ABSTRACT
The urinary system comprises kidneys, ureters, bladder, and urethra with its primary function being excretion, referring to the physiological process of transporting substances that are harmful or surplus out of the body. The male reproductive system consists of gonads (testis), vas deferens, and accessory glands such as the prostate. According to classical immunology theory, the tissues and organs mentioned above are not thought to produce immunoglobulins (Igs), and any Ig present in the relevant tissues under physiological and pathological conditions is believed to be derived from B cells. For instance, most renal diseases are associated with uncontrolled inflammation caused by pathogenic Ig deposited in the kidney. Generally, these pathological Igs are presumed to be produced by B cells. Recent studies have demonstrated that renal parenchymal cells can produce and secrete Igs, including IgA and IgG. Glomerular mesangial cells can express and secrete IgA, which is associated with cell survival and adhesion. Likewise, human podocytes demonstrate the ability to produce and secrete IgG, which is related to cell survival and adhesion. Furthermore, renal tubular epithelial cells also express IgG, potentially involved in the epithelial-mesenchymal transition (EMT). More significantly, renal cell carcinoma, bladder cancer, and prostate cancer have been revealed to express high levels of IgG, which promotes tumour progression. Given the widespread Ig expression in the urinary and male reproductive systems, continued efforts to elucidate the roles of Igs in renal physiological and pathological processes are necessary.
Subject(s)
Immunoglobulins , Humans , Male , Immunoglobulins/metabolism , Immunoglobulins/genetics , Immunoglobulins/immunology , Urinary Tract/immunology , Urinary Tract/metabolism , Urinary Tract/pathology , Genitalia, Male/immunology , Genitalia, Male/metabolism , Genitalia, Male/pathology , Animals , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Immunoglobulin G/immunology , Clinical RelevanceABSTRACT
Aquaporins (AQPs), also known as water channels, appear to be particularly promising in maintaining male reproductive potential. Therefore, this study aimed to determine the presence of classical AQPs in the bovine (Bos taurus) reproductive system and analyze changes in their expression with age using immunohistochemistry and Western blotting. Of the six classical AQPs, AQP0, AQP1, AQP4, AQP5 and AQP6 were detected, while AQP2 was absent. In the testis, AQP0 was visible in Leydig cells in selected animals, while AQP1 was found in myoid cells surrounding the seminiferous tubules of mature individuals. This characteristic expression patterns of AQP0, limited only to certain bulls, is difficult to explain unequivocally. It is possible that AQP0 expression in cattle is subject to individual variability or changes in response to specific physiological conditions. In the caput and corpus epididymis, AQP0 showed weak expression in epithelial cells of immature animals and stronger expression in basal and principal cells of reproductive bulls. In all animals, AQP1 was present on the apical surface of epithelial cells in the initial segment of the caput epididymis. AQP4, AQP5 and AQP6 were identified in principal and basal cells along the entire epididymis of reproductive bulls. The abundance of AQP4 and AQP6 increased from the caput to the cauda epididymis with the growth and development of the animals. In all males, AQP4, AQP5 and AQP6 were observed in epithelial cells of the vas deferens, and their expression in this section increased with age. In conclusion, the abundance and distribution of the classical AQPs in various cell types and parts of the male reproductive system indicate their crucial role in maintaining water homeostasis, which is essential for normal reproductive function in cattle.
