Function Of Reproductive System Research Articles

Clinical and pharmacological basis of the use of testosterone drugs for hormonal replacement therapy for hypogonadism in men

Hypogonadism is a condition associated with a decrease in the functional activity of the testicles, accompanied by a decrease in the level of androgens and (or) a violation of the process of spermatogenesis. It is known that androgens and their main representative, testosterone, are of fundamental importance for the development and maintenance of the reproductive and sexual functions of the male reproductive system. At the same time, low testosterone levels are associated with both reproductive and metabolic disorders, including phosphorus-calcium, fat, carbohydrate, and protein metabolism. In addition, to date, data have been accumulated on the correlation of hypogonadism with cardiovascular diseases, which once again emphasizes the problem of testosterone deficiency, especially for patients of the middle and older age groups. However, carrying out testosterone replacement therapy always requires a strict and competent choice of a «target audience» among patients from a specialist. Today, on the pharmaceutical market, there is a wide arsenal of testosterone-containing drugs in various forms for use, which have an unequal «efficacy-safety» profile. In this review, we have analyzed modern approaches to the diagnosis and treatment of hypogonadism, the selection of a target group of patients to obtain the most effective and safe treatment outcome and described testosterone preparations and their dosage forms with potential advantages and disadvantages. Thus, the information presented in the article is aimed at optimizing the management of men with hypogonadism.

​Research Progress on New Methods to Prevent and Treat Ovarian Senescence: A Review

Ovarian senescence is a special type of organ senescence and the ovaries are the earliest aging organs. The ovaries have approximately 1 million to 2 million follicles at birth, but only approximately 1000 primordial follicles are left in menopause. Ovarian function also decreases with age. Women’s fertility also declines. The ovaries are the core female reproductive organs and are of great significance for maintaining reproductive system function and endocrine stability. Ovarian aging is also considered an indicator of female body aging, which drives the aging of many organs of the body. Therefore, how to prevent and treat ovarian aging has become a research question that has been widely studied by biomedical scientists and geriatric researchers in recent years. Recently, studies have shown that bone marrow mesenchymal stem cells (BMSCs) can prevent and treat ovarian aging. This article reviews the characteristics of ovarian aging, the advantages and disadvantages of various clinical treatment measures and the advantages of bone marrow mesenchymal stem cell therapy, aiming to provide references for the prevention and treatment of ovarian aging. My article was written at the Basic Medical Laboratory of the 920th Hospital of the Joint Logistics Support Force of PLA and written from 2021 to 2022.

Carbamate Pesticides: Shedding Light on Their Impact on the Male Reproductive System.

Carbamates are widely used and known around the world as pesticides in spite of also having medical applications. This class of chemicals is classified as acetylcholinesterase inhibitors, blocking acetylcholine hydrolyzation in a reversible manner. Their lack of species selectivity and their reported high toxicity can induce, upon exposure, adverse outcomes in male fertility that may lead to infertility. In addition, they are also considered endocrine-disrupting chemicals and can interfere with the hypothalamic–pituitary–testicular axis, essential for the normal function of the male reproductive system, thus being able to provoke male reproductive dysfunctions. Although the molecular mechanisms are not fully understood, various signaling pathways, such as those mediated by acetylcholine or kisspeptin, are affected by exposure to carbamates, thus compromising steroidogenesis and spermatogenesis. Over the last decades, several studies, both in vitro and in vivo, have reported a myriad of negative effects of carbamates on the male reproductive system. In this review, an up-to-date overview of the impact of carbamates on the male reproductive system is discussed, with an emphasis on the role of these compounds on acetylcholine regulation and the male endocrine system.

The influence of insulin and diabetes mellitus on male reproductive health

Diabetes mellitus affects the function of the male reproductive system through glucose metabolism and endocrine influences of insulin. Glucose metabolism is an important event in spermatogenesis and the maintenance of the activity of specific functions of motility and the ability of spermatozoa to fertilize, and metabolic disorders are caused by absolute or relative insulin deficiency and insulin resistance, which leads to the degradation of male reproduction. Inadequate effects of insulin are aimed at changing the morphological and functional characteristics of the seed material, the physiological state of the hypothalamic-pituitary-gonadal axis, testicular function, testosterone synthesis and spermatogenesis disorders. Thus, this article elucidates the impact of diabetes on spermatogenesis and some insulin-dependent mechanisms on male fertility.

