choice for female traits that tend to be associated with high fertility. I develop quantitative genetic models of a female trait and a male preference to show when such a male preference can evolve. I find that a disagreement between the fertility maximum and the viability maximum of the female trait is necessary for directional male preference (preference for extreme female trait values) to evolve. Moreover, when there is a shortage of available male partners or variance in male nongenetic quality, strong male preference can evolve. Furthermore, I also show that males evolve to exhibit a stronger preference for females that are more feminine (less resemblance to males) than the average female when there is a sexual dimorphism caused by fertility selection which acts only on females.

Fertility concerns in men with genitourinary malignancies: Treatment dilemmas, fertility options, and medicolegal considerations.

PubMed

Polland, Allison; Berookhim, Boback M

2016-09-01

With increasing genitourinary cancer survivorship in patients of reproductive age, fertility preservation has become a greater focus in the management of these patients. We performed a review of articles pertaining to male infertility, fertility preservation, and genitourinary cancers. The aim was to review causes of infertility in patients with cancer, current options for fertility preservation, research that may expand preservation options, and ethical as well as medicolegal considerations. There are multiple causes of infertility in male patients with cancer, including the malignancy itself, and the treatments required to achieve a potential cure. Surgery can affect the normal pathways for erection, emission, and ejaculation. Chemotherapy can have a profound negative effect on spermatogenesis by causing chromosomal aberrations, maturation arrest, mutagenesis, and impaired spermatozoa motility. Radiation can cause cellular apoptosis with resultant reduction in spermatogonial stem cells. There are numerous methods to secure fertility before cancer treatment with the aid of cryopreservation ranging from simple patient-provided semen samples to complex sperm retrieval techniques. Research in the field of spermatogenic stem cells may lead to improved treatment options such as autotransplant of stem cells for repopulation of the testes after cancer treatment. Early discussion of possible fertility effects in patients undergoing genitourinary cancer treatment is critical in this era of increasing survivorship. Although current cancer treatments can cause infertility, there are well-established options for fertility preservation and current research will likely lead to improved treatment options. Copyright © 2016 Elsevier Inc. All rights reserved.

Patients' preferences for selection of endpoints in cardiovascular clinical trials.

PubMed

Chow, Robert D; Wankhedkar, Kashmira P; Mete, Mihriye

2014-01-01

To reduce the duration and overall costs of cardiovascular trials, use of the combined endpoints in trial design has become commonplace. Though this methodology may serve the needs of investigators and trial sponsors, the preferences of patients or potential trial subjects in the trial design process has not been studied. To determine the preferences of patients in the design of cardiovascular trials. Participants were surveyed in a pilot study regarding preferences among various single endpoints commonly used in cardiovascular trials, preference for single vs. composite endpoints, and the likelihood of compliance with a heart medication if patients similar to them participated in the trial design process. One hundred adult English-speaking patients, 38% male, from a primary care ambulatory practice located in an urban setting. Among single endpoints, participants rated heart attack as significantly more important than death from other causes (4.53 vs. 3.69, p=0.004) on a scale of 1-6. Death from heart disease was rated as significantly more important than chest pain (4.73 vs. 2.47, p<0.001), angioplasty/PCI/CABG (4.73 vs. 2.43, p<0.001), and stroke (4.73 vs. 2.43, p<0.001). Participants also expressed a slight preference for combined endpoints over single endpoint (43% vs. 57%), incorporation of the opinions of the study patient population into the design of trials (48% vs. 41% for researchers), and a greater likelihood of medication compliance if patient preferences were considered during trial design (67% indicated a significant to major effect). Patients are able to make judgments and express preferences regarding trial design. They prefer that the opinions of the study population rather than the general population be incorporated into the design of the study. This novel approach to study design would not only incorporate patient preferences into medical decision making, but it also has the potential to improve compliance with cardiovascular medications.

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

PubMed Central

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

2015-01-01

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

Cryptic female choice enhances fertilization success and embryo survival in chinook salmon

PubMed Central

2016-01-01

In this study, we investigated two potentially important intersexual postcopulatory gametic interactions in a population of chinook salmon (Oncorhynchus tshawytscha): (i) the effect of female ovarian fluid (OF) on the behaviour of spermatozoa during fertilization and (ii) the effects of multilocus heterozygosity (MLH) (as an index of male quality) and female–male genetic relatedness on sperm behaviour and male fertilization success when there is sperm competition in the presence of that OF. To do this, we conducted a series of in vitro competitive fertilization experiments and found that, when ejaculates from two males are competing for access to a single female's unfertilized eggs, fertilization success was significantly biased towards the male whose sperm swam fastest in the female's OF. Embryo survival—a measure of fitness—was also positively correlated with both sperm swimming speed in OF and male MLH, providing novel evidence that cryptic female choice is adaptive for the female, enhancing the early survival of her offspring and potentially influencing her fitness. PMID:27009221

Mice lacking the USP2 deubiquitinating enzyme have severe male subfertility associated with defects in fertilization and sperm motility.

PubMed

Bedard, Nathalie; Yang, Yaoming; Gregory, Mary; Cyr, Daniel G; Suzuki, João; Yu, Xiaomin; Chian, Ri-Cheng; Hermo, Louis; O'Flaherty, Cristian; Smith, Charles E; Clarke, Hugh J; Wing, Simon S

2011-09-01

The ubiquitin-proteasome system plays an important role in spermatogenesis. However, the functions of deubiquitinating enzymes in this process remain poorly characterized. We previously showed that the deubiquitinating enzyme USP2 is induced in late elongating spermatids. To identify its function, we generated mice lacking USP2. Usp2 -/- mice appeared normal, and the weights of major organs, including the testis, did not differ from wild type (Usp2 +/+). However, although the numbers of testicular spermatids and epididymal spermatozoa were normal in Usp2 -/- males, these animals had a severe defect in fertility, yielding only 12% as many offspring as Usp2 +/+ littermates. Spermatogenesis in Usp2 -/- mice was morphologically normal except for the presence of abnormal aggregations of elongating spermatids and formation of multinucleated cells in some tubules. The epididymal epithelium was morphologically normal in Usp2 -/- mice, but some abnormal cells other than sperm were present in the lumen. Usp2 -/- epididymal spermatozoa manifested normal motility when incubated in culture media, but rapidly became immotile when incubated in PBS in contrast to Usp2 +/+ spermatozoa, which largely maintained motility under this condition. Usp2 -/- and +/+ spermatozoa underwent acrosome reactions in vitro with similar frequency. In vitro fertilization assays demonstrated a severe defect in the ability of Usp2 -/- spermatozoa to fertilize eggs. This could be bypassed by intracytoplasmic sperm injection or removal of the zona pellucida, which resulted in fertilization rates similar to that of Usp2 +/+ mice. We demonstrate for the first time, using mouse transgenic approaches, a role for the ubiquitin system in fertilization.

Male adiposity impairs clinical pregnancy rate by in vitro fertilization without affecting day 3 embryo quality.

PubMed

Merhi, Zaher O; Keltz, Julia; Zapantis, Athena; Younger, Joshua; Berger, Dara; Lieman, Harry J; Jindal, Sangita K; Polotsky, Alex J

2013-08-01

Male adiposity is detrimental for achieving clinical pregnancy rate (CPR) following assisted reproductive technologies (ART). The hypothesis that the association of male adiposity with decreased success following ART is mediated by worse embryo quality was tested. Retrospective study including 344 infertile couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles was performed. Cycle determinants included number of oocytes retrieved, zygote PN-score, total number of embryos available on day 3, number of embryos transferred, composite day 3 grade for transferred embryos, composite day 3 grade per cycle, and CPR. Couples with male body mass index (BMI) over 25 kg m(-2) (overweight and obese) exhibited significantly lower CPR compared to their normal weight counterparts (46.7% vs. 32.0% respectively, P = 0.02). No significant difference was observed for any embryo quality metrics when analyzed by male BMI: mean zygote PN-scores, mean composite day 3 grades for transferred embryos or composite day 3 grades per cycle. In a multivariable logistic regression analysis adjusting for female age, female BMI, number of embryos transferred and sperm concentration, male BMI over 25 kg m(-2) was associated with a lower chance for CPR after IVF (OR = 0.17 [95% CI: 0.04-0.65]; P = 0.01) but not after ICSI cycles (OR = 0.88 [95% CI: 0.41-1.88]; P = 0.75). In this cohort, male adiposity was associated with decreased CPR following IVF but embryo quality was not affected. Embryo grading based on conventional morphologic criteria does not explain the poorer clinical pregnancy outcomes seen in couples with overweight or obese male partner. Copyright © 2013 The Obesity Society.

Nuclear-cytoplasmic male-sterility in diploid dandelions.

PubMed

van der Hulst, R G M; Meirmans, P; van Tienderen, P H; van Damme, J M M

2004-07-01

Male-sterility was found in diploid dandelions from two widely separated populations from France, and its inheritance was analysed by crossing a diploid male-sterile dandelion to diploid sexuals and triploid apomicts. Nuclear genetic variation, found in full-sib families, segregated for male-fertility, partial male-sterility, and full male-sterility, and also segregated for small-sized versus normally sized pollen. The crossing results are best explained by a cytoplasmic male-sterility factor in combination with two dominant restorer genes. Involvement of the cytoplasmic male-sterility factor was further investigated by chloroplast haplotyping. Male-sterility was exclusively associated with a rare chloroplast haplotype (designated 16b). This haplotype was found in seven male-sterile plants and one (apparently restored) male-fertile individual but does not occur in 110 co-existing male-fertile plants and not in several hundreds of individuals previously haplotyped. Apomicts with cytoplasmic male sterility were generated in some test crosses. This raises the question as to whether the male sterility found in natural dandelion apomicts, is of cytoplasmic or of nuclear genetic nature. As many breeding systems in Taraxacum are involved in shaping population structure, it will be difficult to predict the evolutionary consequences of nuclear-cytoplasmic male-sterility for this species complex.

The Goddard and Saturn Genes Are Essential for Drosophila Male Fertility and May Have Arisen De Novo

PubMed Central

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

2017-01-01

New genes arise through a variety of mechanisms, including the duplication of existing genes and the de novo birth of genes from noncoding DNA sequences. While there are numerous examples of duplicated genes with important functional roles, the functions of de novo genes remain largely unexplored. Many newly evolved genes are expressed in the male reproductive tract, suggesting that these evolutionary innovations may provide advantages to males experiencing sexual selection. Using testis-specific RNA interference, we screened 11 putative de novo genes in Drosophila melanogaster for effects on male fertility and identified two, goddard and saturn, that are essential for spermatogenesis and sperm function. Goddard knockdown (KD) males fail to produce mature sperm, while saturn KD males produce few sperm, and these function inefficiently once transferred to females. Consistent with a de novo origin, both genes are identifiable only in Drosophila and are predicted to encode proteins with no sequence similarity to any annotated protein. However, since high levels of divergence prevented the unambiguous identification of the noncoding sequences from which each gene arose, we consider goddard and saturn to be putative de novo genes. Within Drosophila, both genes have been lost in certain lineages, but show conserved, male-specific patterns of expression in the species in which they are found. Goddard is consistently found in single-copy and evolves under purifying selection. In contrast, saturn has diversified through gene duplication and positive selection. These data suggest that de novo genes can acquire essential roles in male reproduction. PMID:28104747

Process of egg formation in the female body cavity and fertilization in male eggs of Phytoseiulus persimilis (Acari: Phytoseiidae).

PubMed

Toyoshima, S; Nakamura, M; Nagahama, Y; Amano, H

2000-01-01

The process of egg formation in the body cavity of a phytoseiid mite, Phytoseiulus persimilis, was observed to examine fertilization of male eggs. After insemination, one of the ova at the periphery of the ovary began to expand, taking up yolk. Two pronuclei appeared in the expanded egg, located dorsally in the ovary, and yolk granules were formed gradually. After the egg became filled with yolk granules the two pronuclei fused. The egg moved via the narrow entrance at the ventral region into the oviduct, where the eggshell was formed. When the eggshell was complete, and while embryogenesis proceeded, the egg was deposited. In the meantime some ova began to expand sequentially and two joining pronuclei appeared in expanding eggs. The joining pronuclei in the first egg proved male diploidy. This is additional evidence of pseudo-arrhenotoky in this phytoseiid mite species, since the first eggs developed into males.

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

A case report of an incidental finding of a 46,XX, SRY-negative male with masculine phenotype during standard fertility workup with review of the literature and proposed immediate and long-term management guidance.

PubMed

Ryan, Neil A J; Akbar, Shahnaz

2013-04-01

To describe and explore the current literature on the rare genetic condition of 46,XX SRY-negative males. In addition, we propose comprehensive clinical guidelines in the management of this condition to aid fertility clinicians in their management of affected individuals. Case report with expert consensus-derived clinical management guidance. Fertility outpatient clinic at a tertiary referral center. A 40-year-old male found to have 46,XX disorder of sex development (DSD) on routine fertility screening. A review of the literature, expert consultation, and formulation of comprehensive clinical guidance. We report an interesting and rare case of a phenotypical male with the karyotype 46,XX DSD without an SRY region. There is limited literature exploring this condition, and its etiology remains poorly understood. There is currently no clinical guidance available for fertility clinicians to follow when treating this condition. A male phenotype with a 46 karyotype without the sex-defining region of the Y chromosome. A multidisciplinary approach should be adopted in the management of 46,XX individuals. All patients with azoospermia must be karyotyped. Sperm donation remains the only fertility treatment available. The 46,XX patients need lifelong followup led by an endocrinologist with regular imaging of the gonads, bone density measurements, baseline blood tests, and T supplementation. Psychological support is a key part of a holistic approach. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cryptic female choice enhances fertilization success and embryo survival in chinook salmon.

PubMed

Rosengrave, Patrice; Montgomerie, Robert; Gemmell, Neil

2016-03-30

In this study, we investigated two potentially important intersexual postcopulatory gametic interactions in a population of chinook salmon (Oncorhynchus tshawytscha): (i) the effect of female ovarian fluid (OF) on the behaviour of spermatozoa during fertilization and (ii) the effects of multilocus heterozygosity (MLH) (as an index of male quality) and female-male genetic relatedness on sperm behaviour and male fertilization success when there is sperm competition in the presence of that OF. To do this, we conducted a series of in vitro competitive fertilization experiments and found that, when ejaculates from two males are competing for access to a single female's unfertilized eggs, fertilization success was significantly biased towards the male whose sperm swam fastest in the female's OF. Embryo survival--a measure of fitness--was also positively correlated with both sperm swimming speed in OF and male MLH, providing novel evidence that cryptic female choice is adaptive for the female, enhancing the early survival of her offspring and potentially influencing her fitness. © 2016 The Author(s).

Coevolution of female ovulatory signals and male-male competition in primates.

PubMed

Nakahashi, Wataru

2016-03-07

Visual signals of ovulation vary among primate species. Although slight ovulatory signals are considered primate ancestral traits of which some species still exhibit, some show prominent swelling of their perineal skin (exaggerated sexual swellings) and others do not exhibit any signals of ovulation (concealed ovulation). These signals strongly affect male mating behaviors. I develop an evolutionary model of female ovulatory signals and male-male competition. I assume that each male allocates his effort between attraction of females and male-male competition for dominance. Each female gains a benefit if she is fertile and free from the alpha male who always guards one of the most fertile females in the group, but suffers a cost if she expresses a different ovulatory signal from an ancestral trait. I show that various types of ovulatory signals may evolve and can be multistable. Male-male competition becomes intense when the signal honestly indicates ovulation. Ovulatory signals may evolve to be less exaggerated in unimale groups than in multimale groups and monogamy is more likely to evolve when ovulation is concealed. These results may partly explain why various types of primate ovulatory signals evolved and how they have affected primate societies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Paternity in horseshoe crabs when spawning in multiple-male groups.