Subject(s)
Aquaporins , Animals , Male , Cattle , Aquaporins/metabolism , Aquaporins/genetics , Epididymis/metabolism , Genitalia, Male/metabolism , Testis/metabolism , ImmunohistochemistryABSTRACT
Nerve growth factor (NGF) has long been known as the main ovulation-inducing factor in induced ovulation species, however, recent studies suggested the NGF role also in those with spontaneous ovulation. The first aim of this study was to evaluate the presence and gene expression of NGF and its cognate receptors, high-affinity neurotrophic tyrosine kinase 1 receptor (NTRK1) and low-affinity p75 nerve growth factor receptor (p75NTR), in the ram genital tract. Moreover, the annual trend of NGF seminal plasma values was investigated to evaluate the possible relationship between the NGF production variations and the ram reproductive seasonality. The presence and expression of the NGF/receptors system was evaluated in the testis, epididymis, vas deferens ampullae, seminal vesicles, prostate, and bulbourethral glands through immunohistochemistry and real-time PCR (qPCR), respectively. Genital tract samples were collected from 5 adult rams, regularly slaughtered at a local abattoir. Semen was collected during the whole year weekly, from 5 different adult rams, reared in a breeding facility, with an artificial vagina. NGF seminal plasma values were assessed through the ELISA method. NGF, NTRK1 and p75NTR immunoreactivity was detected in all male organs examined. NGF-positive immunostaining was observed in the spermatozoa of the germinal epithelium, in the epididymis and the cells of the secretory epithelium of annexed glands, NTRK1 receptor showed a localization pattern like that of NGF, whereas p75NTR immunopositivity was localized in the nerve fibers and ganglia. NGF gene transcript was highest (p < 0.01) in the seminal vesicles and lowest (p < 0.01) in the testis than in the other tissues. NTRK1 gene transcript was highest (p < 0.01) in the seminal vesicles and lowest (p < 0.05) in all the other tissues examined. Gene expression of p75NTR was highest (p < 0.01) in the seminal vesicles and lowest (p < 0.01) in the testis and bulbourethral glands. NGF seminal plasma concentration was greater from January to May (p < 0.01) than in the other months. This study highlighted that the NGF system was expressed in the tissues of all the different genital tracts examined, confirming the role of NGF in ram reproduction. Sheep are short-day breeders, with an anestrus that corresponds to the highest seminal plasma NGF levels, thus suggesting the intriguing idea that this factor could participate in an inhibitory mechanism of male reproductive activity, activated during the female anestrus.
Subject(s)
Genitalia, Male , Nerve Growth Factor , Receptor, trkA , Seasons , Semen , Animals , Male , Semen/chemistry , Semen/metabolism , Receptor, trkA/genetics , Receptor, trkA/metabolism , Genitalia, Male/metabolism , Genitalia, Male/chemistry , Sheep/metabolism , Nerve Growth Factor/genetics , Nerve Growth Factor/metabolism , Receptor, Nerve Growth Factor/genetics , Receptor, Nerve Growth Factor/metabolism , Gene Expression Regulation/physiologyABSTRACT
As an important gas signaling molecule, hydrogen sulfide (H2S) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary, reproductive systems. In particular, H2S not only regulates female reproductive function but also holds great promise in the treatment of male reproductive diseases and disorders, such as erectile dysfunction, prostate cancer, varicocele, and infertility. In this review, we summarize the relationship between H2S and male reproductive organs, including the penis, testis, prostate, vas deferens, and epididymis. As lower urinary tract symptoms have a significant impact on penile erection disorders, we also address the potential ameliorative effects of H2S in erectile dysfunction resulting from bladder disease. Additionally, we discuss the regulatory role of H2S in cavernous smooth muscle relaxation, which involves the NO/cGMP pathway, the RhoA/Rho-kinase pathway, and K+ channel activation. Recently, various compounds that can alleviate erectile dysfunction have been reported to be at least partly dependent on H2S. Therefore, understanding the role of H2S in the male reproductive system may help develop novel strategies for the clinical treatment of male reproductive system diseases.
Subject(s)
Genitalia, Male , Hydrogen Sulfide , Hydrogen Sulfide/metabolism , Humans , Male , Genitalia, Male/metabolism , Animals , Erectile Dysfunction/drug therapy , Erectile Dysfunction/metabolism , Signal TransductionABSTRACT
Like other lepidopteran insects, males of the tobacco cutworm moth, Spodoptera litura produce two kinds of spermatozoa, eupyrene (nucleate) and apyrene (anucleate) sperm. Formed in the testis, both kinds of sperm are released into the male reproductive tract in an immature form and are stored in the duplex region of the tract. Neither type of sperm is motile at this stage. When stored apyrene sperm from the duplex are treated in vitro with an extract of the prostatic region of the male tract, or with mammalian trypsin, they become motile; activation is greater and achieved more rapidly with increasing concentration of extract or enzyme. The activating effect of prostatic extract is blocked by soybean trypsin inhibitor (SBTI), also in a dose-dependent way. These results suggest that the normal sperm-activating process is due to an endogenous trypsin-like protease produced in the prostatic region. Proteomic analysis of S. litura prostatic extracts revealed a Trypsin-Like Serine Protease, TLSP, molecular weight 27 kDa, whose 199-residue amino acid sequence is identical to that of a predicted protein from the S. litura genome and is highly similar to predicted proteins encoded by genes in the genomes of several other noctuid moth species. Surprisingly, TLSP is only distantly related to Serine Protease 2 (initiatorin) of the silkmoth, Bombyx mori, the only identified lepidopteran protein so far shown to activate sperm. TLSP has features typical of secreted proteins, probably being synthesized as an inactive precursor zymogen, which is later activated by proteolytic cleavage. cDNA was synthesized from total RNA extracted from the prostatic region and was used to examine TLSP expression using qPCR. tlsp mRNA was expressed in both the prostatic region and the accessory glands of the male tract. Injection of TLSP-specific dsRNA into adult males caused a significant reduction after 24 h in tlsp mRNA levels in both locations. The number of eggs laid by females mated to adult males that were given TLSP dsRNA in 10 % honey solution, and the fertility (% hatched) of the eggs were reduced. Injecting pupae with TLSP dsRNA caused the later activation of apyrene sperm motility by adult male prostatic extracts to be significantly reduced compared to controls. Exposure of S. litura pupae to ionizing radiation significantly reduced expression of tlsp mRNA in the prostatic part and accessory gland of irradiated males in both the irradiated generation and also in their (unirradiated) F1 progeny. The implications of these findings for the use of the inherited sterility technique for the control of S. litura and other pest Lepidoptera are discussed.