Abstract 3015: Serine starvation silences estrogen receptor signaling through histone hypoacetylation

Abstract Estrogen receptor (ER) plays important roles in regulating normal development and female reproductive system function. Loss of ER pathway activity is a hallmark of breast cancer progression, associated with accelerated tumor proliferation and resistance to endocrine therapy. How ER loss occurs remains poorly understood. Here, we show that serine starvation, a metabolic stress often found in solid tumors, downregulates estrogen receptor alpha (ERα) expression, represses transcriptional targets such as progesterone receptor (PR), and reduces sensitivity to antiestrogens, suggesting a transition of ER-positive (ER+) breast cancer cells to an ER/PR-negative (ER-/PR-) state. ER downregulation under serine starvation is accompanied by a global loss of histone acetylation. These chromatin changes are driven by metabolic reprogramming triggered by serine starvation, particularly lower glucose flux through glycolysis and the TCA cycle, leading to reduced acetyl-CoA levels and histone hypoacetylation. Supplementation with acetate or glycerol triacetate (GTA), precursors of acetyl-CoA, restores H3K27 acetylation and ERα expression under serine starvation. Therefore, a major consequence of serine starvation in breast cancer could be global chromatin changes that influence lineage-specific gene expression. Citation Format: Albert M. Li, Yang Li, Bo He, Haowen Jiang, Chao Lu, Joshua J. Gruber, Erinn B. Rankin, Jiangbin Ye. Serine starvation silences estrogen receptor signaling through histone hypoacetylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3015.

Impact of Chronic Prenatal Stress on Maternal Neuroendocrine Function and Embryo and Placenta Development During Early-to-Mid-Pregnancy in Mice.

Psychological stress, both leading up to and during pregnancy, is associated with increased risk for negative pregnancy outcomes. Although the neuroendocrine circuits that link the stress response to reduced sexual motivation and mating are well-described, the specific pathways by which stress negatively impacts gestational outcomes remain unclear. Using a mouse model of chronic psychological stress during pregnancy, we investigated 1) how chronic exposure to stress during gestation impacts maternal reproductive neuroendocrine circuitry, and 2) whether stress alters developmental outcomes for the fetus or placenta by mid-pregnancy. Focusing on the stress-responsive neuropeptide RFRP-3, we identified novel contacts between RFRP-3-immunoreactive (RFRP-3-ir) cells and tuberoinfundibular dopaminergic neurons in the arcuate nucleus, thus providing a potential pathway linking the neuroendocrine stress response directly to pituitary prolactin production and release. However, neither of these cell populations nor circulating levels of pituitary hormones were affected by chronic stress. Conversely, circulating levels of steroid hormones relevant to gestational outcomes (progesterone and corticosterone) were altered in chronically-stressed dams across gestation, and those dams were qualitatively more likely to experience delays in fetal development. Together, these findings suggest that, up until at least mid-pregnancy, mothers appear to be relatively resilient to the effects of elevated glucocorticoids on reproductive neuroendocrine system function. We conclude that understanding how chronic psychological stress impacts reproductive outcomes will require understanding individual susceptibility and identifying reliable neuroendocrine changes resulting from gestational stress.

