Important Role In Male Reproduction Research Articles

VD3/VDR attenuates bisphenol A-induced impairment in mouse Leydig cells via regulation of autophagy.

Bisphenol A (BPA) is an endocrine disruptor with reproductive toxicity. Further, 1,25-dihydroxyvitamin D3 (VD3) plays an important role in male reproduction by binding vitamin D receptor (VDR) and mediating the pleiotropic biological actions that include spermatogenesis. However, whether VD3/VDR regulates the effect of BPA on Leydig cells (LCs) injury remains unknown. This study aimed to explore the effects of VD on BPA-induced cytotoxicity in mouse LCs. Hereby, LCs treated with BPA, VD3, or both were subjected to the assays of cell apoptosis, proliferation, autophagy, and levels of target proteins. This study unveiled that cell viability was dose-dependently reduced after exposure to BPA. BPA treatment significantly inhibited LC proliferation, induced apoptosis, and also downregulated VDR expression. By jointly analyzing transcriptome data and Comparative Toxicogenomics Database (CTD) data, autophagy signaling pathways related to testicular development and male reproduction were screened out. Therefore, the autophagy phenomenon of cells was further detected. The results showed that BPA treatment could activate cell autophagy, Vdr-/- inhibits cell autophagy, and active VD3 does not have a significant effect on the autophagy of normal LCs. After VD3 and BPA were used in combination, the autophagy of cells was further enhanced, and VD3 could alleviate BPA-induced damage of LCs. In conclusion, this study found that supplementing VD3 could eliminate the inhibition of BPA on VDR expression, further enhance LCs autophagy effect, and alleviate the inhibition of LCs proliferation and induction of apoptosis by BPA, playing a protective role in cells. The research results will provide valuable strategies to alleviate BPA-induced reproductive toxicity.

Identification of biallelic variations of CEP70 in patients with male infertility.

Male infertility is a severe health issue caused by complex and multifactorial pathological conditions. Genetic factors are a major cause of male infertility. CEP70, a centrosomal protein, has been reported to play an important role in male reproduction in mice. However, the role of CEP70 in human male infertility is limited. Whole exome sequencing and Sanger sequencing were used to identify the genetic cause of the infertile patients. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy were further conducted to explore morphological and ultrastructural defects in spermatozoa from the patient. Immunofluorescence staining was used to detect the pathogenicity of the identified variants and the particular expression of CEP70 in testis. In this study, we identified biallelic mutations of CEP70 in two unrelated infertile male individuals with oligoasthenoteratozoospermia that followed a recessive inheritance pattern. Papanicolaou staining, scanning electron microscopy and transmission electron microscopy showed that morphological and ultrastructural defects in the acrosome and flagellum of sperm from the patient in a pattern strikingly similar to that in Cep70-/- male mice. The results of immunofluorescence staining suggested that CEP70 was normally expressed in the acrosome and flagellum of control sperm but was hardly detected in the sperm of patient carrying CEP70 variation. We also explored the particular expression pattern of CEP70 during spermatogenesis in humans and mice. Biallelic mutations of CEP70 might be a novel genetic cause of human male infertility, which could potentially serve as a basis for genetic counseling and diagnosis of male infertility.

Effect of Organic Zinc Supplementation on Semen Production and Quality in Kankrej Bulls

Background: Zinc is found in very high concentration in semen and male reproductive tract and acts as a hormone receptor modulator for testosterone production in Leydig cells. Thus, it plays a very important role in male reproduction. Moreover, Indian soils are very deficient in zinc as per earlier reports and recent studies have shown that supplementation of zinc has improved qualitative as well as the quantitative aspects of semen quality in bulls. So, a study has been planned to study the effect of organic zinc supplementation on semen production and quality in kankrej bulls. Methods: A total of 8 healthy Kankrej bulls under semen collection were selected for the study. Basal diet (concentrate mixture, green and dry fodder) was fed during pre-supplementation and zinc propionate @ 100 ppm/bull was supplemented to the basal diet during post-supplementation for a period of 60 days to complete one spermatogenic cycle. A total of 128 ejaculates (64 pre-supplementation and 64 post-supplementation) were collected. Result: Mean semen volume was non-significant (P greater than 0.05) between the treatment groups. Mean sperm concentration was 1325.68±80.08 and 2162.36±112.0 million/ml pre- and post-supplementation, respectively. Feeding of zinc propionate significantly (P less than 0.01) increased semen sperm concentration. The average mass motility of sperms was significantly (P less than 0.01) higher during post-supplementation (3.92%) than the pre-supplementation (3.78%). The overall live sperms were significantly (P less than 0.01) higher during post-supplementation (73.33±0.91%) than the pre-supplementation (63.53±1.03%). It may be concluded that supplementation of 100 ppm of zinc propionate in the diet of Kankrej bulls improved semen quality in terms of quantitative and qualitative characteristics of semen.

