Reproductive Toxicity In Mice Research Articles

Polystyrene microplastics induce male reproductive toxicity in mice by activating spermatogonium mitochondrial oxidative stress and apoptosis

Microplastics have emerged as environmental hazards in recent years. This study was intended to prove the toxic effects of microplastics on the male reproductive system and further elucidate its mechanism. C57bl/6 mice were exposed to ultrapure water or different doses (0.25, 0.5 and 1 mg/d) of 5 μm polystyrene microplastics (PS-MPs) for 4 weeks, and the GC-1 mouse spermatogonium was treated with different concentrations of PS-MPs. The results showed that sperm count and motility were decreased, and sperm deformity rate was increased after exposure to PS-MPs. The morphology of testes in PS-MPs groups exhibited pathological changes, such as abnormal development of spermatogenic tubules, and inhibited spermatogonium function. Furthermore, the fluorescence intensity of TUNEL staining and the BAX/BCL2 ratio were increased. Exposure to PS-MPs resulted in impaired mitochondrial morphology of spermatogonium, decreased activity of GSH-px and SOD, and increased the MDA level. In vitro, after treatment with PS-MPs, the cell apoptosis rate of spermatogonium was significantly increased, mitochondrial membrane potential was decreased, mitochondrial morphology was damaged, and exposure to PS-MPs increased mitochondrial reactive oxygen species, inducing an oxidative stress state in spermatogonia. In summary, PS-MPs induced a decrease in sperm quality by activating spermatogonium mitochondrial oxidative stress and apoptosis, offering novel insights into mitigating the reproductive toxicity of microplastics.

Two-Generation Toxicity Study of the Antioxidant Compound Propyl-Propane Thiosulfonate (PTSO).

Propyl-propane thiosulfonate (PTSO), an antioxidant organosulfur compound present in the genus Allium, has become a potential natural additive for food and feed, as well as a possible biopesticide for pest control in plants. A toxicological assessment is necessary to verify its safety for livestock, consumers, and the environment. As part of the risk assessment of PTSO, this study was designed to explore its potential reproductive toxicity in mice following the OECD 416 guideline. The investigation spans two generations to comprehensively evaluate potential reproductive, teratogenic, and hereditary effects. A total of 80 CD1 mice per sex and generation were subjected to PTSO exposure during three phases (premating, gestation, and lactation). This evaluation encompassed three dose levels: 14, 28, and 55 mg PTSO/kg b.w./day, administered through the feed. No clinical changes or mortality attributed to the administration of PTSO were observed in the study. Some changes in the body weight and food consumption were observed, but not related to sex or in a dose-dependent manner. The two parental generations (F0, F1) exhibited normal reproductive performance, and the offspring (F1 and F2) were born without any abnormalities. The serum sexual hormone levels (progesterone -P-, testosterone -T-, estradiol -E2-, follicular stimulating hormone -FSH-, and luteinizing hormone -LH-) were in a normal range. Although significant changes were observed in the sperm analysis in the case of F0 group, no variation was found for F1 group, and no alterations in fertility were recorded either. The absolute organ weights and relative organ weight/body weight and organ weight/brain weight ratios, and the complete histopathological study, showed no significant alterations in males and females for all the generations considered. Considering all the results obtained, PTSO is not considered a reproductive or developmental toxicant in mice under the assayed conditions. These results support the good safety profile of PTSO for its potential application in the agrifood sector.