The effect of 3-Methyl-4-Nitrophenol on the early ovarian follicle development in mice by disrupting the clock genes expression

3-Methyl-4-Nitrophenol (PNMC) is the main degradation product of organophosphate insecticide fenitrothion and a major component of diesel exhaust particles, which is now becoming a widely spread environmental endocrine disruptor. Previous reports showed PNMC exposure can affect the female reproductive system and ovarian function; however, the mechanism remains unclear. The main purpose of this study is to clarify the mechanism underlying the adverse effects of neonatal PNMC treatment on ovarian functions. The neonatal female mice were exposed to 10 mg/kg PNMC and the ovaries were collected on the 7th day after birth. The changes of follicular composition in mice ovaries were analyzed by histological staining, which showed that the proportion of primordial follicles in the ovaries treated by PNMC decreased, while the proportion of secondary follicles increased. The ovarian function was also investigated by detecting the expressions of steroidogenic enzymes (Star, Cyp11a1, Hsd3b1, Cyp17a1, Cyp19a1), gonadotropin receptors (Fshr and Lhr), androgen receptor (Ar), and estrogen receptors (Esr1 and Esr2) by immunohistochemistry or/and real-time quantitative PCR. The expression of Hsd3b1, Cyp17a1 and Esr2 were increased significantly in the PNMC exposed ovaries. Moreover, the expression patterns of clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2 and Nr1d1) were disrupted in the ovaries after PNMC exposure. Furthermore, either the expression of DNA Methyltransferase Dnmt3b, or the methylation ratio of CpG islands in the upstream of Cry1 promoter regions were significantly decreased in PNMC exposed ovaries. Altogether, these results indicate that PNMC exposure affects follicle development and ovarian function by interfering with the epigenetic modification and disrupting the expression of clock genes.

Water Blooms-A Potential Threat to Male Reproduction: Clues From Aquatics and Rodents.

Toxic cyanobacteria blooms are a potential threat to global aquatic ecosystems and human health. Microcystin-leucine-arginine (MC-LR) is the most toxic variant of microcystins (MCs), and exposure to MCs can damage the male reproductive system. Two electronic databases were searched for controlled studies of rodents and fishes published before September 2020. Effect sizes were calculated for eight main reproductive parameters, including sperm count, sperm motility, sperm morphology, serum testosterone, testis weight, serum follicle stimulating hormone (FSH), serum luteinising hormone (LH) and serum estradiol. Nine meta-analyses of individual parameters were conducted using R version 4.0.2. Fifteen studies were included in the meta-analysis. In the studies of rodents, exposure to MC-LR by intraperitoneal injection or intragastric administration yielded statistically significant effects on sperm count (standardised mean difference (SMD) = -1.7426 (95% CI: -2.2098 to -1.2754)), abnormal sperm rate (SMD = 1.6714 (95% CI: 0.9702 to 2.3726)), sper5% CI: -3.9811 to -1.7834)), testis weight (SMD = -2.8822 (95% CI: -3.9811 to -1.7834)) and serum FSH (SMD = 0.4707 (95% CI: 0.0659 to 0.8756) changes in serum testosterone (SMD = 0.5521 (95% CI: 0.1652; 0.9391)) and estradiol (SMD = 0.6398 (95% CI: 0.1896 to 1.0900)) concentrations are considered to be statistically significant. Dose–response analysis reflected the dynamic changes of male reproductive function caused by MC. Short-term exposure to MC-LR can affect the function of the male reproductive system in rodents and fish. Elevated dosage or extended exposure time may worsen the damage. Human-related research on MC-LR exposure is very necessary to protect health and the water environment.

Immunological uterine response to pig embryos before and during implantation.

The establishment of a successful pregnancy can only occur through a concerted functioning of the entire female reproductive system, allowing for fertilization, subsequent embryo development and implantation of the conceptus. In this context, the uterine immunological responses responsible for rejection or tolerance of the conceptus are of critical importance. The aim of the present review is to summarize our current knowledge about those cellular and molecular immunological events occurring at the uterine level during pre-implantation and implantation stages of pregnancy in the pig. Advancing our understanding of the immune mechanisms involved in the success or failure of pregnancy will provide cues to develop novel strategies augmenting endometrial receptivity, finally increasing the efficiency of assisted reproductive technologies in pigs.

