Male Reproductive Function Research Articles

Effects of dioxin exposure on reproductive and thyroid hormone levels and male sexual function in airbase military workers in Vietnam.

Dioxins are endocrine disruptors that may disturb male sexual and reproductive function. Studies on human populations are limited, and their results are controversial. This study evaluated the impact of dioxin exposure on reproductive and thyroid hormone levels and sexual function in men. A total of 140 men working in four military airbases (three bases were formerly contaminated with dioxin by the herbicide spraying campaign in the Vietnam War) were recruited to measure the serum dioxin levels. Four reproductive hormones (testosterone, follicle-stimulating hormone, luteinizing hormone (LH), and prolactin) and three thyroid hormones (free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone) were measured. Male sexual function endpoints including sexual drive, erection, ejaculation, problems, and overall satisfaction were assessed by the Brief Male Sexual Function Inventory. The percentage of subjects with low testosterone and LH levels was 19.6% and 16.7%, respectively. Dioxins, especially 2,3,7,8-tetrachlorodibenzo-P-dioxin and toxic equivalent concentrations of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans, were inversely associated with testosterone and prolactin levels, but positively associated with FT3 and FT4, and showed adverse relationships with sexual function, such as sexual drive, problems, and overall satisfaction. Our results suggested that exposure to dioxin disrupts the homeostasis of reproductive and thyroid hormones leading to adverse effects on male sexual function.

Impact of COVID-19 on Male Reproductive Function (Literature Review)

Impact of COVID-19 on Male Reproductive Function (Literature Review)

Association between post-COVID-19 conditions and male semen quality in Japan: A descriptive investigation

Some reports suggest that coronavirus disease 2019 (COVID-19) may affect male reproductive function. There is also concern in Japan that COVID-19 may contribute to the pre-existing decline in male fertility; however, no studies have investigated the effects of COVID-19 on male reproductive function. In this study, we aimed to analyze the semen quality of men who had recovered from COVID-19. Male patients who had recovered from COVID-19 between February 2020 and September 2021 were recruited for this study. Participants were sent a semen collection kit; they were asked to collect semen at home and deliver it to a laboratory at Osaka University. We used these samples to analyze sperm concentration, total sperm count, and semen volume. In total, 125 participants were included in this study. The median age of all patients was 46 years (interquartile range (IQR): 38–52 years). The severity of COVID-19 was mild in 80 patients; 19 were moderate I, 22 were moderate II, and four were severe. The median semen volume was 2.5 mL (IQR: 1.8–3.1), the median sperm concentration was 98.9 million/mL (IQR: 43.8–162.2), and the median total sperm count was 212.1 million (IQR: 89.7–368.2). In a previous study in Japan, the median sperm count in adult men was reported to be 201 million. Participants in our study did not have lower sperm counts than this, despite their older age. Our results suggest that the long-term effects of COVID-19 on spermatogenesis are minimal.

The role of nitric oxide in the development of diseases of the male reproductive system and its potential applications in clinical practice

Nitric oxide (NO), a reactive nitrogen species, is a molecule of high physiological and pathological importance. Physiological mechanisms mediated by NO mainly include angiogenesis, growth, puberty, and senescence. NO has vital roles in normal reproduction, including steroidogenesis, gametogenesis, and the regulation of germ-cell apoptosis. In males, NO is a key player in steroidogenesis, erectile functions, sperm capacitation, and acrosome reaction. Moreover, NO is also a regulator of Sertoli cell-germ cell interaction and maintenance of the blood-testis barrier. In pathological conditions such as infections, increased nitric oxide synthase activities stimulate the excessive synthesis of NO which acts as a proinflammatory mediator inducing oxidative stress, detrimental to reproductive functions in males. Excessive NO synthesis disrupts gonadal functions and induces germ cell apoptosis and oxidative damage to the germ cells. This review elucidates how the differences in NO expression levels account for its beneficial and adverse impacts on male fertility.