Expression of G-Protein-Coupled Estrogen Receptor (GPER) in Whole Testicular Tissue and Laser-Capture Microdissected Testicular Compartments of Men with Normal and Aberrant Spermatogenesis.

Simple SummaryNowadays, there is no doubt that estrogens play an important role in male reproduction, affecting testicular cell differentiation, proliferation, apoptosis and metabolism. It is also widely believed that intratesticular balance of androgens and estrogens is crucial for the testicular development and function and that the increased testicular estrogen production may be associated with spermatogenic failure. There is also growing epidemiological evidence that the exposure of men to endocrine disruptors demonstrating estrogenic activity (xenoestrogens) may lead to impairment of male fertility via interference with estrogen signaling pathways. Besides the two classical nuclear estrogen receptors, the membrane-bound G protein-coupled estrogen receptor (GPER) was described in human testicular tissue. However, there are little data on its expression in testes with disturbed spermatogenesis. In this study, we investigated the GPER expression pattern in biopsies of azoospermic men with complete and aberrant spermatogenesis. Our results showed an increased expression of the GPER in testes with impaired spermatogenesis. Moreover, they indicate a possible involvement of estrogen signaling through GPER in disturbed function of Sertoli cells—the cells that support spermatogenic process.In this study, we retrospectively investigated GPER expression in biopsies of azoospermic men with complete (obstructive azoospermia—OA) and aberrant spermatogenesis (nonobstructive azoospermia—NOA). Each biopsy was histologically evaluated with morphometry. The testicular GPER expression was analyzed by the immunohistochemistry and RT-PCR technique in the whole testicular tissue and in seminiferous tubules and Leydig cells after laser-capture microdissection. In laser-microdissected compartments, we also analyzed transcriptional expression of selected Leydig (CYP17A1, HSD17B3, StAR) and Sertoli cell (AMH, SCF, BMP4) function markers. Immunohistochemical staining revealed expression of GPER in the cytoplasm of Leydig and Sertoli cells. Its stronger intensity was observed in Sertoli cells of NOA biopsies. The RT-PCR analysis of the GPER mRNA level unequivocally showed its increased expression in seminiferous tubules (i.e., Sertoli cells), not Leydig cells in NOA biopsies. This increased expression correlated positively with the transcriptional level of AMH—a marker of Sertoli cell immaturity, as well as FSH serum level in NOA but not in the OA group. Our results clearly demonstrate altered GPER expression in testes with primary spermatogenic impairment that might be related to Sertoli cell maturity/function.

Expression of genes and localization of enzymes involved in polyunsaturated fatty acid synthesis in rabbit testis and epididymis

The metabolism of polyunsaturated fatty acids (PUFAs) plays an important role in male reproduction. Linoleic and alpha-linolenic acids need to be provided in the diet and they are converted into long chain polyunsaturated fatty acids by steps of elongation and desaturation, exerted by elongases 2 (ELOVL2) and 5 (ELOVL5) and Δ5- (FADS1) and Δ6-desaturase (FADS2). This study aims to assess the gene expression and localization of enzymes involved in the synthesis of n-3 and n-6 long-chain PUFAs in control rabbits and those fed diets containing 10% extruded flaxseed. Enzyme and PUFA localization were assessed in the testes and epididymis by immunofluorescence. Testes showed high gene expression of FADS2, ELOVL2 and ELOVL5 and low expression of FADS1. Intermediate metabolites, enzymes and final products were differently found in Leydig, Sertoli and germinal cells. FADS2 was localized in interstitial cells and elongated spermatids; ELOVL5 in meiotic cells; FADS1 was evident in interstitial tissue, Sertoli cells and elongated spermatids; ELOVL2 in interstitial cells. Epididymal vesicles were positive for FADS1, ELOVL2 and ELOVL5 as well as docosahexaenoic, eicosapentaenoic, and arachidonic acids. This knowledge of fatty acids (FA) metabolism in spermatogenesis and the influence of diet on FA profile could help identify causes of male infertility, suggesting new personalized therapy.