Histological and ultrastructural changes observed in testicles, epididymides, seminal vesicles and liver of rat after intraperitoneal administration of aluminum and indium

BackgroundAluminum (Al) and indium (In) have been largely used in medicine, pharmacy, dentistry, manufacturing, engineering, clothing as well as food processing and packaging. Our previous study showed that In was accumulated as electron-dense materials in lysosomes of Sertoli and Leydig testicular cells and the liver ones, when administered to male rats as soluble form. For this reason, we have undertaken to confirm whether Al have the same behavior as In and to enlarge this behavior to other organs of the male reproductive system: epididymis and seminal vesicle. MethodsExperiments were performed on 24 adult male Wistar rat weighing approximately 250 g. Animals were divided to 3 groups, received Al, In or saline solution as 7 chronic intraperitoneal injections over a period of two weeks and were sacrificed 24 h after the last injection. For ultrastructure study we used The Transmission Electron Microscopy (TEM). ResultsThe TEM showed the presence of electron-dense granules in lysosomes of testicular cells (Sertoli and Leydig cells), and in the principal epididymal and seminal vesicle cells of Al and In treated rats. Impairments were observed in the endoplasmic reticulum and mitochondria and many vacuoles were identified in the cells cytoplasm. Our results concluded that lysosomes of Leydig and Sertoli cells, principal epididymis, and seminal vesicle cells as well as liver cells, played a central role in the extraction and concentration of Al and In under insoluble form after their introduction into the body as a soluble route. This mechanism intended to protect the organism against exogenous toxic and non-recognized mineral elements after their intrusion into the body. ConclusionIt looks important to proceed with the study of Al and In impact on the endocrine and exocrine functions of the male rat reproductive system.

Evaluation of the protective effect of coenzyme Q10 on the growth process of embryos from in vitro fertilization in laboratory mice treated with cyclophosphamide

"Cyclophosphamide is an anticancer drug that acts as an alkylating agent after metabolism in the liver. Despite its many clinical applications in cancer treatment, this drug has toxic effects on the body's organs, especially the genitals. One of the most critical side effects is a change in the function of the female reproductive system, which can lead to infertility. This study aimed to investigate the antioxidant effects of coenzyme Q10 on cyclophosphamide-induced toxicity in vitro fertilized embryos in mice. In this experimental study, 24 female mice weighing 25 g 4 groups of 6 were divided and treated for 21 days. The first group (control group), solvent (cyclophosphamide) including DMSO and PBS (0.1 ml intraperitoneally), the second group (sham group), cyclophosphamide at a dose of 10 mg/kg was injected as a single dose, and the third group (experimental group), along with single-dose cyclophosphamide, coenzyme Q10 at a dose of 200 mg/kg/day was injected intraperitoneally and the fourth group (positive control group), only coenzyme Q10 at a dose of 200 mg/kg/day was injected intraperitoneally. At the end of the treatment period, ovulation stimulation was performed using PMSG and HCG hormones. Six adult male mice were used to prepare normal sperm. The animals were facilitated after anesthesia. After extraction of regular eggs and sperm and fertilization in HTF + 4 mg BSA medium, the fertilized eggs were incubated for 120 hours, and the embryonic developmental stages were examined during this period. Were analyzed by ANOVA and comparison of ratios. Cyclophosphamide significantly reduced oocyte quality, fertilization rate, pre-implantation embryonic development, and embryo quality. Coenzyme Q10 (Co Q10) significantly reduced the adverse effects of cyclophosphamide. The present study showed that crocin could protect the fertility of the female sex against damage caused by cyclophosphamide. "

A microengineered biomimetic model of the placental barrier to study environmental exposures during pregnancy