Subject(s)
Insect Proteins , Spermatozoa , Spodoptera , Animals , Male , Spodoptera/genetics , Spodoptera/enzymology , Insect Proteins/metabolism , Insect Proteins/genetics , Spermatozoa/radiation effects , RNA Interference , Amino Acid Sequence , Genitalia, Male/metabolism , Genitalia, Male/radiation effects , Proteomics , Serine Proteases/metabolism , Serine Proteases/genetics , Radiation, Ionizing , Serine Endopeptidases/metabolism , Serine Endopeptidases/genetics , TranscriptomeABSTRACT
After aging in the environment, some nanoplastics will carry different charges and functional groups, thereby altering their toxicological effects. To evaluate the potential impact of aging of nanoplastics on the mammalian reproductive system, we exposed C57BL/6 male mice to a dose of 5 mg/kg/d polystyrene nanoparticles (PS-NPs) with different functional groups (unmodified, carboxyl functionalized and amino functionalized) for 45 days for this study. The results suggest that PS-NPs with different functional groups triggered oxidative stress, a decreased in the testis index, disruption of the outer wall of the seminiferous tubules, reduction in the number of spermatogonia cells and sperm counts, and an increased in sperm malformations. We performed GO and KEGG enrichment analysis on the differentially expressed proteins, and found they were mainly enriched in protein transport, RNA splicing and mTOR signaling. We confirmed that the PI3K-AKT-mTOR pathway is over activated, which may lead to reduction of spermatogonia stem cells by over differentiation. Strikingly, PS-NPs with functional group modifications are more toxic than those of unmodified polystyrene, and that PS-NPs with positively charged amino modifications are the most toxic. This study provides a new understanding for correctly evaluating the toxicological effects of plastic aging, and of the mechanism responsible for the reproductive toxicity caused by nanoplastics.
Subject(s)
Nanoparticles , Water Pollutants, Chemical , Animals , Mice , Male , Polystyrenes/toxicity , Polystyrenes/metabolism , Microplastics , Mice, Inbred C57BL , Phosphatidylinositol 3-Kinases , Water Pollutants, Chemical/toxicity , Semen , Nanoparticles/toxicity , Nanoparticles/metabolism , Genitalia, Male/metabolism , TOR Serine-Threonine Kinases , Mammals/metabolismABSTRACT
The prostate is a male reproductive gland which secretes prostatic fluid that enhances male fertility. During development and instigated by fetal testosterone, prostate cells arise caudal to the bladder at the urogenital sinus (UGS), when the urogenital mesenchyme (UGM) secretes signals to the urogenital epithelium (UGE). These initial mesenchymal signals induce prostate-specific gene expression in the UGE, after which epithelial progenitor cells form prostatic buds. Although many important factors for prostate development have been described using UGS organ cultures, those necessary and sufficient for prostate budding have not been clearly identified. This has been in part due to the difficulty to dissect the intricate signaling and feedback between epithelial and mesenchymal UGS cells. In this study, we separated the UGM from the UGE and tested candidate growth factors to show that when FGF10 is present, testosterone is not required for initiating prostate budding from the UGE. Moreover, in the presence of low levels of FGF10, canonical WNT signaling enhances the expression of several prostate progenitor markers in the UGE before budding of the prostate occurs. At the later budding stage, higher levels of FGF10 are required to increase budding and retinoic acid is indispensable for the upregulation of prostate-specific genes. Lastly, we show that under optimized conditions, female UGE can be instructed towards a prostatic fate, and in vitro generated prostate buds from male UGE can differentiate into a mature prostate epithelium after in vivo transplantation. Taken together, our results clarify the signals that can induce fetal prostate buds in the urogenital epithelium in the absence of the surrounding, instructive mesenchyme.
