Male Reproductive Dysfunction Research Articles

Protective effects of green and chemical zinc oxide nanoparticles on testis histology, sperm parameters, oxidative stress markers and androgen production in rats treated with cisplatin.

Cancer treatment with cisplatin (CP) is associated with adverse side effects on male reproductive tissues. Although beneficial effects of zinc oxide nanoparticles (ZnO NPs) in cancer therapy have received considerable attention, data related to the protective effects of green ZnO NPs against CP-induced male reproductive dysfunctions are limited. Forty-five rats were divided into 9 groups including G1 (control), G2 (sham), G3 (ZnO bulk), G4 (green ZnO NPs), G5 (chemical ZnO NPs), G6 (CP), G7 (CP + ZnO bulk), G8 (CP + green ZnO NPs), and G9 (CP + chemical ZnO NPs). CP was administrated (5mg/kg/week) for 4weeks, and animals were simultaneously treated with different forms of ZnO (5mg/kg/day). Testis histology, sperm parameters, oxidative stress markers, testosterone concentration, and expression of genes related in steroidogenesis were analyzed in different experimental groups. Testis tissue damage and epididymal sperm disorders induced by CP attenuated when animals were treated with different forms of ZnO, especially green ZnO NPs. Decreased testosterone concentration and increased MDA level in CP-treated rats were reversed following administration different forms of ZnO, especially green and chemical ZnO NPs. Co-administration of ZnO NPs to CP-treated rats restored the suppressive effects of CP on activities of antioxidant enzymes (SOD, GPX, CAT) and the transcription of the STAR gene. None of the ZnO forms had a significant regulatory effect on the expression of CYP11A1 in CP-treated rats. The results showed that in most of the evaluated factors, green ZnO NPs showed a greater protective effect than other forms of ZnO.

Diabetes Mellitus Causes Male Reproductive Dysfunction: A Review of the Evidence and Mechanisms

The metabolic disorders caused by diabetes can lead to various complications, including dysfunction of the male reproductive system. In patients with diabetes, long-term hyperglycemia results in diabetic vascular neuropathy, oxidative stress injury, abnormal zinc metabolism, and insulin resistance syndrome. In addition, insulin deficiency and resistance in diabetes can damage the hypothalamus, pituitary gland, gonads, and perigonads. This can reduce the secretion of sex hormones including gonadotropin-releasing hormone, follicle stimulating hormone, luteinizing hormone, and testosterone, and can lead to testicular atrophy, stromal cell atrophy, seminiferous tubule damage, spermatogenic cell damage, and other structural injuries of the male reproductive organs. These actions can affect male fertility and reproductive health. Herein, we review studies that report a causative role of diabetes in male reproductive function. We also discuss the evidence-based mechanisms involved in the processes of diabetes-related male sexual and reproductive dysfunction as well as the progress in treatment.

Endocrine-disrupting activity of mancozeb.

The objective of the present study was to review the existing data on the mechanisms involved in the endocrine disrupting activity of mancozeb (MCZ) in its main targets, including thyroid and gonads, as well as other endocrine tissues that may be potentially affected by MCZ. MCZ exposure was shown to interfere with thyroid functioning through impairment of thyroid hormone synthesis due to inhibition of sodium-iodine symporter (NIS) and thyroid peroxidase (TPO) activity, as well as thyroglobulin expression. Direct thyrotoxic effect may also contribute to thyroid pathology upon MCZ exposure. Gonadal effects of MCZ involve inhibition of sex steroid synthesis due to inhibition of P450scc (CYP11A1), as well as 3β-HSD and 17β-HSD. In parallel with altered hormone synthesis, MCZ was shown to down-regulate androgen and estrogen receptor signaling. Taken together, these gonad-specific effects result in development of both male and female reproductive dysfunction. In parallel with clearly estimated targets for MCZ endocrine disturbing activity, namely thyroid and gonads, other endocrine tissues may be also involved. Specifically, the fungicide was shown to affect cortisol synthesis that may be mediated by modulation of CYP11B1 activity. Moreover, MCZ exposure was shown to interfere with PPARγ signaling, being a key regulator of adipogenesis. The existing data also propose that endocrine-disrupting effects of MCZ exposure may be mediated by modulation of hypothalamus-pituitary-target axis. It is proposed that MCZ neurotoxicity may at least partially affect central mechanisms of endocrine system functioning. However, further studies are required to unravel the mechanisms of MCZ endocrine disrupting activity and overall toxicity.