Exposure to toxic heavy metals contributes to the development of pregnancy complications that can adversely affect fetal development. Despite increasing evidence suggesting the negative health impact of heavy metals, investigating their adverse effects in the context of human pregnancy remains a major challenge due to the difficulty of human subject research and the limited capacity of animal models to properly represent the anatomy and function of the human reproductive system. Motivated by problem, here we describe a microengineered in vitro model designed to reverse engineer the maternal-fetal interface in the human placenta. This biomimetic system enables advanced capabilities to grow human trophoblast cells and fetal vascular endothelial cells in a physiological spatial arrangement and dynamic culture conditions to engineer the placental barrier in vitro that can emulate regulated material transport between maternal and fetal circulations. Using cadmium (CdCl2 ) as a representative example of heavy metals, we investigate whether and how this environmental chemical affects the human placental barrier and its physiological function as a gatekeeper. Our study also examines the role of membrane transporters in the maternal-to-fetal transfer of cadmium to provide insights into efflux transporter-medicated protection against environmental exposures during pregnancy.We used soft lithography to construct a compartmentalized elastomeric device consisting of two overlapping chambers separated by a thin semipermeable membrane. After sterilization and surface coating with extracellular matrix protein, the device was seeded with BeWo b30 human trophoblast cells and primary human villous endothelial cells on the opposite sides of the membrane. The bi-layer tissue was then cultured under perfusion conditions by using syringe pumps connected to each chamber. To mimic the physiological process of placental development, we treated the trophoblast cell layer in the maternal chamber with forskolin (50 µM) to induce syncytialization.Our microengineered model of the human placental barrier formed a tight barrier (evaluated by expression of E-cadherin and VE-cadherin), secreted the pregnancy hormone human chorionic gonadotropin beta (hCGβ), and supported physiological maternal-to-fetal transport of glucose. Following CdCl2 treatment (0.5-50 µM), we observed concentration-dependent deleterious responses of the maternal and fetal tissues as demonstrated by reduced cell viability and placental hormone secretion, compromised barrier function, and increased secretion of proinflammatory cytokines. The results also indicated upregulated expression of metallothioneins IA and IIA (MT-IA/IIA) metal binding proteins.The placenta-on-a-chip is an innovative and translational in vitro platform for the study of environmental chemical toxicity in the human placenta. With further improvements, this technology may advance our ability to model, interrogate, and predict the potential of xenobiotics to disrupt placentation and maintenance of human pregnancy.

English

Black seeds from papaya plants are utilized as traditional medicine in African and Asian cultures to improve the functioning of the male reproductive system and management of prostate cancer. This study analyzed the phytochemical composition, antiproliferative activity and cytotoxicity of Carica papaya black seeds against the prostate cancer cells and Vero cells. Phytochemical screening was performed by standard procedures. Methyl tetrazolium bromide (MTT) cell viability assay was used to evaluate the antiproliferative effect of crude extracts in prostate cancer cells against the control.  Phytocompounds, namely flavonoids, alkaloids, tannins, terpenoids, glycosides and saponins were found in the crude extracts. All papaya seeds’ extracts had antiproliferative activity towards prostate cancer cells. Ethyl acetate extract was found with higher antiproliferative activity with IC50 of 3.64 µg/ml. The crude extracts were not toxic towards Vero cells as compared to the control. Isolation and characterization of active compounds from herein crude extracts and papaya black seeds are therefore recommended for future studies. Key words: Prostate cancer, Carica papaya, extracts, phytochemical analysis, antiproliferative.

Sexual and reproductive health knowledge of secondary school adolescents in Fako, Cameroon.

Introductionthe correct sexual and reproductive health knowledge of adolescents remains important to empower them for healthy decision-making. The study aimed to assess the sexual and reproductive health knowledge of secondary school adolescents in Fako, Cameroon.Methodsa cross-sectional survey of 1180 adolescents from nine schools in Fako, was conducted using a structured interviewer - guided questionnaire. Data were analysed using SPSS version 26. Descriptive statistics and logistic regression analysis were used to outline knowledge and to identify predictors of knowledge respectively. Statistical significance was set at p<0.05.Resultsmore than half (54.0%) of the participants had overall good sexual and reproductive health knowledge. However, 63.1% and 55.3% of the participants had poor knowledge on reproductive system functions and sexually transmissible infections respectively. In addition, 56.0% had overall good contraceptive knowledge, with 51.6% having poor knowledge on condom. Being male (AOR=0.43, 95% CI=0.20, 0.92) and using the internet to search for sexuality related information (AOR=0.46, 95% CI= 0.22, 0.94) were associated with good knowledge. Being in lower secondary school was an independent predictor of poor knowledge (AOR= 3.83, 95% CI= 1.67, 8.81).Conclusionalthough slightly above half of adolescent secondary school students had good sexual and reproductive health knowledge, there existed several gaps in such knowledge. Policymakers especially in the education sector need to evaluate the current state of school-based sexual and reproductive health education in Cameroon, in order to design comprehensive curricula, that will begin from lower secondary school. Internet-based comprehensive sexuality education is also needed.

