Male Reproductive Function Research Articles

Влияние COVID-19 на спермиологические показатели у мужчин репродуктивного возраста

Introduction: The new coronavirus infection is dangerous not only in the acute period of the disease, but also during the period of convalescence, causing various complications. The long-term effects of the SARS-CoV 2 virus on male reproductive function are an important prognostic factor requiring comprehensive study. Purpose of the study: to study the long-term results of the impact of COVID-19 mild to moderate severity on spermological indicators in men of reproductive age. Materials and Methods: the study included 14 healthy men of reproductive age who were not vaccinated against COVID 19, who had negative results of an STI examination, normal spermological parameters, TUNEL test values <15%, who subsequently suffered a viral infection caused by the SARS-CoV 2 virus of mild and moderate severity, with persistent negative results of an STI examination. Results: а comparative analysis of the results of spermograms of patients before and after COVID 19 showed that the total number of spermatozoa before and after the disease (422.5 ± 53.9 and 410.2 ± 176.9 million, respectively), the indicator of the number of spermatozoa with progressive translational (PR) mobility (56.4 ± 8.7 and 54.4 ± 8.0%, respectively), morphologically normal male gametes before and after 3 months after COVID-19 (21.2 ± 4.3 and 20.2 ± 3.6%, respectively) are comparable. Normozoospermia was observed in all cases, TUNEL test values <15%. Conclusion: in the conducted study, mild and moderate COVID-19 did not have a clinically significant effect on the spermological parameters of men 3 months after COVID-19. Keywords: COVID-19, SARS-CoV 2 virus, spermological indicators, TUNEL-test.

The Impact of Vitamin D on Androgens and Anabolic Steroids among Adult Males: A Meta-Analytic Review.

Recent studies indicate that vitamin D impacts male reproductive function, with deficiency linked to infertility. This review evaluates the effect of vitamin D supplementation on male fertility, focusing on total testosterone, free testosterone, the free androgen index (FAI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex-hormone-binding globulin (SHBG), and estradiol. We systematically searched Medline, Web of Science, Cochrane Library, and Scopus from their inception until July 2024 for randomized controlled trials (RCTs) involving adult males. The primary focus of these studies was on reproductive hormone parameters, analyzed using a random-effects meta-analysis and weighted mean difference (WMD). Evidence quality was assessed using ROB2 and GRADE. Meta-regression and dose-response analyses were performed. Seventeen studies met the criteria for quantitative analysis. Vitamin D supplementation significantly increased total testosterone levels (WMD 0.38, 95% CI 0.06-0.70, n = 15, I2 = 67.03). However, it had no significant effect on other hormone parameters: free testosterone (WMD 0.00, 95% CI -0.02-0.03, n = 9, I2 = 48.12), FSH (WMD -0.02, 95% CI -0.57-0.53, n = 7, I2 = 48.72), LH (WMD -0.09, 95% CI -0.30-0.12, n = 8, I2 = 0.00), SHBG (WMD 0.73, 95% CI -1.14-2.61, n = 10, I2 = 69.05), FAI (WMD -0.92, 95% CI -2.12-0.27, n = 6, I2 = 0.00), and estradiol (WMD -0.02, 95% CI -2.95-2.92, n = 5, I2 = 20.63). This meta-analysis shows that vitamin D supplementation may increase total testosterone levels in men. However, further well-designed RCTs are needed to determine vitamin D's effects on other reproductive hormone parameters.

Sub-acute bisphenol A exposure induces proteomic alterations and impairs male reproductive health in mice.