Apoptosis and DNA damage mediated by ROS involved in male reproductive toxicity in mice induced by Nickel

Nickel (Ni) is the most important environmental pollution in the world. Ni has been confirmed to have multi-organ toxicology and carcinogenicity. Recently, Ni also can impair the male reproductive system, however, its precious mechanism still has not been clarified. The current work found that nickel chloride (NiCl2) induced histopathological lesions in testis. And, the Johnsen's score, seminiferous tubule diameter, and spermatogenic epithelium thickness were decreased in NiCl2-treated mice. The number of spermatogonium, primary spermatocyte, and round spermatid also were significantly reduced after Ni treatment. Next the potential molecular mechanism was measured. NiCl2 treatment elevated ROS production in the testis. Additionally, NiCl2 was found to induce apoptosis with features including up-regulation of Bax, cleaved-caspase-3, cleaved-caspase-8, caspase-9, and caspase-12, while down-regulation of Bcl-2 expression. In the meantime, the marker protein of DNA damage γ-H2AX was significantly increased in NiCl2-primed mice testis. To clarify effects of reactive oxygen species (ROS) in apoptosis and DNA damage induced by NiCl2, NiCl2 was used to co-treat antioxidant NAC (N-Acetyl-L-cysteine). NAC weakened ROS production induced by NiCl2, and played an inhibition role in apoptosis and DNA damage. Moreover, co-treatment using NiCl2 and NAC group also eliminated spermatogenesis disorders. In summary, research results reveal the relations of spermatogenesis disorder induced by NiCl2 with apoptosis and DNA damage mediated by ROS and apoptosis in the testis.

The male reproductive toxicity after nanoplastics and microplastics exposure: Sperm quality and changes of different cells in testis

Nanoplastics (NPs) and Microplastics (MPs) pollution has become a severe threat to the planet and is a growing concern. However, their effects on male reproductive toxicity remain poorly understood. In this study, a series of morphological analyses were completed to explore the influence of NPs and MPs exposure on the testis in mice. After 12-weeks exposure, although both NPs and MPs exposure can lead to reproductive toxicity, compared with NPs exposure, exposure to MPs leads to a more significant increase in reproductive toxicity dependent on some particle size. Moreover, increased reproductive toxicities, including increased spermatogenesis disorders, and sperm physiological abnormality, oxidative stress, testis inflammation was more associated with MPs group than NPs group. Ultra-pathological structure observed by transmission electron microscopy indicated that both NPs and MPs have different effects on spermatogonia, spermatocytes and Sertoli cells. Exposure to MPs resulted in decreased Sertoli cell numbers and reduced Leydig cell area, and showed no effects on differentiation of Leydig cells by the expression level of the Insulin-Like factor 3 (INSL3) in Leydig cells. Transcriptomic sequencing analysis provided valuable insights into the differential effects of NPs and MPs on cellular processes. Specifically, our findings demonstrated that NPs were predominantly involved in the regulation of steroid biosynthesis, whereas MPs primarily influenced amino acid metabolism. This study demonstrates the effect of adult-stage reproductive toxicity in mice after exposure to NPs and MPs, which will deep the understanding of the NPs and MPs induced toxicity.

Co-exposure to polystyrene microplastics and microcystin-LR aggravated male reproductive toxicity in mice

Microplastics (MPs) are plastic pollutants with a diameter of less than 5 mm and microcystins (MCs) are natural toxins produced by cyanobacteria. In recent years, the pollution of MPs and MCs attracted widespread attention. However, our understanding about the toxic effects of co-exposure of MPs and MCs on male reproduction is limited. Mice were continuously exposed to 0.04mg/(kg*bw) microcystin-leucine-arginine (MC-LR) or 45 mg/(kg*bw) polystyrene microplastics (PS-MPs) or a mixed solution of 0.04mg/(kg*bw) MC-LR and 45 mg/(kg*bw) PS-MPs by gavage for 28 days in this study. The results showed that PS-MPs could absorb MC-LR in ddH2O and MC-LR content in testis was increased in the group with combined exposure when compared to the group only exposed to MC-LR. Exposure to PS-MPs or MC-LR individually could destroy testis structure, increase the level of tissue apoptosis and decrease the quality of sperm, while the co-exposure enhanced the toxic effects. Furthermore, PS-MPs could carry MC-LR into testis Leydig cells, reduce testosterone levels and mRNA expression levels of key molecules involved in testosterone synthesis (StAR, P450scc, P450c17,3β-HSD and 17β-HSD). Among them, the combined effect of PS-MPs-MC-LR was the most severe. In summary, this study provides new insights into the toxicity of MPs and MCs in mammals.