Subject(s)
Prostate , Urogenital System , Mice , Male , Female , Animals , Epithelium/metabolism , Genitalia, Male/metabolism , Testosterone/metabolismABSTRACT
Aquaporins-small, "unusual" proteins, whose discovery revolutionized the view of membrane transport of water and other small molecules, are essential for all living organisms. Aquaporins located in the male reproductive system seem to play a key role in the proper course of many processes occurring within it, thus maintaining a high reproductive potential.
Subject(s)
Aquaporins , Genitalia, Male , Reproduction , Humans , Male , Aquaporins/physiology , Genitalia, Male/metabolism , Reproduction/physiologyABSTRACT
Fertilization is a very sophisticated and unique process involving several key steps resulting in a zygote's formation. Recent research has indicated that some immune system-related cell surface molecules (CD molecules from the tetraspanin superfamily) may have a role in fertilization. Extracellular vesicles are undeniably involved in a variety of cellular functions, including reproduction. Tetraspanin proteins identified in extracellular vesicles are now used mostly as markers; mounting evidence indicates that they also participate in cell targeting, cargo selection, and extracellular vesicle formation. Their significance and potential in mammalian reproduction are currently being studied extensively. Despite the fact that the current data did not establish any theory, the crucial function of tetraspanins in the fertilization process was not ruled out, and the specific role of tetraspanins is still unknown. In this review, we bring insight into the existing knowledge regarding the expression of tetraspanins in spermatozoa and seminal fluid and their role in gamete binding and fusion.
Subject(s)
Fertilization , Tetraspanins , Animals , Male , Tetraspanin 29/genetics , Tetraspanin 29/metabolism , Tetraspanins/genetics , Tetraspanins/metabolism , Spermatozoa/metabolism , Genitalia, Male/metabolism , Mammals/metabolismABSTRACT
Infertility is a worldwide health issue defined by the World Health Organization (WHO) as the inability to establish a pregnancy after 12 months or more of regular and unprotected sexual intercourse. Male infertility etiology can be related to either congenital or acquired factors. The therapeutical approach to male infertility depends on the underlying causes and includes medical and surgical treatments. In recent studies, the potential role of nerve growth factor (NGF) in male reproductive physiology has been proposed. It has been hypothesized that neurotrophins might be involved in testis morphogenesis and regulation of several aspects of spermatogenesis. Moreover, it has been shown that NGF exerts its role on gonadotropin-releasing hormone (GnRH) neurons through the activation of the PKC/p-ERK1/2/p-CREB cascade, which leads to the activation of hypothalamic cells and the consequent activation of hypothalamus-pituitary-gonadal axis (HPG) with the secretion of GnRH. Lastly, it has been shown that the physiology of mature sperm is affected by both exogenous and endogenous NGF. The NGF impact on the HPG axis and its effect on GnRH neurons might be exploited in the therapy of male hypogonadism or used as a protective strategy against gonadal dysfunction related to chemotherapeutic agents. Moreover, the improving effect of NGF on sperm motility and vitality could be useful to enhance assisted reproduction outcomes. NGF could be supplemented to cryopreserved sperm samples to counteract the oxidative stress induced by the frozen and thawing processes. Indeed, the potential clinical applications of NGF in male infertility treatment have been discussed.
Subject(s)
Infertility, Male , Nerve Growth Factor , Humans , Pregnancy , Female , Male , Nerve Growth Factor/pharmacology , Sperm Motility , Semen/metabolism , Gonadotropin-Releasing Hormone/metabolism , Infertility, Male/drug therapy , Infertility, Male/etiology , Genitalia, Male/metabolismABSTRACT
Although the role of estrogens in the development and function of tissues in the reproductive and other systems has long been recognized, their relative concentrations in target tissues have received scant attention. In this regard, the significance of local metabolism of estrogens is clearly shown by incubation of tissues with radiolabeled estrogens.