PubMed

Brockmann; Nguyen; Potts

2000-12-01

Unpaired or satellite male horseshoe crabs, Limulus polyphemus, are attracted to and often form a group around a pair (a female with an attached male) that is nesting in the high intertidal zone. These males are engaged in sperm competition. We observed nesting pairs and their associated satellites in the wild, collected and reared their eggs and used genetic markers to examine paternity. We found that the unpaired, satellite males are highly successful at fertilizing eggs; two satellites can leave the attached male with few fertilizations. Two satellites together are each as successful as one spawning with a pair. A satellite's location around the female greatly affects his success, and males compete for access to a position over the dorsal canal between the prosoma and opisthosoma of the female and under the front margin of the paired male where they are most likely to fertilize eggs. Although eggs and sperm retain their viability for some time after spawning, nearly all eggs are fertilized by the satellites that are around the nesting pair at the time of egg laying and by the attached male. A number of factors including beach current, female size and male behaviour affect the outcome of sperm competition in this externally fertilizing species. Copyright 2000 The Association for the Study of Animal Behaviour.

Modelling female fertility traits in beef cattle using linear and non-linear models.

PubMed

Naya, H; Peñagaricano, F; Urioste, J I

2017-06-01

Female fertility traits are key components of the profitability of beef cattle production. However, these traits are difficult and expensive to measure, particularly under extensive pastoral conditions, and consequently, fertility records are in general scarce and somehow incomplete. Moreover, fertility traits are usually dominated by the effects of herd-year environment, and it is generally assumed that relatively small margins are kept for genetic improvement. New ways of modelling genetic variation in these traits are needed. Inspired in the methodological developments made by Prof. Daniel Gianola and co-workers, we assayed linear (Gaussian), Poisson, probit (threshold), censored Poisson and censored Gaussian models to three different kinds of endpoints, namely calving success (CS), number of days from first calving (CD) and number of failed oestrus (FE). For models involving FE and CS, non-linear models overperformed their linear counterparts. For models derived from CD, linear versions displayed better adjustment than the non-linear counterparts. Non-linear models showed consistently higher estimates of heritability and repeatability in all cases (h 2  < 0.08 and r < 0.13, for linear models; h 2  > 0.23 and r > 0.24, for non-linear models). While additive and permanent environment effects showed highly favourable correlations between all models (>0.789), consistency in selecting the 10% best sires showed important differences, mainly amongst the considered endpoints (FE, CS and CD). In consequence, endpoints should be considered as modelling different underlying genetic effects, with linear models more appropriate to describe CD and non-linear models better for FE and CS. © 2017 Blackwell Verlag GmbH.

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.

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

PubMed Central

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

2016-01-01

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

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. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Biomarkers and surrogate endpoints in glaucoma clinical trials

PubMed Central

Medeiros, Felipe A

2015-01-01

Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies. PMID:25034049

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

The Goddard and Saturn Genes Are Essential for Drosophila Male Fertility and May Have Arisen De Novo.

PubMed

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

2017-05-01

New genes arise through a variety of mechanisms, including the duplication of existing genes and the de novo birth of genes from noncoding DNA sequences. While there are numerous examples of duplicated genes with important functional roles, the functions of de novo genes remain largely unexplored. Many newly evolved genes are expressed in the male reproductive tract, suggesting that these evolutionary innovations may provide advantages to males experiencing sexual selection. Using testis-specific RNA interference, we screened 11 putative de novo genes in Drosophila melanogaster for effects on male fertility and identified two, goddard and saturn, that are essential for spermatogenesis and sperm function. Goddard knockdown (KD) males fail to produce mature sperm, while saturn KD males produce few sperm, and these function inefficiently once transferred to females. Consistent with a de novo origin, both genes are identifiable only in Drosophila and are predicted to encode proteins with no sequence similarity to any annotated protein. However, since high levels of divergence prevented the unambiguous identification of the noncoding sequences from which each gene arose, we consider goddard and saturn to be putative de novo genes. Within Drosophila, both genes have been lost in certain lineages, but show conserved, male-specific patterns of expression in the species in which they are found. Goddard is consistently found in single-copy and evolves under purifying selection. In contrast, saturn has diversified through gene duplication and positive selection. These data suggest that de novo genes can acquire essential roles in male reproduction. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Surrogate endpoints in randomized cardiovascular clinical trials.

PubMed

Domanski, Michael; Pocock, Stuart; Bernaud, Corine; Borer, Jeffrey; Geller, Nancy; Revkin, James; Zannad, Faiez

2011-08-01

Surrogate endpoints predict the occurrence and timing of a clinical endpoint of interest (CEI). Substitution of a surrogate endpoint for a CEI can dramatically reduce the time and cost necessary to complete a Phase III clinical trial. However, assurance that use of a surrogate endpoint will result in a correct conclusion regarding treatment effect on a CEI requires prior rigorous validation of the surrogate. Surrogate endpoints can also be of substantial use in Phase I and II studies to assess whether the intended therapeutic pathway is operative, thus providing assurance regarding the reasonableness of proceeding to a Phase III trial. This paper discusses the uses and validation of surrogate endpoints. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

On the difficulties of discriminating between major and minor hybrid male sterility factors in Drosophila by examining the segregation ratio of sterile and fertile sons in backcrossing experiments.

PubMed

Maside, X R; Naveira, H F

1996-10-01

The observation of segregation ratios of sterile and fertile males in offspring samples from backcrossed hybrid females is, in principle, a valid method to unveil the genetic basis of hybrid male sterility in Drosophila. When the female parent is heterozygous (hybrid) for a sterility factor with major effects, equal proportions of fertile and sterile sons are expected in her offspring. However, intact (not recombined) chromosome segments of considerable length are expected to give segregation ratios that can not be easily differentiated from the 1:1 ratio expected from a single factor. When the phenotypic character under analysis can be determined by combinations of minor factors from the donor species spanning a certain chromosome length, very large offspring samples may be needed to test this alternative hypothesis against the null hypothesis of a single major factor. This is particularly the case of hybrid male sterility determinants in Drosophila.

Biomarkers and surrogate endpoints in glaucoma clinical trials.

PubMed

Medeiros, Felipe A

2015-05-01

Surrogate endpoints are often used as replacements for true clinically relevant endpoints in several areas of medicine, as they enable faster and less expensive clinical trials. However, without proper validation, the use of surrogates may lead to incorrect conclusions about the efficacy and safety of treatments. This article reviews the general requirements for validating surrogate endpoints and provides a critical assessment of the use of intraocular pressure (IOP), visual fields, and structural measurements of the optic nerve as surrogate endpoints in glaucoma clinical trials. A valid surrogate endpoint must be able to predict the clinically relevant endpoint and fully capture the effect of an intervention on that endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has ever been conducted for any class of IOP-lowering treatments. Evidence has accumulated with regard to the role of imaging measurements of optic nerve damage as surrogate endpoints in glaucoma. These measurements are predictive of functional losses in the disease and may explain, at least in part, treatment effects on clinically relevant endpoints. The use of composite endpoints in glaucoma trials may overcome weaknesses of the use of structural or functional endpoints in isolation. Unless research is dedicated to fully develop and validate suitable endpoints that can be used in glaucoma clinical trials, we run the risk of inappropriate judgments about the value of new therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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.

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

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

PubMed Central

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

2015-01-01

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

Assessment of forestry best management practices II: patterns in stream biological endpoints in terms of natural variability and fertilization

Treesearch

Camille Flinders; Daniel L. McLaughlin; Larry Korhnak; William J. Arthurs; Joan Ikoma; Matthew J. Cohen; Erik B. Schilling

2016-01-01

Watersheds dominated by forest cover typically have high quality water. In managed forests, fertilizers may be periodically applied during the growing period. The Florida Forest Service has developed Best Management Practices (BMPs) for managed forests to minimize the potential impacts of forestry operations, including fertilization, to forest streams and maintain ...

Evaluation of Mysidopsis bahia fecundity endpoint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Griffin, D.; Wahl, E.; Krause, P.R.

1995-12-31

The M. bahia chronic toxicity test is commonly used to test estuarine and marine effluent discharges. The test evaluates three endpoints: survival, growth, and fecundity. The fecundity endpoint is often erratic over time and does not necessarily predict accurately other endpoints of effluent toxicity. Therefore, an analysis of the fecundity endpoint was performed to evaluate its use in compliance testing. The endpoint analysis was conducted in three phases: a literature search, analysis of M. bahia data from 24 separate testing events, and interviews with various policy makers, statisticians, and biologists. The literature search revealed a dozen publications, none of whichmore » evaluated fecundity using the EPA method. The literature suggested that evaluating fecundity was labor-intensive and inadequate for practical compliance testing applications. Analysis of the 24 tests revealed that fecundity was evaluated only half of the time (i.e. when at least 50% of the females in the control were fecund). There was a high coefficient of variation (C.V.) between replicates for fecundity (range = 9.--1209.3,x = 85.2%) as compared to survival (range = 0.0--24.0,x = 13.7 %) and growth (range = 7.5--43.9,x = 19.1%). The fecundity results were erratic and did not always follow a dose-response curve, due in part to the small sample size per replicate. Interviews showed that the fecundity endpoint was being evaluated differently by different laboratories. Some were using fecundity for compliance while others were not. Most people interviewed recognized there were inconsistencies with the endpoint. The conclusions drawn from the evaluation were that (1) fecundity does not lend itself for use as a compliance endpoint, (2) the fecundity evaluation process is time consuming and labor intensive, and (3) interpretation of the results is not consistent from laboratory to laboratory and from region to region.« less

Cancer and Fertility Program Improves Patient Satisfaction With Information Received

PubMed Central

Thom, Bridgette; Benedict, Catherine; Carter, Jeanne; Corcoran, Stacie; Dickler, Maura N.; Goodman, Karyn A.; Margolies, Allison; Matasar, Matthew J.; Noy, Ariela; Goldfarb, Shari B.

2016-01-01

Purpose A cancer and fertility program was established at a large cancer center to support clinicians in discussing treatment-related fertility risks and fertility preservation (FP) options with patients and in referring patients to reproductive specialists. The program provides resources, clinician education, and fertility clinical nurse specialist consultation. This study evaluated the program’s impact on patient satisfaction with information received. Patients and Methods Retrospective cross-sectional surveys assessed satisfaction before (cohort 1 [C1]) and after (cohort 2 [C2]) program initiation. Questionnaires were investigator-designed, gender-specific, and anonymous. Results Most C1 (150 males, 271 females) and C2 (120 males, 320 females) respondents were 2 years postdiagnosis; the most frequently reported cancers were testicular, breast, and lymphoma. A significant difference in satisfaction with the amount of information received was seen between C1 and C2. For males, satisfaction with information on fertility risks was high in both cohorts but significantly greater in C2 for information on sperm banking (χ2 = 9.3, P = .01) and finding a sperm bank (χ2 = 13.3, P = .001). For females, satisfaction with information was significantly greater in C2 for information on fertility risks (χ2 = 62.1, P < .001), FP options (χ2 = 71.9, P < .001), help with decision making (χ2 = 80.2, P < .001), and finding a reproductive endocrinologist (χ2 = 60.5, P < .001). Among patients who received and read information materials, 96% of males and 99% of females found them helpful. Among C2 females, fertility clinical nurse specialist consultation was associated with significantly greater satisfaction with information on FP options (χ2 = 11.2, P = .004), help with decision making (χ2 = 10.4, P = .006), and finding a reproductive endocrinologist (χ2 = 22.6, P < .001), with 10% reporting lack of knowledge as a reason for not pursuing FP. Conclusion Improvements in

Education, labor-force participation, and fertility in the USSR.

PubMed

Berliner, J S

1983-01-01

The effect of education on Soviet fertility and female labor participation is analyzed in terms of the neoclassical theory of the household. Using this theory, child worth in terms of services and real consumption or distribution of income are analyzed as factors in fertility decision making. The hypotheses are tested by multivariate analysis of Soviet census data. The contribution of husband and wife to family income is different from that in the West. The effect of female education on fertility should be in the range of small and negative to moderately positive. The effect of male education should be moderately negative. The effect of an individual family's education level on its fertility is often influenced by the community's education level. Rising educational levels of males have contributed most to the decline of Soviet fertility recently. The rising education of females has tended to offset this negative influence, however. The rural Soviet data support this. The female labor-force participation rates are negative and significant. Of the total (positive) effect of female higher education on fertility; half operates indirectly-by decreasing labor participation which in turn increases fertility. The other half affects fertility directly. These results imply a backward-bending female labor supply curve at the higher education level.

Garlic (Allium sativum L.) fertility: transcriptome and proteome analyses provide insight into flower and pollen development

PubMed Central

Shemesh-Mayer, Einat; Ben-Michael, Tomer; Rotem, Neta; Rabinowitch, Haim D.; Doron-Faigenboim, Adi; Kosmala, Arkadiusz; Perlikowski, Dawid; Sherman, Amir; Kamenetsky, Rina

2015-01-01

Commercial cultivars of garlic, a popular condiment, are sterile, making genetic studies and breeding of this plant challenging. However, recent fertility restoration has enabled advanced physiological and genetic research and hybridization in this important crop. Morphophysiological studies, combined with transcriptome and proteome analyses and quantitative PCR validation, enabled the identification of genes and specific processes involved in gametogenesis in fertile and male-sterile garlic genotypes. Both genotypes exhibit normal meiosis at early stages of anther development, but in the male-sterile plants, tapetal hypertrophy after microspore release leads to pollen degeneration. Transcriptome analysis and global gene-expression profiling showed that >16,000 genes are differentially expressed in the fertile vs. male-sterile developing flowers. Proteome analysis and quantitative comparison of 2D-gel protein maps revealed 36 significantly different protein spots, 9 of which were present only in the male-sterile genotype. Bioinformatic and quantitative PCR validation of 10 candidate genes exhibited significant expression differences between male-sterile and fertile flowers. A comparison of morphophysiological and molecular traits of fertile and male-sterile garlic flowers suggests that respiratory restrictions and/or non-regulated programmed cell death of the tapetum can lead to energy deficiency and consequent pollen abortion. Potential molecular markers for male fertility and sterility in garlic are proposed. PMID:25972879

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…

[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.

Fertility counseling and preservation practices in youth with lupus and vasculitis undergoing gonadotoxic therapy.

PubMed

Nahata, Leena; Sivaraman, Vidya; Quinn, Gwendolyn P

2016-11-01

To assess fertility counseling and preservation practices among children, adolescents, and young adults with rheumatic diseases undergoing cyclophosphamide (CTX) treatment. Retrospective chart review (2006-2016). Academic pediatric center. Male and female patients with systemic lupus erythematosus, Wegener's granulomatosis/granulomatosis with polyangiitis, or other vaculitides, receiving CTX treatment. None. Documentation of fertility counseling and fertility preservation. A total of 58 subjects met the inclusion criteria; 5 were excluded due to incomplete records, thus N = 53. Of these 75% were female (N = 40). Median age was 14 years at diagnosis and 15 years at first CTX treatment. A total of 51% of subjects (69% of males and 45% of females) had no documentation about potential fertility loss before CTX treatment. Among females where fertility counseling was documented, the only fertility preservation option discussed was leuprolide acetate (LA), which was pursued in all of these cases. Of 13 males (77% postpubertal), 3 were offered sperm banking, of whom 2 declined and the other attempted after treatment began and was azoospermic. Of 53 patients, 1 was referred to a fertility specialist. Mean cumulative CTX dose was 9.2 g in males and 8 g in females. Based on these findings, increasing awareness about infertility risk, fertility preservation options, and referral to fertility specialists is needed among pediatric rheumatologists. Prospective studies are needed to assess fertility outcomes in this patient population (including effectiveness of LA with regard to pregnancy rates [PRs]), as well as barriers/facilitators to fertility counseling and fertility preservation. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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…

Diversity and functional convergence of small noncoding RNAs in male germ cell differentiation and fertilization

PubMed Central

García-López, Jesús; Alonso, Lola; Cárdenas, David B.; Artaza-Alvarez, Haydeé; Hourcade, Juan de Dios; Martínez, Sergio; Brieño-Enríquez, Miguel A.; del Mazo, Jesús

2015-01-01

The small noncoding RNAs (sncRNAs) are considered as post-transcriptional key regulators of male germ cell development. In addition to microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), other sncRNAs generated from small nucleolar RNAs (snoRNAs), tRNAs, or rRNAs processing may also play important regulatory roles in spermatogenesis. By next-generation sequencing (NGS), we characterized the sncRNA populations detected at three milestone stages in male germ differentiation: primordial germ cells (PGCs), pubertal spermatogonia cells, and mature spermatozoa. To assess their potential transmission through the spermatozoa during fertilization, the sncRNAs of mouse oocytes and zygotes were also analyzed. Both, microRNAs and snoRNA-derived small RNAs are abundantly expressed in PGCs but transiently replaced by piRNAs in spermatozoa and endo-siRNAs in oocytes and zygotes. Exhaustive analysis of miRNA sequence variants also shows an increment of noncanonical microRNA forms along male germ cell differentiation. RNAs-derived from tRNAs and rRNAs interacting with PIWI proteins are not generated by the ping-pong pathway and could be a source of primary piRNAs. Moreover, our results strongly suggest that the small RNAs-derived from tRNAs and rRNAs are interacting with PIWI proteins, and specifically with MILI. Finally, computational analysis revealed their potential involvement in post-transcriptional regulation of mRNA transcripts suggesting functional convergence among different small RNA classes in germ cells and zygotes. PMID:25805854

Biomarkers and surrogate endpoints in clinical trials.