The Impact of Conventional Cigarettes, Nicotine-containing and Nicotine-free Electric Cigarettes on Testicular Weight of Male Wistar Rats

E-cigarettes are gaining increasing popularity worldwide. The World Health Organization (WHO) estimates that there are nearly one billion (984 million) smokers globally, accounting for approximately one-fifth of the adult population. The use of e-cigarettes in Southeast Asian countries has also seen a rise since 2015, although at a slower pace compared to high-income countries. Presently, Indonesia has the highest prevalence of e-cigarette use in Southeast Asia at 11.8%, while Thailand has the lowest prevalence at 3.3%. Testes play a crucial role in male reproductive function. Decreased testicular size can lead to disruptions in testicular function, resulting in infertility. Testicular size is significantly correlated with sperm density in both fertile and infertile men. The objective of this study is to investigate changes in testicular weight due to exposure to conventional cigarettes, nicotine-containing, and nicotine-free e-cigarettes. This experimental research utilizes a post-test control only design. The sample comprises 24 male Wistar rats divided into four groups: Group A (control), Group B (exposed to conventional cigarettes), Group C (exposed to nicotine e-cigarettes), and Group D (exposed to non-nicotine e-cigarettes). Exposure to cigarettes lasts for 30 days, after which the rats undergo surgery to remove their testes. The research findings indicate a decrease in testicular size due to exposure to conventional cigarettes, nicotine e-cigarettes, and non-nicotine e-cigarettes. There is no significant difference observed among the three types of exposure. In conclusion, conventional cigarettes, nicotine-containing, and nicotine-free e-cigarettes elicit similar effects in reducing testicular weight in male Wistar rats.

Consequences of gene editing of PRLR on thermotolerance, growth, and male reproduction in cattle.

Global warming is a major challenge to the sustainable and humane production of food because of the increased risk of livestock to heat stress. Here, the example of the prolactin receptor (PRLR) gene is used to demonstrate how gene editing can increase the resistance of cattle to heat stress by the introduction of mutations conferring thermotolerance. Several cattle populations in South and Central America possess natural mutations in PRLR that result in affected animals having short hair and being thermotolerant. CRISPR/Cas9 technology was used to introduce variants of PRLR in two thermosensitive breeds of cattle - Angus and Jersey. Gene-edited animals exhibited superior ability to regulate vaginal temperature (heifers) and rectal temperature (bulls) compared to animals that were not gene-edited. Moreover, gene-edited animals exhibited superior growth characteristics and had larger scrotal circumference. There was no evidence for deleterious effects of the mutation on carcass characteristics or male reproductive function. These results indicate the potential for reducing heat stress in relevant environments to enhance cattle productivity.

Variation of sperm quality and circular RNA content in men exposed to environmental contamination with heavy metals in 'Land of Fires', Italy.