Variance in lifetime reproductive success of male polar bears

Abstract Despite the important role that population density plays in ecological and evolutionary processes, studies of solitary species that occur at low densities remain scarce. In the context of mating systems, density is expected to influence the ability of males to find and monopolize mates, in turn, influencing variance in lifetime mating/reproductive success and the opportunity for selection. Herein, we investigate variance in male lifetime mating success (LMS), lifetime reproductive success (LRS), and the mating system of a sexually dimorphic carnivore that occurs at low densities, the polar bear (Ursus maritimus). Across 17 cohorts, born from 1975 to 1991, male LMS ranged from 0 to10 mates and LRS from 0 to 14 cubs; 40% of known-age males were not known to have reproduced. The opportunity for sexual selection (Is = 1.66, range = 0.60–4.99) and selection (I = 1.76, range: 0.65–4.89) were low compared to species with similar levels of sexual size dimorphism. Skew in male LRS was also low but significant for most cohorts indicating nonrandom reproductive success. Age-specific reproductive success was biased toward males from 11 to 17 years of age, with variation in fecundity (54%) but not longevity (10%) playing an important role in male reproduction. Our results support a growing body of evidence that suggests that male-biased size dimorphism and polygynous mating systems need not be associated with high variance in male mating and/or reproductive success.

Estrogens in Human Male Gonadotropin Secretion and Testicular Physiology From Infancy to Late Puberty.

Several reports in humans as well as transgenic mouse models have shown that estrogens play an important role in male reproduction and fertility. Estrogen receptor alpha (ERα) and beta (ERβ) are expressed in different male tissues including the brain. The estradiol-binding protein GPER1 also mediates estrogen action in target tissues. In human testes a minimal ERα expression during prepuberty along with a marked pubertal up-regulation in germ cells has been reported. ERβ expression was detected mostly in spermatogonia, primary spermatocytes, and immature spermatids. In Sertoli cells ERβ expression increases with age. The aromatase enzyme (cP450arom), which converts androgens to estrogens, is widely expressed in human tissues (including gonads and hypothalamus), even during fetal life, suggesting that estrogens are also involved in human fetal physiology. Moreover, cP450arom is expressed in the early postnatal testicular Leydig cells and spermatogonia. Even though the aromatase complex is required for estrogen synthesis, its biological relevance is also related to the regulation of the balance between androgens and estrogens in different tissues. Knockout mouse models of aromatase (ArKO) and estrogen receptors (ERKOα, ERKOβ, and ERKOαβ) provide an important tool to study the effects of estrogens on the male reproductive physiology including the gonadal axis. High basal serum FSH levels were reported in adult aromatase-deficient men, suggesting that estrogens are involved in the negative regulatory gonadotropin feedback. However, normal serum gonadotropin levels were observed in an aromatase-deficient boy, suggesting a maturational pattern role of estrogen in the regulation of gonadotropin secretion. Nevertheless, the role of estrogens in primate testis development and function is controversial and poorly understood. This review addresses the role of estrogens in gonadotropin secretion and testicular physiology in male humans especially during childhood and puberty.

Oral Administration of a Vermiculite‐Nanocellulose Hybrid Boosts Sperm Parameters and Gonadotropin Levels in Rats

The safety of vermiculite‐nanocellulose (VEN) hybrid on the male reproductive system is not known. Hence we investigated the effects of VEN on the biochemical and hormonal indices of rats. Animals were orally exposed to VEN at 0, 5, 10 and 20 mg/kg body weight for 14 consecutive days. Administration of VEN had no effect on organo‐somatic index of the testes. Although Gamma –glutamyl transferase, catalase and superoxide dismutase activities and hydrogen peroxide level remained unaffected, exposure of rats to VEN significantly depleted myeloperoxidase, glutathione peroxidase and malondialdehyde levels in the testes of treated rats, when compared to control. The spermiogram of VEN‐exposed rats showed a significantly higher sperm count and lower sperm morphology rates than control group. Treatment with VEN also significantly increased circulatory concentrations of follicle‐stimulating hormone and luteinizing hormone, and decreased testosterone levels at the 20 mg/kg dose. Histoarchitecture of the testes, in the treatment groups, except at the 20 mg/kg dose, revealed normal looking Leydig and Sertoli cells. The epididymis presented with tubules completely filled with spermatids across all treatment groups. Taken together, our study show that VEN could play an important role in male reproduction in rats, especially in redox regulation and stimulation of the gonadotropins.Support or Funding InformationThis research was done without specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Taurine Increases Spermatozoa Quality and Function in Asthenospermia Rats Impaired by Ornidazole.