Apoptosis and Blood-Testis Barrier Disruption in PAHS of Different Molecular Weights-Induced Male Reproductive Dysfunction

Apoptosis and Blood-Testis Barrier Disruption in PAHS of Different Molecular Weights-Induced Male Reproductive Dysfunction

Wuzi Yanzong Pill-Based on Network Pharmacology and In Vivo Evidence-Protects Against Spermatogenesis Disorder via the Regulation of the Apoptosis Pathway.

The crisis of male infertility is an issue of human reproductive health worldwide. The Wuzi Yanzong pill (WZYZP) is a traditional Chinese medicine prescription that shows efficacy in kidney reinforcement and essence benefit to ameliorate male reproductive dysfunctions. However, the pharmacological mechanisms of the WZYZP on male infertility have not been investigated and clarified clearly. This study was designed to investigate the effects of the WZYZP on spermatogenesis disorder and explore its underlying pharmacological mechanisms. First, based on a network pharmacology study, 39 bioactive compounds and 40 targets of the WZYZP associated with spermatogenesis disorder were obtained, forming a tight compound-target network. Molecular docking tests showed tight docking of these compounds with predicted targeted proteins. The protein–protein interaction (PPI) network identified TP53, TNF, AKT1, Bcl-XL, Bcl-2, and IκBA as hub targets. The Kyoto Encyclopedia of Genes and Genomes pathway network and pathway-target-compound network revealed that the apoptosis pathway was enriched by multiple signaling pathways and multiple targets, including the hub targets. Subsequently, the chemical characterization of WZYZP was analyzed using liquid chromatography to quadrupole/time-of-flight mass spectrometry, and 40 compounds in positive ion mode and 41 compounds in negative ion mode in the WZYZP were identified. Furthermore, based on the prediction of a network pharmacology study, a rat model of spermatogenesis disorder was established to evaluate the curative role and underlying mechanisms of the WZYZP. The results showed that WZYZP treatment improved rat sperm quality and attenuated serum hormone levels, reversed histopathological damage of the testis, reduced cell apoptosis in testis tissues, and ameliorated the expression of the predicted hub targets (TP53, TNF-α, AKT1, NFκB, and IκBA) and the apoptosis related proteins (Bcl-XL, Bcl-2, Bax, Caspase 3, and Caspase 9). These results indicated that the WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy.

Artemisia judaica L. diminishes diabetes-induced reproductive dysfunction in male rats via activation of Nrf2/HO-1-mediated antioxidant responses.

Diabetes mellitus is a well-known danger element for the progression of male reproductive dysfunctions. Available evidence supports oxidative stress to be the underlying mechanism for the manifestation of testicular dysfunctions during diabetes, and this relation represents an attractive target to antagonize these complications. Artemisia judaica L. is known to have antidiabetic and antioxidant characteristics. The possible protective effect of Artemisia judaica against diabetes-induced testicular disorders was not explored. In this investigation, we planned to estimate the possible protective effect of Artemisia judaica extract against diabetes-induced testicular disorders in male rats. The blood levels of insulin, glucose, glycosylated hemoglobin, testosterone, luteinizing hormone and follicle stimulating hormone were evaluated in rats after 12weeks of Artemisia judaica treatment. Further, oxidative stress markers were determined in their testicular tissue. Epididymal fluid and testicular histological changes were also assessed. Expression of proliferating cell nuclear antigen has been evaluated in testis. Testicular mRNA expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 as the significant transcription factors in controlling antioxidant system were evaluated by real-time polymerase chain reaction. Artemisia judaica extracts have the ability to ameliorate the elevation in the serum glucose and blood glycosylated hemoglobin and the reduction in insulin, testosterone, follicle stimulating hormone and luteinizing hormone caused by streptozotocin-induced diabetes. It induced a significant recovery of the testicular oxidative stress markers, sperm characteristics and improved histopathological findings of the testes. Treatment with Artemisia judaica extracts led to an increase in proliferating cell nuclear antigen protein expression. Reduction of testicular oxidative stress potential in streptozotocin-treated groups was confirmed by upregulation of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1.