PubMed

Fleming, Thomas R; Powers, John H

2012-11-10

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. Copyright © 2012 John Wiley & Sons, Ltd.

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

Testosterone, Plumage Colouration and Extra-Pair Paternity in Male North-American Barn Swallows

PubMed Central

Eikenaar, Cas; Whitham, Megan; Komdeur, Jan; van der Velde, Marco; Moore, Ignacio T.

2011-01-01

In most monogamous bird species, circulating testosterone concentration in males is elevated around the social female's fertile period. Variation in elevated testosterone concentrations among males may have a considerable impact on fitness. For example, testosterone implants enhance behaviours important for social and extra-pair mate choice. However, little is known about the relationship between natural male testosterone concentration and sexual selection. To investigate this relationship we measured testosterone concentration and sexual signals (ventral plumage colour and tail length), and determined within and extra-pair fertilization success in male North American barn swallows (Hirundo rustica erythrogaster). Dark rusty coloured males had higher testosterone concentrations than drab males. Extra-pair paternity was common (42% and 31% of young in 2009 and 2010, respectively), but neither within- nor extra-pair fertilization success was related to male testosterone concentration. Dark rusty males were less often cuckolded, but did not have higher extra-pair or total fertilization success than drab males. Tail length did not affect within- or extra-pair fertilization success. Our findings suggest that, in North American barn swallows, male testosterone concentration does not play a significant direct role in female mate choice and sexual selection. Possibly plumage colour co-varies with a male behavioural trait, such as aggressiveness, that reduces the chance of cuckoldry. This could also explain why dark males have higher testosterone concentrations than drab males. PMID:21853105

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.

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 ...

Monoclonal antibodies, immunofluorometric assay, and detection of human semenogelin in male reproductive tract: no association with in vitro fertilizing capacity of sperm.

PubMed

Koistinen, Hannu; Soini, Tuuli; Leinonen, Jari; Hyden-Granskog, Christel; Salo, Jaakko; Halttunen, Mervi; Stenman, Ulf-Håkan; Seppälä, Markku; Koistinen, Riitta

2002-03-01

Semenogelin plays an important role in sperm clotting and is degraded into smaller fragments by prostate-specific antigen (PSA) during clot liquefaction. Semenogelin and its fragments inhibit sperm motility in vitro. We studied the expression of semenogelin I mRNA and its localization in various tissues of the male genital tract. We also studied semenogelin concentrations with respect to sperm parameters and the outcome of in vitro fertilization. Semenogelin protein was detected by immunohistochemical staining and semenogelin I mRNA was detected by Northern blot analysis in the seminal vesicles and ampullary part of the vas deferens, whereas specimens from the prostate, epididymis, testis, and the female genital tract were negative. Using monoclonal antibodies against semenogelin, an immunofluorometric assay was developed to measure semenogelin levels in seminal plasma and to evaluate possible correlations with sperm parameters and fertilization in vitro. No correlation was found between the semenogelin concentration and the volume of the ejaculate, sperm concentration, sperm motility, or in vitro fertilization rate. Semenogelin levels were positively correlated with the total protein concentration in seminal plasma, and there was an inverse correlation between the concentration of semenogelin and that of PSA. The levels of semenogelin appear to bear no relationship to the in vitro fertilization capacity of the spermatozoa.

Validated surrogate endpoints needed for peri-implantitis.

PubMed

Lee, Dong Won

2011-01-01

Pubmed, Cochrane and Lilac databases, Google, Google Scholar, hand searching of websites of major dental journals. The reference list of five recently published systematic reviews on peri-implantitis treatment were also screened for potential studies. Randomised controlled trials and non-randomised studies in English, German, French, Spanish and Italian on peri-implantitis treatment in humans were included. Case series, case reports and cross sectional or non-therapy studies were excluded from the assessment of endpoints. No minimum follow up time was set for studies that were included. Data were extracted in duplicate by two reviewers and disagreements were resolved by consensus. True endpoints for peri-implantitis treatment were considered only if they provided evidence of tangible benefit to the patient. The outcome variables regarded as true endpoints were implant failure, aesthetic assessment and variables related to quality of life, but these were only considered if they were clearly identified as an objective of the research, not as an outcome of treatment. Surrogate endpoints were considered as those measurements of clinical outcomes such as probing pocket depth and clinical attachment level. Fourteen studies were included in this review with data on implant failure presented solely as consequence of peri-implantitis therapy. No true endpoint was described for any study on peri-implantitis. Mean pocket probing depth, clinical attachment level and bleeding on probing were the three surrogate endpoints cited most often in the literature. All endpoints used in the trials reviewed are surrogates of clinical events, such as implant failure. Clinical surrogate endpoints should be validated to assess the real effect of these measures on true endpoints.

Effect of pre-fixation delay and freezing on mink testicular endpoints for environmental research.

PubMed

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.

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Postmating sexual conflict and female control over fertilization during gamete interaction.

PubMed

Firman, Renée C

2018-06-01

Males and females rarely have identical evolutionary interests over reproduction, and when the fitness of both sexes is dependent upon paternity outcomes, sexual conflict over fertilization is inevitable. In internal fertilizers, the female tract is a formidable selective force on the number and integrity of sperm that reach the egg. Selection on sperm quality is intensified when females mate multiply and rival males are forced to compete for fertilizations. While male adaptations to sperm competition have been well documented (e.g., increased sperm fertilizing capacity), much less attention has been given to the evolutionary consequences of postmating sexual conflict for egg form and function. Specifically, increased sperm competitiveness can be detrimental by giving rise to an elevation in reproductive failure resulting from polyspermy. Spanning literature on both internal and external fertilizers, in this review I discuss how females respond to sperm competition via fertilization barriers that mediate sperm entry. These findings, which align directly with sexual conflict theory, indicate that females have greater control over fertilization than has previously been appreciated. I then consider the implications of gametic sexual conflict in relation to the development of reproductive isolation and speculate on potential mechanisms accounting for "egg defensiveness." Finally, I discuss the functional significance of egg defensiveness for both the sexes, and sperm selection for females. © 2018 New York Academy of Sciences.

Reduced fecundity in male ALS gene-carriers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, W.G.; Lustenberger, A.; Lucek, P.R.

1995-11-06

In order to study genetic aspects in multicase families, 89 amyotrophic lateral sclerosis (ALS) and 214 Parkinson disease (PD) kindreds were analyzed in parallel studies. Obligate gene-carriers were identified as described previously. There were fewer children per gene-carrier male (2.42) than per gene-carrier female (3.25, Student`s t-test, P<.0003) for ALS but not for other diseases. The data taken together suggest that fecundity in ALS gene-carriers was reduced in males, possibly as a result of reduced fertility. Since childbearing is usually accomplished well before the onset of neurological symptoms in ALS, and since reduced fecundity was found in male ALS gene-carriers,more » these findings raise the possibility that an ALS gene might have a pleiotrophic effect on fertility in males occurring decades before the onset of neurological symptoms. Evidence is presented linking reactive oxygen species to reduced fertility in males. Alternatively, decreased or nonfunctional androgen receptors could play a role. 22 refs., 1 fig., 2 tabs.« less

THE FERTILITY MOTIVATIONS OF YOUTH PREDICT LATER FERTILITY OUTCOMES: A PROSPECTIVE ANALYSIS OF NLSY DATA*

PubMed Central

Miller, Warren B.; Rodgers, Joseph Lee; Pasta, David J.

2010-01-01

We examine how the motivational sequence that leads to childbearing predicts fertility outcomes across reproductive careers. Using a motivational traits-desires-intentions theoretical framework, we test a structural equation model using prospective male and female data from the National Longitudinal Survey of Youth. Specifically, we take motivational data collected during the 1979–1982 period, when the youths were in their teens and early twenties, to predict the timing of the next child born after 1982 and the total number of children born by 2002. Separate models were estimated for males and females but with equality constraints imposed unless relaxing these constraints improved the overall model fit. The results indicate substantial explanatory power of fertility motivations for both short-term and long-term fertility outcomes. They also reveal the effects of both gender role attitude and educational intentions on these outcomes. Although some sex differences in model pathways occurred, the primary hypothesized pathways were essentially the same across the sexes. Two validity substudies support the soundness of the results. A third substudy comparing the male and female models across the sample split on the basis of previous childbearing revealed a number of pattern differences within the four sex-by-previous childbearing groups. Several of the more robust of these pattern differences offer interesting insights and support the validity and usefulness of our theoretical framework. PMID:20463915

Dynamic F-actin movement is essential for fertilization in Arabidopsis thaliana

PubMed Central

Kawashima, Tomokazu; Maruyama, Daisuke; Shagirov, Murat; Li, Jing; Hamamura, Yuki; Yelagandula, Ramesh; Toyama, Yusuke; Berger, Frédéric

2014-01-01

In animals, microtubules and centrosomes direct the migration of gamete pronuclei for fertilization. By contrast, flowering plants have lost essential components of the centrosome, raising the question of how flowering plants control gamete nuclei migration during fertilization. Here, we use Arabidopsis thaliana to document a novel mechanism that regulates F-actin dynamics in the female gametes and is essential for fertilization. Live imaging shows that F-actin structures assist the male nucleus during its migration towards the female nucleus. We identify a female gamete-specific Rho-GTPase that regulates F-actin dynamics and further show that actin–myosin interactions are also involved in male gamete nucleus migration. Genetic analyses and imaging indicate that microtubules are dispensable for migration and fusion of male and female gamete nuclei. The innovation of a novel actin-based mechanism of fertilization during plant evolution might account for the complete loss of the centrosome in flowering plants. DOI: http://dx.doi.org/10.7554/eLife.04501.001 PMID:25303363

Biomarkers and surrogate endpoints in kidney disease.

PubMed

Hartung, Erum A

2016-03-01

Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. "Hard" endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease.

Biomarkers and surrogate endpoints in kidney disease

PubMed Central

2015-01-01

Kidney disease and its related comorbidities impose a large public health burden. Despite this, the number of clinical trials in nephrology lags behind many other fields. An important factor contributing to the relatively slow pace of nephrology trials is that existing clinical endpoints have significant limitations. “Hard” endpoints for chronic kidney disease, such as progression to end-stage renal disease, may not be reached for decades. Traditional biomarkers, such as serum creatinine in acute kidney injury, may lack sensitivity and predictive value. Finding new biomarkers to serve as surrogate endpoints is therefore an important priority in kidney disease research and may help to accelerate nephrology clinical trials. In this paper, I first review key concepts related to the selection of clinical trial endpoints and discuss statistical and regulatory considerations related to the evaluation of biomarkers as surrogate endpoints. This is followed by a discussion of the challenges and opportunities in developing novel biomarkers and surrogate endpoints in three major areas of nephrology research: acute kidney injury, chronic kidney disease, and autosomal dominant polycystic kidney disease. PMID:25980469

21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

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... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

21 CFR 601.41 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Approval based on a surrogate endpoint or on an... Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival or... uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical...

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

PubMed

Holton, Sara; Rowe, Heather; Kirkman, Maggie; Jordan, Lynne; McNamee, Kathleen; Bayly, Christine; McBain, John; Sinnott, Vikki; Fisher, Jane

2016-02-15

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. To identify public opinion about sexual and reproductive health in Australia. 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. 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. 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.

Standardized quassinoid-rich Eurycoma longifolia extract improved spermatogenesis and fertility in male rats via the hypothalamic-pituitary-gonadal axis.

PubMed

Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

2013-02-13

Eurycoma longifolia Jack, a small Simaroubaceae tree, known locally as 'Tongkat Ali' is popularly used as a sexual tonic in traditional medicine for aphrodisiac activity and improvement of fertility and male libido. To investigate the effects of the standardized bioactive fraction of E. longifolia and its chemical constituents on the male fertility and the mechanisms of action involved. The powdered roots of E. longifolia were extracted separately with methanol and water. The organic extract upon further fractionation on HP 20 resin and elution with the methanol/water mixture afforded four fractions (F1-F4). These fractions, together with the crude aqueous (W) and organic extracts were standardized following their respective major quassinoid content and profile. The effects of the fractions on the rat spermatogenesis were compared with that of the aqueous extract (W) to determine the bioactive fraction. The effects of the bioactive fraction on the sperm count and quality, the histological morphometric changes on the spermatogenesis cycle, fertility and hormonal changes of plasma testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and estrogen in the animals upon oral administration were determined. The effects of the bioactive quassinoids on the testosterone release from the isolated testicular interstitial cells rich in Leydig cells, were also described. The male rats orally administered with 25mg/kg of F2 and 250mg/kg of W, significantly increased the sperm concentration when compared with that of the control animals (P<0.05). High performance liquid chromatography analysis revealed that 25mg/kg of F2 and 250mg/kg of W were almost similar in concentration of eurycomanone, the major and most potent quassinoid. Microscopic morphometrical analysis of the rat testis following treatment with F2, showed significant increase in the number of spermatocytes and round spermatids at Stage VII of the spermatogenesis cycle when compared to that of the

Deletion analysis of male sterility effects of t-haplotypes in the mouse.

PubMed

Bennett, D; Artzt, K

1990-01-01

We present data on the effects of three chromosome 17 deletions on transmission ratio distortion (TRD) and sterility of several t-haplotypes. All three deletions have similar effects on male TRD: that is, Tdel/tcomplete genotypes all transmit their t-haplotype in very high proportion. However, each deletion has different effects on sterility of heterozygous males, with TOr/t being fertile, Thp/t less fertile, and TOrl/t still less fertile. These data suggest that wild-type genes on chromosomes homologous to t-haplotypes can be important regulators of both TRD and fertility in males, and that the wild-type genes concerned with TRD and fertility are at least to some extent different. The data also provide a rough map of the positions of these genes.

Ultrasound and radiology surrogate endpoints in pharmacological studies.

PubMed

Agewall, S; DeGroot, E; Marcos-Alberca, P; Zamorano, J L; Barrero, A A; Badano, L P; Perrone-Filardi, P

2012-09-01

Cardiovascular studies investigating therapeutic intervention with clinical endpoints are costly due to the need for considerable duration and large number of patients, or both. Therefore, for evaluation of novel cardiovascular drug efficacy, surrogate endpoints are used. Cardiovascular imaging endpoints have proven their worth. Sometimes the relevance of imaging is questioned and other methods are suggested instead. There is also some confusion about the strengths of imaging endpoints. The aim of the present paper is to review ultrasound and radiology imaging techniques as surrogate endpoints in pharmacological trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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.

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.

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

Female mediation of competitive fertilization success in Drosophila melanogaster.

PubMed

Lüpold, Stefan; Pitnick, Scott; Berben, Kirstin S; Blengini, Cecilia S; Belote, John M; Manier, Mollie K

2013-06-25

How females store and use sperm after remating can generate postcopulatory sexual selection on male ejaculate traits. Variation in ejaculate performance traits generally is thought to be intrinsic to males but is likely to interact with the environment in which sperm compete (e.g., the female reproductive tract). Our understanding of female contributions to competitive fertilization success is limited, however, in part because of the challenges involved in observing events within the reproductive tract of internally fertilizing species while discriminating among sperm from competing males. Here, we used females from crosses among isogenic lines of Drosophila melanogaster, each mated to two genetically standardized males (the first with green- and the second with red-tagged sperm heads) to demonstrate heritable variation in female remating interval, progeny production rate, sperm-storage organ morphology, and a number of sperm performance, storage, and handling traits. We then used multivariate analyses to examine relationships between this female-mediated variation and competitive paternity. In particular, the timing of female ejection of excess second-male and displaced first-male sperm was genetically variable and, by terminating the process of sperm displacement, significantly influenced the relative numbers of sperm from each male competing for fertilization, and consequently biased paternity. Our results demonstrate that females do not simply provide a static arena for sperm competition but rather play an active and pivotal role in postcopulatory processes. Resolving the adaptive significance of genetic variation in female-mediated mechanisms of sperm handling is critical for understanding sexual selection, sexual conflict, and the coevolution of male and female reproductive traits.