Probiotics improve polystyrene microplastics-induced male reproductive toxicity in mice by alleviating inflammatory response

As a new type of environmental pollutant, microplastics have been garnered increasing attention, especially in regard to their effects on the reproductive system. However, researchers have yet to report whether prevention and treatment measures exist for reproductive injury caused by microplastics. The aim of this study was therefore to explore the mechanism of spermatogenic injury induced by polystyrene microplastics (PS-MPs) and the intervention effect of probiotics based on the gut microbiota-testis axis. Mice were orally exposed for 35 days to 5 µm of PS-MPs with a gavage dose was 0.1 mg/day, and the intervention group was given probiotics (Lactobacillus, Bifidobacterium longum, and Enterococcus) orally. Fecal samples were then subjected to 16 S rRNA sequencing analysis, and sperm motion was analyzed by a Hamilton-Thorne Sperm analyzer. The results showed that PS-MPs exposed mice had significant spermatogenic dysfunction and testicular inflammation. In addition, the intestinal microbial structure of exposed mice changed significantly; the abundance of Lactobacillus decreased, and the abundance of Prevotella increased. Furthermore, with fecal microbiota transplantation, the recipient mice showed a significant decrease in sperm quality. However, probiotics supplementation helped inhibit the activation of IL-17A signaling driven by gut microbes, thereby alleviating the inflammatory response and improving sperm quality decline caused by PS-MPs. These results may provide a scientific basis for further understanding of the mechanism of male reproductive damage caused by environmental pollutants such as microplastics and for novel reproductive damage intervention measures.

2,3,7,8-tetrachlorodibenzo-p-dioxin induces multigenerational testicular toxicity and biosynthetic disorder of testosterone in BALB/C mice: Transcriptional, histopathological and hormonal determinants

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent environmental contaminant, is an endocrine disrupter with a proven reproductive toxicity in mammals. However, its effects on male fertility across generations are still elusive. The current work evaluates the toxicity of dioxin on male reproductive system in two separate groups of BALB/C mice; a group of pubertal males directly exposed to TCDD (referred to as DEmG), and a group of indirectly exposed males (referred to as IDEmG) comprises of F1, F2 and F3 males born from TCDD-exposed pregnant females. Both groups were exposed to 25 μg TCDD/kg body weight for a week. Our data show that males of TCDD-DEmG exhibited significant alterations in the expression of certain genes involved in the detoxification of TCDD and the biosynthesis of testosterone. This was accompanied with testicular pathological symptoms, including a sloughing in the germinal epithelium and a congestion of blood vessels in interstitial tissue with the presence of multinuclear cells into seminiferous tubule, with a 4-fold decline in the level of serum testosterone and reduced sperm count. Otherwise, the male reproductive toxicity across F1, F2 and F3 generations from TCDD-IDEmG was mainly characterized by: i) a reduce in body and testis weight. ii) a decrease in gene expression of steriodogenesis enzyme, e.g., AhR, CYP1A1, CYP11A1, COX1, COX2, LOX5 and LOX12. iii) a remarked and similar testicular histopathology that found for DEmG, iv) a serious decline in serum testosterone. v) a decreased male-to-female ratio. vi) a low sperm count with increasing abnormalities. Thus, pubertal or maternal exposure to TCDD provokes multigenerational male reproductive toxicity in mice, ultimately affecting the spermatogenesis and suggesting that the hormonal alternation and sperm abnormality are the most marked effects of the indirect exposure of mammalian male to TCDD.