Bisphenol S perturbs Sertoli cell junctions in male rats via alterations in cytoskeletal organization mediated by an imbalance between mTORC1 and mTORC2

Bisphenol S (BPS) is now used as an alternative of bisphenol A (BPA), but has been implicated in male reproductive dysfunction—including diminished sperm number and quality and altered hormonal concentrations. However, the mechanisms of action subserving these effects remains unclear. In the present study, BPS at doses of 50 mg/kg bw and 100 mg/kg bw caused defects in the integrity of the blood-testis barrier (BTB) and apical ectoplasmic specialization (ES), and we also delineated an underlying molecular mechanism of action. BPS induced F-actin and α-tubulin disorganization in seminiferous tubules, which in turn led to the truncation of actin filaments and microtubules. Additionally, BPS was found to perturb the expression of the actin-binding proteins Arp3 and Eps8, which are critical for the organization of the actin filaments. mTORC1 and mTORC2 manifest opposing roles in Sertoli cell junctional function, and we demonstrated that mTORC1/rpS6/Akt/MMP9 signaling was increased and that mTORC2/rictor activity was also attenuated. In summary, we showed that BPS-induced disruption of the BTB and apical ES perturbed normal spermatogenic function that was mediated by mTORC1 and mTORC2. The imbalance in mTORC1 and mTORC2, in turn, altered the expression of actin-binding proteins, resulting in the impairment of F-actin and MT organization, and inhibited the expression of junctional proteins at the BTB and apical ES.

The effect of Nigella sativa oil and metformin on male seminal parameters and testosterone in Wistar rats exposed to an obesogenic diet

Obesity is a significant global health and socio-economic challenge, and considered an important risk factor for poor health outcomes including male reproductive dysfunction and infertility. As excess adiposity causes testicular dysfunction and infertility, novel therapeutic strategies require investigation. Nigella sativa (Ns) seed oil and metformin have both demonstrated a potential positive effect on obesity, although both remain poorly investigated in male fertility. Therefore, this study aimed to determine the effect of Ns oil and metformin on total body weight (TBW), mitochondrial membrane potential (MMP), serum testosterone and semen parameters in an obese animal model. Wistar rats (n = 54) were divided into six groups: normal chow (NC), high sugar diet (HSD) only, HSD and saline, HSD and metformin (75 mg/Kg/day), HSD and Ns (200 mg/Kg/day) (NS200), HSD and Ns (400 mg/Kg/day) (NS400). Intervention was force fed for the last 8 weeks of the 14 weeks dietary exposures. Results showed that the HSD increased TBW (P = 0.001) and reduced sperm concentration (P = 0.013) and progressive motility (P = 0.009) compared to the NC group. Metformin, NS200 and NS400 improved TBW (P = 0.035, P = 0.006 and P = 0.005, respectively) and testosterone (P < 0.001) compared to the HSD saline group, where metformin and NS400 improved sperm concentration (P < 0.001 and P = 0.049, respectively) and MMP (P < 0.001). There were no changes in sperm motility and viability for all experimental exposures, although NS400 (P = 0.047) negatively affected sperm viability. Metformin and Ns may be novel treatment options in obesity-induced infertility, although a potential negative impact on viability is cautioned for high dose Ns. These results warrant further investigation of Ns and Metformin for the management of obese infertile males.