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...

The intermediate endpoint effect in logistic and probit regression

PubMed Central

MacKinnon, DP; Lockwood, CM; Brown, CH; Wang, W; Hoffman, JM

2010-01-01

Background An intermediate endpoint is hypothesized to be in the middle of the causal sequence relating an independent variable to a dependent variable. The intermediate variable is also called a surrogate or mediating variable and the corresponding effect is called the mediated, surrogate endpoint, or intermediate endpoint effect. Clinical studies are often designed to change an intermediate or surrogate endpoint and through this intermediate change influence the ultimate endpoint. In many intermediate endpoint clinical studies the dependent variable is binary, and logistic or probit regression is used. Purpose The purpose of this study is to describe a limitation of a widely used approach to assessing intermediate endpoint effects and to propose an alternative method, based on products of coefficients, that yields more accurate results. Methods The intermediate endpoint model for a binary outcome is described for a true binary outcome and for a dichotomization of a latent continuous outcome. Plots of true values and a simulation study are used to evaluate the different methods. Results Distorted estimates of the intermediate endpoint effect and incorrect conclusions can result from the application of widely used methods to assess the intermediate endpoint effect. The same problem occurs for the proportion of an effect explained by an intermediate endpoint, which has been suggested as a useful measure for identifying intermediate endpoints. A solution to this problem is given based on the relationship between latent variable modeling and logistic or probit regression. Limitations More complicated intermediate variable models are not addressed in the study, although the methods described in the article can be extended to these more complicated models. Conclusions Researchers are encouraged to use an intermediate endpoint method based on the product of regression coefficients. A common method based on difference in coefficient methods can lead to distorted

Efficient estimation of the distribution of time to composite endpoint when some endpoints are only partially observed

PubMed Central

Daniel, Rhian M.; Tsiatis, Anastasios A.

2014-01-01

Two common features of clinical trials, and other longitudinal studies, are (1) a primary interest in composite endpoints, and (2) the problem of subjects withdrawing prematurely from the study. In some settings, withdrawal may only affect observation of some components of the composite endpoint, for example when another component is death, information on which may be available from a national registry. In this paper, we use the theory of augmented inverse probability weighted estimating equations to show how such partial information on the composite endpoint for subjects who withdraw from the study can be incorporated in a principled way into the estimation of the distribution of time to composite endpoint, typically leading to increased efficiency without relying on additional assumptions above those that would be made by standard approaches. We describe our proposed approach theoretically, and demonstrate its properties in a simulation study. PMID:23722304

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

Interactions between observer and stimuli fertility status: Endocrine and perceptual responses to intrasexual vocal fertility cues.

PubMed

Ostrander, Grant M; Pipitone, R Nathan; Shoup-Knox, Melanie L

2018-02-01

Both men and women find female voices more attractive at higher fertility times in the menstrual cycle, suggesting the voice is a cue to fertility and/or hormonal status. Preference for fertile females' voices provides males with an obvious reproduction advantage, however the advantage for female listeners is less clear. One possibility is that attention to the fertility status of potential rivals may enable women to enhance their own reproductive strategies through intrasexual competition. If so, the response to having high fertility voices should include hormonal changes that promote competitive behavior. Furthermore, attention and response to such cues should vary as a function of the observer's own fertility, which influences her ability to compete for mates. The current study monitored variation in cortisol and testosterone levels in response to evaluating the attractiveness of voices of other women. All 33 participants completed this task once during ovulation then again during the luteal phase. The voice stimuli were recorded from naturally cycling women at both high and low fertility, and from women using hormonal birth control. We found that listeners rated high fertility voices as more attractive compared to low fertility, with the effect being stronger when listeners were ovulating. Testosterone was elevated following voice ratings suggesting threat detection or the anticipation of competition, but no stress response was found. Copyright © 2017 Elsevier Inc. All rights reserved.

Knowledge about factors that influence fertility among Australians of reproductive age: a population-based survey.

PubMed

Hammarberg, Karin; Setter, Tracey; Norman, Robert J; Holden, Carol A; Michelmore, Janet; Johnson, Louise

2013-02-01

To explore knowledge about the effects on fertility of age, obesity, smoking, and timing of intercourse among Australians of reproductive age. Telephone survey of a representative sample of Australians. Not applicable. Australians aged 18 to 45 years who wish to have a child or another child now or in the future. None. Knowledge about the effect on fertility of age, obesity, smoking, and timing of intercourse. A total of 462 interviews were conducted. The majority of respondents underestimated, by about 10 years, the age at which male and female fertility starts to decline. Only one in four correctly identified that female fertility starts to decline before age 35, and one in three identified that male fertility starts to decline before age 45. Most (59%) were aware that female obesity and smoking affect fertility, but fewer recognized that male obesity (30%) and smoking (36%) also influence fertility. Almost 40% of respondents had inadequate knowledge of when in the menstrual cycle a woman is most likely to conceive. Considerable knowledge gaps about modifiable factors that affect fertility were identified. These are targeted in a national education campaign to promote awareness of factors that influence fertility. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Sample size determination for equivalence assessment with multiple endpoints.

PubMed

Sun, Anna; Dong, Xiaoyu; Tsong, Yi

2014-01-01

Equivalence assessment between a reference and test treatment is often conducted by two one-sided tests (TOST). The corresponding power function and sample size determination can be derived from a joint distribution of the sample mean and sample variance. When an equivalence trial is designed with multiple endpoints, it often involves several sets of two one-sided tests. A naive approach for sample size determination in this case would select the largest sample size required for each endpoint. However, such a method ignores the correlation among endpoints. With the objective to reject all endpoints and when the endpoints are uncorrelated, the power function is the production of all power functions for individual endpoints. With correlated endpoints, the sample size and power should be adjusted for such a correlation. In this article, we propose the exact power function for the equivalence test with multiple endpoints adjusted for correlation under both crossover and parallel designs. We further discuss the differences in sample size for the naive method without and with correlation adjusted methods and illustrate with an in vivo bioequivalence crossover study with area under the curve (AUC) and maximum concentration (Cmax) as the two endpoints.

Zebrafish reproduction: revisiting in vitro fertilization to increase sperm cryopreservation success.

PubMed

Hagedorn, Mary; Carter, Virginia L

2011-01-01

Although conventional cryopreservation is a proven method for long-term, safe storage of genetic material, protocols used by the zebrafish community are not standardized and yield inconsistent results, thereby putting the security of many genotypes in individual laboratories and stock centers at risk. An important challenge for a successful zebrafish sperm cryopreservation program is the large variability in the post-thaw in vitro fertilization success (0 to 80%). But how much of this variability was due to the reproductive traits of the in vitro fertilization process, and not due to the cryopreservation process? These experiments only assessed the in vitro process with fresh sperm, but yielded the basic metrics needed for successful in vitro fertilization using cryopreserved sperm, as well. We analyzed the reproductive traits for zebrafish males with a strict body condition range. It did not correlate with sperm volume, or motility (P>0.05), but it did correlate with sperm concentration. Younger males produced more concentrated sperm (P<0.05). To minimize the wastage of sperm during the in vitro fertilization process, 10(6) cells/ml was the minimum sperm concentration needed to achieve an in vitro fertilization success of ≥ 70%. During the in vitro process, pooling sperm did not reduce fertilization success (P>0.05), but pooling eggs reduced it by approximately 30 to 50% (P<0.05). This reduction in fertilization success was due not to the pooling of the females' eggs, but to the type of tools used to handle the eggs. Recommendations to enhance the in vitro process for zebrafish include: 1) using males of a body condition closer to 1.5 for maximal sperm concentration; 2) minimizing sperm wastage by using a working sperm concentration of 10(6) motile cells/ml for in vitro fertilization; and 3) never using metal or sharp-edged tools to handle eggs prior to fertilization.

Zebrafish Reproduction: Revisiting In Vitro Fertilization to Increase Sperm Cryopreservation Success

PubMed Central

Hagedorn, Mary; Carter, Virginia L.

2011-01-01

Although conventional cryopreservation is a proven method for long-term, safe storage of genetic material, protocols used by the zebrafish community are not standardized and yield inconsistent results, thereby putting the security of many genotypes in individual laboratories and stock centers at risk. An important challenge for a successful zebrafish sperm cryopreservation program is the large variability in the post-thaw in vitro fertilization success (0 to 80%). But how much of this variability was due to the reproductive traits of the in vitro fertilization process, and not due to the cryopreservation process? These experiments only assessed the in vitro process with fresh sperm, but yielded the basic metrics needed for successful in vitro fertilization using cryopreserved sperm, as well. We analyzed the reproductive traits for zebrafish males with a strict body condition range. It did not correlate with sperm volume, or motility (P>0.05), but it did correlate with sperm concentration. Younger males produced more concentrated sperm (P<0.05). To minimize the wastage of sperm during the in vitro fertilization process, 106 cells/ml was the minimum sperm concentration needed to achieve an in vitro fertilization success of ≥ 70%. During the in vitro process, pooling sperm did not reduce fertilization success (P>0.05), but pooling eggs reduced it by approximately 30 to 50% (P<0.05). This reduction in fertilization success was due not to the pooling of the females' eggs, but to the type of tools used to handle the eggs. Recommendations to enhance the in vitro process for zebrafish include: 1) using males of a body condition closer to 1.5 for maximal sperm concentration; 2) minimizing sperm wastage by using a working sperm concentration of 106 motile cells/ml for in vitro fertilization; and 3) never using metal or sharp-edged tools to handle eggs prior to fertilization. PMID:21698162

Endpoint Model of Exclusive Processes

NASA Astrophysics Data System (ADS)

Dagaonkar, Sumeet; Jain, Pankaj; Ralston, John P.

2018-07-01

The endpoint model explains the scaling laws observed in exclusive hadronic reactions at large momentum transfer in all experimentally important regimes. The model, originally conceived by Feynman and others, assumes a single valence quark carries most of the hadron momentum. The quark wave function is directly related to the momentum transfer dependence of the reaction. After extracting the momentum dependence of the quark wave function from one process, it explains all the others. Endpoint quark-counting rules relate the number of quarks in a hadron to the power-law. A universal linear endpoint behavior explains the proton electromagnetic form factors F1 and F2, proton-proton scattering at fixed-angle, the t-dependence of proton-proton scattering at large s>> t, and Compton scattering at fixed t. The model appears to be the only comprehensive mechanism consistent with all experimental information.

Spermatozoid life-span of two brown seaweeds, Saccharina japonica and Undaria pinnatifida, as measured by fertilization efficiency

NASA Astrophysics Data System (ADS)

Li, Jing; Pang, Shaojun; Liu, Feng; Shan, Tifeng; Gao, Suqin

2013-07-01

During sexual reproduction of seaweeds, spermatozoid (sperm) discharge is triggered by chemical messengers (pheromones) released by the female gametes. The chemotactic ability of the sperm ensures fertilization success. Using unialgal male and female gametophyte material under designated standard gametogenesis testing (SGT) conditions, the potential life-span of the sperm of two seaweeds, Saccharina japonica and Undaria pinnatifida, was assessed by their ability to fertilize eggs. Results show that within 20-30 min after being discharged, sperm of both species could complete fertilization without an apparent decline in fertilization rate. Although fertilization rate 60-120 min after sperm discharge dropped significantly in both species, some sperm were viable enough to fertilize the eggs. In S. japonica, at 12°C, some sperm were able to fertilize eggs up to 12 h after discharge. In both species, egg discharge rates (EDR) in the male and female mixed positive controls were significantly higher than those of all the sperm-testing groups. Doubling the seeded male gametophytes of S. japonica in the SGT tests significantly increased the EDR, further confirming the effect of the presence of the male on the female in terms of facilitating egg discharge from oogonia.

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

Implementation strategy for achieving replacement level fertility.

PubMed

1993-01-01

The recommendation of the Bali Declaration on Population and Sustainable Development at the ESCAP regional conference was to adopt strategies for attaining replacement-level fertility of 2.1 or 2.2 children by 2010. East Asian countries, except Mongolia and the Democratic People's Republic of Korea, and the Southeast Asian countries Singapore and Thailand have already reached replacement-level fertility. Most larger Oceanic countries have also done so. Only South Asian Sri Lanka and southern India have attained replacement level. The following conditions slow or hinder the goal, but they do not provide an "absolute" barrier to fertility decline: social welfare schemes and old age security, son preference, lack of government family planning, poverty, relatively high mortality, low status of women, and education status. Theories of demographic transition have postulated that economic and social development initially brings a decline in mortality, and later brings a decline in fertility; and high fertility was an adaptation to high mortality. Policy gets caught in the lag between mortality and fertility decline. Eventually the cultural motives for high fertility are undercut by social and economic development. Although the generalization that economic growth slows fertility is true for South Asia, the correlation is uneven. Forceful government-sponsored family planning programs in Bangladesh and China may lead the way to strategies for decline in ESCAP region. A Thailand study suggested important factors were fundamental social change, the increased cost of children, cultural acceptance of birth control, a latent demand for fertility control, and government efforts in family planning. ESCAP countries have in common relatively high morality and inadequate public health programs, patriarchal structures, and limited female autonomy, poverty and landlessness, lack of community cohesiveness, and inadequate family planning programs. Weaknesses in programs are attributed to

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

PubMed

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

2013-02-01

In previous studies, we reported significant associations of the POU1F1 pathway genes with reproduction and production traits in several dairy cattle populations. Polymorphisms in genes of this pathway were found to be associated with both female and male fertility traits in dairy cattle. The POU1F1 gene is a direct downstream target for the regulation of the prophet of Pit1 (PROP1) gene, also known as PROP paired-like homeobox 1. Interestingly, the position of PROP1 coincides with a quantitative trait locus affecting ovulation rate in cattle. Therefore, the objective of this study was to investigate whether PROP1 affects fertility and milk production traits in Holstein cattle. Using the DNA pooling sequencing approach, a missense single nucleotide polymorphism that replaces a histidine amino acid with an arginine was detected in exon 3 of PROP1. The arginine allele was found to be associated with a decrease in sire conception rate and an increase in productive life, protein yield, and net merit index in a population of 1,951 Holstein bulls. The transcription factors produced from the histidine and arginine isoforms are known to have different transcription, DNA binding, and regulation activities. As such, we propose that the association of the arginine isoform with decreased bull fertility is likely caused by reduced activity of this allele in male functions. The findings of this study suggest PROP1 polymorphisms as candidates in selection programs for fertility, health, and milk production traits in dairy cattle. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Advanced topics in evidence-based urologic oncology: surrogate endpoints.

PubMed

Lavallée, Luke T; Montori, Victor M; Canfield, Stephen E; Breau, Rodney H

2011-01-01

Clinical trials often report surrogate endpoint data. A surrogate endpoint is a biological marker or clinical sign that can be substituted for a patient-important outcome. Using surrogate endpoints correctly may facilitate and expedite clinical trials and may improve medical decisions. However, rigorous criteria must be met for an endpoint to be considered a valid surrogate. The purpose of this article is to review the topic of surrogate endpoints in the context of a urologic encounter. Copyright © 2011 Elsevier Inc. All rights reserved.

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma.

PubMed

Medeiros, Felipe A

2017-05-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials.