Bisphenol A (BPA) is one of the most prevalent endocrine disrupting chemicals (EDCs) and there is widespread concern about the adverse effects of EDCs on human health. However, the exact mechanism of these toxicities has still not been fully deciphered. Additionally, studies have reported the toxicological effects at far low doses to the generally considered no-observed-adverse-effect level (NOAEL) dose. The present study investigates the effects of a sub-acute (28 days) exposure to BPA (10, 50 and 100 mg/kg/day) in adult male mice on various hormones levels, sperm motility, sperm count, functional integrity of sperm plasma membrane, testicular histological changes, oxidative stress markers and DNA damage. The key proteome signatures were quantified by LC-MS/MS analysis using Orbitrap Fusion Lumos Tribrid Mass Spectrometer equipped with nano-LC Easy-nLC 1200. Data suggest that the BPA exposure in all doses (below/above NOAEL dose) have greatly impacted the hormone levels, sperm parameters (sperm count, motility and membrane integrity) and testicular histology. Mass spectrometry-based proteomics data suggested for 1352 differentially expressed proteins (DEPs; 368 upregulated, 984 downregulated) affecting biological process, cellular component, and molecular functions. Specifically searched male reproductive function related proteins suggested a complex network where 46 potential proteins regulating spermatogenesis, sperm structure, activity and membrane integrity while tackling oxidative stress responses were downregulated. These potential biomarkers could shed some more light on our current understanding of the reproductive toxicological effects of BPA and may lead to exploration of novel interventions strategies against these targets for male infertility.

Mitigating Cadmium-Induced Reproductive Toxicity in Male Wistar Rats: Protective Role of STC30, a Polyherbal Formulation

Background: Cadmium, one of the most toxic heavy metals but which finds its presence in many applications and the environment impairs male reproductive function via oxidative stress. There is a growing interest in the development and usage of polyherbal remedies with high antioxidant base. Super Life Total Care (STC30) is one of such remedies. There is however paucity of information on most of its claimed effects and Cadmium-induced male reproductive toxicity. Methods: Twenty male wistar rats were separated into control, Cadmium-only, STC30-only and Cadmium+STC30 groups of 5 rats each. Once daily administration was for 28 days after which blood and testicular samples collected for determination of relevant parameters. Results: Results showed a significantly reduced (p<0.05) sperm count in the Cadmium-only compared with the control though significantly lower (p<0.05) in the Cadmium+STC30 compared with the STC30-only groups. Sperm motility was significantly reduced in STC30-only but increased in STC30-only compared with control. It was significantly higher (p<0.05) in the STC30-only and Cadmium+STC30 than in the Cadmium-only groups. Sperm viability was significantly reduced in the Cadmium-only compared with control. Teratozotospermia was significantly elevated in the Cadmium-only compared with the control but lower in the Cadmium+STC30 and STC30-only compared with Cadmium-only groups. Serum follicle stimulating hormone, luteinizing hormone and testosterone were significantly reduced (p<0.05) in the Cadmium-only compared with the control groups. Testicular malomdialdehyde and thiobarbituric acid were significantly increased (p<0.05) in the Cadmium-only compared with the control groups, but lower in STC30-only and STC30+Cadmium than in the Cadmium-only groups though higher in Cadmium+STC30 than in the STC30-only groups. Testicular superoxide dismutase, glutathione peroxidase and catalase activities as well as total antioxidant capacity were significantly reduced (p<0.05) in the Cadmium-only compared with the control but higher in the Cadmium+STC30 than in the Cadmium-only groups. Conclusion: In conclusion, STC30 ameliorates Cadmium-induced reproductive toxicity and oxidative stress in male wistar rats.

Asprosin regulates male reproduction in teleosts: an in vitro study in Channa punctata.

The novel adipokine asprosin, produced by the furin enzymatic cleavage of profibrillin 1 protein (encoded by the Fbn1 gene), is implicated in regulating many physiological functions, including reproduction in mammals. In males, asprosin is reported to increase sperm density, sperm motility, and steroid production by interacting with Olfr734, which belongs to the G-protein-coupled receptor family (GPCR). In 2023, our group predicted and characterized asprosin in silico for the first time and demonstrated the robust expression of fbn1, and furin in the gonads of teleost spotted snakehead (ss) Channa punctata. Taking it forward, in the current study, we have investigated the effect of asprosin on the testicular functions of the spotted snakehead. As C. punctata is a seasonal breeder, the reproductive-phase-dependent expression of fbn1 in the testis was analyzed, showing significant upregulation during the preparatory and post-spawning phases. Additionally, bacterially overexpressed recombinant asprosin of C. punctata was purified to study the effect of ss asprosin on gametogenesis and steroidogenesis. Ex vivo treatment with recombinant asprosin resulted in significant upregulation of spermatogenic marker genes pcna, aldh1a2, cyp26a1, and sycp3. Asprosin also enhanced the gene expression of gonadotropin receptors, as well as sex steroid receptors, in addition to steroidogenic genes star and cyp17a1. Further exploring the downstream signaling cascade, the second messenger of GPCRs, cAMP levels following asprosin treatment were analyzed. Asprosin treatment prominently enhanced cAMP levels, thereby indicating the involvement of GPCR in the transduction of asprosin action. Hence, the study elucidates the regulation of male reproductive function by asprosin in spotted snakeheads.