Chlorpyrifos induces male infertility in pigs through ROS and PI3K-AKT pathway

Chlorpyrifos (CPF) has been shown to have male reproductive toxicity in mice and rat. However, the association of CPF and male reproduction in pigs remains unknown. Therefore, this study attempts to investigate the damage of CPF on male reproduction in pigs and its potential molecular mechanisms. First, ST cells and porcine sperms were treated with CPF and then cell proliferation, apoptosis, motility of sperm, and oxidative stress levels were examined, respectively. Meanwhile, RNA sequencing was performed on ST cells before and after the treatment of CPF. The results of experiments invitro showed that CPF had broad-spectrum toxic effects on ST cells and porcine sperms. The RNA-sequencing data and WB results indicated that CPF may regulate cell survival through the PI3K-AKT pathway. In conclusion, this study may lay the foundation for improving male fertility in pigs and provide theoretical information for human infertility.

Integrated fecal microbiome and metabolome analysis explore the link between polystyrene nanoplastics exposure and male reproductive toxicity in mice.

Microplastics (MPs) and nanoplastics (NPs) are novel environmental pollutants that are ubiquitous in the environment and everyday life. NPs can easily enter the tissues and have more significant potential health risks due to their smaller diameter. Previous studies have shown that NPs can induce male reproductive toxicity, but the detailed mechanisms remain uncertain. In this study, intragastric administration treated mice with polystyrene NPs (PS-NPs, 50, and 90 nm) at 3 and 15 mg/mL/day doses for 30 days. Then, the fresh fecal samples were collected from those mice that the exposure doses of 50 nm PS-NPs at 3mg/mL/day and 90 nm at 15 mg/mL/day for subsequent investigations of 16S rRNA and metabolomics according to significant toxicological effects (Sperm number, viability, abnormality, and testosterone level). The conjoint analysis findings indicated that PS-NPs disrupted the homeostasis of the gut microbiota, metabolism, and male reproduction, suggesting that abnormal gut microbiota-metabolite pathways may be important in PS-NPs-induced male reproductive toxicity. Meanwhile, the common differential metabolites such as 4-deoxy-Erythronic acid, 8-iso-15-keto-PGE2, apo-10'-violaxanthin, beta-D-glucosamine, isokobusone, oleamide, oxoadipic acid, sphingosine induced by 50 and 90 nm PS-NPs might be used as biomarkers to explore PS-NPs-induced male reproductive toxicity. In addition, this study systematically demonstrated that nano-scale PS-NPs induced male reproductive toxicity via the crosstalk of gut microbiota and metabolites. It also provided valuable insights into the toxicity of PS-NPs, which was conducive to reproductive health risk assessment for public health prevention and treatment.

Bisphenol S induces oxidative stress-mediated impairment of testosterone synthesis by inhibiting the Nrf2/HO-1 signaling pathway.

Bisphenol S (BPS) is an environmental endocrine disruptor widely used in industrial production. BPS induces oxidative stress and exhibits male reproductive toxicity in mice, but the mechanisms by which BPS impairs steroid hormone synthesis are not fully understood. Nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 signaling is a key pathway in improving cellular antioxidant defense capacities. Therefore, this study explored the effects of exposure to BPS on testosterone synthesis in adult male mice and its mechanisms with regard to the Nrf2/HO-1 signaling pathway. Adult male C57BL/6 mice were orally exposed to BPS (2, 20, and 200 mg/kg BW) with sesame oil as a vehicle (0.1 ml/10 g BW) per day for 28 consecutive days. The results showed that compared with the control group, serum testosterone levels were substantially reduced in the 20 and 200 mg/kg BPS treatment groups, and testicular testosterone levels were reduced in all BPS treatment groups. These changes were accompanied by a prominent decrease in the expression levels of testosterone synthesis-related enzymes (STAR, CYP11A1, CYP17A1, HSD3B1, and HSD17B3) in the mouse testis. In addition, BPS induced oxidative stress in the testis by upregulating the messenger RNA and protein levels of Keap1 and downregulating the levels of Nrf2, HO-1, and downstream antioxidant enzymes (CAT, SOD1, and Gpx4). In summary, our results indicate that exposure of adult male mice to BPS can inhibit Nrf2/HO-1 signaling and antioxidant enzyme activity, which induces oxidative stress and thereby may impair testosterone synthesis in testicular tissues, leading to reproductive damage.