Spermatogonial stem cells as a therapeutic alternative for fertility preservation of prepubertal boys

PubMed Central

Galuppo, Andrea Giannotti

2015-01-01

ABSTRACT Spermatogonial stem cells, which exist in the testicles since birth, are progenitors cells of male gametes. These cells are critical for the process of spermatogenesis, and not able to produce mature sperm cells before puberty due to their dependency of hormonal stimuli. This characteristic of the reproductive system limits the preservation of fertility only to males who are able to produce an ejaculate. This fact puts some light on the increase in survival rates of childhood cancer over the past decades because of improvements in the diagnosis and effective treatment in pediatric cancer patients. Therefore, we highlight one of the most important challenges concerning male fertility preservation that is the toxic effect of cancer therapy on reproductive function, especially the spermatogenesis. Currently, the experimental alternative for fertility preservation of prepubertal boys is the testicular tissue cryopreservationfor, for future isolation and spermatogonial stem cells transplantation, in order to restore the spermatogenesis. We present a brief review on isolation, characterization and culture conditions for the in vitro proliferation of spermatogonial stem cells, as well as the future perspectives as an alternative for fertility preservation in prepubertal boys. The possibility of restoring male fertility constitutes a research tool with an huge potential in basic and applied science. The development of these techniques may be a hope for the future of fertility preservation in cases that no other options exist, e.g, pediatric cancer patients. PMID:26761559

Sperm competition, but not major histocompatibility divergence, drives differential fertilization success between alternative reproductive tactics in Chinook salmon.

PubMed

Lehnert, S J; Helou, L; Pitcher, T E; Heath, J W; Heath, D D

2018-01-01

Post-copulatory sexual selection processes, including sperm competition and cryptic female choice (CFC), can operate based on major histocompatibility (MH) genes. We investigated sperm competition between male alternative reproductive tactics [jack (sneaker) and hooknose (guard)] of Chinook salmon (Oncorhynchus tshawytscha). Using a full factorial design, we examined in vitro competitive fertilization success of paired jack and hooknose males at three time points after sperm activation (0, 15 and 60 s) to test for male competition, CFC and time effects on male fertilization success. We also examined egg-mediated CFC at two MH genes by examining both the relationship between competitive fertilization success and MH divergence as well as inheritance patterns of MH alleles in resulting offspring. We found that jacks sired more offspring than hooknose males at 0 s post-activation; however, jack fertilization success declined over time post-activation, suggesting a trade-off between sperm speed and longevity. Enhanced fertilization success of jacks (presumably via higher sperm quality) may serve to increase sneaker tactic competitiveness relative to dominant hooknose males. We also found evidence of egg-mediated CFC (i.e. female × male interaction) influencing competitive fertilization success; however, CFC was not acting on the MH genes as we found no relationship between fertilization success and MH II β 1 or MH I α 1 divergence and we found no deviations from Mendelian inheritance of MH alleles in the offspring. Our study provides insight into evolutionary mechanisms influencing variation in male mating success within alternative reproductive tactics, thus underscoring different strategies that males can adopt to attain success. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

End-point sharpness in thermometric titrimetry.

PubMed

Tyrrell, H J

1967-07-01

It is shown that the sharpness of an end-point in a thermometric titration where the simple reaction A + B right harpoon over left harpoon AB takes place, depends on Kc(A') where K is the equilibrium constant for the reaction, and c(A') is the total concentration of the titrand (A) in the reaction mixture. The end-point is sharp if, (i) the enthalpy change in the reaction is not negligible, and (ii) Kc(A') > 10(3). This shows that it should, for example, be possible to titrate 0.1 M acid, pK(A) = 10, using a thennometric end-point. Some aspects of thermometric titrimetry when Kc(A') < 10(3) are also considered.

Biomarkers and Surrogate Endpoints: Lessons Learned From Glaucoma

PubMed Central

Medeiros, Felipe A.

2017-01-01

With the recent progress in imaging technologies for assessment of structural damage in glaucoma, a debate has emerged on whether these measurements can be used as valid surrogate endpoints in clinical trials evaluating new therapies for the disease. A discussion of surrogates should be grounded on knowledge acquired from their use in other areas of medicine as well as regulatory requirements. This article reviews the conditions for valid surrogacy in the context of glaucoma clinical trials and critically evaluates the role of biomarkers such as IOP and imaging measurements as potential surrogates for clinically relevant outcomes. Valid surrogate endpoints must be able to predict a clinically relevant endpoint, such as loss of vision or decrease in quality of life. In addition, the effect of a proposed treatment on the surrogate must capture the effect of the treatment on the clinically relevant endpoint. Despite its widespread use in clinical trials, no proper validation of IOP as a surrogate endpoint has yet been conducted for any class of IOP-lowering treatments. Although strong evidence has accumulated about imaging measurements as predictors of relevant functional outcomes in glaucoma, there is still insufficient evidence to support their use as valid surrogate endpoints. However, imaging biomarkers could potentially be used as part of composite endpoints in glaucoma trials, overcoming weaknesses of the use of structural or functional endpoints in isolation. Efforts should be taken to properly design and conduct studies that can provide proper validation of potential biomarkers in glaucoma clinical trials. PMID:28475699

Hit or Miss: Fertilization Outcomes of Natural Inseminations by Japanese Quail

PubMed Central

Adkins-Regan, Elizabeth

2015-01-01

Variation in fertilization success underlies sexual selection, yet mating does not guarantee fertilization. The relationship between natural inseminations and fertilization success is essential for understanding sexual selection, yet that relationship and its underlying mechanisms are poorly understood in sperm-storing vertebrates such as birds. Here the relationship is analyzed in mating trials using Japanese quail (Coturnix japonica), which show striking variation in the fertilizing success of inseminations. Failures of males’ inseminations to fertilize eggs were mainly due to failures prior to sperm-egg contact. Fertilization probabilities on any given day were unrelated to whether the female had laid an egg the previous day, arguing against stimulation of sperm release from sperm storage tubules by the events of the daily egg-laying cycle. Instead, an unfertilized egg laid between two fertilized eggs predicted a longer sperm storage interval. Both sexes gained similar numbers of fertilized eggs by mating with a second partner the next day, but males, unlike females in a previous study, did not gain by having two females to mate with at the same time. Instead, they were both behaviorally and sperm limited, whereas females gain by mating twice in quick succession. Even double inseminations often failed to fertilize any eggs, and multiple matings would be needed for an entire clutch to be fertilized with high certainty. Paradoxically, this low and probabilistic fertilization success co-occurs with other notable characteristics of male quail suggestive of past sexual selection for increased success, including vigorous copulatory behavior, forced copulations, foamy secretion aiding in sperm competition, large testes and unusual sperm morphology. PMID:26222780

Testicular connexin 43, a precocious molecular target for the effect of environmental toxicants on male fertility

PubMed Central

Gilleron, Jérôme; Carette, Diane; Segretain, Dominique

2011-01-01

Many recent epidemiological, clinical and experimental findings support the hypothesis that environmental toxicants are responsible for the increasing male reproductive disorders (congenital malformations, declining sperm counts and testicular cancer) over the past 20 years. It has also been reported that exposure to these toxicants, during critical periods of development (fetal and neonatal), represents a more considerable risk for animals and humans than exposure during adulthood. However, the molecular targets for these chemicals have not been clearly identified. Recent studies showed that a family of transmembranous proteins, named connexins, regulates numerous physiological processes involved in testicular development and function, such as Sertoli and germ cell proliferation, differentiation, germ cell migration and apoptosis. In the testis, knockout strategy revealed that connexin 43, the predominant connexin in this organ, is essential for spermatogenesis. In addition, there is evidence that many environmental toxicants could alter testicular connexin 43 by dysregulation of numerous mechanisms controlling its function. In the present work, we propose first to give an overview of connexin expression and intercellular gap junction coupling in the developing fetal and neonatal testes. Second, we underline the impact of maternally chemical exposure on connexin 43 expression in the perinatal developing testis. Lastly, we attempt to link this precocious effect to male offspring fertility. PMID:22332114

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

Construction of a male sterility system for hybrid rice breeding and seed production using a nuclear male sterility gene

PubMed Central

Chang, Zhenyi; Chen, Zhufeng; Wang, Na; Xie, Gang; Lu, Jiawei; Yan, Wei; Zhou, Junli; Tang, Xiaoyan; Deng, Xing Wang

2016-01-01

The breeding and large-scale adoption of hybrid seeds is an important achievement in agriculture. Rice hybrid seed production uses cytoplasmic male sterile lines or photoperiod/thermo-sensitive genic male sterile lines (PTGMS) as female parent. Cytoplasmic male sterile lines are propagated via cross-pollination by corresponding maintainer lines, whereas PTGMS lines are propagated via self-pollination under environmental conditions restoring male fertility. Despite huge successes, both systems have their intrinsic drawbacks. Here, we constructed a rice male sterility system using a nuclear gene named Oryza sativa No Pollen 1 (OsNP1). OsNP1 encodes a putative glucose–methanol–choline oxidoreductase regulating tapetum degeneration and pollen exine formation; it is specifically expressed in the tapetum and miscrospores. The osnp1 mutant plant displays normal vegetative growth but complete male sterility insensitive to environmental conditions. OsNP1 was coupled with an α-amylase gene to devitalize transgenic pollen and the red fluorescence protein (DsRed) gene to mark transgenic seed and transformed into the osnp1 mutant. Self-pollination of the transgenic plant carrying a single hemizygous transgene produced nontransgenic male sterile and transgenic fertile seeds in 1:1 ratio that can be sorted out based on the red fluorescence coded by DsRed. Cross-pollination of the fertile transgenic plants to the nontransgenic male sterile plants propagated the male sterile seeds of high purity. The male sterile line was crossed with ∼1,200 individual rice germplasms available. Approximately 85% of the F1s outperformed their parents in per plant yield, and 10% out-yielded the best local cultivars, indicating that the technology is promising in hybrid rice breeding and production. PMID:27864513

Construction of a male sterility system for hybrid rice breeding and seed production using a nuclear male sterility gene.

PubMed

Chang, Zhenyi; Chen, Zhufeng; Wang, Na; Xie, Gang; Lu, Jiawei; Yan, Wei; Zhou, Junli; Tang, Xiaoyan; Deng, Xing Wang

2016-12-06

The breeding and large-scale adoption of hybrid seeds is an important achievement in agriculture. Rice hybrid seed production uses cytoplasmic male sterile lines or photoperiod/thermo-sensitive genic male sterile lines (PTGMS) as female parent. Cytoplasmic male sterile lines are propagated via cross-pollination by corresponding maintainer lines, whereas PTGMS lines are propagated via self-pollination under environmental conditions restoring male fertility. Despite huge successes, both systems have their intrinsic drawbacks. Here, we constructed a rice male sterility system using a nuclear gene named Oryza sativa No Pollen 1 (OsNP1). OsNP1 encodes a putative glucose-methanol-choline oxidoreductase regulating tapetum degeneration and pollen exine formation; it is specifically expressed in the tapetum and miscrospores. The osnp1 mutant plant displays normal vegetative growth but complete male sterility insensitive to environmental conditions. OsNP1 was coupled with an α-amylase gene to devitalize transgenic pollen and the red fluorescence protein (DsRed) gene to mark transgenic seed and transformed into the osnp1 mutant. Self-pollination of the transgenic plant carrying a single hemizygous transgene produced nontransgenic male sterile and transgenic fertile seeds in 1:1 ratio that can be sorted out based on the red fluorescence coded by DsRed Cross-pollination of the fertile transgenic plants to the nontransgenic male sterile plants propagated the male sterile seeds of high purity. The male sterile line was crossed with ∼1,200 individual rice germplasms available. Approximately 85% of the F1s outperformed their parents in per plant yield, and 10% out-yielded the best local cultivars, indicating that the technology is promising in hybrid rice breeding and production.

Fertility preservation knowledge, counseling, and actions among adolescent and young adult patients with cancer: A population-based study.

PubMed

Shnorhavorian, Margarett; Harlan, Linda C; Smith, Ashley Wilder; Keegan, Theresa H M; Lynch, Charles F; Prasad, Pinki K; Cress, Rosemary D; Wu, Xiao-Cheng; Hamilton, Ann S; Parsons, Helen M; Keel, Gretchen; Charlesworth, Sarah E; Schwartz, Stephen M

2015-10-01

The fertility of adolescent and young adult (AYA) patients with cancer can be threatened by treatments, but to the authors' knowledge little is known regarding the extent to which providers discuss this with patients or recommend fertility preservation, or the patient and physician characteristics associated with these interactions. Questionnaires from 459 AYA patients with cancer who were diagnosed between 2007 and 2008 and recruited through 7 US population-based cancer registries were analyzed using sex-specific multivariable models. The authors assessed characteristics associated with not discussing therapy effects on fertility or fertility preservation options, and not making fertility preservation arrangements. Males without a medical oncologist were more likely not to be told that therapy might affect fertility than those with a medical oncologist (male odds ratio [OR], 2.28; 95% confidence interval [95% CI], 1.03-5.00). Individuals without insurance (male OR, 2.91 [95% CI, 1.41-5.91] and female OR, 5.46 [95% CI, 1.59-18.72]); those raising children aged <18 years; and, among males only, those who received treatment posing no or a low fertility risk (OR, 3.39; 95% CI, 1.60-7.16) were more likely not to discuss fertility preservation with providers. Finally, among males, those without a college degree (OR, 1.98; 95% CI, 1.00-3.97), lacking private insurance (OR, 2.97; 95% CI, 1.16-7.63), and raising children aged <18 years (OR, 3.53; 95% CI, 1.63-7.65) were more likely to not make fertility preservation arrangements; too few females had made fertility preservation arrangements for similar analyses to be performed. Discussion and action surrounding fertility preservation for AYA patients with cancer are associated with medical factors, patient socioeconomic data, and child-rearing status. These results highlight the need for insurance coverage for fertility preservation and increased awareness of fertility preservation options. © 2015 American Cancer Society.

21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on...

21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on...

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... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on...

21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Approval based on a surrogate endpoint or on an... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... the drug product has an effect on a surrogate endpoint that is reasonably likely, based on...

21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Approval based on a surrogate endpoint or on an 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 on...

Stallion fertility: a focus on the spermatozoon.

PubMed

Varner, D D; Gibb, Z; Aitken, R J

2015-01-01

Stallion fertility is a vast subject, with a wide array of permutations that can impact reproductive performance in either positive or negative ways. This review is intended to address a mere segment of the male fertility issue, but the very essence of the male contribution to fertilisation, that of the spermatozoon. Spermatozoal ultrastructure and form-to-function are detailed and spermatozoal metabolism is discussed, with specific reference to distinctive characteristics of stallion spermatozoa. Lastly, methods for assessment of spermatozoal function are considered, with emphasis on spermatozoal motility, the acrosome reaction and spermatozoon-oocyte interactions. Closing comments address the need for development and standardisation of molecular-based assays for use with spermatozoa of stallions whose subfertility cannot be explained with conventional tests. © 2014 EVJ Ltd.

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...

Suppression of fertility in adult cats.

PubMed

Goericke-Pesch, S; Wehrend, A; Georgiev, P

2014-06-01

Cats are animals with highly efficient reproduction, clearly pointing to a need for suppression of fertility. Although surgical contraception is highly effective, it is not always the method of choice. This is predominantly because it is cost-intensive, time-consuming and irreversible, with the latter being of major importance for cat breeders. This article reviews the use of progestins, scleroting agents, immunocontraception, melatonin, GnRH antagonists and finally, GnRH agonists, in adult male and female cats in detail, according to the present state of the art. By now, various scientific and clinical options are available for the suppression of fertility in adult cats and the decision as to which should be chosen - independent of the legal registration of any state - depends on different facts: (i) feral or privately owned animal? (ii) temporary or permanent suppression of fertility wanted/needed? (iii) sex of the animal? New effective and available methods for hormonal contraception include melatonin implants for short-term post ponement of oestrus in adult queens and slow-release GnRH-agonist implants containing deslorelin (Suprelorin(®) ) for short- and long-term contraception in male and female companion and breeding cats. © 2014 Blackwell Verlag GmbH.

Epigenetic disorders and male subfertility.

PubMed

Boissonnas, Céline Chalas; Jouannet, Pierre; Jammes, Hélène

2013-03-01

To provide a link between epigenetics and male subfertility at the DNA, histone-protamine, and RNA levels and its consequences on fertilization and embryo development. Review of the relevant literature. University-based clinical and research laboratories. Fertile and infertile men. None. Critical review of the literature. Epigenetic markers can be modified in infertile patients. Epigenetic modifications include methylation loss or gain on the global level and on imprinted genes, high levels of histone retention in spermatozoa, and deficiencies in some transcripts involved in spermatogenesis. Interestingly, these abnormalities are all linked together, because DNA methylation maintenance depends on DNA histone-protamine configuration which itself is stabilized by spermatozoal RNAs. The paternal genome has long been considered to be silent and passive in embryo formation. The epigenetic processes associated with the paternal DNA genome highlights its importance in male fertility as well as for embryo development. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The risk of male subfecundity attributable to welding of metals. Studies of semen quality, infertility, fertility, adverse pregnancy outcome and childhood malignancy.