Impact of arsenic on male and female reproductive function: a review of the pathophysiology and potential therapeutic strategies.

Arsenic is a ubiquitous metalloid and heavy metal that contributes to the global decline in human fertility. Humans are constantly exposed to arsenic through biotic and abiotic sources, especially ingestion of arsenic-contaminated food and water. Its exposure is associated with several adverse health challenges, including reproductive toxicity. In spite of its reported adverse effects, arsenic exposure remains a global challenge. Hence, this study provides a comprehensive review of the literature on the impact and mechanism of arsenic on male and female reproductive function. Additionally, a review of the potential therapeutic strategies is presented. Evidence from the literature reveals that arsenic upregulates reactive oxygen species (ROS) generation which mediates arsenic-induced suppression of the hypothalamic-pituitary-gonadal axis and inactivation of 3β-HSD and 17β-HSD activities, leading to reduced gonadal steroidogenesis. Through several oxidative stress-dependent signaling, arsenic induces the apoptosis of the germ cells, thus contributing to the development of infertility. At the moment, there is no specific treatment for arsenic-induced reproductive toxicity. However, increasing data form the scientific literature reveals the benefits of antioxidants in ameliorating arsenic-induced reproductive toxicity. These molecules suppress ROS generation and maintain optimal activities of the hypothalamic-pituitary-gonadal axis, leading to optimal steroidogenesis and gametogenesis as well as improved germ cells. Overall, this study revealed the impact and associated mechanism of arsenic-induced reproductive toxicity. It also provides evidence from the literature demonstrating potential therapeutic measures in managing arsenic-induced reproductive toxicity.

A comprehensive review on p38MAPK signaling as a potent radioprotector in testis.

Previous studies have shown that the activation of p38MAPK signaling plays a crucial role in regulating gonadal cell fate decisions in both mouse and human. Excessive activation of p38MAPK by radiation significantly causes testicular damage and negatively affects the male reproductive function. Therefore, fine-tuned regulation of p38MAPK signaling is critical in both physiological and pathological conditions. This review summarizes the impact of p38MAPK signaling on testicular germ cells and microenvironment under normal condition. The relationship between radiation, reactive oxygen species (ROS), and p38MAPK is summarized. In conclusion, radiation exposure triggers the overactivation of p38MAPK, which is regulated by ROS, resulting in testicular damage. Various p38MAPK-targeting agents are discussed, providing guidance for developing new strategies.

Sirtuin 1-mediated autophagy regulates testosterone synthesis in Leydig cells of piglets

Testosterone is secreted by Leydig cells (LCs), which play an important physiological role in preserving male secondary sex characteristics, protecting male reproductive function, and establishing the blood-testis barrier. Studies have shown that autophagy is particularly active in LCs; however, its involvement in testosterone synthesis in porcine LCs has not been fully explored. Therefore, this experiment aimed to investigate the influence of autophagy on testosterone secretion in porcine LCs and its potential regulatory mechanism. Our results demonstrated that both testicular autophagy and serum testosterone levels increased in piglets during postnatal development from 4 to 18 weeks. In addition, autophagy was found to degrade the Na+/H+ exchange regulatory factor 2 (NHERF2), leading to the up-regulation of scavenger receptor class B type 1 (SRB1). This process resulted in increased cholesterol intake and enhanced testosterone production. The observable level of sirtuin 1 (SIRT1) was directly proportional to the level of autophagy. In vitro investigations have shown that SIRT1 can affect the level of autophagy, cholesterol uptake as well as testosterone release. In conclusion, testosterone synthesis during pig development is regulated by SIRT1. SIRT1 mediates the degradation of NHERF2 through autophagy, thereby weakening its negative regulatory effect on the high-density lipoprotein receptor SRB1 in Leydig cells. This process increases cholesterol uptake and enhances testosterone synthesis.