Can illegal discharge of toxic waste into the environment induce a new condition of morpho-epigenetic pathozoospermia in normozoospermic young men? Toxic environmental contaminants promote the onset of a new pathozoospermic condition in young normozoospermic men, consisting of morpho-functional defects and a sperm increase of low-quality circular RNA (circRNA) cargo, tightly linked to contaminant bioaccumulation in seminal plasma. Epidemiological findings have reported several reproductive anomalies depending on exposure to contaminants discharged into the environment, such as germ cell apoptosis, steroidogenesis defects, oxidative stress induction, blood-testis barrier dysfunctions, and poor sperm quality onset. In this scenario, a vast geographical area located in Campania, Italy, called the 'Land of Fires', has been associated with an excessive illegal discharge of toxic waste into the environment, negatively impacting human health, including male reproductive functions. Semen samples were obtained from healthy normozoospermic men divided into two experimental groups, consisting of men living in the 'Land of Fires' (LF; n = 80) or not (CTRL; n = 80), with age ranging from 25 to 40 years. The study was carried out following World Health Organization guidelines. Quality parameters of semen from CTRL- and LF-normozoospermic men were evaluated by computer-assisted semen analysis; high-quality spermatozoa from CTRL and LF groups (n = 80 for each experimental group) were obtained using a 80-40% discontinuous centrifugation gradient. Seminal plasma was collected following centrifugation and used for the dosage of chemical elements, dioxins and steroid hormones by liquid chromatography with tandem mass spectrometry. Sperm morpho-functional investigations (cellular morphology, acrosome maturation, IZUMO1 fertility marker analysis, plasma membrane lipid state, oxidative stress) were assessed on the purified high-quality spermatozoa fraction by immunochemistry/immunofluorescence and western blot analyses. Sperm circRNA cargo was evaluated by quantitative RT-PCR, and the physical interaction among circRNAs and fused in sarcoma (FUS) protein was detected using an RNA-binding protein immunoprecipitation assay. Protein immunoprecipitation experiments were carried out to demonstrate FUS/p-300 protein interaction in sperm cells. Lastly, in vitro lead (Pb) treatment of high-quality spermatozoa collected from normozoospermic controls was used to investigate a correlation between Pb accumulation and onset of the morpho-epigenetic pathozoospermic phenotype. Several morphological defects were identified in LF-spermatozoa, including: a significant increase (P < 0.05 versus CTRL) in the percentage of spermatozoa characterized by structural defects in sperm head and tail; and a high percentage (P < 0.01) of peanut agglutinin and IZUMO1 null signal cells. In agreement with these data, abnormal steroid hormone levels in LF seminal plasma suggest a premature acrosome reaction onset in LF-spermatozoa. The abnormal immunofluorescence signals of plasma membrane cholesterol complexes/lipid rafts organization (Filipin III and Flotillin-1) and of oxidative stress markers [3-nitrotyrosine and 3-nitrotyrosine and 4-hydroxy-2-nonenal] observed in LF-spermatozoa and associated with a sperm motility reduction (P < 0.01), demonstrated an affected membrane fluidity, potentially impacting sperm motility. Bioaccumulation of heavy metals and dioxins occurring in LF seminal plasma and a direct correlation between Pb and deregulated circRNAs related to high- and low-sperm quality was also revealed. In molecular terms, we demonstrated that Pb bioaccumulation promoted FUS hyperacetylation via physical interaction with p-300 and, in turn, its shuttling from sperm head to tail, significantly enhancing (P < 0.01 versus CTRL) the endogenous backsplicing of sperm low-quality circRNAs in LF-spermatozoa. Participants were interviewed to better understand their area of origin, their eating habits as well as their lifestyles, however any information incorrectly communicated or voluntarily omitted that could potentially compromise experimental group determination cannot be excluded. A possible association between seminal Pb content and other heavy metals in modulating sperm quality should be explored further. Future investigations will be performed in order to identify potential synergistic or anti-synergistic effects of heavy metals on male reproduction. Our study provides new findings regarding the effects of environmental contaminants on male reproduction, highlighting how a sperm phenotype classified as normozoospermic may potentially not match with a healthy morpho-functional and epigenetic one. Overall, our results improve the knowledge to allow a proper assessment of sperm quality through circRNAs as biomarkers to select spermatozoa with high morpho-epigenetic quality to use for ART. This study was supported by 'Convenzione Azienda Sanitaria Locale (ASL) Caserta, Regione Campania' (ASL CE Prot. N. 1217885/DIR. GE). The authors have no conflict of interest to declare. N/A.