Caulerpa lentillifera Polysaccharides-Rich Extract Reduces Oxidative Stress and Proinflammatory Cytokines Levels Associated with Male Reproductive Functions in Diabetic Mice

Diabetes mellitus is a chronic metabolic disease that is positively correlated with reproductive dysfunction. Caulerpa lentillifera is an edible green alga with antioxidant and anti-diabetic properties. This study aims to evaluate the ameliorative effects of a polysaccharides-rich extract from C. lentillifera on the reproductive dysfunctions of diabetic male BALB/c mice induced by a high-fat diet (HFD) supplemented with intraperitoneal injections of streptozotocin (STZ). C. lentillifera was obtained from hot water and converted into a powder form (C. lentillifera extract (CLE)) by freeze drying. Mice were fed an HFD for 4 weeks before supplementing with STZ (30 mg/kg). The diabetic mice were divided into five groups, including a control group, a diabetic (DM) group, a DM with administration of a low-dose CLE treatment (DM+CLE1, 600 mg/kg), a DM with administration of a high-dose of CLE (DM+CLE2, 1000 mg/kg) and a DM with metformin treatment as a positive control (DM+Met, 200 mg/kg) for 6 weeks. The results showed that the CLE administration improved hyperglycemia and insulin resistance. Proinflammatory cytokines such as interleukin-1β and tumor necrosis factor-α were found to decrease in the CLE-treated groups. Additionally, CLE was shown to improve sperm motility and testis morphology. Based on the results, it was confirmed that the polysaccharides-rich extract from C. lentillifera extract was able to prevent diabetes-induced male reproductive dysfunction.

Chlorogenic acid abates male reproductive dysfunction in arsenic-exposed mice via attenuation of testicular oxido-inflammatory stress and apoptotic responses

Arsenic, a major environmental pollutant of global concern, is well-known for its reproductive toxicity. In this study, the protective potential of chlorogenic acid (CGA), a caffeoylquinic acid isomer abundantly found in many plants, was investigated against sodium arsenite (NaAsO2)-induced testicular dysfunctions. Adult male Swiss mice were either administered NaAsO2 alone at 5 mg kg−1 or co-treated with CGA at 100 mg kg−1 or 200 mg kg−1 body weight for 4 weeks. Results showed that NaAsO2-treated mice exhibited marked declines in testes weight, sperm count, and viability accompanied by decreases in sexual hormonal levels. Moreover, NaAsO2 toxicity evoked exhaustion of antioxidant markers (SOD, CAT, GPx, GR, and GSH), down-regulation of Nrf2 (nuclear factor erythroid 2–related factor 2) gene expression level, and elevations in malondialdehyde. Further, elevations in inflammatory cytokines (IL-1, TNF-α, and IL-6) together with the up-regulation of pro-apoptotic biomarkers (Bax and caspase- 3) and down-regulation of anti-apoptotic Bcl-2 were observed in NaAsO2 intoxication. Immunohistochemical analysis of testis sections of NaAsO2-treated mice showed high caspase-3 expression. These findings were well supported with testicular histopathological examination. However, pretreatment of mice with CGA resulted in noteworthy improvements in testicular damage induced by arsenic in a dose-dependent manner possibly mediated by the Nrf2 signaling pathway. Conclusively, CGA counteracted arsenic-induced testicular injury through its antioxidant, anti-inflammatory, and anti-apoptotic properties. Therefore, CGA could serve as a favorable intervention in the alleviation of arsenic-induced reproductive toxicity.

Angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas receptor in gonadal and reproductive functions.