The Protective Role of Vitamin E on the Liver, Kidney, and Male Reproductive Functions of Paracetamol Overdose in Male Rabbits

The Protective Role of Vitamin E on the Liver, Kidney, and Male Reproductive Functions of Paracetamol Overdose in Male Rabbits

Cytotoxicity and Apoptotic DNA Fragmentation Evaluation of Ethanolic Extract of Phyllanthus niruri L. in Vero and Primary Feline Testicular Cells

Phyllanthus niruri or Dukung Anak is native to Southeast Asia, particularly in Malaysia and has been used as traditional preparations and as health supplements. However, previous studies have found that P. niruri can impair the male reproductive functions. With booming population of stray animals within the community, a new controlling method that is more affordable and safer must be developed. This study was aimed to explore the safety of P. niruri as a male herbal contraceptive to be used in veterinary medicine as one of the non-surgical sterilisation methods. For the preliminary part of this ongoing research, we have investigated the cytotoxicity activity of P. niruri ethanolic extract on Vero and primary feline testicular cells (FTC) and DNA apoptotic activity in FTC. Phyllanthus niruri extract was prepared using cold maceration method in 50% ethanol. The FTC were prepared from feline testes obtained from post-routine castration from local private veterinary clinics, while Vero cells were obtained from the archived cells of Virology Laboratory, Faculty of Veterinary Medicine Universiti Malaysia Kelantan (FPV UMK). The MTT assay was performed to evaluate the cytotoxicity of these plant extracts on FTC and Vero cells. Apoptosis was assessed using DNA laddering assay on extracted DNA of the treated FTC cells and observed the DNA patterns in gel electrophoresis. The 50% cytotoxic concentration (CC50) of the ethanolic extract of P. niruri was a dose dependent. The DNA laddering assay revealed that the plant extract does not induce apoptosis in FTC. Therefore, the study outcomes indicated that the ethanolic extract of P. niruri is potentially safe for animal use. However, in vivo studies are required to confirm these findings.

Expression of SARS-CoV-2 entry molecules ACE2, NRP1, TMPRSS2, and FURIN in the reproductive tissues of male macaques.

Coronavirus disease 2019 (COVID-19) reportedly affects male reproductive function by causing spermatogenesis dysfunction and suppressing testosterone secretion. However, the relationship between COVID-19 and impaired reproductive function, such as whether these effects on reproductive function are a direct effect of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in male reproductive organs or an indirect effect of high fever, is not known. Here, we examined whether the cell entry molecules of SARS-CoV-2, namely, ACE2, NRP1, TMPRSS2, and FURIN, are expressed in the male reproductive organs using the testes and accessory gonads of macaques during the breeding season. RT-PCR expression analysis showed that the testes alone expressed all four molecules. Immunohistochemical staining of testis tissue sections revealed that ACE2 is expressed in Leydig cells and the apical region of Sertoli cells, whereas NRP1 is expressed in the cell bodies surrounding the Leydig and Sertoli cell nuclei. FURIN is mainly expressed in Leydig cells, secondary spermatocytes, and spermatids. However, TMPRSS2 immunopositive cells were not observed. Therefore, it was not possible to observe cells expressing all four molecules in the gonads and accessory gonads of male primates. These results suggest that SARS-CoV-2 is unlikely to directly affect spermatogenesis in primates or proliferate in cells of the seminiferous tubules and undergo release into the semen through the previously known ACE2-mediated infection route. However, the expression of three molecules, including ACE2, was observed in Leydig cells, suggesting that testosterone synthesis and secretion may be affected when primates, including humans, are infected with SARS-CoV-2.