A network pharmacology-based approach to explore the potentials of Saluang belum (Luvunga sarmentosa) in the male human reproductive system

Background: Saluang belum's root (Luvunga sarmentosa) is one of the local plants in Central Kalimantan and is used by the Dayaknese to increase sexual activity. In previous research, L. sarmentosa root extract compounds have been characterised, but the bioactivity of each on male fertility has not been studied. Objective: To use bioinformatics to study the effects and mechanisms of molecular compounds of L. sarmentosa extract on the biological system of the male fertility complex. Methods: Network pharmacology methods were used to determine target essentially functional proteins in biological system networks. The molecular mechanism of L. sarmentosa compound activity was analysed using molecular docking and dynamic simulation software such as Autodock 4 and MOE. Result: The network pharmacology analysis showed that the Pregnane X receptor (PXR) protein contributed essentially to male reproductive biological functions. Based on the molecular docking simulations of PXR, 6-phenyl-3,4-dihydro-1H-1,4,5-benzotriazocin-2-one was the best. Pharmacological and toxicity parameters also showed that this compound had good characteristics. In addition, the molecular dynamics simulations showed that the best compounds could maintain complex interactions with PXR based on the resulting RMSD values. Conclusion: The compound 6-phenyl-3,4-dihydro-1H-1,4,5-benzotriazocin-2-one had the most potential as a PXR inductor. This compound also had a better activity than the standard inductor.

The level of sex and fertility hormones in the serum of male patients recovered from COVID-19

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that generated the COVID­-19 pandemic is a broad-spectrum infection that besides the respiratory tract, can attack multiple organs, including­ the digestive, circulatory, and urinary systems. However, the negative consequences of SARS-CoV-2 on the male reproductive system have been largely ignored. The aim of this research was to see how SARS-CoV-2 affects the production of hormones, which are the markers of male reproductive function and fertility. The 350 Iraqi male participants were classified into two groups consisting of 150 COVID-19 recovered patients with a mean age of (32 ± 7.9) years and COVID-19 diagnosis confirmed by RT-PCR, and 200 apparently healthy male volunteers of similar age. The patients’ group was further divided into three groups depending on the recovery period of 3, 5 and 7 months. Serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin were measured using the Mindray CL-1000i automated chemiluminescence analyzer provided with matching kits. When comparing the indices of COVID-19 recovered participants to the control group, the results revealed a decrease in testosterone level that was positively associated with the recovery period and an increase in the LH, FSH and prolactin levels that were negatively associated with the recovery period. It is supposed that infection with SARS-CoV-2 may be followed by a temporary condition of testicular failure. Keywords: male fertility, SARS-COV-2, sex hormones

Effectiveness of Herbal medicines on male reproductive system: Evidence from meta-analysis

BackgroundThe increasing prevalence of male infertility has become a global concern. Traditional Chinese and Asian medicines have long been using herbal remedies to promote spermatogenesis. This study aimed to systematically explore the potential of herbal medicines and formulations to enhance the male reproductive function in humans. MethodsTwo prominent databases, MEDLINE and EMBASE, as well as scientific journals indexed in the Web of Science, were used for the literature search until October 2023. The studies included in the analysis focused on the impact of herbal medicines (Mucuna pruriens, Withania somnifera, Eurycoma longifolia, Panax ginseng, Lycopersicon esculentum, Crocus sativus, Vitis vinifera, Nigella sativa, Sesamum indicum, Curcuma longa, Lepidium peruvianum) and Chinese and Korean Polyherbal formulations (Shao-Fu-Zhu-Yu-Tang; 少腹逐瘀汤) on human serum reproductive hormone levels, semen parameters, and antioxidant enzymes. ResultsA total of 23 articles were deemed eligible for the review and meta-analysis, which included 1,194 men from seven countries (China, Korea, Iran, Peru, Japan, Malaysia, and India). Of these, 19 articles were analyzed for semen parameters. The use of herbal medicine increased seminal parameters, including semen volume during each ejaculation (standardized mean difference (SMD) = 0.89; 95 % CI: 0.52, 1.26), sperm concentration (SMD = 1.97; 95 % CI: 1.30, 2.64), total sperm count (SMD = 2.28; 95 % CI: 1.44, 3.11), sperm motility (SMD = 1.07; 95 % CI: 0.68, 1.46), and normal morphology (SMD = 1.47; 95 % CI: 0.62, 2.32). Additionally, 18 articles that analyzed sex hormone levels showed that treatment with herbal medicines favorably reduced serum prolactin (SMD = -0.70; 95 % CI: -1.13, -0.28) and FSH levels (SMD = -1.07; 95 % CI: -1.56, -0.56). Meanwhile, herbal medicines did not affect testosterone levels (SMD = 0.41; 95 % CI: -0.24, 1.06) and LH levels (SMD = 0.45; 95 % CI: -0.33, 1.23). Finally, six articles were analyzed for seminal biochemical and antioxidant profiles, and the results showed that herbal medicine increased the levels of ascorbic acid (SMD = 1.19; 95 % CI: 0.51, 1.86), corrected seminal fructose (SMD = 1.32; 95 % CI: 0.89, 1.76), superoxide dismutase activity (SOD) (SMD = 1.06; 95 % CI: 0.45, 1.68), and catalase activity (SMD = 0.91; 95 % CI: 0.69, 1.44) in seminal plasma. ConclusionHerbal remedies have been found to promote spermatogenesis by optimizing semen parameters, sex hormone levels, and antioxidant profiles. As a result, these treatments should be regarded as complementary approaches to male infertility.