Angiotensin (Ang)-(1-7) is an active peptide formed from Ang I or Ang-(1-9) by multiple proteolytic steps involving angiotensin-converting enzyme (ACE) 1 and other peptidases, or by a single cleavage of Ang II catalyzed chiefly by ACE2. The effects of Ang-(1-7) are mediated by the G protein-coupled receptor Mas (or Mas1), encoded by the protooncogene MAS. The reproductive system expresses ACE2 quite abundantly and therefore is able to generate Ang-(1-7) using precursor peptides produced locally or taken from circulation. In several mammalian species, Ang-(1-7) stimulates ovarian follicle growth, oocyte maturation and ovulation. The peptide is found in human endometrium, mostly during the secretory phase of menstrual cycle when the uterus is receptive to embryo implantation. Rat models and human observational studies suggest that Ang-(1-7) is part of the maternal adaptive response to pregnancy and its deficiency is associated with poor circulation in the placental bed. Knockout mice revealed a relevant participation of Mas-mediated stimulus to the maintenance of normal spermatogenesis, even though the animal can still reproduce without it. In addition, the vasorelaxant effect of Ang-(1-7) participates in the physiological mechanism of corpus cavernosum blood influx and penile erection. We conclude that preclinical evidence encourages the pursuit of treatments for female and male reproductive dysfunctions based on Mas agonists, starting with its natural ligand Ang-(1-7).

Impact of prenatal arsenic exposure on the testes and epididymides of prepubertal rats

Arsenic is a pollutant widely found in the environment due to natural and anthropogenic sources. Exposure to arsenic forms in drinking water has been related with male reproductive dysfunctions in humans and experimental animals at adult age. However, the impact of this pollutant on postnatal reproductive development of male offspring exposed in utero to arsenic is still unknown. Therefore, this study aimed to investigate the effects of prenatal arsenic exposure on the postnatal development of the testes and epididymides of rats, during prepuberty. For this purpose, pregnant female Wistar rats were provided drinking water containing 0 or 10 mg/L sodium arsenite (AsNaO2) from gestational day 1 (GD 1) until GD 21 and the male offspring was evaluated in different periods of prepuberty. Our results showed that prenatal arsenic exposure affected the initial sexual development of male pups, reducing their body weight and relative anogenital distance at postnatal day 1. At different periods of prepuberty, male pups from arsenic exposed dams showed a reduction of body and reproductive organs weights, testosterone levels and testis morphometric parameters. Moreover, these pups presented changes in the expression of SOD1, SOD2, CAT and GSTK1 genes and in the activity of superoxide dismutase, catalase and glutathione s-transferase in the testes and epididymides during prepuberty. Taken together, our results show that prenatal arsenic exposure provoked reproductive disorders in prepubertal male rats, probably due to reproductive reprograming and oxidative stress induced by this pollutant.

The Beneficial Role of Anchomanes difformis in STZ-Induced Reproductive Dysfunction in Male Wistar Rats.

BackgroundProgression of diabetes mellitus has increasingly led to several diabetic complications. Diabetes is one of the major factors implicated in male reproductive system damage. Recent approaches such as the use of medicinal plants have been explored in the management of diabetes and associated complications. Anchomanes difformis (common name: children’s umbrella) has been shown to possess anti-diabetic ability in animal model. Therefore, this study seeks to investigate the potency of Achomanes difformis in ameliorating diabetes-induced reproductive dysfunction.MethodsType 2 diabetes was induced in male Wistar rats with 10% fructose administration for 2 weeks and an intraperitoneal injection of 40mg/kgBW of streptozotocin. Aqueous extract (200mg and 400mg/kgBW) of Anchomanes difformis leaves was administered daily for 6 weeks. The rats were randomly divided into 7 groups with a minimum of eight rats in each (8 rats in normal groups and 10 in diabetic groups). The impact of diabetes and treatment was investigated by estimating sperm concentration, motility indices, viability and morphological parameters in the normal, treatment controls and diabetic rats using CASA-SCA system. Histological examination of the testes and epididymis was performed.ResultsDiabetes induction resulted in significant decrease in sperm concentration, viability and some motility parameters with 40% abnormalities in sperm morphology. The administration of Anchomanes difformis significantly increased sperm concentration and sperm viability, while it significantly improved the percentage of morphologically normal sperm in diabetic rats. Anchomanes difformis ameliorated testicular damage such as vacuolization and loss of germinal epithelium in the diabetic-treated rats when compared to the diabetic controls.ConclusionThe potency Anchomanes difformis displayed against diabetic-induced damage in the reproductive system might be a new and promising tool in the management of male reproductive dysfunctions and associated complications in diabetes mellitus.