Spectacular alterations in the female reproductive system during the ovarian cycle and adaptations for matrotrophy in chernetid pseudoscorpions (Pseudoscorpiones: Chernetidae)

Pseudoscorpions are small matrotrophic chelicerates. The embryos develop in a brood sac and feed on the nutritive fluid provided by the female. It was widely accepted that the nutritive fluid is synthesized in the ovary. Recent studies have shown that in Chelifer cancroides, a representative of Cheliferidae, considered one of the most derived pseudoscorpion families, the nutritive fluid is produced not only in the ovary but also in the oviducts. Since evolution of adaptations for matrotrophy in pseudoscorpions is poorly known, we aimed to verify our hypothesis that pseudoscorpions of the family Chernetidae, closely related to Cheliferidae, share the traits of adaptations to matrotrophy in the structure and function of the female reproductive system with C. cancroides. We analysed the structure of the ovary and oviducts in five representatives of chernetids with light, confocal, and transmission electron microscopy. The results confirmed our hypothesis and provided new data which broaden our knowledge of matrotrophic pseudoscorpions. We show that in chernetids, the ovary and oviducts undergo significant alterations including their size, multistep hypertrophy and polyploidization of the epithelial cells involved in secretion of the nutritive fluid, the complex secretory activity of the epithelial cells, massive degeneration of the epithelial cells that have completed secretion, and epithelium renewal.

Purinergic Signaling in Spermatogenesis.

Adenosine triphosphate (ATP) serves as the essential source of cellular energy. Over the last two decades, however, ATP has also attracted increasing interest as an extracellular signal that activates purinergic plasma membrane receptors of the P2 family. P2 receptors are divided into two types: ATP-gated nonselective cation channels (P2X) and G protein-coupled receptors (P2Y), the latter being activated by a broad range of purine and pyrimidine nucleotides (ATP, ADP, UTP, and UDP, among others). Purinergic signaling mechanisms are involved in numerous physiological events and pathophysiological conditions. Here, we address the growing body of evidence implicating purinergic signaling in male reproductive system functions. The life-long generation of fertile male germ cells is a highly complex, yet mechanistically poorly understood process. Given the relatively sparse innervation of the testis, spermatogenesis relies on both endocrine control and multi-directional paracrine communication. Therefore, a detailed understanding of such paracrine messengers, including ATP, is crucial to gain mechanistic insight into male reproduction.⁠

Effects of bisphenol A exposure on proteins tyrosine phosphorylation in mammalian sperm

Bisphenol A (BPA) is a synthetic estrogen compound, which widely exists in the environment, interferes with mammalian endocrine and affects the function of reproductive system of males. Taking fresh sperm of boar, 17 ℃ preservation boar sperm, and mouse sperm as test materials, we examined the effects of BPA (0, 0.1,1,10,100 μmol∙L-1) on proteins tyrosine phosphorylation in sperm and the molecular mechanism by using wes-tern blot (WB) and immunofluorescence techniques coupled to in vitro culture method. The results showed that low BPA concentration (0.1, 1 μmol∙L-1) markedly accelerated the protein tyrosine phosphorylation of fresh boar capacitated sperm. However, the tyrosine phosphorylation of boar sperm decreased in high BPA concentration (10, 100 μmol∙L-1). The tyrosine phosphorylation of the mouse sperm raised with the increases of BPA concentration. Moreover, BPA affected different kinds of proteins related to tyrosine phosphorylation modification of porcine and mouse sperm capacitation, suggesting that the effect of BPA exposure on mammalian sperm was species-specific. Furthermore, the results of immunofluorescence showed that the effects of BPA on protein tyrosine phosphorylation in sperm mainly occurred in the middle and principal piece of flagellum.