Fluorene-9-bisphenol impaired male fertility through disrupting the testicular function and local microenvironment

Past studies have observed that BHPF induces multi-organ toxicity, however, whether it induces damage to male reproductive system and the specific mechanism remains unclear. In the present study, male mice were given 0, 2, 10 or 50 mg/kg/day of BHPF by gavage for 35 days to observe its effect on reproductive organ and sperm quality. The results indicated that BHPF decreased sperm count and sperm motility in a dose-dependent manner. Besides, our results demonstrated that BHPF triggered the proliferation inhibition and cell death of germ cells in vivo and in vitro. Also, BHPF reduced the expression of function markers for germ cells, Sertoli cells, and Leydig cells, indicating its damage to function of testis cells. Simultaneously, testicular microenvironment was found to be altered by BHPF, as presented with declined testosterone level and decreased expression of local microenvironment regulators. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting testicular function and local microenvironment disturbance as mechanism underlying testicular damage.

Eighteen genes primarily expressed in the testis are not required for male fertility in mice†.

There are approximately 20000 protein-coding genes in humans and mice. More than 1000 of these genes are predominantly expressed in the testis or are testis-specific and thought to play an important role in male reproduction. Through the production of gene knockout mouse models and phenotypic evaluations, many genes essential for spermatogenesis, sperm maturation, and fertilization have been discovered, greatly contributing to the elucidation of their molecular mechanisms. On the other hand, there are many cases in which single-gene knockout models do not affect fertility, indicating that tissue-specific genes are not always critical. Here, we selected 18 genes whose mRNA expression is restricted to the testis or higher than in other tissues, but whose function in male reproduction is unknown. We then created single-gene KO mouse models using the CRISPR/Cas9 system. The established KO males were subjected to mating tests and screened for effects on fecundity, revealing that these genes were not essential for spermatogenesis and male fertility. This knowledge will contribute to understanding the functions of genes characteristic of the testis and identify the cause of male infertility.

Phytochemical Evaluation of Lepidium meyenii, Trigonella foenum-graecum, Spirulina platensis, and Tribulus arabica, and Their Potential Effect on Monosodium Glutamate Induced Male Reproductive Dysfunction in Adult Wistar Rats.

Monosodium glutamate (MSG), a sodium salt derived from glutamic acid, is widely used in commercial food products to improve taste, quality, and preservation. However, its consumption may have detrimental effects on male reproductive function. Nevertheless, plant extracts, such as Lepidium meyenii (Maca), Trigonella foenum-graecum (Fenugreek), Spirulina platensis (Spirulina), and Tribulus arabica (Tribulus), may ameliorate these adverse effects. To this effect, the phytochemical properties of Lepidium meyenii, Trigonella foenum-graecum, Spirulina platensis, and Tribulus arabica were assessed, and their potential impact on MSG-induced impairment of reproductive parameters was examined. The phytochemical composition (steroids, terpenes, phenols, flavonoids) of the plants was profiled through spectrophotometry and the antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Thirty-six male Wistar rats were divided into six groups at random: a control group receiving distilled water, and five experimental groups (MSG, Maca, Fenugreek, Spirulina, and Tribulus) receiving 900 mg/kg/day of MSG dissolved in water for 45 days. Subsequently, the animals in the experimental groups were administered 500 mg/kg/day of the respective plant extract via oral gavage for an additional 35 days, while the MSG group continued to receive water only. Following the treatment period, the animals were sacrificed, and their reproductive tract organs were collected, weighed, and subjected to further analysis. Phytochemical analysis revealed the presence of diverse bioactive elements in the plant extracts, including phenolic and flavonoid compounds. Exposure to MSG negatively impacted total and progressive sperm motility, which was ameliorated by Lepidium meyenii treatment. Sperm morphology showed no significant differences among groups. Treatment of the phytochemical agents diminished histomorphometric alternations of the testicular length, germinal epithelium height, and number of cells in seminiferous tubules, which were caused by the initial administration of MSG. Testosterone and LH levels were reduced in the MSG group but improved in extract-treated groups. The study suggests Lepidium meyenii as a potential remedy for reproductive dysfunction. However, further investigation into its mechanisms and human safety and efficacy is warranted.

