Reproductive System Of Mice Research Articles

Histopathological and Biochemical Comparative Study of Copper Oxide Nanoparticles and Copper Sulphate Toxicity in Male Albino Mice Reproductive System.

Copper (Cu) is an essential trace element for the efficient functioning of living organisms. Cu can enter the body in different ways, and when it surpasses the range of biological tolerance, it can have negative consequences. The use of different nanoparticles, especially metal oxide nanoparticles, is increasingly being expanded in the fields of industry and biomedical materials. However, the impact of these nanoparticles on human health is still not completely elucidated. This comparative study was conducted to evaluate the impacts of copper oxide nanoparticles (CuO NPs) and copper sulphate (CuSO4 0.5 (H2O)) on infertility and reproductive function in male albino mice BALB/c. Body weight, the weight of male reproductive organs, malondialdehyde (MDA) level, caspase-3 level, and the presence of Ki67 and CD68, as detected using the amino-histochemistry technique, were investigated. Animals were treated with 25 and 35 mg/kg of CuO NPs and CuSO4 0.5 (H2O) by oral gavage for 14 days. The control group was given distilled water by oral gavage. Body weight significantly decreased at the end of experiments in both treated groups in a concentration- and time-dependent manner compared with the control group. Weights of testes and epididymis (head and tail), as well as the weight of the seminal vesicle, showed a significant decrease compared with the control. However, the average weights of the seminal vesicle and prostate significantly increased. Caspase-3 and MDA levels increased in the CuO NP and CuSO4 0.5 (H2O) groups compared with the control group, and there was a significant difference between the two concentrations used. Immunohistochemical results detected a significant decrease in Ki67 protein in the treatment groups compared with the control. However, increase in CD68 protein was found in groups treated with CuO NPs and CuSO4 0.5 (H2O) compared with the control group. Overall, this in vivo comparative study of CuO NPs and CuSO4 0.5 (H2O) showed that oral intake of copper NPs at 25 and 23 mg/kg was safer to the mice reproductive system than CuSO4 0.5 (H2O) at the same dose. CuSO4 0.5 (H2O) significantly influenced the histopathological and toxicological alteration responses.

Anatomical Transcriptome Atlas of the Male Mouse Reproductive System During Aging.

The elderly males undergo degenerative fertility and testicular endocrine function that jeopardize the reproductive health and well-being. However, the mechanisms underlying reproductive aging are unclear. Here, we tried to address this by investigating the phenotypes and transcriptomes of seven regions of the male mouse reproductive tract: the testis, efferent ductules, initial segment, caput, corpus and cauda epididymidis, and vas deferens, in adult (3 months) and aged (21 months) mice. Quantitative PCR, immunohistochemistry, immunofluorescent staining, and enzyme-linked immunosorbent assay were performed for the analysis of gene expression in mice, human tissues, and semen samples. Aged male mice showed both systematic and reproductive changes, and remarkable histological changes were detected in the testis and proximal epididymis. Transcriptomes of the male reproductive tract were mapped, and a series of region-specific genes were identified and validated in mouse and/or human tissues, including Protamine 1 (Prm2), ADAM metallopeptidase domain 28 (Adam28), Ribonuclease A family member 13 (Rnase13), WAP four-disulfide core domain 13 (Wfdc13), and Wfdc9. Meanwhile, age-related transcriptome changes of different regions of the male reproductive tract were characterized. Notably, increased immune response was functionally related to the male reproductive aging, especially the T cell activation. An immune response-associated factor, phospholipase A2 group IID (Pla2g2d), was identified as a potential biomarker for reproductive aging in mice. And the PLA2G2D level in human seminal plasma surged at approximately 35 years of age. Furthermore, we highlighted Protein tyrosine phosphatase receptor type C (Ptprc), Lymphocyte protein tyrosine kinase (Lck), Microtubule associated protein tau (Mapt), and Interferon induced protein with tetratricopeptide repeats 3 (Ifit3) as critical molecules in the aging of initial segment, caput, caput, and cauda epididymidis, respectively. This study provides an RNA-seq resource for the male reproductive system during aging in mice, and is expected to improve our understanding of male reproductive aging and infertility.