Perfluorooctane sulfonate-induced Sertoli cell injury through c-Jun N-terminal kinase: a study by RNA-Seq.

Per- and polyfluoroalkyl substances (PFASs) are a family of "forever chemicals" including perfluorooctane sulfonate (PFOS). These toxic chemicals do not break down in the environment or in our bodies. In the human body, PFOS and perfluoroctanoic acid (PFOA) have a half-life (T1/2) of about 4-5 yr so low daily consumption of these chemicals can accumulate in the human body to a harmful level over a long period. Although the use of PFOS in consumer products was banned in the United States in 2022/2023, this forever chemical remains detectable in our tap water and food products. Every American tested has a high level of PFAS in their blood (https://cleanwater.org/pfas-forever-chemicals). In this report, we used a Sertoli cell blood-testis barrier (BTB) model with primary Sertoli cells cultured in vitro with an established functional tight junction (TJ)-permeability barrier that mimicked the BTB in vivo. Treatment of Sertoli cells with PFOS was found to perturb the TJ-barrier, which was the result of cytoskeletal disruption across the cell cytoplasm, disrupting actin and microtubule polymerization. These changes thus affected the proper localization of BTB-associated proteins at the BTB. Using RNA-Seq transcriptome profiling, bioinformatics analysis, and pertinent biochemical and cell biology techniques, it was discovered that PFOS -induced Sertoli cell toxicity through the c-Jun N-terminal kinase (JNK; also known as stress-activated protein kinase, SAPK) and its phosphorylated/active form p-JNK signaling pathway. More importantly, KB-R7943 mesylate (KB), a JNK/p-JNK activator, was capable of blocking PFOS-induced Sertoli cell injury, supporting the notion that PFOS-induced cell injury can possibly be therapeutically managed.NEW & NOTEWORTHY PFOS induces Sertoli cell injury, including disruption of the 1) blood-testis barrier function and 2) cytoskeletal organization, which, in turn, impedes male reproductive function. These changes are mediated by JNK/p-JNK signaling pathway. However, the use of KB-R7943, a JNK/p-JNK activator was capable of blocking PFOS-induced Sertoli cell injury, supporting the possibility of therapeutically managing PFOS-induced reproductive dysfunction.

Effects of Chicory (Cichorium intybus L.) Extract on Male Rat Reproductive System, Pregnancy and Offspring Development.