Subject(s)
Estrogens , Genitalia, Male , Animals , Estrogens/metabolism , Female , Genitalia, Male/metabolism , Lipid Metabolism , Male , Mammals/metabolism , ReproductionABSTRACT
Exosomes are nano-sized structures that are found in semen, epididymal -fluid, endometrium, as well as in follicular fluid. They are responsible for transporting bioactive cargo- proteins, lipids, and nucleic acids. Exosomes have been proven to influence processes in both female and male reproductive systems, including gametogenesis, acrosomal reaction, sperm capacitation, and embryo implantation in the endometrium. Exosomes are made of the same particles as the cells they come from and are secreted by normal and pathological cells. Therefore, exosomes can reflect the physiological state of cells. Moreover, due to the transportation of biomolecules, they participate in intercellular communication and can be used as biomarkers of many diseases, including ovarian, endometrial and prostate cancer. Identification of exosomes as biomarkers could contribute to a better understanding of genital dysfunction and fertility disorders.
Subject(s)
Exosomes/metabolism , Reproduction/physiology , Aging , Biomarkers , Drug Carriers/metabolism , Embryo Implantation/physiology , Female , Genital Diseases, Female/pathology , Genital Diseases, Male/pathology , Genitalia, Female/metabolism , Genitalia, Male/metabolism , Humans , Inflammation , Male , Signal Transduction/physiologyABSTRACT
Vitiligo is a polygenetic multifactorial disease leading to melanocytic loss in skin and sometimes in hair. Genital areas may be involved and represent a specific therapeutic challenge. Surprisingly, data on male genital vitiligo remain scarce. This review aims to collate current knowledge on male genital vitiligo and to discuss the risks and benefits of the various therapeutic approaches. Male genital vitiligo is relatively frequent and often induces marked impairment of quality of life, with a specific impact on sex life. Prompt recognition of activity remains mandatory to halt disease progression, as repigmentation remains difficult to achieve in most cases. Thanks to progress in understanding of the pathophysiology of vitiligo, new therapeutic approaches are under development. Topical ruxolitinib, a JAK pathway inhibitor, is currently the product in the most advanced stage of development, with a very encouraging repigmentation rate on the face, although specific efficacy in genital area remains to be assessed. The next generation of treatments, such as topical WNT agonists, could be of great interest in genital vitiligo as they will not require combination with UV therapy and they may be able to enhance the differentiation and proliferation of melanocyte stem cells in this difficult-to-treat area.
Subject(s)
Hypopigmentation , Vitiligo , Genitalia, Male/metabolism , Humans , Male , Melanocytes , Quality of Life , Vitiligo/therapyABSTRACT
Endocannabinoid system (ECS) is known for its modulatory role in numerous physiological processes in the body. Endocannabinoids (eCBs) are endogenous lipid molecules which function both centrally and peripherally. The ECS is best studied in the central nervous system (CNS), immune system as well as in the metabolic system. The role of ECS in male reproductive system is emerging and the presence of a complete enzymatic machinery to synthesize and metabolize eCBs has been demonstrated in male reproductive tract. Endocannabinoid concentrations and alterations in their levels have been reported to affect the functioning of spermatozoa. A dysfunctional ECS has also been linked to the development of prostate cancer, the leading cause of cancer related mortality among male population. This review is an attempt to provide an insight into the significant role of endocannabinoids in male reproduction and further summarize recent findings that demonstrate the manner in which the endocannabinoid system impacts male sexual behavior and fertility.