Asthenospermia has been considered as one of the crucial causes of male infertility, which was closely related to epididymal dysfunction. Lots of documents have revealed that taurine palys an important role in male reproduction, including antioxidation, membrane stabilization, stimulation of sexual hormone secretion and elevation of sperm quality. The objective of this study was to expose the effect of taurine on spermatozoa quality and function in ornidazole-induced asthenospermia rats. We found that taurine treatment could obviously recover the decline of cauda epididymal sperm count, viability and motility, and the elevation of sperm abnormality in asthenospermia animals. Spermatozoa acrosin, LDH-X, SDH and CCO activities of model rats also were notably increased by taurine administration. The present data indicated that taurine could raise spermatozoa quality and function by elevating mitochondrial energy metabolism. Notably, taurine supplementation markedly raised serum GnRH, LH and T levels in asthenospermia rays, suggesting taurine rescued asthenosperm by means of stimulating hypothalamic-pituitary-testicular axis secretion. We also found that concentrations of asthenospermia epididymal carnitine, SA, α-Glu and ACP, and mRNA expression levels of MMP7 and IDO2 were significantly rised by taurine administration, indicating taurine may protect epididymal epithelium structure, improve secretion activity, and maintain intraluminal microenvironment homeostasis. Finally, the present results showed taurine effectively increased cauda epididymal SOD, GSH and γ-GT levels in model rats, reduced ROS and MDA production, suggesting epididymal antioxidant ability of asthenospermia rats could be elevated by taurine treatment. To sum up, our results indicated that taurine can promote spermatozoa quality and function in ornidazole-induced asthenospermia rats by facilitating epididymal epithelium secretion and luminal microenvironment homeostasis.

Positive Selection in the Evolution of Mammalian CRISPs.

Cysteine-RIch Secretory Proteins (CRISPs) constitute a versatile family, with functions in reptilian venom and mammalian reproduction. Mammals generally express three CRISPs, four in mice, and all are highly expressed in male reproductive tissues, either testis or accessory organs. Because reproductive proteins often evolve adaptively in response to post-copulatory sexual selection, we hypothesized that mammalian CRISPs, with important roles in male reproduction, could have undergone positive selection promoting their divergence. We explored the molecular adaptation of mammalian CRISPs applying phylogenetic methods. Our analyses revealed the evidence of positive selection in all mammalian CRISPs. The intensity of positive selection was heterogeneous among CRISP members, being stronger in CRISP3 than in CRISP1 and CRISP2, and also across functional domains, having stronger impact on Pathogenesis-Related 1 (PR-1) in CRISP2 and on Ion Channel Regulator (ICR) in CRISP1 and CRISP3. In addition, we discovered a new CRISP in some rodent species, suggesting that the acquisition of new CRISP components could contribute to male reproductive success or to acquire new physiological roles. Signatures of positive selection were not focused on any particular mammalian group, suggesting that adaptive evolution is a recurrent pattern in mammalian CRISPs. Our findings support a model of CRISP family diversification driven by episodes of duplication and posterior neofunctionalization, and provide potential adaptive changes responsible for interspecific differences in CRISPs activity.

H19 regulates the proliferation of bovine male germline stem cells via IGF-1 signaling pathway.