PubMed

Bonde, J P

1993-08-01

These studies were initiated by the results of two Danish investigations of infertility clients, which indicated the reduced fecundity of male metal welders. The objective was to refute or corroborate the effects of welding on male reproductive capability and--if there was any effect--to identify the causal exposures. The initial hypothesis postulated reduced spermatogenesis, spontaneous abortion, congenital malformation and childhood malignancy following exposure to hexavalent chromium among stainless steel welders. Subsequently, a hypothesis concerned with the significance of exposure to radiant heat on reduced semen quality was put forward. These studies comprised a case-referent study of infertility, cross-sectional and longitudinal studies of semen quality and historical cohort studies of fertility, pregnancy outcome and cancer in offspring. Exposure to welding was reported with a higher frequency during periods of infertility than prior to conception in the case-referent study (OR 2.0, 95% CI 1.0-4.0). This finding is consistent with the main cross-sectional study showing reduced semen quality in welders [average reduction ranging from 8% (sperm penetration rate in eggwhite) to 28% (total sperm count)] and with the cohort study revealing reduced fertility in relation to welding (OR 0.89, 95% CI 0.83-0.97). However, reduced semen quality and fertility were not attributable to the welding of stainless steel but to the welding of mild steel; and no relationship was found between biological measures of exposure to chromium and parameters of semen quality. If the unexpected association between mild steel welding and reduced fecundity is causal, the biological mechanisms involved are obscure. A separate longitudinal study leaves little doubt that moderate radiant heat exposure may cause reversible deterioration of semen quality, but it is not justified to generalize this observation to the entire population of welders. Male-mediated effects on occurrence of

Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice.

PubMed

Glenn, David R J; McClure, Neil; Cosby, S Louise; Stevenson, Michael; Lewis, Sheena E M

2009-03-01

To determine the effects of sildenafil citrate, a cyclic monophosphate-specific type 5 phosphodiesterase inhibitor known to affect sperm function, on fertilization and early embryo cleavage. This acute mammal study included male and female mice assigned randomly, the females sacrificed after mating and their oocytes/embryos evaluated at four time periods after treatment. Academic research environment. Male and female CBAB(6) mice. Female mice were injected intraperitoneally with 5 IU gonadotropin (hCG) to stimulate follicular growth and induce ovulation. They were each caged with a male that had been gavaged with sildenafil citrate (0.06 mg/0.05 mL) and allowed to mate. After 12, 36, 60, and 84 h, females were killed, their oviducts were dissected out, and retrieved embryos were assessed for blastomere number and quality. Fertilization rates and numbers of embryos were evaluated after treatment. Fertilization rates (day 1) were markedly reduced (-33%) in matings where the male had taken sildenafil citrate. Over days 2-4, the numbers of embryos developing in the treated group were significantly fewer than in the control group. There was also a trend for impaired cleavage rates within those embryos, although this did not reach significance. The impairments to fertility caused by sildenafil citrate have important implications for infertility centers and for couples who are using this drug precoitally while attempting to conceive.

Effect of war on fertility: a review of the literature.

PubMed

Abu-Musa, Antoine A; Kobeissi, Loulou; Hannoun, Antoine B; Inhorn, Marcia C

2008-01-01

The aim of this study was to review the existing literature on the effect of war on female and male fertility. A MEDLINE search for studies that included participants defined as infertile because they were unsuccessful in achieving a pregnancy after a year and studies that assessed the effect of war on semen parameters and menstrual dysfunction were performed. Twenty articles were included in this review. For female fertility, studies showed that women who were prisoners of war or who were living in areas exposed to bombardment had increased risk of menstrual abnormalities. For male fertility, the results were conflicting. The Vietnam War was not associated with difficulty in conception although one study revealed a decrease in sperm characteristics. Studies of male US and Danish 1990/91 Gulf war veterans showed no evidence of reduced fertility; however, studies of UK and Australian veterans reported increased risk of infertility. The Lebanese and Slovenian civil wars were associated with a decrease in sperm parameters. Exposure to mustard gas was also associated with abnormal semen parameters; however, exposure to depleted uranium had no effect on semen characteristics. Most of the studies examined had major limitations including recall bias and small number of cases included.

Sensitivity of submersed freshwater macrophytes and endpoints in laboratory toxicity tests.

PubMed

Arts, Gertie H P; Belgers, J Dick M; Hoekzema, Conny H; Thissen, Jac T N M

2008-05-01

The toxicological sensitivity and variability of a range of macrophyte endpoints were statistically tested with data from chronic, non-axenic, macrophyte toxicity tests. Five submersed freshwater macrophytes, four pesticides/biocides and 13 endpoints were included in the statistical analyses. Root endpoints, reflecting root growth, were most sensitive in the toxicity tests, while endpoints relating to biomass, growth and shoot length were less sensitive. The endpoints with the lowest coefficients of variation were not necessarily the endpoints, which were toxicologically most sensitive. Differences in sensitivity were in the range of 10-1000 for different macrophyte-specific endpoints. No macrophyte species was consistently the most sensitive. Criteria to select endpoints in macrophyte toxicity tests should include toxicological sensitivity, variance and ecological relevance. Hence, macrophyte toxicity tests should comprise an array of endpoints, including very sensitive endpoints like those relating to root growth.

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

PubMed

Izquierdo-Vega, Jeannett A; Sánchez-Gutiérrez, Manuel; Del Razo, Luz María

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 (DeltaPsi(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(2)(-)), iv) lipid peroxidation concentration, v) ultrastructural analyses of spermatozoa using transmission electron microscopy, vi) DeltaPsi(m), vii) acrosome reaction, and viii) IVF capability. Spermatozoa from fluoride-treated rats exhibited a significant decrease in SOD activity (~33%), accompanied with a significant increase in the generation of O(2)() (~40%), a significant decrease in DeltaPsi(m) (~33%), and a significant increase in lipid peroxidation concentration (~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.

Study of the role of epididymal alpha-glucosidase in the fertility of male rats by the administration of the enzyme inhibitor castanospermine.

PubMed

Yeung, C H; Cooper, T G

1994-11-01

The activity of epididymal alpha-glucosidase in adult rats was rapidly suppressed to histochemically undetectable levels within 2 days by the continuous release of the enzyme inhibitor castanospermine via a peritoneal osmotic pump at a rate of 100-200 nmol h-1. It was established that mating activities overnight depleted 72% of the spermatozoa in the distal cauda, which was replenished in 2 days, and that fertility began to decline 3 weeks after efferent duct ligation. Male rats of proven mating proficiency and fertility were treated with castanospermine, or buffered saline as control, for up to 30 days and enzyme inhibition was confirmed at the end of treatment by histochemistry. Fertility was normal at the first mating test on day 7, significantly decreased at the second mating on day 9, but recovered in a stepwise manner at subsequent matings on days 12 and 14. Delaying the third mating until day 25 did not sustain the transient subfertility. However, prolonging sperm storage in the distal cauda epididymides and preventing replenishment with freshly matured spermatozoa, by efferent duct ligation for 14 days performed on day 15 during castanospermine administration, caused a decrease in fertility and a change in the kinematics of epididymal spermatozoa of the castanospermine-treated group. In control rats, binding of epididymal spermatozoa to Vicia faba, a lectin specific for glucose and glucosamine, and mannose and mannosamine residues, decreased from the proximal caput to the distal corpus coincident with the increase in alpha-glucosidase activity on the epithelial brush border. Lectin binding then increased in the cauda where enzyme activity was absent. However, castanospermine treatment did not significantly alter this binding profile. The findings suggest that epididymal alpha-glucosidase does not play a crucial role in the development of sperm fertilizing capacity, but may be involved in the preparation of spermatozoa for storage.

Fertility, Pregnancy, and Lactation in Rheumatoid Arthritis.

PubMed

de Jong, Pascal H P; Dolhain, Radboud J E M

2017-05-01

Fertility is impaired in women with rheumatoid arthritis (RA), whereas less is known about male fertility problems. Pregnancy outcome in patients with RA is slightly less favorable compared with the general population, especially in patients with active disease. Disease activity usually improves during pregnancy, but less than previously thought. Although several antirheumatic drugs are contraindicated in pregnancy, more treatment options are available. There is evidence on the safety of TNF inhibitors in pregnancy. Given the impact of active disease on fertility and pregnancy outcome, a treat-to-target strategy is recommended for patients who are pregnant or have a wish to conceive. Copyright © 2016 Elsevier Inc. All rights reserved.

Male facial attractiveness and masculinity may provide sex- and culture-independent cues to semen quality.

PubMed

Soler, C; Kekäläinen, J; Núñez, M; Sancho, M; Álvarez, J G; Núñez, J; Yaber, I; Gutiérrez, R

2014-09-01

Phenotype-linked fertility hypothesis (PLFH) predicts that male secondary sexual traits reveal honest information about male fertilization ability. However, PLFH has rarely been studied in humans. The aim of the present study was to test PLFH in humans and to investigate whether potential ability to select fertile partners is independent of sex or cultural background. We found that on the contrary to the hypothesis, facial masculinity was negatively associated with semen quality. As increased levels of testosterone have been demonstrated to impair sperm production, this finding may indicate a trade-off between investments in secondary sexual signalling (i.e. facial masculinity) and fertility or status-dependent differences in investments in semen quality. In both sexes and nationalities (Spanish and Colombian), ranked male facial attractiveness predicted male semen quality. However, Spanish males and females estimated facial images generally more attractive (gave higher ranks) than Colombian raters, and in both nationalities, males gave higher ranks than females. This suggests that male facial cues may provide culture- and sex-independent information about male fertility. However, our results also indicate that humans may be more sensitive to facial attractiveness cues within their own populations and also that males may generally overestimate the attractiveness of other men to females. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

Physicians' self-reported practice behaviour regarding fertility-related discussions in paediatric oncology in Sweden.

PubMed

Armuand, G M; Nilsson, J; Rodriguez-Wallberg, K A; Malmros, J; Arvidson, J; Lampic, C; Wettergren, L

2017-10-01

The aim of this study was to investigate practice behaviours of Swedish physicians with regard to discussing the impact of cancer treatment on fertility with paediatric oncology patients and their parents, and to identify factors associated with such discussions. A cross-sectional survey study was conducted targeting all physicians in Sweden working in paediatric oncology care settings. Participants responded to a questionnaire measuring practice behaviour, attitudes, barriers, and confidence in knowledge. Multivariable logistic regression was used to determine factors associated with seldom discussing fertility. More than half of the physicians routinely talked with their patients/parents about the treatment's potential impact on fertility (male patients: 62%; female patients: 57%; P = 0.570). Factors associated with less frequently discussing fertility with patients/parents were working at a non-university hospital (male patients: OR 11.49, CI 1.98-66.67; female patients: OR 33.18, CI 4.06-271.07), concerns that the topic would cause worry (male patients: OR 8.23, CI 1.48-45.89; female patients: OR 12.38, CI 1.90-80.70), and perceiving the parents as anxious (male patients: OR 7.18, CI 1.20-42.85; female patients: OR 11.65, CI 1.32-103.17). Based on our findings, we recommend structured training in how to communicate about fertility issues in stressful situations, which in turn might increase fertility-related discussions in paediatric oncology. © 2017 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.

Fertility and hatchability in RIR and WL breeds as functionally modified by crossing them in alternate sex combinations (Gallus domesticus).

PubMed

Zelleke, G; Moudgal, R P; Asmare, A

2005-02-01

(1) Four breeding groups of Rhode Island Red and White Leghorn domestic fowl (RIR (female) x RIR (male), RIR (female) x WL (male), WL (female) x RIR (male) and WL (female) x WL (male)) were compared for fertility, hatchability, and their post-insemination sustainability, egg weight loss during incubation and uncovered yolk in abdominal cavity of dead in shell in order to understand the problems associated with the RIR breed in these respects. (2) Crossing RIR (female) with WL (male) or in reverse sex combinations did not improve fertility in comparison to pure RIR chickens and all these groups were less fertile than the pure WL. (3) Unlike fertility, hatchability in RIR improved with the change to either sex partner of the WL breed but the WL (female) x RIR (male) combination was similar to the pure WL (97.72 and 97.12%, respectively). In contrast, crossing RIR (female) with WL (male) resulted in an improvement (86.67%) as compared to pure RIR (76.67%) but still lower than the pure WL and WL (female) x RIR (male) cross. (4) Egg weight loss during incubation was more (20.16%) in pure RIR as compared to RIR (female) x WL (male) (17.13%), followed by WL (female) x RIR (male) (10.28%) and pure WL (9.57%). (5) There were more dead-in-shell embryos with yolks outside their abdominal cavity in pure RIR and their crosses as compared to pure WL breeds. (6) Fertility was sustained for longer in WL than other combinations with post-artificial insemination using constant number of spermatozoa. Fertility after a week of insemination tended to decrease more rapidly than hatchability on a fertile egg basis. (7) It is concluded that both sexes are responsible for the poor fertility in RIR but the female is responsible for poor hatchability and this poor performance is mainly due to greater egg weight loss during incubation.

Choice of saccade endpoint under risk

PubMed Central

Ackermann, John F.; Landy, Michael S.

2013-01-01

Eye movements function to bring detailed information onto the high-resolution region of the retina. Previous research has shown that human observers select fixation points that maximize information acquisition and minimize target location uncertainty. In this study, we ask whether human observers choose the saccade endpoint that maximizes gain when there are explicit rewards associated with correctly detecting the target. Observers performed an 8-alternative forced-choice detection task for a contrast-defined target in noise. After a single saccade, observers indicated the target location. Each potential target location had an associated reward that was known to the observer. In some conditions, the reward at one location was higher than at the other locations. We compared human saccade endpoints to those of an ideal observer that maximizes expected gain given the respective human observer's visibility map, i.e., d′ for target detection as a function of retinal location. Varying the location of the highest reward had a significant effect on human observers' distribution of saccade endpoints. Both human and ideal observers show a high density of saccades made toward the highest rewarded and actual target locations. But humans' overall spatial distributions of saccade endpoints differed significantly from the ideal observer as they made a greater number of saccade to locations far from the highest rewarded and actual target locations. Suboptimal choice of saccade endpoint, possibly in combination with suboptimal integration of information across saccades, had a significant effect on human observers' ability to correctly detect the target and maximize gain. PMID:24023277

Soviet fertility, labor-force participation, and marital stability.

PubMed

Kuniansky, A

1983-06-01

A simultaneous-equations model of Soviet fertility and labor-force participation is estimated from a cross section of 72 oblast's of the Russian Republic (RSFSR) reported in the 1970 census. The construction of the model is based on the neoclassical theory of household behavior. Simulated changes capture effects of policy changes in the exogenous variables on Soviet fertility and the female labor supply. The exogenous variables investigated are child care facilities (CC), urbanization ratio (URB), male education (MALED), and female education (FEMED). It was found that an increase in FEMED affects labor force participation (LFP) directly and indirectly through impact on birth rate (BR). Increase in CC raise both LFP and BR; increases in FEMED causes womens withdrawal from the labor force and one would expect this to raise BR; however, FEMED raises the opportunity costs of fertility sufficiently to neutralize this effect. Increasing urbanization does not affect participation in a significant way, but it does retard fertility. This effect works through LFP's impact on BR and the indirect effect working through marital stability. A final set of simulations captured the impact of upward shocks of LFP, BR, and the ratio of divorces to marriages (DIV/MAR) on the endogenous variables. Such changes could occur through changes in abortion laws, tightening of divorce laws, or changes in labor legislation. Participation is reduced by the fertility shock, just as fertility is retarded by the LPF and marital stability shocks. Evidence of a backward-bending labor-supply curve was also found. The model is illustrated by tables and charts.

Male Infertility during Antihypertensive Therapy: Are We Addressing Correctly The Problem?