The Relationship of Preconception Urinary Phthalate Levels with Fecundability and Pregnancy Loss

Background/Aim: Phthalates are endocrine disrupting chemicals widely used as plasticizers and in personal care products. In utero exposure has been linked to pregnancy complications, childhood developmental delay and male reproductive dysfunction; however, studies of impact on establishing pregnancy are limited.Methods: The EAGeR trial enrolled 1,228 women attempting pregnancy with 1-2 prior pregnancy losses and followed them for up to 6 menstrual cycles and throughout pregnancy if they became pregnant. Pregnancy was assessed in each cycle using hCG testing and pregnancy loss determined when a positive hCG was followed by an observed loss. Twenty phthalate metabolites, including mono-(2-ethylhexyl) phthalate (mEHP), monobutyl phthalate (mBP) and monobenzyl phthalate (mBzP), were measured in a pooled sample of three consecutive daily spot urines from the beginning of the first menstrual cycle of follow-up to reduce exposure misclassification. Discrete-time survival and log-binomial models evaluated fecundability and pregnancy loss adjusting for creatinine and participant characteristics.Results: Phthalate concentrations were similar to other U.S. cohorts (e.g. median 6.6, interquartile range 4.1-12.4 ng/mL for mEHP). Overall, mEHP, mBP and mBzP were associated with lower fecundability (fecundability odds ratio [FOR] 0.90, 95% confidence interval [CI] 0.82-0.98 per log[mEHP]). Effect modification was observed by C-reactive protein (CRP) and body mass index (BMI), with mEHP, mEHP metabolites, mBP and mBzP associated with lower fecundability among those with higher CRP (FOR 0.77, 95% CI 0.65-0.90 for CRP≥1.95 mg/L and FOR 0.98, 95% CI 0.88-1.09 for CRP&lt;1.95 mg/L per log[mEHP]) and higher BMI (FOR 0.69, 95% CI 0.56-0.85 for BMI≥30 kg/m2 and FOR 0.99, 95% CI 0.88-1.11 for BMI&lt;25 kg/m2 per log[mEHP]). No relationship was observed between phthalates and pregnancy loss.Conclusions: Higher exposure to certain phthalates was associated with lower fecundability. Associations were strongest among women with higher BMI and inflammation, who may represent a key target group for screening and intervention.

Effect of Nano-Titanium Dioxide on Blood-Testis Barrier and MAPK Signaling Pathway in Male Mice.

Some studies have found that nano-sized titanium dioxide (nano-TiO2) has adverse effects on the male reproductive system. Blood-testis barrier (BTB), as one of the tightest blood-tissue restriction, is crucial to the male reproductive system. However, the potential effects on BTB and signaling pathway changes in testis tissue induced by nano-TiO2 remain poorly understood. Therefore, in this study, 60 Institute of Cancer Research mice were divided randomly into four groups (per group = 15). The mice of four groups were intragastrically administered with 0, 10, 50, and 100mg/kg BW nano-TiO2 respectively for 30days to analyze the changes of BTB structure, BTB-related proteins, and MAPK signal pathways. Besides, testosterone level, estradiol level, and sperm parameter (sperm count, sperm motility, and sperm malformation rate) changes were also studied in this research. The results indicated that nano-TiO2 could induce the BTB structural damage and accompanied by the BTB main protein (ZO-1, Claudin-11, and F-actin) elevation of irritability. Nano-TiO2 could also activate the MAPK signaling pathways (p38, JNK, and ERK) of mice testis tissue. The testosterone and estradiol levels in serum reduced. Besides when the mice were administered with nano-TiO2, we also found the sperm motility rate decreased, and sperm malformation increased. The above changes may be associated with BTB damage and the activation of MAPK signaling pathways, thereby causing male reproductive dysfunction.