Whole-body exposure to filtered fraction of diesel exhaust induced localized testicular damage through attenuated functional response of glutathione-s-transferase in adult male Wistar rats

The possible vulnerability of the male reproductive system to environmental pollutants such as air pollution necessitates a thorough investigation of the underlying mechanisms involved in the dysregulation of male reproductive function. The present study was designed to investigate the influence of the filtered fraction of diesel exhaust (predominantly comprising gases) on male reproductive function in Wistar rat model. Adult male rats were randomly assigned into three groups (n=8/group): Control (unexposed) group (CG-A), the Clean air group in WBE chamber (CAG-A), and Filtered diesel exhaust group in WBE chamber (FDG-A). The exposure protocol for CAG-A and FDG-A was 6 h/day x 5d/week x 6 weeks,evaluation of sperm parameters, testicular histopathology, quantification of hormones (testosterone, LH, FSH, 17β-Estradiol, and prolactin), and GST levels were performed. Results showed that WBE to FDE leads to a significant decline in sperm concentration (p=0.008, CG-A vs FDG-A; p=0.014, CAG-A vs FDG-A), motility (p=0.008, CG-A vs FDG-A; p=0.029, CAG-A vs FDG-A), serum testosterone (p=0.024, CG-A vs FDG-A; p=0.007, CAG-A vs FDG-A), testicular testosterone (p=0.008, CG-A vs FDG-A; p=0.028, CAG-A vs FDG-A), 17β-Estradiol (p=0.007, CG-A vs FDG-A), and GST levels (p=0.0002, CG-A vs FDG-A; p=0.0019, CAG-A vs FDG-A). These findings demonstrate the disruption of testosterone-estradiol balance in the intratesticular milieu without significant alterations in other principal pituitary hormones in adult rats exposed to FDE. The predominant presence of gaseous components in FDE can cause testicular damage due to oxidative imbalance. This underscores the causality of FDE exposure and impaired male reproductive outcomes.

Effect of Humanin and MOTS-c on ameliorating reproductive damage induced by prepubertal cyclophosphamide chemotherapy in male mice

Male patients who undergo prepubertal chemotherapy face the dual problems of fertility preservation in adulthood, including low testosterone, hypersexual function, and infertility. Humanin, as a small polypeptide coded within the mitochondrial DNA, with the mitochondrial short open reading frame named MOTS-c, both was believed to regulate mitochondrial homeostasis, be anti-inflammatory, improve metabolism, anti-apoptosis, and multiple pharmacological effects. However, there exists little evidence that reported Humanin and MOTS-c 's effects on moderating male spermatogenic function of patients after prepubertal chemotherapy. Here, we found that in vivo, mitochondrial polypeptides Humanin analog (HNG) and MOTS-c efficaciously protected the testicular spermatogenic function from reproductive injury. Moreover, transcriptomic sequencing analysis was performed to verify the differentially expressed genes such as Piwil2, AGT (angiotensinogen), and PTGDS (glycoprotein prostaglandin D2 synthase), which are related to the regulation of male reproductive function of male mice induced by prepubertal chemotherapy. Collectively, our data revealed that both Humanin analogs HNG and MOTS-c are the feasible approaches attached to the protective effect on the male reproductive function damaged by prepubertal chemotherapy.

Mumps: A case report

The widespread of mumps and its medical and social significance determine the relevance of further study of the etiology, epidemiology, diagnosis, treatment, and prevention of mumps infection. Despite the lack of mortality, the possible occurrence of complications that affect the suppression of male reproductive function makes mumps a priority. Official statistics show the annual incidence of mumps in the Russian Federation, estimated in hundreds of cases up to several thousand (2017–2018). The continued spread of mumps is associated with violations of immunization regimens, underestimation of the unvaccinated population or unreliability of the reported data, introduction of new viral genotypes capable of bypassing vaccine immunity, and natural weakening of post-vaccination immunity. The presented clinical case refers to an outpatient case of mumps in a 53-year-old man with a delayed diagnosis despite the typical clinical manifestations. The clinical case demonstrates the lack of awareness of outpatient practitioners about the manifestations of mumps. The causes of mumps in older age groups and possible ways to solve the problem are discussed.