Combined Analysis of Gut Microbiota and Plasma Metabolites Reveals the Effect of Red-Fleshed Apple Anthocyanin Extract on Dysfunction of Mice Reproductive System Induced by Busulfan.

Busulfan is currently an indispensable anti-cancer drug, but the side effects on male reproductive system are so serious. Meanwhile, red-fleshed apples are natural products with high anthocyanin content. In this research, we analyzed the effect of red-fleshed apple anthocyanin extract (RAAE) on busulfan-treated mice. Compared with the busulfan group, main plasma biochemical indicators were significantly improved after RAAE treatment. Compared with BA0 (busulfan without RAAE) group, total antioxidant capacity(T-AOC) and the activity of superoxide dismutase (SOD) and glutathione catalase (GSH-Px) in RAAE treatment groups were obviously increased, while the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly decreased. Malondialdehyde (MDA) was significantly decreased in the RAAE groups. In addition, we found RAAE alleviated busulfan-disrupted spermatogenesis through improving genes expression which are important for spermatogenesis, such as DDX4, PGK2, and TP1. Furthermore, we found that RAAE increased beneficial bacteria Akkermansia and Lactobacillaceae, and significantly depleted harmful bacteria Erysipelotrichia. The correlation studies indicated that RAAE ameliorated busulfan-induced rise in LysoPC levels through regulating gut microbial community and their associated metabolites. In conclusion, this study extends our understanding of the alleviated effect of RAAE on busulfan-induced male reproductive dysfunction through regulating the relationships between gut microbiota and metabolites.

Effects of aqueous and hydro-alcoholic extracts of Seidlitzia rosmarinus on male mouse reproductive system: An experimental study.

This study investigated the effects of aqueous and hydro-alcoholic extracts of Seidlitzia rosmarinus on reproductive hormones, sperm variables, and antioxidant enzymes level in the mice testis. In this experimental study, 24 three-month-old male NMRI mice weighing (25-30g) were divided into three groups: control, aqueous and hydro-alcoholic extracts of Seidlitzia rosmarinus 100mg/kg. Dissolved extracts were gavaged orally for 35 days. One day after receiving the last dose of the extract, the blood sample, testis, and the epididymis tail were taken for plasma hormonal, testicular antioxidants level, sperm count, and vitality assessments. Testicular level of malondialdehyde increased in aqueous and hydro-alcoholic extracts groups (p=0.04); total antioxidant capacity decreased in aqueous and hydro-alcoholic extracts groups (p=0.008); and the consumption of aqueous (p<0.001) and hydro-alcoholic (p=0.03) extracts decreased catalase in comparison with the control group. The plasma level of luteinizing hormone decreased in the aqueous extracts administrated group (p=0.009); the follicle-stimulating hormone increased in aqueous (p=0.03), and hydro-alcoholic extracts administered mice; and the testosterone level decreased in aqueous extract-treated animals versus the control group (p<0.001). The sperm count was increased in aqueous (p=0.04) and hydro-alcoholic (p=0.009) extracts groups, but its vitality was decreased (p=0.008) in comparison with the control group. In conclusion, Seidlitzia rosmarinus has an adverse effect on male reproductive hormones and sperm viability via increased lipid peroxidation and reduced antioxidant defense system performance.

The protective effect of C-phycocyanin in male mouse reproductive system.