PubMed

Laganà, Antonio Simone; Vitale, Salvatore Giovanni; Iaconianni, Paola; Gatti, Simona; Padula, Francesco

2016-01-01

Male fertility significantly decreased in the last 50 years, as showed in several studies reporting a reduction of sperm counts per ml in the seminal fluid. Several "acute" pharmacological treatments, as antibiotics, could cause subclinical and temporary reduction of male fertility; conversely, long-term medical treatment may severely affect male fertility, although this effect could be considered transient in most of the cases. Thus, nowadays, several long-term pharmacological treatments may represent a clinical challenge. The association between several kind of antihypertensive drugs and reduction of male fertility has been showed in the mouse model, although the modification(s) which may alter this fine-regulated machinery are still far to be elucidated. Furthermore, well-designed observational studies and randomized controlled trials are needed to accurately define this association in human model, meaning a narrative overview synthesizing the findings of literature retrieved from searches of computerized databases. We strongly solicit future human studies (both observational and randomized clinical trials) on large cohorts with adequate statistical power which may clarify this possible association and the effects (reversible or permanent) of each drug. Furthermore, we suggest a close collaboration between general practitioners, cardiologists, and andrologists in order to choose the most appropriate antihypertensive therapy considering also patient's reproductive desire and possible risk for his fertility.

Auxin production couples endosperm development to fertilization.

PubMed

Figueiredo, Duarte D; Batista, Rita A; Roszak, Pawel J; Köhler, Claudia

2015-11-23

In flowering plants, seed development is preceded by a double fertilization event, whereby two male sperm cells fuse with two female gametes: the egg and central cells. The fertilized egg cell will form the embryo, and the fertilized central cell will give rise to the triploid endosperm, whose function is to nourish and support the embryo. Even though the endosperm has an unparalleled role for human nutrition, the molecular bases for its development are yet to be understood. Our results reveal that increasing auxin levels after fertilization drive the replication of the central cell in Arabidopsis thaliana. Auxin is sufficient to trigger central cell division and is necessary for correct endosperm development, a process dependent on the MADS-box transcription factor AGL62 (AGAMOUS-LIKE 62). We propose that the epigenetic regulators of the Polycomb group (PcG) family block central cell division before fertilization by repressing the expression of auxin biosynthesis genes in the female gametophyte.

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.

Live-Cell Imaging of F-Actin Dynamics During Fertilization in Arabidopsis thaliana.

PubMed

Susaki, Daichi; Maruyama, Daisuke; Yelagandula, Ramesh; Berger, Frederic; Kawashima, Tomokazu

2017-01-01

Fertilization comprises a complex series of cellular processes leading to the fusion of a male and female gamete. Many studies have been carried out to investigate each step of fertilization in plants; however, our comprehensive understanding of all the sequential events during fertilization is still limited. This is largely due to difficulty in investigating events in the female gametophyte, which is deeply embedded in the maternal tissue. Recent advances in confocal microcopy assisted by fluorescent marker lines have contributed to visualizing subcellular dynamics in real time during fertilization in vivo. In this chapter, we describe a method focusing on the investigation of F-actin dynamics in the central cell during male gamete nuclear migration. This method also allows the study of a wide range of early sexual reproduction events, from pollen tube guidance to the early stage of seed development.

Evaluating Candidate Principal Surrogate Endpoints

PubMed Central

Gilbert, Peter B.; Hudgens, Michael G.

2009-01-01

Summary Frangakis and Rubin (2002, Biometrics 58, 21–29) proposed a new definition of a surrogate endpoint (a “principal” surrogate) based on causal effects. We introduce an estimand for evaluating a principal surrogate, the causal effect predictiveness (CEP) surface, which quantifies how well causal treatment effects on the biomarker predict causal treatment effects on the clinical endpoint. Although the CEP surface is not identifiable due to missing potential outcomes, it can be identified by incorporating a baseline covariate(s) that predicts the biomarker. Given case–cohort sampling of such a baseline predictor and the biomarker in a large blinded randomized clinical trial, we develop an estimated likelihood method for estimating the CEP surface. This estimation assesses the “surrogate value” of the biomarker for reliably predicting clinical treatment effects for the same or similar setting as the trial. A CEP surface plot provides a way to compare the surrogate value of multiple biomarkers. The approach is illustrated by the problem of assessing an immune response to a vaccine as a surrogate endpoint for infection. PMID:18363776

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

PubMed

Bedford, J Michael

2014-02-01

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

New frontiers in nonhormonal male contraception.

PubMed

Cheng, C Yan; Mruk, Dolores D

2010-11-01

The world's population is nearing 6.8 billion, and we are in need of a male contraceptive that is safe, effective, reversible and affordable. Hormonal approaches, which employ different formulations of testosterone administered in combination with other hormones, have shown considerable promise in clinical trials, and they are currently at the forefront of research and development. However, the long-term effects of using hormones throughout a male's reproductive life for contraception are unknown, and it may take decades before this information becomes available. Because of this, many investigators are aiming to bring a nonhormonal male contraceptive to the consumer market. Indeed, there are several distinct but feasible avenues in which fertility can be regulated without affecting the hypothalamus-pituitary-testis axis. In this review, we discuss several approaches for fertility control involving the testis that one day may lead to the development of a nonhormonal male contraceptive. Copyright © 2010 Elsevier Inc. All rights reserved.

Endpoint titration and immunotherapy.

PubMed

King, H C

1985-11-01

Inhalant allergy, or "atopy" as it is now termed, is the best understood form of allergy today. In some circles, it is the only recognized form of allergy. While an overall picture of its effects on the body and a reasonable approach to its treatment now exist, many problems remain to be solved and much improvement in its treatment will probably occur within the next several years. Many new approaches to treatment of aeroallergens are now available; however, all are compared with the skin test, which is and has been the baseline for testing and treatment. Endpoint titration provides a quantitative means for undertaking treatment of aeroallergen sensitivity. In no other way does it differ from the forms of skin testing that have been widely used for generations. The practitioners of endpoint titration feel that this difference is highly significant in simplifying, validating, and shortening the necessary period of therapy. While the concept of endpoint titration is not difficult, it is by definition a quantitative form of testing and requires a degree of expertise in performing it correctly. While a good understanding of the method may be gained from the literature, adequate hands-on experience should be obtained by any physician prior to instituting the technique as a treatment modality. Once mastered, it becomes a reliable baseline for all forms of inhalant allergy care.

Delineating the roles of males and females in sperm competition

PubMed Central

Evans, Jonathan P.; Rosengrave, Patrice; Gasparini, Clelia; Gemmell, Neil J.

2013-01-01

Disentangling the relative roles of males, females and their interactive effects on competitive fertilization success remains a challenge in sperm competition. In this study, we apply a novel experimental framework to an ideally suited externally fertilizing model system in order to delineate these roles. We focus on the chinook salmon, Oncorhynchus tshawytscha, a species in which ovarian fluid (OF) has been implicated as a potential arbiter of cryptic female choice for genetically compatible mates. We evaluated this predicted sexually selected function of OF using a series of factorial competitive fertilization trials. Our design involved a series of 10 factorial crosses, each involving two ‘focal’ rival males whose sperm competed against those from a single ‘standardized’ (non-focal) rival for a genetically uniform set of eggs in the presence of OF from two focal females. This design enabled us to attribute variation in competitive fertilization success among focal males, females (OF) and their interacting effects, while controlling for variation attributable to differences in the sperm competitive ability of rival males, and male-by-female genotypic interactions. Using this experimental framework, we found that variation in sperm competitiveness could be attributed exclusively to differences in the sperm competitive ability of focal males, a conclusion supported by subsequent analyses revealing that variation in sperm swimming velocity predicts paternity success. Together, these findings provide evidence that variation in paternity success can be attributed to intrinsic differences in the sperm competitive ability of rival males, and reveal that sperm swimming velocity is a key target of sexual selection. PMID:24266039

Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures, and pregnancy outcomes among couples undergoing in vitro fertilization.

PubMed

Carignan, Courtney C; Mínguez-Alarcón, Lidia; Williams, Paige L; Meeker, John D; Stapleton, Heather M; Butt, Craig M; Toth, Thomas L; Ford, Jennifer B; Hauser, Russ

2018-02-01

Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos

Simultaneous determination of androgenic and estrogenic endpoints in the threespine stickleback (Gasterosteus aculeatus) using quantitative RT-PCR.

PubMed

Hogan, Natacha S; Wartman, Cheryl A; Finley, Megan A; van der Lee, Jennifer G; van den Heuvel, Michael R

2008-12-11

A method to evaluate the expression of three hormone responsive genes, vitellogenin (estrogens), spiggin (androgens), and an androgen receptor (ARbeta) using real-time PCR in threespine stickleback is presented. Primers were designed from previously characterised spiggin and ARbeta sequences, while a homology cloning strategy was used to isolate a partial gene sequence for stickleback vitellogenin (Vtg). Spiggin mRNA was significantly higher in kidneys of field-caught males compared to females by greater than five orders of magnitude while ARbeta levels were only 1.4-fold higher in males. Female fish had four order of magnitude higher liver Vtg expression than wild-captured males. To determine the sensitivity of these genes to induction by hormones, male and female sticklebacks were exposed to 1, 10 and 100 ng/L of methyltestosterone (MT) or estradiol (E2) in a flow-through exposure system for 7 days. Spiggin induction in females, and Vtg induction in males were both detectable at 10 ng/L of MT and E2, respectively. MT exposure did not induce ARbeta expression in the kidneys of female stickleback. In vitro gonadal steroid hormones production was measured in testes and ovaries of exposed stickleback to compare gene expression endpoints to an endpoint of hormonal reproductive alteration. Reduction in testosterone production in ovaries at all three MT exposure concentrations, and ovarian estradiol synthesis at the 100 ng/L exposure were the only effects observed in the in vitro steroidogenesis for either hormone exposure. Application of these methods to assess both androgenic, estrogenic, and anti-steroidogenic properties of environmental contaminants in a single fish species will be a valuable tool for identifying compounds causing reproductive dysfunction in fishes.

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...

Should Attractive Males Sneak: The Trade-Off between Current and Future Offspring

PubMed Central

Candolin, Ulrika; Vlieger, Leon

2013-01-01

Alternative reproductive tactics are predicted to be adopted by less competitive males when competition for fertilization is intense. Yet, in some species, competitively superior males use an alternative tactic alongside the conventional tactic. This can jeopardize their success through the conventional tactic, but surprisingly little attention has been paid to this cost. We investigated 1) the degree to which competitive males sneak fertilize eggs in the polygamous threespine stickleback, Gasterosteus aculeatus, and 2) if males balance the cost of sneaking against its benefit. We found competitive males that succeeded in establishing a territory and in attracting spawning females to perform most sneak fertilizations. However, when we reduced the benefit of sneak attempts, by reducing visibility and the success rate of sneak attempts, males sneaked less. When we increased the cost of sneak attempts, by increasing the perceived value of current offspring (by mating males to preferred females rather than unpreferred females or no females), the interest of males in sneak opportunities decreased. Intriguingly, larger males, who presumably had a higher probability of future reproduction, were more willing to risk their current offspring for sneak opportunities. These findings suggest that competitive males that are attractive to females carefully balance costs against benefits in their sneaking decisions. More broadly, our results imply that changes in the environment can influence the cost-benefit ratio of sneaking and alter the distribution of fertilizations in a population. We end with discussing the implications that alterations in sneaking behavior could have for the operation of sexual selection in changing environments. PMID:23516423

Automatic streak endpoint localization from the cornerness metric

NASA Astrophysics Data System (ADS)

Sease, Brad; Flewelling, Brien; Black, Jonathan

2017-05-01

Streaked point sources are a common occurrence when imaging unresolved space objects from both ground- and space-based platforms. Effective localization of streak endpoints is a key component of traditional techniques in space situational awareness related to orbit estimation and attitude determination. To further that goal, this paper derives a general detection and localization method for streak endpoints based on the cornerness metric. Corners detection involves searching an image for strong bi-directional gradients. These locations typically correspond to robust structural features in an image. In the case of unresolved imagery, regions with a high cornerness score correspond directly to the endpoints of streaks. This paper explores three approaches for global extraction of streak endpoints and applies them to an attitude and rate estimation routine.

Outcome switching in randomized controlled oncology trials reporting on surrogate endpoints: a cross-sectional analysis.

PubMed

Falk Delgado, Alberto; Falk Delgado, Anna

2017-08-23

Inconsistent reporting of clinical trials is well-known in the literature. Despite this, factors associated with poor practice such as outcome switching in clinical trials are poorly understood. We performed a cross-sectional analysis to evaluate the prevalence of, and the factors associated with outcome switching. PubMed and Embase were searched for pharmaceutical randomized controlled trials (RCTs) in oncology reporting on a surrogate primary outcome published in 2015. Outcome switching was present in 18% (39/216). First-author male sex was significantly more likely associated with outcome switching compared to female sex with an OR of 3.05 (95% CI 1.07-8.64, p = 0.04) after multivariable adjustment. For-profit funded RCTs were less likely associated with outcome switching compared to non-profit funded research with an OR of 0.22 (95% CI 0.07-0.74, p = 0.01). First author male sex was more likely associated with outcome switching compared to female sex in drug oncology RCTs reporting on a primary surrogate endpoint. For-profit funded research was less likely associated with outcome switching compared to research funded by non-profit organizations. Furthermore, 18 percent of drug oncology trials reporting on a surrogate endpoint could have a higher risk of false positive results due to primary outcome switching.

Vitamin D is necessary for reproductive functions of the male rat.

PubMed

Kwiecinski, G G; Petrie, G I; DeLuca, H F

1989-05-01

The effect of vitamin D deficiency on the fertility and reproductive capacity of male rats was investigated. Male weanling rats were fed vitamin D-deficient or vitamin D-replete diets until maturity, and mated to age-matched, vitamin D-replete females. Vitamin D-deficient males were capable of reproduction. However, successful matings, i.e., presence of sperm in the vaginal tract of the female, by vitamin D-deficient males were reduced by 45% when compared to matings by vitamin D-replete males. Fertility (successful pregnancies in sperm-positive females) was reduced by 73% in litters from vitamin D-deficient male inseminations when compared to litters from females inseminated by vitamin D-replete males. These results demonstrate that vitamin D and its metabolites are necessary for normal reproductive functions in the male rat.

Nutrition-dependent fertility response to juvenile hormone in non-social Euodynerus foraminatus wasps and the evolutionary origin of sociality.

PubMed

Tibbetts, Elizabeth A; Mettler, Alexander; Donajkowski, Kellie

2013-03-01

The reproductive ground plan hypothesis (RGPH) proposes that the ovarian cycle in solitary insects provides the basis for social evolution, so similar mechanisms are predicted to influence reproductive plasticity in social and solitary species. Specifically, reproductive plasticity in social species originated via modification of nutrition-dependent fertility response to juvenile hormone (JH) in solitary insects. Testing this prediction requires information about the factors that influence fertility in non-social relatives of the eusocial hymenoptera. However, no previous studies have examined how JH or nutritional condition influence fertility in Eumenines, the non-social group most closely related to social wasps. Here, we find support for the RGPH, as JH increases Euodynerus foraminatus fertility. Fertility is also condition-dependent, as heavy E. foraminatus are more fertile than light E. foraminatus. In addition, we measure the factors associated with mating success in E. foraminatus, finding that multiple factors influence mating success, including male weight, male mating experience, and female age. There is also higher variance in male than female reproductive success, suggesting that males may experience substantial sexual selection in this species. Overall, the relationships between JH, body weight, and fertility in E. foraminatus support the RGPH for the origin of sociality by demonstrating that there are strong parallels in the mechanisms that mediate fertility of social and non-social wasps. Copyright © 2012 Elsevier Ltd. All rights reserved.

Current strategies and future perspectives in fertility preservation for cancer patients.

PubMed

Micu, Romeo; Petrut, Bogdan; Zlatescu-Marton, Cristina; Traila, Alexandra; Harsa, Radu; Achimas-Cadariu, Patriciu

2017-01-01

Nowadays, cancer is being detected at younger ages. Health care providers should consider cancer patients' desire towards fertility preservation before the initiation of possibly sterilizing treatments. The aim of the current review was to register the current state of fertility preservation procedures available for male and female cancer patients.