Are Vitamin E Supplementation Beneficial for Female Gynaecology Health and Diseases?

Vitamin E is known as an essential vitamin, and many studies had demonstrated the importance of vitamin E throughout the reproductive process, such as miscarriage, premature birth, preeclampsia, and intrauterine growth restriction, which could be caused by a lack of vitamin E during pregnancy. Its potent antioxidant properties can counteract the oxidative stress induced by oxygen free radicals and imbalance of oxidative-antioxidant levels, hence it may play a role in maintaining the normal function of the female reproductive system. Despite the fact that vitamin E is acknowledged as the substance needed for reproduction, its beneficial effects on female fertility, gynaecological health, and diseases are still poorly understood and lacking. Therefore, the goal of this paper is to provide a summary of the known roles of vitamin E supplementation in women for gynaecological health and reproductive-related diseases, as well as its future perspective.

Genome-wide association study for frozen-thawed sperm motility in stallions across various horse breeds.

The semen quality of stallions including sperm motility is an important target of selection as it has a high level of individual variability. However, effects of the molecular architecture of the genome on the mechanisms of sperm formation and their preservation after thawing have been poorly investigated. Here, we conducted a genome-wide association study (GWAS) for the sperm motility of cryopreserved semen in stallions of various breeds. Semen samples were collected from the stallions of 23 horse breeds. The following semen characteristics were examined: progressive motility (PM), progressive motility after freezing (FPM), and the difference between PM and FPM. The respective DNA samples from these stallions were genotyped using Axiom Equine Genotyping Array. We performed a GWAS search for single nucleotide polymorphism (SNP) markers and potential genes related to motility properties of frozen-thawed semen in the stallions of various breeds. As a result of the GWAS analysis, two SNP markers, rs1141327473 and rs1149048772, were identified that were associated with preservation of the frozen-thawed stallion sperm motility, the relevant putative candidate genes being NME/NM23 family member 8 (NME8), olfactory receptor family 2 subfamily AP member 1 (OR2AP1), and olfactory receptor family 6 subfamily C member 4 (OR6C4). Potential implications of effects of these genes on sperm motility are herein discussed. The GWAS results enabled us to localize novel SNPs and candidate genes for sperm motility in stallions. Implications of the study for horse breeding and genetics are a better understanding of genomic regions and candidate genes underlying stallion sperm quality, and improvement in horse reproduction and breeding techniques. The identified markers and genes for sperm cryotolerance and the respective genomic regions are promising candidates for further studying the biological processes in the formation and function of the stallion reproductive system.

Microenvironment for spermatogenesis and sperm maturation.

The male reproductive system consists of testes, a series of ducts connecting the testes to the external urethral orifice, accessory sex glands, and the penis. Spermatogonial stem cells differentiate and mature in testes and epididymides, and spermatozoa are ejaculated with exocrine fluids secreted by accessory sex glands. Many studies have clarified the detailed structure and function of the male reproductive system, and have shown that various biologic controls, including genomics, epigenetics, and the neuroendocrine-immune system regulate proliferation, differentiation, and maturation of germ cells. In other words (1) genetic deletion or abnormalities, (2) aberration of DNA methylation and histone modifications, as well as small RNA dysfunction, and (3) neuroendocrine-immune disorders are involved in functional failure of the male reproductive system. In this article, we review these three factors for germ cell microcircumstance, especially focused on the immunoendocrine environment. In particular, the relation between factors protecting germ cells with strong auto-immunogenicity and opposite factors compromising this protection are discussed. Reductions in sperm count, concentration, and semen quality are serious problems in developed countries, although the causes are complex and remain unclear. The accumulation of basic knowledge regarding the structure, function, and regulation of the male reproductive system under various experimental conditions will be important to resolve these problems.