Subject(s)
Endocannabinoids/metabolism , Endocannabinoids/physiology , Genitalia, Male/metabolism , Animals , Cannabinoids/metabolism , Fertility/drug effects , Humans , Immune System/metabolism , Male , Prostate/pathology , Receptors, Cannabinoid/physiology , Reproduction/drug effects , Reproduction/physiology , Spermatozoa/drug effectsABSTRACT
Inflammation is among the core causatives of male infertility. Despite male infertility being a serious global issue, "bits and pieces" of its complex etiopathology still remain missing. During inflammation, levels of proinflammatory mediators in the male reproductive tract are greater than usual. According to epidemiological research, in numerous cases of male infertility, patients suffer from acute or chronic inflammation of the genitourinary tract which typically occurs without symptoms. Inflammatory responses in the male genital system are inextricably linked to oxidative stress (OS). OS is detrimental to male fertility parameters as it causes oxidative damage to reproductive cells and intracellular components. Multifarious male infertility causative factors pave the way for impairing male reproductive functions via the common mechanisms of OS and inflammation, both of which are interlinked pathophysiological processes, and the occurrence of any one of them induces the other. Both processes may be simultaneously found in the pathogenesis of male infertility. Thus, the present article aims to explain the role of inflammation and OS in male infertility in detail, as well as to show the mechanistic pathways that link causative factors of male reproductive tract inflammation, OS induction, and oxidant-sensitive cellular cascades leading to male infertility.
Subject(s)
Oxidative Stress/physiology , Cytokines/metabolism , Genitalia, Male/metabolism , Humans , Infertility/physiopathology , Inflammation/metabolism , Inflammation/physiopathology , Male , Oxidative Stress/genetics , Reactive Oxygen Species/metabolismABSTRACT
The aim of this study was to investigate the effect of heated and unheated palm olein in different doses on the male reproductive system of rats. Forty male rats were randomly classified into five groups (n = 8) including Control, Low palm, High palm, Heated low palm and Heated high palm. The palm olein was administrated orally for 6 months. Histological and biochemical parameters of the male reproductive system were measured. There was a significant reduction in sexual hormones, serum levels of superoxide dismutase, high-density lipoprotein, testis weight and sperm parameters in the high dose and heated palm olein groups compared to the other group (p < 0.05). The levels of malondialdehyde, apoptosis rate, proteins levels (TNF-α, IL-1ß, IL-6), low-density lipoprotein, cholesterol, triglyceride and the weight of the rats were significantly higher in the high dose and heated palm olein groups than the others (p < 0.05). High dose and heated palm olein treatment could damage the male rat's reproductive indices that were related to increased inflammatory markers, decreased sex hormone levels, and negative effects on testicular tissue and sperm parameters.
Subject(s)
Genitalia, Male , Palm Oil , Animals , Diet , Genitalia, Male/metabolism , Genitalia, Male/physiology , Male , Palm Oil/adverse effects , RatsABSTRACT
ADAMTSs (A disintegrin and metalloproteinase with thrombospondin motifs) are a family of 19 secreted zinc metalloproteinases that play a major role in the assembly and degradation of the extracellular matrix (ECM) during development, morphogenesis, tissue repair, and remodeling. ADAMTS18 is a poorly characterized member of the ADAMTS family. Previously, ADAMTS18 was found to participate in the development of female reproductive tract in mice. However, whether ADAMTS18 also plays a role in the development of male reproductive system remains unclear. In this study, Adamts18 mRNA was found to be highly expressed in the basal cells of the developing preputial gland. Male Adamts18 knockout (Adamts18-/-) mice exhibit abnormal preputial gland morphogenesis, including reduced size and sharp outline. Histological analyses of preputial gland from 2-week-old male Adamts18-/- mice showed significant atrophy of the whole gland. Preputial glands from 7 months and older Adamts18-/- mice appeared macroscopic swelling on their surface. Histologically, preputial gland swelling is characterized by tissue fibrosis and thicker keratinized squamous cell layer. Preputial gland lesions in age-matched male Adamts18+/+ mice were barely detected. ADAMTS18 deficiency does not lead to significant changes in morphogenesis of prostate and testis in male mice. These results indicate that ADAMTS18 is required for normal morphogenesis and homeostasis of the preputial gland in male mice.
Subject(s)
ADAMTS Proteins/metabolism , Fibrosis/pathology , Gene Expression Regulation, Developmental/physiology , Genital Diseases, Male/pathology , Genitalia, Male/abnormalities , ADAMTS Proteins/genetics , Animals , Embryo Culture Techniques , Fibrosis/metabolism , Genital Diseases, Male/metabolism , Genitalia, Male/metabolism , Homeostasis , Male , Mice , Mice, Knockout , RNA, Messenger/genetics , RNA, Messenger/metabolism , TranscriptomeABSTRACT
Successful reproduction is dependent on the transfer of male seminal proteins to females upon mating. These proteins arise from secretory tissues in the male reproductive tract, including the prostate and seminal vesicles in mammals and the accessory gland in insects. Although detailed functional studies have provided important insights into the mechanisms by which accessory gland proteins support reproduction, much less is known about the molecular mechanisms that regulate their expression within this tissue. Here we show that the Drosophila HR39 nuclear receptor is required for the proper expression of most genes that encode male accessory gland proteins. Consistent with this role, HR39 mutant males are infertile. In addition, tissue-specific RNAi and genetic rescue experiments indicate that HR39 acts within the accessory glands to regulate gene expression and male fertility. These results provide new directions for characterizing the mammalian orthologs of HR39, the SF-1 and LRH-1 nuclear receptors, both of which are required for glandular secretions and reproduction. In addition, our studies provide a molecular mechanism to explain how the accessory glands can maintain the abundant levels of seminal fluid production required to support fertility.