C-phycocyanin from Spirulina platensis has pharmacological effects such as anti-oxidation, anti-cancer, anti-inflammatory and anti-atherosclerosis activities as well as liver and kidney protection. However, there is little research on C-phycocyanin applied in the field of reproductive medicine, and it is therefore the focus of the current study. In this study, a GC-1 spg cell model and male mouse reproductive injury model were constructed by TNF α + Smac mimetic + zVAD-fmk (TSZ) and cyclophosphamide (Cy), respectively. It has been proved that C-phycocyanin can increase cell viability and reduce cell death in GC-1 spg cells induced by TSZ. C-phycocyanin could protect the reproductive system of male mice from cyclophosphamide, improve spermatogenesis, sperm quality and fertility, increase the release of testosterone, stabilize the feedback regulation mechanism, and ensure the spermatogenic ability of mice. It could also improve the ability of anti-oxidation. In addition, C-phycocyanin could play a protective role by down-regulating RIPK1, RIPK3, and p-MLKL to inhibit the necroptotic signaling pathway. These results suggest that C-phycocyanin could protect GC-1 spg cells and the reproductive system of male mice from TSZ and cyclophosphamide, and the protective mechanism may be achieved by inhibiting the signal pathway of necroptosis. Therefore, C-phycocyanin could serve as a promising reproductive system protective agent. C-phycocyanin may enter public life as a health product in the future.

METRONIDAZOLE INDUCES SIGNIFICANT PATHOLOGICAL ALTERATIONS IN THE MALE REPRODUCTIVE SYSTEM OF MICE

The present study was aimed to investigate the possible effects caused by the antibiotic, metronidazole, on the histology of the testis and the morphology of the sperms of mice. To achieve this, adult male albino Swiss Mice were orally administrated with 0.1 ml (100 mg\ kg ) of the commercially used metronidazole (Flagyl) for 60 consecutive days. The results showed significant decreases (p&lt;0.05) in the mean weight of body and testis in the treated mice as compared to the distilled water-treated control group. The treatment also caused several histopathological changes in the testis which included necrosis, congestion, hemorrhage, edema, germ cell downfall and rupture in the seminiferous tubules. The tests of the sperm morphology revealed a number of deformations as a result of the treatment, such as the appearance of headless, bend, broken-tailed, hook-tailed, and two-headed sperms, as well as sperms with cytoplasmic droplets. We conclude that from these results that orally administered Metronidazole exerts negative effects on the male reproductive system of mice .

Combinational exposure to Bisphenol A and a high-fat diet causes trans-generational Malfunction of the female reproductive system in mice

Bisphenol A (BPA) is a common endocrine disruptor and a high-fat diet (HFD) also affects fertility. However, little is known about the long-term consequences of simultaneous exposure to BPA and a HFD on reproductive health. Herein, we assessed the effects of maternal exposure to BPA in combination with a HFD on reproductive function in subsequent generations of female mice and evaluated its effects on the hypothalamic-pituitary-gonadal axis. We found that the combination of maternal exposure to BPA and a HFD led to increased urine BPA levels, precocious puberty, altered estrous cyclicity, decreased follicle numbers, and altered hypothalamic Kiss1 methylation status in F1 and F2 mice. Therefore, we demonstrated that maternal exposure to BPA in combination with a HFD exerts a trans-generational effect on female reproduction.

Luman/CREB3 knock-down inhibit hCG induced MLTC-1 apoptosis

Luman has been reported to be involved in the formation of COP II-mediated transport vesicles that affect protein transportation and secretion. Western blotting, immunohistochemistry, immunofluorescence, and RT-qPCR indicated that Luman is widely expressed in the male mouse reproductive system. In sperm, Luman was mainly located in the sperm tail, and the expression level increased with sperm maturity. In the testis, Luman was located in Leydig cells. In MLTC-1, a high-concentration hCG treatment significantly increased GRP78, ATF6, p-IRE1, and p-EIF2S1 expression but had no effect on Luman expression. To investigate the role of Luman in hCG-induced ER stress (ERS), experiments were conducted to examine the consequences of short hairpin RNA (shRNA)-mediated Luman knockdown in MLTC-1 cells. Luman knockdown decreased the percentage of S phase cells and up-regulated Cyclin A1, Cyclin B1, and Cyclin D2 expression. ELISA and WB results showed that with Luman knockdown, Cyp11a1, p-IRE1, and p-EIF2S1 expression and testosterone secretion were significantly increased, while GRP78 and CHOP expression were decreased. Flow cytometry results showed that Luman knockdown reduced MLTC-1 cell apoptosis. RT-qPCR and WB results showed that Luman knockdown significantly up-regulated BCL-2 expression and decreased Caspase-3 and BAX expression. These data suggest that Luman is widely expressed in the male mouse reproductive system. In MLTC-1 cells, Luman knockdown up-regulated p-IRE1, p-EIF2S1, and BCL-2 expression and decreased GRP78, CHOP, BAX, and Caspase-3 expression. We propose that Luman knockdown reduces cell apoptosis through the ERS pathway, thereby promoting cell survival and testosterone secretion. These findings provide new insights into the role of Luman in hCG-induced ERS.