We recently reported that extract prepared from the aerial part of Cichorium intybus L. (CE) possesses hepatoprotective, hypolipidemic, and hypoglycemic properties. This paper focuses on the effects of CE on the male rat reproductive system and the effects of this treatment on pregnancy and offspring development. The experimental male rats received 100 mg/kg bw/day, 500 mg/kg bw/day, and 1000 mg/kg bw/day of CE orally for 60 consecutive days. Rats that received tap water were used as controls. After treatment, we evaluated the effects of CE on the male reproductive system, fertility, and offspring development. For CE-treated male rats, there was a significant increase in the (1) diameter of seminiferous tubules, (2) spermatogenic index, (3) number of total and motile spermatozoa, and (4) testosterone levels. Additionally, there was a decrease in the pre- and post-implantation death of the embryos in the CE-treated group. All pups born from CE-treated males demonstrated normal development. CE treatment significantly improved male reproductive functions. No adverse effects on pregnancy and offspring development were observed when males were treated with CE. Further clinical evaluation of CE should lead to the development of a safe and effective phytodrug for treating male infertility.

NGF, EPO, and IGF-1 in the Male Reproductive System.

Several studies have demonstrated interesting results considering the implication of three growth factors (GFs), namely nerve growth factor (NGF), erythropoietin (EPO), and the insulin-like growth factor-I (IGF-1) in the physiology of male reproductive functions. This review provides insights into the effects of NGF, EPO, and IGF-1 on the male reproductive system, emphasizing mainly their effects on sperm motility and vitality. In the male reproductive system, the expression pattern of the NGF system varies according to the species and testicular development, playing a crucial role in morphogenesis and spermatogenesis. In humans, it seems that NGF positively affects sperm motility parameters and NGF supplementation in cryopreservation media improves post-thaw sperm motility. In animals, EPO is found in various male reproductive tissues, and in humans, the protein is present in seminal plasma and testicular germ cells. EPO receptors have been discovered in the plasma membrane of human spermatozoa, suggesting potential roles in sperm motility and vitality. In humans, IGF-1 is expressed mainly in Sertoli cells and is present in seminal plasma, contributing to cell development and the maturation of spermatozoa. IGF-1 seems to modulate sperm motility, and treatment with IGF-1 has a positive effect on sperm motility and vitality. Furthermore, lower levels of NGF or IGF-1 in seminal plasma are associated with infertility. Understanding the mechanisms of actions of these GFs in the male reproductive system may improve the outcome of sperm processing techniques.

The male reproductive toxicity after 5-Fluorouracil exposure: DNA damage, oxidative stress, and mitochondrial dysfunction in vitro and in vivo

5-Fluorouracil (5-FU), a chemotherapeutic drug used to treat a variety of cancers, can enter the environment through different routes, causing serious public health and environmental concerns. It has been reported that 5-FU exposure adversely affects male reproductive function, and its effects on this system cannot be avoided. In this study, using western blotting and quantitative polymerase chain reaction studies, we found that 5-FU promoted testicular injury by inducing oxidative stress, which was accompanied by the inhibition of nuclear factor erythroid 2-related factor 2/antioxidant response element signaling. Accumulation of reactive oxygen species (ROS) aggravated 5-FU-mediated mitochondrial dysfunction and apoptosis in murine cell lines and testes, indicating oxidative stress and mitochondrial-dependent apoptotic signaling play crucial roles in the damage of spermatogenic cells caused. N-Acetyl-L-cysteine, an antioxidant that scavenges intracellular ROS, protected spermatogenic cells from 5-FU-induced oxidative damage and mitochondrial dysfunction, revealing the important role of ROS in testicular dysfunction caused by 5-FU. We found that 5-FU exposure induces testicular cell apoptosis through ROS-mediated mitochondria pathway in mice. In summary, our findings revealed the reproductive toxicological effect of 5-FU on mice and its mechanism, provided basic data reference for adverse ecological and human health outcomes associated with 5-FU contamination or poisoning.