Lead and cadmium exposure induces male reproductive dysfunction by modulating the expression profiles of apoptotic and survival signal proteins in tea-garden workers

The aim of this study was to evaluate the impact of Lead (Pb) and Cadmium (Cd) exposure at the molecular level on the reproductive status of tea garden workers in North-East India. Using semen samples, we experimentally determined sperm analysis as well as oxidative stress parameters in all samples and evaluated the expression levels of apoptotic and cell survival proteins [p53, phospho-Akt, nuclear factor-κB (NF-κB, p50 subunit) and B cell lymphoma 2 (Bcl2)]. Our data revealed significant differences in the average heavy metal concentrations and various semen analysis profile between the infertile and normal groups. Increasing Pb and Cd concentrations in semen samples of patients showed positive associations with increasing number of multiple defects in sperm and the level of seminal oxidative stress markers in the high Pb and Cd concentration groups. These groups also exhibited positive correlations between high metal concentrations and the average p53 expression levels, but negative correlations with the mean p-Akt cascade protein levels in sperm cells. In the low Pb and Cd concentrations groups, we also observed reverse mean range and correlation patterns. Therefore, our findings may suggest that graded levels of metal exposure significantly influence the relative fluctuation in the levels of p53 and Akt cascade proteins in the sperm cells of infertile subjects. Furthermore, this may be a regulating factor of sperm cell fate, in turn, determining the fertility outcome of the men working in the tea gardens.

Diet-induced obesity is associated with altered expression of sperm motility-related genes and testicular post-translational modifications in a mouse model

Obesity is a metabolic disease and its relation with male subfertility has aroused a growing concern. However, it is unclear whether gene expression and post-translational modifications (PTMs), two vital molecular mechanisms regulating cellular functions, are associated with obesity-induced male reproductive dysfunction. In this study, male obesity with compromised sperm motility was induced by a high-fat diet (HFD) using a mouse model. The expression of motility related-genes, the level of histone modifications, and the global profiles of post-translational modifications (PTMs), were examined in testes of HFD and control mice by quantitative real-time PCR and western blot, respectively. Outer dense fiber protein 2, a major component of outer dense fibers in the sperm tail, is the most obviously down-regulated gene out of 11 evaluated genes, showing a reduction of about 50% RNA level in testes of obese male mice compared with that in control mice. Semi-quantitative analysis of the western blot demonstrated that ∼56% enrichment of di-methylated histone (H)3 lysine (K)36, ∼59% enrichment of 2-hydroxyisobutyrylated H4K8, ∼32% decrease of propionylated H3K23, ∼33% decrease of crotonylated H4K8, and ∼45% decrease of acetylated H3K122 and H4K8 were detected in testes of male HFD mice compared with that in control mice. In addition, male obesity up-regulated the testicular levels of ubiquitination by ∼18%, tyrosine nitration by ∼20%, lysine succinylation by ∼25%, lysine benzoylation by ∼28%, lysine malonylation by ∼32%, lysine glutarylation by ∼36%, lysine propionylation by ∼42%, lysine 2-hydroxyisobutyrylation by ∼45%, and SUMO1 modification by ∼59%, and down-regulated the testicular levels of O-GlcNAcylation by ∼12%, lysine crotonylation by ∼22%, and lysine acetylation by 35%. These findings indicate that altered gene expression and PTMs are associated with the obesity-induced male reproductive dysfunction.

Dietary restriction and/or exercise training impairs spermatogenesis in normal rats.