A review of pharmacological effects of xylopic acid

Xylopic acid (15β-acetyloxy-kaur-16-en-19-oic acid) is a kaurene diterpene that can be obtained from various Xylopia spp. Xylopic acid has demonstrated several pharmacological activities in vitro and in vivo. The compound has shown promising effect as a potent analgesic, anti-inflammatory and anti-allergic agent. Xylopic acid is a CNS depressant and was able to ameliorate anxiety-like symptoms in mice in addition to its neuroprotective effects. Deleterious effects of xylopic acid on the reproductive system of mice have been well documented but extensive toxicity study detailing effect of the acid upon chronic exposure needs to be determined. Due to the heavy consumption of X. aethiopica fruits, it is recommended that the pharmacokinetics of xylopic acid be determined to ascertain the possible food-drug interaction that may occur when conventional drugs are taken together with foods containing xylopic acid.

Selenium and L-Carnitine Ameliorate Reproductive Toxicity Induced by Cadmium in Male Mice.

Cadmium (Cd) has been reported to reduce male fertility, impair reproductive capacity, and play a major role in the pathogenesis of infertility. This study was conducted to investigate the possible protective role of Selenium(Se) and L-carnitine (LC) against the adverse effects induced by Cd on the male reproductive system in mice. Animals were randomly divided into seven groups (n = 10); control group and six treated groups, as follows: Cd (0.35mg/kg), Se (0.87mg/kg), LC (10mg/kg), and a combination of either Se or LC and then a combination of both with Cd, and all animals were injected for a period of 30days. Exposure of Cd showed a significant decrease in enzymatic antioxidant activities, deficiency in reproductive performance, decrease serum testosterone level, severe changes in the histopathological architecture, and higher degree of damages and appearance of unblemished DNA strands. Treatment with Se and LC has the highly synergistic and ameliorates the damaging effect of Cd on the testis through the elevation of the enzymatic antioxidant and diminish histopathological abnormalities and DNA damage.

Multigenerational analysis of the functional status of male reproductive system in mice after exposure to realistic doses of manganese

The present study aimed to analyze the effect of multigenerational exposure to Mn at realistic doses on the functional quality of the male reproductive system of mice. Females and males (generation F0) were treated for 60 days with MnCl2, via gavage, at the doses of 0, 0.013, 0.13, and 1.3 mg/kg/day. Treatment of F0 dams continued throughout gestation and lactation periods. At the time of weaning, the offspring (F1 generation) was divided into: animals that were not exposed after weaning – parental exposure (PE); and those exposed via parental generation and directly (PDE) for additional 60 days, at the same dose of F0 generation. F0 and F1 males were euthanized for assessment of sperm parameters and redox changes in the reproductive system. There was a decrease in the sperm concentration of the F0 generation. In addition, the sperm parameters of F1 generation were drastically affected. The activity of antioxidant enzymes was significantly reduced in PE animals. It was possible to verify that the biochemical damages were higher in the PE individuals, as demonstrated by the integrated biomarker response index. Our results show that Mn, even at low doses, is able to promote a reduction in sperm quality over a generation.