Testis–Gut-Reproduction Axis: The Key to Reproductive Health

Reproductive health is an important issue for humanity. In the context of the increasing incidence rate of male infertility, it is essential to find the factors that affect male reproductive health. Gastrointestinal health is closely related to reproductive health. Gastrointestinal hormones (GIH) and gut microbiota (GM), as important material foundations for gastrointestinal function, can promote or inhibit testicular reproductive function, including spermatogenesis, sperm maturation, androgen synthesis, and even broader male diseases such as sexual function, prostate cancer, etc. On the contrary, the functional health of the testes is also of great significance for the stability of gastrointestinal function. This review mainly discusses the important regulatory effects of GIH and GM on male reproductive function.

Microcystin-LR Induces Estrogenic Effects at Environmentally Relevant Concentration in Black-Spotted Pond Frogs (Pelophylax nigromaculatus): In Situ, In Vivo, In Vitro, and In Silico Investigations.

Harmful cyanobacterial blooms are frequent and intense worldwide, creating hazards for aquatic biodiversity. The potential estrogen-like effect of Microcystin-LR (MC-LR) is a growing concern. In this study, we assessed the estrogenic potency of MC-LR in black-spotted frogs through combined field and laboratory approaches. In 13 bloom areas of Zhejiang province, China, the MC-LR concentrations in water ranged from 0.87 to 8.77 μg/L and were correlated with sex hormone profiles in frogs, suggesting possible estrogenic activity of MC-LR. Tadpoles exposed to 1 μg/L, an environmentally relevant concentration, displayed a female-biased sex ratio relative to controls. Transcriptomic results revealed that MC-LR induces numerous and complex effects on gene expression across multiple endocrine axes. In addition, exposure of male adults significantly increased the estradiol (E2)/testosterone (T) ratio by 3.5-fold relative to controls. Downregulation of genes related to male reproductive endocrine function was also identified. We also showed how MC-LR enhances the expression of specific estrogen receptor (ER) proteins, which induce estrogenic effects by activating the ER pathway and hypothalamic-pituitary-gonadal (HPG) axis. In aggregate, our results reveal multiple lines of evidence demonstrating that, for amphibians, MC-LR is an estrogenic endocrine disruptor at environmentally relevant concentrations. The data presented here support the need for a shift in the MC-LR risk assessment. While hepatoxicity has historically been the focus of MC-LR risk assessments, our data clearly demonstrate that estrogenicity is a major mode of toxicity at environmental levels and that estrogenic effects should be considered for risk assessments on MC-LR going forward.

Gut microbiota is involved in male reproductive function: a review.

Globally, ~8%-12% of couples confront infertility issues, male-related issues being accountable for 50%. This review focuses on the influence of gut microbiota and their metabolites on the male reproductive system from five perspectives: sperm quality, testicular structure, sex hormones, sexual behavior, and probiotic supplementation. To improve sperm quality, gut microbiota can secrete metabolites by themselves or regulate host metabolites. Endotoxemia is a key factor in testicular structure damage that causes orchitis and disrupts the blood-testis barrier (BTB). In addition, the gut microbiota can regulate sex hormone levels by participating in the synthesis of sex hormone-related enzymes directly and participating in the enterohepatic circulation of sex hormones, and affect the hypothalamic-pituitary-testis (HPT) axis. They can also activate areas of the brain that control sexual arousal and behavior through metabolites. Probiotic supplementation can improve male reproductive function. Therefore, the gut microbiota may affect male reproductive function and behavior; however, further research is needed to better understand the mechanisms underlying microbiota-mediated male infertility.

Differentiation of bone marrow mesenchymal stem cells into Leydig-like cells with testicular extract liquid in vitro.