Self-renewal and differentiation of male germline stem cells (mGSCs) provide the basic function for continual spermatogenesis. Studies of in vitro culture of germline stem cells are important and meaningful for basic biological research and practical application. Growth factors, such as GDNF, bFGF, CSF1, and EGF, could maintain the self-renewal of mGSCs. Insulin-like growth factor 1 (IGF-1), an important growth factor, and its pathway have been reported to maintain the survival of several types of stem cells and play important roles in male reproduction. However, the mechanism through which the IGF-1 pathway acts to regulate the self-renewal of mGSCs remains unclear. We analyzed the effect of IGF-1 on the proliferation and apoptosis of bovine mGSCs. We evaluated the expression profile of long noncoding RNA (LncRNA) H19 in bovine and mouse tissues. Moreover, we investigated whether LncRNA H19 could regulate the IGF-1 pathway. Results showed that IGF-1 could activate the phosphorylation of AKT and ERK signaling pathways, and the IGF-1 pathway played an important role in regulating the proliferation and apoptosis of bovine mGSCs. The proliferation rate of mGSCs decreased, whereas the apoptosis rate of mGSCs increased when the IGF-1 receptor (IGF-1R) was blocked using the IGF-1R-specific inhibitor (picropodophyllin). LncRNA H19 could regulate the IGF-1 signaling pathway and, consequently, the proliferation and apoptosis of mGSCs. The number of cells in the seminiferous tubule decreased when H19 was interfered by injecting a virus-containing supernatant. Hence, LncRNA H19 participated in the regulation of the proliferation and apoptosis of mGSCs via the IGF-1 signaling pathway.

LncRNA AK015322 promotes proliferation of spermatogonial stem cell C18-4 by acting as a decoy for microRNA-19b-3p.

Long noncoding RNAs (lncRNAs) have been reported to play important roles in male reproduction. In our previous research, we studied the expression profile of lncRNAs in mouse male germ cells including spermatogonial stem cell, type A spermatogonia, pachytene spermatocyte, and round spermatid by microarray method, which showed that testis-enriched lncRNA AK015322 is highly expressed in spermatogonial stem cell. In this study, we found that AK015322 promotes proliferation of mouse spermatogonial stem cell line C18-4 in vitro. Furthermore, bioinformatic analysis, real-time PCR, and luciferase assay validated that AK015322 serves as a decoy of microRNA-19b-3p (miR-19b-3p), antagonizes its function, and attenuates the repression of its endogenous target transcriptional factor Ets-variant 5 (ETV5) which was a pivotal gene for spermatogonial stem cell self-renewal. Taken together, our results suggest that a variety of lncRNAs may regulate male reproduction through serving as competing-endogenous RNAs to modulate the function of germ cells.

Effects of Gold Nanorods on Imprinted Genes Expression in TM-4 Sertoli Cells.

Gold nanorods (GNRs) are among the most commonly used nanomaterials. However, thus far, little is known about their harmful effects on male reproduction. Studies from our laboratory have demonstrated that GNRs could decrease glycine synthesis, membrane permeability, mitochondrial membrane potential and disrupt blood-testis barrier factors in TM-4 Sertoli cells. Imprinted genes play important roles in male reproduction and have been identified as susceptible loci to environmental insults by chemicals because they are functionally haploid. In this original study, we investigated the extent to which imprinted genes become deregulated in TM-4 Sertoli cells when treated with low dose of GNRs. The expression levels of 44 imprinted genes were analyzed by quantitative real-time PCR in TM-4 Sertoli cells after a low dose of (10 nM) GNRs treatment for 24 h. We found significantly diminished expression of Kcnq1, Ntm, Peg10, Slc22a2, Pwcr1, Gtl2, Nap1l5, Peg3 and Slc22a2, while Plagl1 was significantly overexpressed. Additionally, four (Kcnq1, Slc22a18, Pwcr1 and Peg3) of 10 abnormally expressed imprinted genes were found to be located on chromosome 7. However, no significant difference of imprinted miRNA genes was observed between the GNRs treated group and controls. Our study suggested that aberrant expression of imprinted genes might be an underlying mechanism for the GNRs-induced reproductive toxicity in TM-4 Sertoli cells.

Effects of different dietary n-6/n-3 polyunsaturated fatty acid ratios on boar reproduction.