Cylindrospermopsin induces oocyte maturation and disrupts gene expression in zebrafish ovarian follicles

There is evidence that cylindrospermopsin (CYN) exerts reproductive toxicity in mice. However, little information is available concerning the toxicity of CYN in nonmammalian vertebrates. Here, we investigated the direct action of CYN on female reproduction by studying germinal vesicle breakdown, transcript abundance, caspase-3 activity, and testosterone production using cultured follicle-enclosed zebrafish oocytes as a model system. Treatment of follicles with 1,000 μg/L CYN significantly increased GVBD, Caspase-3 activity, and hCG-induced testosterone secretion. Exposure to CYN also reduced the abundance of 3βhsd as well as hCG-induced fshr and era transcripts and increased cyp19a1 mRNA levels. In summary, this study provides a framework for a better understanding of the adverse action of CYN on female reproduction in zebrafish and other vertebrate species. The findings are also relevant to developing valid biomarkers for CYN by measuring zebrafish oocyte maturation and gene expression.

Pseudoephedrine Nanoparticles Alleviate Adriamycin-Induced Reproductive Toxicity Through the GnRhR Signaling Pathway

PurposePseudoephedrine (PSE) has rapid absorption and metabolism, which limits its pharmacologic actions. We postulated that pseudoephedrine nanoparticles (PSE-NPs) with high bioavailability could overcome this limitation. The defensive function of PSE-NPs nanoparticles against adriamycin-induced reproductive toxicity in mice was studied.MethodsWe encapsulated PSE in polylactide-polyglycolide nanoparticles (PLGA-NPs) and verified their protective activity against testicular injury in vivo and in vitro.ResultsWe report a promising delivery system that loads PSE into PLGA-NPs and finally assembles it into a nanocomposite particle. In vitro, PSE-NPs reduced the adriamycin-induced apoptosis of GC-1 cells significantly, improved mitochondrial energy metabolism and promoted expression of the proteins related to the gonadotropin-releasing hormone (GnRh) receptor signaling pathway. In vivo, evaluation of sperm indices and histology showed that adriamycin could induce testicular toxicity. PSE-NPs significantly increased the sperm motility of mice, reduced the percent apoptosis and oxidative stress of testes, increased serum levels of GnRh, activated the GnRhR signaling pathway in testes and promoted expression of meiosis-related factors.ConclusionIn view of their safety and efficiency, these PSE-NPs have potential applications in alleviating adriamycin-induced reproductive toxicity.

Polystyrene microplastics induced female reproductive toxicity in mice

Plastics have caused serious environmental pollution. In recent years, microplastics (MPs) have caused widespread concern about their potential toxicity on animals and humans, especially on organ and tissue deposition. However, there is little known about the reproductive toxic effects of MPs in female mammals. In this study, the reproductive toxicity of polystyrene MPs (PS-MPs) in female mice was evaluated after continued exposure for 35 days. Results showed that PS-MPs could accumulate in heart, liver, spleen, lung, kidney, brain, large intestine, small intestine, uterus, ovary and blood of exposed mice. Moreover, PS-MPs exposure increased the IL-6 level and decreased malondialdehyde (MDA) level in mouse ovaries. The results also showed that PS-MPs exposure decreased the first polar body extrusion rate and the survival rate of superovulated oocytes. Meanwhile, PS-MPs reduced the level of glutathione (GSH), mitochondrial membrane potential (MMP), endoplasmic reticulum calcium ([Ca2+]ER) and increased reactive oxygen species (ROS) in oocytes. In conclusion, our study illustrated that PS-MPs exposure induced the inflammation of ovaries and reduced the quality of oocytes in mice, which provided a basis for studying the reproductive toxic mechanism of PS-MPs in female mammals.