Ovarian dysfunction following prenatal exposure to an insecticide, chlordecone, associates with altered epigenetic features

Chlordecone (CD) is an insecticide that was used in the French West Indies for several years to control the banana root borer pest. Given its nonsignificant degradation, it persists in the environment. CD is a carcinogenic compound with reproductive and developmental toxicity and is a recognized endocrine-disrupting chemical. In this study, we examined the effects of CD on female reproductive system of mice with the focus on epigenetic features in ovary. Our data show that gestational exposure to low dose of CD affects meiotic double-strand breaks repair in female embryos. In adult mice derived from CD-treated pregnant females, we observed delayed puberty, decreased number of primordial and increased number of atretic follicles. Gene expression analysis revealed that Rcbtb2 and Rbpms genes were not expressed in embryonic gonads. Estrogen signaling- and oocyte maturation-associated genes were downregulated in adult ovaries. The morphological changes were associated with altered epigenetic features: increased H2Aub and increased H3K27me3 and decreased H4ac and H3K4me3 in embryonic oocytes. The DNA damage-associated, γH2AX marks were detected in the follicles of treated but not control adult ovaries. We also found reduced H3K4me3 and H4ac in fully grown oocytes of the treated ovaries. The ChIP-seq analysis of H3K4me3 in adult ovaries showed that target genes of ZFP57 and TRIM28, which regulate pluripotency and imprinting, were significantly enriched in altered regions. Our study clearly demonstrates that gestational exposure to a low dose of CD impairs the function of female reproductive system and the changes are associated with altered epigenetic features.

Effects of Iron Oxide Nanoparticles on Mouse Sperm Parameters and Testicular Tissue

Background: Iron oxide nanoparticles are commonly used for various purposes, such as biomedical, medical, and cosmetic services and research. However, there is a little information about the effects of the nanoparticles on human health. The current investigation was conducted to evaluate the adverse effects of iron oxide nanoparticles (FeNP) on the reproductive organs of mice, such as the testicular tissue and sperm cells. Methods: Twenty-eight male NMRI mice were randomly divided in four groups (N=7). The control group received only a regular diet. The experimental groups were administered FeNP in doses of 50, 150 and 300 mg/Kg intraperitoneally (IP), over four days. Epididymal sperm parameters, such as sperm number and motility were assessed by computer-assisted sperm analysis (CASA). Stereological analysis was also conducted on the histological sections. Results: The results demonstrated that FeNP (300 mg/Kg/day) caused a significant decrease in the sperm parameters, such as motility, spermatogonia, primary spermatocytes, spermatid, Sertoli, Leydig cells, total length of seminiferous tubules, and testicular interstitial tissue volumes. Conclusion: In summary, FeNP affected several reproductive tissue and cellular parameters at the administered dosage. Further research is required to examine the mechanism of action of FeNP the mice reproductive system.

Uji Teratogen Ekstrak Akar Jarong (Stachytarpheta jamaicensis (L.) Vahl.) terhadap Sistem Reproduksi Mencit (Mus musculus L.) Betina

This study aim to determine the teratogens effect of jarong (Stachytarpheta jamaicensis (L.) Vahl) roots extract on the reproductive system of mice (Mus musculus L.) female Swiss Webster organogenesis during pregnancy.The method used in this study is the method of extraction and  examination of vaginal smears.. The experiment was conducted in August-December 2010, at the Laboratory of Zoology, Department of  Biology Cenderawasih University, Jayapura. The Experiment was carried out by dividing the 20 female mice into 4 groups. One group is a control group and with no treatmen and the  other 3 groups  were tretaed with oral treatments.. The results obtained in the qualitative descriptive analysis. It could be concluded that ethanol extract of jarong (Stachytarpheta jamaicensis (L.) Vahl) roots cause of accidental poisoning in mice, embryotoxic and causes the effects of teratogens. Key words: Jarong (Stachytarpheta jamaicensis (L.) Vahl), teratogens effect, mice (Mus musculus L.).Â

Protective effects of hydro-alcoholic extract of Quercus brantii against lead-induced oxidative stress in the reproductive system of male mice.