Subject(s)
DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Infertility, Male/metabolism , Receptors, Steroid/genetics , Receptors, Steroid/metabolism , Animals , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Fertility/genetics , Gene Expression/genetics , Gene Expression Regulation/genetics , Genitalia, Male/metabolism , Infertility, Male/genetics , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Male , Prostate/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Reproduction/geneticsABSTRACT
Testicular androgen is a master endocrine factor in the establishment of external genital sex differences. The degree of androgenic exposure during development is well known to determine the fate of external genitalia on a spectrum of female- to male-specific phenotypes. However, the mechanisms of androgenic regulation underlying sex differentiation are poorly defined. Here, we show that the genomic environment for the expression of male-biased genes is conserved to acquire androgen responsiveness in both sexes. Histone H3 at lysine 27 acetylation (H3K27ac) and H3K4 monomethylation (H3K4me1) are enriched at the enhancer of male-biased genes in an androgen-independent manner. Specificity protein 1 (Sp1), acting as a collaborative transcription factor of androgen receptor, regulates H3K27ac enrichment to establish conserved transcriptional competency for male-biased genes in both sexes. Genetic manipulation of MafB, a key regulator of male-specific differentiation, and Sp1 regulatory MafB enhancer elements disrupts male-type urethral differentiation. Altogether, these findings demonstrate conservation of androgen responsiveness in both sexes, providing insights into the regulatory mechanisms underlying sexual fate during external genitalia development.
Subject(s)
Genitalia, Male/metabolism , Sex Differentiation , Acetylation , Androgens , Animals , CRISPR-Cas Systems , Female , Gene Expression Regulation , Histones/metabolism , MafB Transcription Factor , Male , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mice, Knockout , Receptors, Androgen , Transcription Factors/metabolismABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19), which causes serious respiratory illnesses such as pneumonia and lung failure, was first reported in mid-December 2019 in China and has spread around the world. In addition to causing serious respiratory illnesses such as pneumonia and lung failure, there have been conflicting reports about the presence of SARS-CoV-2 in the semen of patients who were previously diagnosed with COVID-19 and possible implications for the male reproductive tract. OBJECTIVE: The goal for the present study was to review the current status of the literature concerning COVID-19 and male reproduction. MATERIAL AND METHODS: An electronic literature search was done by using PubMed and Google Scholar databases. Relevant papers, concerning SARS-COV-2 and COVID-19 and male reproduction, published between January 2020 and December 2020 were selected, analyzed and eventually included in the present literature review. RESULTS: SARS-CoV-2 may infect any cell type expressing angiotensin-converting enzyme 2 (ACE2), including reproductive cells. Besides the presence of the SARS-CoV-2 receptor, the expression of host proteases, such as transmembrane serine protease 2 (TMPRSS2), is needed to cleave the viral S protein, allowing permanent fusion of the viral and host cell membranes. Here, we aimed to review the current status of the literature concerning COVID-19 and male reproduction. The lack of co-expression of ACE2 and TMPRSS2 in the testis suggests that sperm cells may not be at increased risk of viral entry and spread. However, the presence of orchitis in COVID-19-confirmed patients and compromised sex-related hormonal balance among these patients intrigues reproductive medicine. DISCUSSION: SARS-CoV-2 may use alternate receptors to enter certain cell types, or the expression of ACE2 and TMPRSS2 may not be detected in healthy individuals. CONCLUSION: COVID-19 challenges all medical areas, including reproductive medicine. It is not yet clear what effects, if any, the COVID-19 pandemic will have on male reproduction. Further research is needed to understand the long-term impact of SARS-CoV-2 on male reproductive function.