BackgroundN-3 and N-6 polyunsaturated fatty acids are widely used in reproduction, yet few studies have addressed the effects of dietary n-6/n-3 ratios on boar reproduction. The present study aimed to determine the effects of different dietary n-6/n-3 ratios on the reproductive performance ofn breeding boars. Thirty-two boars with body weights of 15.0 ± 1.4 kg were divided into four treatments (C, T1, T2, T3) and fed diets with different n-6/n-3 fatty acid ratios (29.06:1, 20.07:1, 1:1, 1:17.96, respectively) for 174 days.ResultsThe highest testis index was observed for treatment T2. Sperm density and total sperm number per ejaculate in the T2 treatment were significantly higher than those in all other treatments, whereas the sperm deformity rate was the lowest. Interestingly, the fatty acid compositions and ratios of sperm were consistent with dietary treatments. Acid phosphatase and fructose concentration of seminal plasma, and the total superoxide dismutase and glutathione peroxidase of sperm in T2 were higher than those in other treatments. The concentration of testosterone and prostaglandin E2 increased in boars fed on diets supplemented with fatty acids as compared with boars subjected to the C grouptreatment, reaching a peak at n-6/n-3 fatty acid ratios of 1:1. Furthermore, higher expression of Δ6-fatty acid desaturase and peroxisome proliferator activated receptor-α in spermatozoa of the T2 treatment were observed, indicating more vigorous metabolism and intensive hormonal regulation.ConclusionsOur data suggest that the ideal n-6/n-3 ratio in the diet of breeding boars is 1:1, and proper balancing of n-6/n-3 fatty acids plays an important role in male reproduction.

Immunolocalization of G protein-coupled estrogen receptor in the rat epididymis.

BackgroundEstrogen plays an important role in male reproduction, and males lacking estrogen signaling in the reproductive tissues are infertile. Estrogen signaling is mediated via two nuclear receptors, ERα and ERβ, but it was recently found that a G protein-coupled estrogen receptor (GPER) is present in the testis. It is believed that GPER is a membrane form of the estrogen receptor and mediates non-classical estrogen signaling. However, the cellular localization of GPER in the epididymis is unknown. Therefore, the objective of this study was to determine the cellular and regional expression of GPER in the rat epididymis.FindingsTo localize expression, immunohistochemistry (IHC) was performed using fixed epididymal tissue. Three strains and ages of rats were used to identify whether GPER expression is strain or age specific. Our results are the first to demonstrate immunostaining of GPER in epididymal epithelial cells. Expression was highest near the apical membrane followed by the cytoplasm, consistent with a membrane bound receptor. The highest expression in adult rats was observed in corpus followed by cauda. Western blotting analysis of epididymal tissues from Sprague Dawley rats confirmed specificity of the antibody and regional expression.ConclusionsExpression of GPER in the corpus and cauda suggests a role for non-classical estrogen signaling in sperm maturation in the corpus, and sperm protection/storage in the cauda. GPER expression pre-pubertally suggests that estrogen may have a role in epithelial cell development in addition to regulation of adult function.

Hedgehog signaling in prostate epithelial–mesenchymal growth regulation

The prostate gland plays an important role in male reproduction, and is also an organ prone to diseases such as benign prostatic hyperplasia (BPH) and prostate cancer. The prostate consists of ducts with an inner layer of epithelium surrounded by stroma. Reciprocal signaling between these two cell compartments is instrumental to normal prostatic development, homeostasis, regeneration, as well as tumor formation. Hedgehog (HH) signaling is a master regulator in numerous developmental processes. In many organs, HH plays a key role in epithelial–mesenchymal signaling that regulates organ growth and tissue differentiation, and abnormal HH signaling has been implicated in the progression of various epithelial carcinomas. In this review, we focus on recent studies exploring the multipotency of endogenous postnatal and adult epithelial and stromal stem cells and studies addressing the role of HH in prostate development and cancer. We discuss the implications of the results for a new understanding of prostate development and disease. Insight into the cellular and molecular mechanisms underlying epithelial–mesenchymal growth regulation should provide a basis for devising innovative therapies to combat diseases of the prostate.

Association of polymorphisms in estrogen receptors (ESR1 and ESR2) with male infertility: a meta-analysis and systematic review