Exposure to heavy metals such as lead (Pb) results in oxidative stress induction in the male reproductive system. Herbal medicine can be utilized as antioxidant agents against oxidative stress. Quercus brantii (QB) has shown antioxidant activity in previous studies. The aim of the present study was to evaluate effects of QB hydro-alcoholic extract against Pb-induced oxidative stress in the male mice reproductive system. Forty-two NMRI adult male mice were randomly divided into 7 groups of 6 animals each. Group I was the control group that received no treatment. Group II was the sham group and received 0.2 ml distilled water. Groups III and IV received QB hydro-alcoholic extract 500 and 1000 mg/kg bw, respectively. Group V received Pb 1000 ppm/kg bw. Group VI and VII received Pb 1000 ppm/kg bw and QB extract 500 and 1000 mg/kg bw, respectively. All groups received treatment via oral gavage. After 35 days, sperm parameters (i.e. sperm motility, count and morphology) were evaluated. Levels of sex hormones including LH, FSH, and testosterone, total antioxidant capacity (TAC), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured in animals' serum. Exposure to Pb negatively affected sperm parameters (i.e. sperm motility, count and morphology), decreased serum concentrations of sex hormones (i.e. LH, FSH, and testosterone), TAC and SOD activity but increased MDA levels. However, co-administration of 500 and 1000 mg/kg bw QB hydro-alcoholic extract and Pb considerably improved sperm parameters (i.e. sperm motility, count and morphology), increased sex hormones (i.e.LH, FSH, and testosterone), TAC, and SOD activity while decreased MDA levels in animals' serum. Administration of QB extracts (Low dose and high dose) is able to protect the male reproductive system of mice against Pb-induced oxidative stress.

Trypanosoma brucei triggers a marked immune response in male reproductive organs.

African trypanosomiasis is caused by the protozoan parasite Trypanosoma brucei, transmitted between mammals by the bite of a tsetse. It has been recently shown that parasites accumulate in large numbers in various organs and tissues, including the mouse testis. Whether parasites are protected from the immune system in the male reproductive organ or can be transmitted through sexual route remains unknown. Here we show that parasites can be detected by fine needle aspiration cytology of the male reproductive system in mice, and histopathological analysis revealed that T. brucei accumulates in the stroma of the epididymis, epididymal adipose tissue and fibrous tunics of the testis. No parasites were found in the lumen of intact epididymal ducts or seminiferous tubules of the testis, indicating that the large majority of the parasites are not located in immune-privileged sites. In fact, these parasites are associated with marked inflammatory cell infiltration, parasite degeneration, and severe tissue damage and rupture of epididymal ducts, which may be related with reduced fertility. Overall, we show that just like in the bloodstream and most other tissues, in the male reproductive organs, T. brucei are exposed to a strong immune response. The detection of a very high number of parasites in this organ and its accessibility opens the possibility of using fine needle aspiration cytology as a complementary diagnostic tool in Animal African Trypanosomiasis.

Di-(2-Ethylhexyl) Phthalate Increases Obesity-Induced Damage to the Male Reproductive System in Mice.

Objective This study evaluated the effects of di-(2-ethylhexyl) phthalate (DEHP) and obesity on male reproductive organ function in male mice and the potential mechanism of male secondary hypogonadism (SH) in such mice. Methods 140 mice were assigned to six groups for 12 weeks: normal, DEHP, DIO, DIO + DEHP low, DIO + DEHP middle, and DIO + DEHP high. The effects of DEHP and obesity upon the reproductive organs were determined by measuring sperm count and motility, relative testis and epididymis weight, hormone level, and pathological changes. Oxidative stress was evaluated by determining malondialdehyde, T-AOC, SOD, GSH, H2O2, CAT, and GSH-PX in testicular tissues. Nrf2 and Keap1 protein were measured by Western blotting. Results DEHP and obesity reduced sperm count and motility, relative testis and epididymis weight, and testosterone level but increased the levels of MDA, H2O2, leptin, and estradiol. Pathological injury was observed in the testicular Leydig cells. Moreover, the activity of CAT, SOD, and GSH-Px enzymes was inhibited. Nrf2 protein expression was reduced but that of Keap1 was increased. Conclusions DEHP and obesity jointly caused damage to male productive function. Oxidative stress in testicular tissue, and a high level of leptin, may provide some evidence to clarify the mechanisms of male SH with DEHP and obesity.

