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BackgroundThis study was performed to determine the effects of human placenta mesenchymal stem cell (hPMSC) transplantation on granulosa cell apoptosis and anti-Müllerian hormone (AMH) and follicle-stimulating hormone receptor (FSHR) expression in autoimmune drug-induced premature ovarian failure (POF) mice. The aim of this research is to investigate the mechanisms of hPMSCs on ovarian reserve capacity.MethodsThe POF mice model was established by injection of zona pellucida 3 peptide (pZP3). hPMSC transplantation was conducted by intravenous injection into mice following pZP3 treatment. The follicle number was examined by histopathology. The serum levels of FSH, LH, E2, AMH and anti-zona pellucida antibody (AzpAb) were measured by enzyme-linked immunosorbent assay. AMH and FSHR expression in the ovary was analyzed by immunohistochemistry and western blot analysis. Granulosa cell apoptosis of the ovaries was examined by In Situ Cell Death Detection Kit. Granulosa cells were isolated and treated with SiAmh interference and hPMSC supernatant to observe the effects of AMH expression on granulosa cell apoptosis in vitro.ResultsThe results showed that hPMSC transplantation can significantly recover the estrus cycle in the POF group. Morphological staining showed that the basal follicles and sinus follicles after hPMSC transplantation were higher in POF mice than in those without treatment, and the follicle number was significantly decreased with atresia. The serum levels of FSH, LH and AzpAb in the hPMSC transplantation group were reduced considerably, but the E2 and AMH levels were significantly increased. After hPMSC transplantation, the AMH and FSHR expression in ovarian tissue was significantly higher than in the POF group as determined by immunochemistry and western blot analysis. The FSHR expression was shown in granulosa cells only, and FSHR expression increases with AMH expressed in the ovary; granulosa cell apoptosis was decreased following hPMSC transplantation. The same results were observed from the in-vitro study.ConclusionshPMSC transplantation can significantly improve the serum levels of high gonadotropin and low estrogen of POF mice, promote follicular development, inhibit excessive follicular atresia and granulosa cell apoptosis, and improve the ovarian reserve capacity. The mechanism may be achieved by increasing the expression of AMH and FSHR in ovaries.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0745-5) contains supplementary material, which is available to authorized users.

BackgroundHuman placenta-derived mesenchymal stem cell (hPMSC) transplantation has been demonstrated to be an effective way of recovering ovarian function in mice with autoimmune induced premature ovarian failure (POF). But the exact mechanism remains unclear. The goal of the present study is to investigate the role of immune factors (T-helper 17 (Th17), cytotoxic T (Tc17) and regulatory T (Treg) cells) in the recovery of ovarian function and whether the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway is involved in the regulation.MethodsThe inhibitor of PI3K/Akt was administered to observe its effect on ovarian function recovery and immune regulation. Serum levels of estradiol (E2), follicle stimulation hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH)) and anti-Zona pellucida antibody (AZPAb) were measured by ELISA to evaluate ovarian function. The morphological changes of ovaries were observed by HE staining. Apoptosis of granular cells (GCs) was determined by detecting the expression of capase-3. Expression of p-Akt protein was detected by immunohistochemistry and western blot assay in ovarian tissues. The MTT assay was performed to assess GC proliferation. GC apoptosis was performed using flow cytometry analysis. Percentages of Th17, Tc17 and Treg cells were detected by flow cytometry. Expression of interleukin (IL)-17 in serum was measured by ELISA.ResultsLY294002 administration decreased serum levels of E2 and AMH, while the levels of FSH, LH and AZPAb in serum were increased compared with mice in the hPMSC transplantation group. The ovarian morphology presented as atrophy and fibrosis, with functional follicles exhausted. The expression of p-Akt in ovarian tissue was significantly decreased. Also, LY294002 administration significantly decreased proliferation and increased cell apoptosis in GCs, and for immune factors the ratios of Th17/Tc17 and Th17/Treg cells were significantly increased, as well as the serum levels of IL-17.ConclusionsOur data suggest that the PI3K/Akt signal pathway is involved in the recovery of ovarian function by changing the ratios of Th17/ Tc17 and Th17/Treg cells in POF mice following hPMSC transplantation.

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As a persistent organic pollutant, microplastics (MPs) have been reported to induce sperm quantity decrease in male rats. However, the related mechanism remains obscure. Therefore, this study is intended to explore the effects of polystyrene microplastics (PS-MPs) on male reproduction and its related mechanism of blood-testis barrier (BTB) impairment. Thirty-two adult male Wistar rats were divided randomly into four groups fed with PS-MPs for 90 days at the dose of 0 mg/d (control group), 0.015 mg/d, 0.15 mg/d and 1.5 mg/d respectively. The present results have showed that PS-MPs exposure led to the damage of seminiferous tubule, resulted in apoptosis of spermatogenic cell and decreased the motility and concentration of sperm, while the abnormality of sperm was elevated. Meanwhile, PS-MPs could induce oxidative stress and activate p38 MAPK pathway and thus deplete the nuclear factor erythroid-2 related factor 2 (Nrf2). Noteworthily, the adverse effect of PS-MPs on BTB is only signi cant in 0.15 mg/d and 1.5 mg/d groups ,which demonstrated that high-dose PS-MPs exposure may lead to the destruction of BTB integrity and the apoptosis of spermatogenic cells through the activation of MAPK-Nrf2 pathway. The current study provided novelty evidence for elucidating the effects of PS-MPs on male reproductive toxicity and its potential mechanism.

The extensive existing of microplastics (MPs) in the ecosystem have increased considerable attention concerning their potential adverse effects, the toxicities and the underlying mechanism of MPs are still scarce. To explore the effect of MPs on cardiac tissue in Wistar rats and unravel the mechanism of pyroptosis and oxidative stress in the process of cardiomyocytes injury, 32 male Wister rats were divided into control group and three model groups, which were exposed to 0.5 mm PS MPs at 0.5, 5 and 50 mg/L for 90 days. Results revealed that MPs could damage cardiac structure and function with impaired mitochondria integrity, as well as increased levels of creatine kinase‐MB and cardiac troponinI (cTnI). Moreover, MPs administration triggered oxidative stress as indicated by increased levels of malondialdehyde and decreased activity of superoxide dismutase, glutathione peroxidase and catalase. Treatment with MPs resulted in apoptosis and pyroptosis as evidenced by increasing expressions of interleukin (IL)‐1β, IL‐18. Additionally, MPs were shown to induce the NOD‐like receptor protein 3 inflammasomes activation in cardiac tissue, enabling activation of Caspase‐1‐dependent signaling pathway induced by inflammatory stimuli resulting from oxidative stress. In summary, these results illustrated that pyroptosis played a vital role in polystyrene MPs‐induced cardiotoxicity, which might be helpful to understand the mechanism of cardiac dysfunction and induced by MPs.

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