Useful pharmacodynamic endpoints in children: selection, measurement, and next steps

PubMed Central

Kelly, Lauren E; Sinha, Yashwant; Barker, Charlotte I S; Standing, Joseph F; Offringa, Martin

2018-01-01

Pharmacodynamic (PD) endpoints are essential for establishing the benefit-to-risk ratio for therapeutic interventions in children and neonates. This article discusses the selection of an appropriate measure of response, the PD endpoint, which is a critical methodological step in designing pediatric efficacy and safety studies. We provide an overview of existing guidance on the choice of PD endpoints in pediatric clinical research. We identified several considerations relevant to the selection and measurement of PD endpoints in pediatric clinical trials, including the use of biomarkers, modeling, compliance, scoring systems, and validated measurement tools. To be useful, PD endpoints in children need to be clinically relevant, responsive to both treatment and/or disease progression, reproducible, and reliable. In most pediatric disease areas, this requires significant validation efforts. We propose a minimal set of criteria for useful PD endpoint selection and measurement. We conclude that, given the current heterogeneity of pediatric PD endpoint definitions and measurements, both across and within defined disease areas, there is an acute need for internationally agreed, validated, and condition-specific pediatric PD endpoints that consider the needs of all stakeholders, including healthcare providers, policy makers, patients, and families. PMID:29667952

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Reliability of testicular stiffness quantification using shear wave elastography in predicting male fertility: a preliminary prospective study.

PubMed

Yavuz, Alpaslan; Yokus, Adem; Taken, Kerem; Batur, Abdussamet; Ozgokce, Mesut; Arslan, Harun

2018-05-02

To evaluate the reliability of testicular stiffness quantification using shear wave elastography in predicting the fertility potential of males and for the pre-diagnosis of disorders based upon sperm quantification. One hundred males between the ages of 19-49 years (mean age of 28.77±6.11), ninety of whom with complaints of infertility, were enrolled in this prospective study. Scrotal grey-scale, Doppler ultrasound (US), and mean testicular shear wave velocity quantifications (SWVQs) were performed. The volumes of testes, as well as the grade of varicocele if present, were recorded. The mean shear wave velocity values (SWVVs) of each testis and a mean testicular SWVV for each patient were calculated. The semen-analyses of patients were consecutively performed. There were significant negative correlations between the mean testicular SWVVs of patients and their sperm counts or the testis volumes (r=-0.399, r=-0.565; p<0.01, respectively). A positive correlation was found between testicular volumes and sperm counts (r=0.491, p<0.01). The cut-off values regarding mean testicular SWVV to distinguish normal sperm count from azoospermia and oligozoospermia were 1.465 m/s (75.0% sensitivity and 75.0% specificity) and 1.328 m/s (64.3% sensitivity and 68.2% specificity), respectively, and the value to distinguish oligozoospermia from azoospermia was 1.528 m/s (66.7% sensitivity, 60.7% specificity). The mean testicular SWVQ using the ARFI shear wave technique was a reliable, non-invasive and acceptably stable method for predicting male infertility, especially related to sperm count issues.

Heat stress affects male reproduction in a parasitoid wasp.

PubMed

Nguyen, Thanh Manh; Bressac, Christophe; Chevrier, Claude

2013-03-01

In insects, reproductive success and survival are affected by temperature. Reproduction is more sensitive than other physiological traits. While the effects of heat stress on females are well known, the effects on males are less clear. Hymenopteran parasitoids are valuable for studying the consequences of heat stress on male reproduction. In these species, through arrhenotoquous parthenogenesis, the sex ratio of the offspring is directly dependent on the sperm stock acquired by females during copulation. In the lab, heat temperature treatments (32-44°C) were applied for 3 days in the pupal stage of Anisopteromalus calandrae males, and development was completed at 30°C. Three different effects were observed depending on the temperature: mortality above 42°C, sterility of emerging males at 40°C, and sub-fertility at 38°C. This sub-fertility is characterized by a dramatic decrease in male sperm supplies, of up to 7% compared to control males. In the course of ageing, the sperm stock of sub-fertile males increases but never reaches the level of control males. Survival was significantly higher in control (30°C) males than those treated at 38°C. Male mating ability was similar whatever the treatment (control and 38°C), but females mated with 38°C-treated males stored 100 times less sperm on average than those mated with control males. The offspring sex ratio of females mated with 38°C-treated males was strongly male biased. The physiological mechanisms are as yet unknown. The relationship between temperature, sperm stock and sex ratio should be taken into account in the management of parasitoids for integrated pest management. Copyright © 2012 Elsevier Ltd. All rights reserved.

The future of male contraception: a fertile ground

PubMed Central

Zillioux, Jacqueline; Eisenfrats, Kevin; Foley, Daniel; Smith, Ryan

2018-01-01

The continued and rapid expansion of the Earth’s population mandates the need for safe and effective measures of contraception. While a plethora of options exist for women, methods of contraception for the male partner are limited to condoms and vasectomy. The sequela of this discrepancy has led to the family planning burden falling disproportionately on the female partner. For the past several decades, extensive research has been undertaken exploring the feasibility of hormonal male contraception. This proposed method of contraception has focused on suppressing spermatogenesis by exploiting the hypothalamic-pituitary-gonadal (HPG) axis. Beginning with proof of concept studies in the early nineties, administration of testosterone in healthy male subjects has been shown to be an efficacious method of inducing sterility. Owing to ethnic differences in spermatogenesis suppression and the comparatively low rate of azoospermia in Caucasian men with androgen-only regimens, investigators have explored the addition of progestins to further enhance the efficacy of hormonal contraception. Though studies have revealed promise with androgen-progestin regimens, the lack of long-term studies has precluded the development of a marketable product. Recently, more research has been directed towards identifying non-hormonal alternatives to male contraception. These non-hormonal options have ranged from the development of devices facilitating reversible occlusion of the vas deferens lumen to medications disrupting various pathways in the process of spermatogenesis. Underlying the development of hormonal and non-hormonal strategies is the shared enthusiasm men and women have towards these male directed methods. The willingness of couples to pursue these alternatives combined with the global need to reduce the psychological and socioeconomic implications of unintended pregnancy ensures that research will continue to bring this goal to fruition.

Reduced fertility among overweight and obese men.

PubMed

Sallmén, Markku; Sandler, Dale P; Hoppin, Jane A; Blair, Aaron; Baird, Donna Day

2006-09-01

Overweight and obese men have been reported to have lower sperm counts and hormonal changes, but data are lacking regarding effects on couple fertility. We examined the relationship between male body mass index (BMI) and infertility in couples enrolled in the Agricultural Health Study in the United States. The analysis sample was limited to couples (wife <40 years old) with an attempt at pregnancy in the last 4 years based on pregnancy and fertility data provided by wives. Infertility was defined as not conceiving a pregnancy after at least 12 months of unprotected intercourse regardless of whether or not a pregnancy ultimately occurred. Self-reported weight and height were used to calculate BMI (kg/m). Adjusted odds ratios (aORs) for infertility associated with increases in male BMI were calculated with logistic regression. Adjusting for potential confounders, a 3-unit increase in male BMI was associated with infertility (aOR = 1.12; 95% confidence interval = 1.01-1.25; n = 1329). There was a dose-response relationship, and the BMI effect was stronger when the data were limited to couples with the highest-quality infertility data. The association between BMI and infertility was similar for older and younger men, suggesting that erectile dysfunction in older men does not explain the association. This report of lower fertility in overweight and obese men needs replication. If the findings are robust, programs to prevent obesity may improve men's reproductive health and save medical costs for infertility treatment.

High Temperature Induced Glume Closure Resulted in Lower Fertility in Hybrid Rice Seed Production.

PubMed

Yan, Haoliang; Zhang, Binglin; Zhang, Yunbo; Chen, Xinlan; Xiong, Hui; Matsui, Tsutomu; Tian, Xiaohai

2016-01-01

Predicted climate changes, in particular, the increased dimension and frequency of heat waves, are expected to affect crop growth in the future seriously. Hybrid rice relies on seed production from male sterile and restorer lines. Experiments were conducted over two consecutive years to compare the high temperature tolerance of parents of different hybrid rice combinations, in terms of fertility rate, flowering pattern, pollination and physiological parameters of the lodicule. Three male sterile lines and a broad compatibility restorer line (as pollen donor and conventional variety as well) were grown to heading stage and then treated with average daily temperatures of 26°C (range 23-30°C), 28°C (25-32°C), and 30°C (26-34°C), respectively, continued for 5-7 days each in a natural light phytotron which simulated the local typical high temperature weather in the field. The results indicated that male sterile lines were more sensitive to high temperature than the restorer line for fertility rate, and the sensitivity varied between varieties. The fertility rate of the restorer line was maintained at about 90% under the high temperature treatments, while it decreased in the male sterile lines by 23.3 and 48.1% at 28 and 30°C, respectively. The fertility rate of the most sensitive line declined by 70%, and the tolerant line declined by 34% at 30°C. Glume closure in the male sterile lines was a major reason for the reduced fertility rate under high temperature, which is closely correlated with carbohydrates content and the vascular bundle pattern in the lodicule. The present study identified a useful trait to select male sterile lines with high temperature tolerance for seed production.

Endoscopic Vasectomy of Male Feral Pigeons (Columba livia) as a Possible Method of Population Control.

PubMed

Heiderich, Elisabeth; Schildger, Bernd; Lierz, Michael

2015-03-01

To evaluate whether single-entry endoscopic vasectomy of male feral pigeons (Columba livia) significantly reduced fertility and would potentially be valuable for control of feral pigeon populations, 252 male feral pigeons were caught in the city of Berne and endoscopically vasectomized. In this procedure, approximately 1 cm of the deferent duct was removed bilaterally. Rapid, uneventful recoveries occurred in 94% (237/252) of the pigeons, whereas 6% (15/252) died because of complications associated with the procedure, consisting of perforation of the ureter (9/15), major hemorrhage (5/15), and respiratory arrest (1/15). Mean anesthesia time was 23±6 minutes. The vasectomized males were habituated to 2 pigeon houses together with fertile females. Another pigeon house with fertile pairs acted as control. All eggs laid were candled weekly to assess fertility. In the 2 pigeon houses with vasectomized males, the mean fertilization rate was 0.9% (5/563), while in the control pigeon house, the rate was 100% (39/39). The results indicate that endoscopic vasectomy of male feral pigeons may be a promising tool for field control of feral pigeon populations, especially in combination with other methods such as pigeon houses.

C4 Protein of Sweet Potato Leaf Curl Virus Regulates Brassinosteroid Signaling Pathway through Interaction with AtBIN2 and Affects Male Fertility in Arabidopsis

PubMed Central

Bi, Huiping; Fan, Weijuan; Zhang, Peng

2017-01-01

Sweepoviruses have been identified globally and cause substantial yield losses and cultivar decline in sweet potato. This study aimed to investigate the interaction between sweepovirus and plant host by analyzing the function of the viral protein C4 of Sweet potato leaf curl virus-Jiangsu (SPLCV-JS), a sweepovirus cloned from diseased sweet potato plants in East China. Ectopic expression of the C4 in Arabidopsis altered plant development drastically with phenotypic changes including leaf curling, seedling twisting, deformation of floral tissues and reduction of pollen fertility, and seed number. Using bimolecular fluorescence complementation analysis, this study demonstrated that the SPLCV-JS C4 protein interacted with brassinosteroid-insensitive 2 (AtBIN2) in the plasma membrane of Nicotiana benthamiana cells. The C4 AtBIN2 interaction was further confirmed by yeast two-hybrid assays. This interaction led to the re-localization of AtBIN2-interacting proteins AtBES1/AtBZR1 into the nucleus which altered the expression of brassinosteroid (BR)-response genes, resulting in the activation of BR-signaling pathway. The interaction of SPLCV-JS C4 and AtBIN2 also led to the down-regulated expression of key genes involved in anther and pollen development, including SPROROCYTELESS/NOZZLE, DEFECTIVE IN TAPEL DEVELOPMENT AND FUNCTION 1, and ABORTED MICROSPORES, which caused abnormal tapetal development, followed by defective exine pattern formation of microspores and pollen release. Consequently, male fertility in the C4 transgenic Arabidopsis was reduced. The present study illustrated how the sweepovirus C4 protein functioned in host cells and affected male fertility by interacting with the key components of BR-signaling pathway. PMID:29021807

Mucuna pruriens improves male fertility by its action on the hypothalamus-pituitary-gonadal axis.

PubMed

Shukla, Kamla Kant; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem; Shankhwar, Satya Narain; Rajender, Singh; Jaiswar, Shyam Pyari

2009-12-01

To understand the mechanism of action of Mucuna pruriens in the treatment of male infertility. Prospective study. Departments of Biochemistry, Urology, and Obstetrics and Gynecology, C.S.M. Medical University, Lucknow, India. Seventy-five normal healthy fertile men (controls) and 75 men undergoing infertility screening. High-performance liquid chromatography assay for quantitation of dopa, adrenaline, and noradrenaline in seminal plasma and blood. Estimation by RIA of hormonal parameters in blood plasma, namely T, LH, FSH, and PRL. Before and after treatment, serum T, LH, FSH, PRL, dopamine, adrenaline, and noradrenaline in seminal and blood plasma were measured. Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment. Treatment with M. pruriens regulates steroidogenesis and improves semen quality in infertile men.

Transcription of Gypsy Elements in a Y-Chromosome Male Fertility Gene of Drosophila Hydei

PubMed Central

Hochstenbach, R.; Harhangi, H.; Schouren, K.; Bindels, P.; Suijkerbuijk, R.; Hennig, W.

1996-01-01

We have found that defective gypsy retrotransposons are a major constituent of the lampbrush loop pair Nooses in the short arm of the 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, ay1. 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 ay1 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 ay1 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 ay1 and gypsy thus appears to be of a functional significance. PMID:8852843

Mares Prefer the Voices of Highly Fertile Stallions

PubMed Central

Lemasson, Alban; Remeuf, Kévin; Trabalon, Marie; Cuir, Frédérique; Hausberger, Martine

2015-01-01

We investigated the possibility that stallion whinnies, known to encode caller size, also encoded information about caller arousal and fertility, and the reactions of mares in relation to type of voice. Voice acoustic features are correlated with arousal and reproduction success, the lower-pitched the stallion’s voice, the slower his heart beat and the higher his fertility. Females from three study groups preferred playbacks of low-pitched voices. Hence, females are attracted by frequencies encoding for large male size, calmness and high fertility. More work is needed to explore the relative importance of morpho-physiological features. Assortative mating may be involved as large females preferred voices of larger stallions. Our study contributes to basic and applied ongoing research on mammal reproduction, and questions the mechanisms used by females to detect males’ fertility. PMID:25714814

The exposure to Trichilia catigua (catuaba) crude extract impairs fertility of adult female rats but does not cause reproductive damage to male offspring.

PubMed

Dos Santos, Alice Hartmann; Ramos, Aline Camargo; Silveira, Kennia Moura; Kiss, Ana Carolina Inhasz; Longhini, Renata; Diniz, Andréa; de Mello, João Carlos Palazzo; Gerardin, Daniela Cristina Ceccatto

2015-05-26

Trichilia catigua is broadly used in folk medicine due to its mental and physical tonic activities and stimulant effects. In animal models, its antidepressant-like effects have been associated with the dopaminergic (DA) system modulation, which has an important role on maternal behavior and male offspring reproductive development. Since little is known about the adverse effects of the exposure to T. catigua crude extract (CAT) in rats, specially regarding maternal homeostasis and offspring development, the aim of the present study was to evaluate whether CAT exposure may influence maternal toxicity parameters and behavior or disrupt male offspring physical and reproductive development. Dams were treated daily (by gavage) with 400mg/kg of CAT or vehicle (control=CTR) throughout pregnancy and lactation. Fertility and maternal behavior tests were conducted in dams. Male offspring reproductive and behavioral parameters were analyzed. Dams exposed to CAT showed increased pre- and post-implantation losses rates when compared to CTR group. No significant changes regarding maternal behavior or male offspring parameters were observed. In conclusion, maternal exposure to CAT interfered with implantation during the initial phases of pregnancy but did not induce changes on maternal behavior or male offspring reproductive and behavioral parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.