Dietary restriction and/or exercise has been shown to have multiple benefits for health. However, its effects on reproductive health and the mechanisms by which it regulates reproductive function remain unclear. Here, to evaluate its effects on spermatogenesis and sperm function, rats were divided into 4 groups: adlibitum-fed sedentary control, dietary restriction (DR), exercise training (ET), and dietary restriction plus exercise training (DR+ET) groups. Results indicated that body weight, epididymal fat pad weight, and sperm counts were significantly reduced in the DR, ET, and DR+ET groups. Moreover, sperm motility and capacitation-associated protein tyrosine phosphorylation were suppressed in the DR and DR+ET groups, but not the ET group. Microarray analysis revealed that the number of downregulated genes was higher than that of upregulated genes in the DR and/or ET groups. About half of the downregulated genes are common after exercise training and/or diet restriction. Gene ontology analysis showed that downregulated genes in the DR, ET, and DR+ET groups affected spermatogenesis through overlapping pathways, including glucocorticoid, corticosteroid, extracellular structure organization, and estradiol responses. Our findings suggest that diet restriction and/or exercise training may present potential risks to male reproductive dysfunction by disrupting normal gene expression patterns in the testis. Novelty: Dietary restriction and/or exercise can lead to the damage of spermatogenesis as well as sperm maturation. Sperm functional changes are more sensitive to dietary restriction than exercise training. Dietary restriction and exercise impair spermatogenesis through overlapping biological pathways in the testis.

Antiapoptotic and antioxidant capacity of phytochemicals from Roselle (Hibiscus sabdariffa) and their potential effects on monosodium glutamate-induced testicular damage in rat.

Monosodium glutamate (MSG), common flavor enhancer and feed additive, causes male reproductive dysfunction. However, Roselle tea, popular Hibiscus sabdariffa (HS) beverage, has a controversial effectiveness on male fertility. Therefore, the current study aimed to investigate either the adverse effect of aqueous HS extract (HSE) on the testicle or its potential ameliorative role including some stress markers, biochemical and immunohistochemical expressions in rats subjected to MSG. Here, the animals were divided into four groups that were given distilled water, HSE, MSG, and HSE + MSG respectively via gavage. After 6weeks from the beginning of experiment, blood samples were collected for hormonal analysis. Additionally, testicular specimens were excised and processed for oxidative/antioxidant parameters determination, histological examination, and immunohistochemical evaluation of Bax and PCNA positive spermatogenic cells. Preliminary phytochemical analyses as well as antioxidant capacity of the HSE were tested. Our results revealed a strong inhibitory activity of the HSE phytochemical constituents against DPPH radical. MSG group revealed a significant decrease of testosterone, LH, FSH, and antioxidant parameters with elevated MDA compared with control and HSE groups. Additionally, an alteration of the testicular histo-architecture was observed among MSG group along with increased Bax and decreased PCNA positive cells. Meanwhile, the HSE showed a potent protective effect against testicular damage as well as oxidative stress induced by MSG. On the whole, our findings provide evidence that HSE can ameliorate MSG-induced testicular toxicity via induction of cell proliferation along with reduction of oxidative stress and cellular apoptosis in adult rat that attributed to the antioxidant and antiapoptotic effects of its phytochemical constituents.

Polystyrene microplastics induced male reproductive toxicity in mice

Microplastics (MPs) have become hazardous materials, which have aroused widespread concern about their potential toxicity. However, the effects of MPs on reproductive systems in mammals are still ambiguous. In this study, the toxic effects of polystyrene MPs (PS-MPs) in male reproduction of mice were investigated. The results indicated that after exposure for 24 h, 4 μm and 10 μm PS-MPs accumulated in the testis of mice. Meanwhile, 0.5 μm, 4 μm, and 10 μm PS-MPs could enter into three kinds of testicular cells in vitro. In addition, sperm quality and testosterone level of mice were declined after exposure to 0.5 μm, 4 μm, and 10 μm PS-MPs for 28 days. H&E staining showed that spermatogenic cells abscissed and arranged disorderly, and multinucleated gonocytes occurred in the seminiferous tubule. Moreover, PS-MPs induced testicular inflammation and the disruption of blood-testis barrier. In summary, this study demonstrated that PS-MPs induced male reproductive dysfunctions in mice, which provided new insights into the toxicity of MPs in mammals.