Estrogens play an important role in male reproduction via interacting with estrogen receptors (ERs), whose expression can be regulated by the polymorphisms in different regions of ESR1 and ESR2 genes. However, results from published studies on the association between four well-characterized polymorphisms (PvuII, XbaI, RsaI, and AluI) in the gene of ERs (ESR1 and ESR2) and male infertility risk are inconclusive. To investigate the strength of relationship of PvuII and XbaI in ESR1 and RsaI and AluI in ESR2 with male infertility, we conducted a meta-analysis of 12 eligible studies with odds ratio (OR) and its corresponding 95% confidence intervals (95% CI). Overall, ESR1 PvuII and ESR2 RsaI polymorphisms were significantly associated with male infertility risk. The subgroup analyses by ethnicities demonstrated that in Asians, ESR1 PvuII, XbaI and ESR2 RsaI polymorphisms were significantly associated with a decreased infertility risk, while in Caucasians both ESR1 PvuII and ESR2 RsaI polymorphisms increased the susceptibility to male infertility. As for ESR2 AluI polymorphism, no significant association was detected in either overall analysis or subgroup analyses by ethnicities/genotyping methods. This meta-analysis suggested that polymorphisms in the genes of ERs (ESR1 and ESR2) may have differential roles in the predisposition to male infertility according to the different ethnic backgrounds. Further well-designed and unbiased studies with larger sample size and diverse ethnic backgrounds should be conducted to verify our findings.

Panax ginseng induces the expression of CatSper genes and sperm hyperactivation.

The cation channel of sperm (CatSper) protein family plays important roles in male reproduction and infertility. The four members of this family are expressed exclusively in the testis and are localized differently in sperm. To investigate the effects of Panax ginseng treatment on the expression of CatSper genes and sperm hyperactivation in male mice, sperm motility and CatSper gene expression were assessed using a computer-assisted semen analysis system, a Fluoroskan Ascent microplate fluorometer to assess Ca2+ influx, real-time polymerase chain reaction, Western blotting and immunofluorescence. The results suggested that the Ca2+ levels of sperm cells treated with P. ginseng were increased significantly compared with the normal group. The P. ginseng-treated groups showed increased sperm motility parameters, such as the curvilinear velocity and amplitude of lateral head displacement. Taken together, the data suggest that CatSper messenger ribonucleic acid levels were increased significantly in mouse testes in the P. ginseng-treated group, as was the protein level, with the exception of CatSper2. In conclusion, P. ginseng plays an important role in improving sperm hyperactivation via CatSper gene expression.

Prostatitis and male infertility

The prostate gland plays an important role in male reproduction. Inflammation of the prostate gland (prostatitis) is a common health problem affecting many young and middle aged men. Prostatitis is considered a correctable cause of male infertility, but the pathophysiology and appropriate treatment options of prostatitis in male infertility remain unclear. This literature review will focus on current data regarding prostatitis and its impact on male infertility.

Ubiquitin-specific protease (USP26) gene alterations associated with male infertility and recurrent pregnancy loss (RPL) in Iranian infertile patients

The human X chromosome is enriched with testis-specific genes that may be crucial for male fertility. Mutations in USP26 gene have been proposed to be associated with male infertility. Moreover, the importance of the ubiquitin pathway during different stages of mammalian fertilization and even embryo development has been addressed. Some mutations and haplotypes on this gene have been proposed to be associated with male infertility. In this study, five different mutations on USP26 were investigated: 1737G > A, 1090 C > T, 370-371ins ACA, 494T > C and 1423 C > T. The study included 166 infertile men with non-obstructive azoospermia, 72 male partners of couples who had previously experienced ≥3 clinical first trimester spontaneous abortions and 60 fertile men. Besides family history of reproduction, hormonal evaluation and semen analysis were performed. DNA was extracted from blood samples. PCR-SSCP, PCR-RFLP and PCR Product Cloning methods were used and resumed by sequencing to insure about the mutations. Moreover, USP26 gene expression was studied by Real-Time PCR after RNA extraction followed by cDNA synthesis from 24 testis biopsies in obstructive and non-obstructive azoospermia patients. The results indicate that there is a haplotype between three observed mutations in Iranian population include: 370-371insACA, 1423C > T and 494T > C. This haplotype was seen in control group as well. Surprisingly, total frequency of mutations in men with history of idiopathic RPL and azoospermic cases were significantly higher than that of in control groups (p < 0.05). Serum testosterone concentrations and testicular volume did not differ in the mutation positive group compared with the non-mutation group. About the USP26 gene expression, there is a significant difference between the expression levels of obstructive azoospermia, complete maturation arrest samples and SCO samples (P < 0.05). According to our results, the USP26 gene may play an important role in male reproduction. The alterations of this gene may be involved in male infertility and RPL in Iranian population and may negatively affect testicular function.