Differentiation of Leydig cells plays a key role in male reproductive function. Bone marrow mesenchymal stem cells (BMSCs) have emerged as a potential cell source for generating Leydig-like cells due to their multipotent differentiation capacity and accessibility. This study aimed to investigate the morphological and genetic expression changes of BMSCs during differentiation into Leydig-like cells. Testicular extract liquid, which simulates the microenvironment in vivo, induced the third passage BMSCs differentiated into Leydig-like cells. Changes in cell morphology were observed by microscopy, the formation of lipid droplets of androgen precursor was identified by Oil Red Staining, and the expression of testicular specific genes 3β-HSD and SF-1 in testicular stromal cells was detected by RT-qPCR. BMSCs isolated from the bone marrow of Sprague-Dawley (SD) rats were cultured for 3 generations and identified as qualified BMSCs in terms of morphology and cell surface markers. After 14 days of induction with testicular tissue lysate, lipid droplets appeared in the cytoplasm of P3 BMSCs by Oil Red O staining. RT-qPCR detection was performed on BMSCs on the 3rd, 7th, 14th, and 21st day after induction. Relative expression levels of 3β-HSD mRNA significantly increased after 14 days of induction, while the relative expression of SF-1 mRNA increased after 14 days of induction but was not significant. BMSCs can differentiate into testicular interstitial cells with reserve androgen precursor lipid droplets after induction by testicular tissue lysate. The differentiation ability of BMSCs provides the potential to reconstruct the testicular microenvironment and is expected to fundamentally improve testicular function and provide new treatment options for abnormal spermatogenesis diseases.

Deoxynivalenol Inhibits Progenitor Leydig Cell Development by Stimulating Mitochondrial Fission in Rats.

Deoxynivalenol (DON) is a common food contaminant that can impair male reproductive function. This study investigated the effects and mechanisms of DON exposure on progenitor Leydig cell (PLC) development in prepubertal male rats. Rats were orally administrated DON (0-4 mg/kg) from postnatal days 21-28. DON increased PLC proliferation but inhibited PLC maturation and function, including reducing testosterone levels and downregulating biomarkers like HSD11B1 and INSL3 at ≥2 mg/kg. DON also stimulated mitochondrial fission via upregulating DRP1 and FIS1 protein levels and increased oxidative stress by reducing antioxidant capacity (including NRF2, SOD1, SOD2, and CAT) in PLCs in vivo. In vitro, DON (2-4 μM) inhibited PLC androgen biosynthesis, increased reactive oxygen species production and protein levels of DRP1, FIS1, MFF, and pAMPK, decreased mitochondrial membrane potential and MFN1 protein levels, and caused mitochondrial fragmentation. The mitochondrial fission inhibitor mdivi-1 attenuated DON-induced impairments in PLCs. DON inhibited PLC steroidogenesis, increased oxidative stress, perturbed mitochondrial homeostasis, and impaired maturation. In conclusion, DON disrupts PLC development in prepubertal rats by stimulating mitochondrial fission.

Male reproductive function before and after the adjustment of the COVID-19 prevention policy: a multicenter study in China.

At the end of 2022, the adjustment of the coronavirus disease 2019 (COVID-19) pandemic control policy in China resulted in a large-scale increase in public infection. To compare the fertility parameters of male patients before and after the adjustments of the COVID-19 pandemic control policy in China, we collected data on patients' medical histories and laboratory examinations on their first visits between June 2022 and March 2023 in five different hospitals. Data were divided into five groups according to the timeline of the policy adjustment. The data we collected from male patients included semen quality and serum reproductive hormone levels, and intergroup comparisons were made using the Mann-Whitney U and Chi-square tests. In total, 16 784 cases underwent regular semen analysis, 11 180 had sperm morphology assessments, and 7200 had reproductive hormone analyses. The data showed declining trends in semen volume, sperm motility, and the progressive sperm motility rate after the policy adjustment. Subgroup comparison revealed an initial decrease and gradual recovery in progressive motility rate. Sperm morphology analysis showed increased neck and tail abnormalities after the policy adjustment. No significant change in hormone levels was observed. Following the adjustment of the COVID-19 prevention policy in China, a decline in sperm motility and morphology was observed. This trend may gradually recover over 2 months. After the policy adjustment, reproductive hormone levels were relatively stable throughout, except for an increase in luteinizing hormone (LH). These changes in semen parameters suggest that the policy adjustment had a short- to medium-term impact on male reproductive function.