Multi-omics analyses reveal the mechanisms of Arsenic-induced male reproductive toxicity in mice

Arsenic (As), a widespread environmental contaminant, can induce serious male reproductive injury; however, the underlying mechanisms remain unclear. Multi-omics analyses, including transcriptome, proteome, and phosphoproteome could promote our understanding of As-induced male reproductive toxicity. Here, we established the reproductive injured mice model by intraperitoneal injection of NaAsO2 (8 mg/kg body weight), which was validated by reduced reproductive cells, sperm motility, and litter size. The followed multi-omics analyses of mice revealed that As exposure inhibited ATP production by decreasing the expression of proteins HK1, and GAPDHS, and the enzymatic activities of PDH and SDH. The inhibition of mitochondrial activity and increase in HDAC2 and MTA3 dysregulated the lysine acetylation levels of histone and global proteins. Specifically, the downregulated histones H4K5ac and H4K12ac and upregulated histone H3K9ac disordered the distribution of TP1 to interfere with spermatogenesis. Moreover, As could reduce the expression of COL1A1, RAB13, and LSR to disrupt the junctions between seminiferous tubules, and thereinto, the inhibition of RAB13 increased PKA-dependent phosphorylation. Our study reveals that As causes male reproductive toxicity through decreasing energy production, altering histone acetylation, and impairing cell junctions. Our findings provide basic data for further studies on As reproductive toxicity.

TiO2 NPs induce the reproductive toxicity in mice with gestational diabetes mellitus through the effects on the endoplasmic reticulum stress signaling pathway

The effect of one of the most widely studied nanomaterials at present, TiO2 nanoparticles (NPs), on pregnancy-related diseases is not clear. In this study, the adverse effects of TiO2 NPs on mice with gestational diabetes mellitus (GDM) and their possible mechanism were investigated. GDM mice were orally administered 0, 10, 50 and 250 mg/kg TiO2 NPs for 14 days. GDM reduced the weight of pregnant mice, destroyed the placental structure and caused abnormal fetal development. After exposure to increasing doses of TiO2 NPs, blood glucose levels increased significantly and body weight further decreased in GDM mice. The accumulation of the Ti content was detected in the placenta and fetus, which may further damage the placental structure in GDM mice, thereby exacerbating abnormal fetal development. In addition, the MDA and SOD activities were obviously increased, and the expression of genes associated with endoplasmic reticulum stress (ERS) (PERK, eIF2α, AFT4, IRE1α, and XBP1s) and apoptosis (CHOP, JNK, Bax/Bcl-2, Caspase-12, Caspase-9, and Caspase-3) were also obviously increased in the placenta, which reflected the possible activation of apoptosis. It could be speculated that the reproductive toxicity of TiO2 NPs in GDM mice triggered oxidative stress that subsequently activated ERS pathways to induce cell apoptosis.

Cylindrospermopsin directly disrupts spermatogenesis in isolated male zebrafish testis

Cylindrospermopsin (CYN) is a cytotoxin, and its documented effects in mammals include damage to several organs. CYN also has hormone-disrupting properties, including estrogenic activity, progesterone production inhibition, and apoptosis induction. While CYN has been reported to exert reproductive toxicity in mice, little is known about its effect on fish reproductive function. Using ex vivo organ culture, we investigated the direct action of CYN on the male reproductive system. Isolated zebrafish testis was exposed to 250, 500, and 1000 µg/L CYN for 24 h and 7 d, followed by histo-morphological analysis. The results demonstrate that exposure to CYN led to a decrease in cell types from all three phases of spermatogenesis in zebrafish testis. There were also significant changes in fshr, lhr, and igf3 transcript levels, as well as testosterone secretion following exposure to CYN. In summary, this study provides novel information on the adverse effects of CYN on testicular spermatogenesis and male reproduction in zebrafish. These results provide a framework for a better understanding of CYN toxicity and the mechanism underlying the adverse action of CYN on male reproduction in fish.

Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice.

A representative congener of polybrominated diphenyl ethers in the environment, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), is associated with male reproductive toxicity, yet the underlying mechanisms remain largely unclear. In this study, mice were administered environmentally relevant concentrations of BDE-47 for six weeks. Histopathological observations showed that BDE-47 induced inflammatory reactions and damaged the testes. By conducting an integrated proteomic and metabolomic analysis coupled with a bioinformatic analysis using ingenuity pathway analysis (IPA) methods, we found that BDE-47 mainly affected the molecules involved in free radical scavenging, cell death and survival, neurological disease, and inflammatory response. IPA canonical pathways showed inflammatory and apoptosis pathways, including hepatic fibrosis/hepatic stellate cell activation, the GP6 signaling pathway, tight junction signaling, acute phase response signaling, LXR/RXR activation, unfolded protein response, and FXR/RXR activation, which are related to male reproductive toxicity. Key transcriptional regulator networks were activated via a focus on upstream regulator analysis. The expression of MYC and Clu as the core transcriptional factor and targeted protein, respectively, was verified. It is further proposed that MYC may contribute to the etiology of male reproductive toxicity. These findings will improve our understanding of the mechanisms responsible for BDE-47-induced male reproductive toxicity, which may promote the discovery of useful biomarkers indicative of BDE-47 exposure.

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.

Exposure to polystyrene microplastics causes reproductive toxicity through oxidative stress and activation of the p38 MAPK signaling pathway.

Microplastics (MP) are receiving increased attention as a harmful environmental pollutant, however information on the reproduction toxicity of MP in terrestrial animals, especially mammals, is limited. In this experiment, we investigated the impact of polystyrene microplastics (micro-PS) on the reproductive system of male mice. Healthy Balb/c mice were exposed to saline or to different doses of micro-PS for 6 weeks. The results showed that micro-PS exposure resulted in a significant decrease in the number and motility of sperm, and a significant increase in sperm deformity rate. We also detected a decrease in the activity of the sperm metabolism-related enzymes, succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH), and a decrease in the serum testosterone content in the micro-PS exposure group. We found that micro-PS exposure caused oxidative stress and activated JNK and p38 MAPK. In addition, we found that when N-acetylcysteine (NAC) scavenges ROS, and when the p38 MAPK-specific inhibitor SB203580 inhibits p38MAPK, the micro-PS-induced sperm damage is alleviated and testosterone secretion improves. In conclusion, our findings suggest that micro-PS induces reproductive toxicity in mice through oxidative stress and activation of the p38 MAPK signaling pathways.

Sulphur dioxide and arsenic affect male reproduction via interfering with spermatogenesis in mice

As two potential environmental hazards, sulphur dioxide (SO2) and arsenic have adverse effects on male reproduction, but the mechanism of which and their combined toxicity are not clear. In this study, we investigate male reproductive toxicity with a focus on spermatogenesis by treating mice with 5 mg/m3 SO2 and/or 5 mg/L arsenic. Our results showed that arsenic exposure caused significant decreases in water and food consumption and body weight in mice, whereas these changes were not observed in the SO2-only group. Both SO2 and arsenic reduced sperm counts, increased the percentage of sperm malformation, and induced abnormal testicular pathological changes. Elevated H2O2 and MDA contents, declined T-SOD activity, decreased spermatogenic cell counts, enhanced caspase-3 activity, and increased TUNEL-positive cells were also observed in mice exposed to SO2 and/or arsenic. Moreover, SO2 and arsenic co-exposure changed the mRNA levels of Bax and Bcl-2, decreased serum testosterone levels, and downregulated the expression of steroidogenic-related genes (LHR, StAR, and ABP) in mice. These findings provide a new theoretical basis for understanding how SO2 and arsenic interfere with spermatogenesis leading to infertility. These results also suggest that SO2 and arsenic co-exposure likely result in an additive effect on male reproductive toxicity in mice.