MASLD does not affect fertility and senolytics fail to prevent MASLD progression in male mice

Senescent cells have been linked to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effectiveness of senolytic drugs in reducing liver damage in mice with MASLD is not clear. Additionally, MASLD has been reported to adversely affect male reproductive function. Therefore, this study aimed to evaluate the protective effect of senolytic drugs on liver damage and fertility in male mice with MASLD. Three-month-old male mice were fed a standard diet (SD) or a choline-deficient western diet (WD) until 9 months of age. At 6 months of age mice were randomized within dietary treatment groups into senolytic (dasatinib + quercetin [D + Q]; fisetin [FIS]) or vehicle control treatment groups. We found that mice fed choline-deficient WD had liver damage characteristic of MASLD, with increased liver size, triglycerides accumulation, fibrosis, along increased liver cellular senescence and liver and systemic inflammation. Senolytics were not able to reduce liver damage, senescence and systemic inflammation, suggesting limited efficacy in controlling WD-induced liver damage. Sperm quality and fertility remained unchanged in mice developing MASLD or receiving senolytics. Our data suggest that liver damage and senescence in mice developing MASLD is not reversible by the use of senolytics. Additionally, neither MASLD nor senolytics affected fertility in male mice.

Identification of Catecholamine and Drug Target α2A-Adrenoceptor in Human Testis and Human Testicular Peritubular Cells.

Background: Clonidine has been used in clinical medicine, e.g., to treat high blood pressure and other conditions. Animal studies have linked its use to impairments of male reproductive functions, and although only a few reports exist for the human species, such actions may exist in man as well. The underlying reasons and, specifically, possible actions of clonidine at the level of the testis are not known. Introduction: Clonidine is an agonist at the α2A-adrenoceptor (ADRA2A), which, as data bank mining indicated, is expressed by several cells of the human testis. The human testis and most of its cells are, however, not readily accessible to experimental testing. Cells from the peritubular wall compartment (human testicular peritubular cells; HTPCs) are the exception. Methods and Results: As shown by immunohistochemical/immunocytochemical and PCR techniques these cells express ADRA2A and retain expression upon isolation and culture. When tested over a concentration range (1-1000 µM) and 24 h, clonidine did not visibly affect HTPC morphology but significantly stimulated IL6 mRNA levels in a concentration-dependent manner. ELISA measurements of cell culture supernatants confirmed a stimulatory action of clonidine (10 µM) on secreted IL6. When examined in collagen gel contraction assays of HTPCs, clonidine (10 µM) exerted a slight relaxing action, while a proteomic study revealed that clonidine (10 µM) did not significantly change cellular protein abundance of HTPCs after 24 h (data available via ProteomeXchange with identifier PXD052220). Conclusion: Thus, ADRA2A-bearing cells in the human testis are targets for catecholamines and drugs such as clonidine. The results of this HTPCs-focused study only show the tip of the iceberg. It is likely that catecholamines/catecholaminergic drugs have the potential to interfere with human testicular functions.

Toxicity to the Male Reproductive System after Exposure to Polystyrene Nanoplastics: A Macrogenomic and Metabolomic Analysis.

Nanoplastics (NPs) cause serious contamination of drinking water and potential damage to human health. This study aimed to investigate the effects of NPs with different particle sizes and concentrations on the reproductive function of male mice. In this study, free drinking water exposure was used to expose male BALB/C mice to PS-NPs (20 nm, 200 nm, and 1000 nm) at 0.1 mg/L, 1 mg/L, and 5 mg/L for 4 months. The male reproductive function of the mice was assessed after NPs exposure, and fecal and blood samples were collected for macrogenomics and metabolomics. The results showed that PS-NPs resulted in mice with reduced testicular organ coefficients, decreased sperm quality, altered testicular tissue structure, disturbed sex hormone levels, and abnormal levels of inflammatory factors and oxidative stress. Furthermore, this study found that NP exposure affected the alteration of gut communities and metabolic pathways related to male reproduction, such as Clostridium and glutathione metabolism. Importantly, we found an effect of NP particle size on reproductive function. In the future, more attention should be paid to the smaller particle sizes of NPs.