Reproductive toxicity of melamine against male mice and the related mechanism

Melamine is a nitrogen-containing heterocyclic organic compound with a triazine skeleton, which has been widely applied in industrial and chemical fields. Previous toxicity studies of melamine mainly focused on renal toxicity and hepatic pathological changes, but its toxicity against the reproductive system has seldom been assessed. We investigated the effects of melamine on the reproductive system of male mice. Forty healthy male Kunming mice were randomly divided into a normal saline negative control group, a low-dose melamine group, a medium-dose melamine group and a high-dose melamine group (n = 10). The mice were administered for five consecutive days and killed on the 35th day after first administration. In melamine administration groups, seminiferous tubules had disordered, loose arrangement, and spermatogenic cells at all levels obviously decreased. The sperm count and motility decreased significantly, and the sperm deformity rate increased significantly. Melamine induced apoptosis of testicular spermatogenic cells. To further explore the mechanism, we detected metabolism-related enzymes sorbitol dehydrogenase (SDH) and lactate dehydrogenase (LDH) as well as oxidative stress indices superoxide dismutase (SOD) and malondialdehyde (MDA). The activities of SDH, LDH and SOD in melamine treatment groups decreased significantly, and the MDA level increased obviously. The expressions of apoptosis-related proteins Bcl-2, Bax and caspase-3 were detected by immunohistochemistry. The expression of Bcl-2 significantly increased, but those of Bax and caspase-3 significantly reduced (p < 0.05). In conclusion, melamine damaged the reproductive system of mice via the oxidative stress pathway and by inducing cell apoptosis.

Prenatal and postnatal exposure to low levels of permethrin exerts reproductive effects in male mice

Permethrin, a pyrethroid chemical, is widely used as a pesticide because of its rapid insecticidal activity. Although permethrin is considered to exert very low toxicity on mammalian reproductive organs, the effects of early low-level and chronic exposure on adult spermatogenesis are unclear. We exposed mice to environmentally relevant concentrations of permethrin (0, 0.3, and 30ppm) in drinking water during prenatal and postnatal period and examined the effects on the testis in mice offspring when they reached maturity (12 weeks of age). Using methyl green-pyronin staining, we found an abnormal accumulation of RNA in the seminiferous epithelia of mice treated with permethrin; this accumulation may be derived from an enlargement of the residual body. Additionally, permethrin may cause a decline of Sertoli cell functions. Our findings demonstrate that low-level and chronic permethrin exposure during prenatal and postnatal period has distinct effects on male reproductive system in mice.

RIPK1-RIPK3-MLKL-dependent necrosis promotes the aging of mouse male reproductive system.

A pair of kinases, RIPK1 and RIPK3, as well as the RIPK3 substrate MLKL cause a form of programmed necrotic cell death in mammals termed necroptosis. We report here that male reproductive organs of both Ripk3- and Mlkl-knockout mice retain 'youthful' morphology and function into advanced age, while those of age-matched wild-type mice deteriorate. The RIPK3 phosphorylation of MLKL, the activation marker of necroptosis, is detected in spermatogonial stem cells in the testes of old but not in young wild-type mice. When the testes of young wild-type mice are given a local necroptotic stimulus, their reproductive organs showed accelerated aging. Feeding of wild-type mice with an RIPK1 inhibitor prior to the normal onset of age-related changes in their reproductive organs blocked the appearance of signs of aging. Thus, necroptosis in testes promotes the aging-associated deterioration of the male reproductive system in mice.