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There is evidence of an association between exposure to ambient fine particulate matter (PM2.5) and female ovarian dysfunction in adults. However, it is not fully clear whether maternal exposure to PM2.5 negatively affects the ovarian function in offspring. The size of primordial follicle pool, definitely assembled during fetal life, determines ovarian reserve and ovarian function. In this study, female C57BL/6 mice were exposed to either ambient PM2.5 (mean daily concentration 49 µg/m3) or filtered air through a whole-body exposure system for 4 weeks before mating, and remained exposed until postpartum. We found that maternal exposure to PM2.5 reduces the initial size of primordial follicle pool and impairs its development in offspring mice. The number of primordial follicles and total follicles was decreased in PM2.5-exposed offspring mice on postnatal day 3 (PND3) and postnatal day 7 (PND7). Maternal PM2.5 exposure promoted the activation of primordial follicles and upregulated the level of p-AKT in offspring mice, accelerating the depletion of primordial follicle pool. While LY294002, a specific inhibitor of PI3K, reversed the overactivation of primordial follicles induced by PM2.5. Besides, maternal PM2.5 exposure induced follicular atresia and granulosa cell apoptosis, increased the accumulation of lipid peroxidation products 4-HNE, and elevated the expression of oxidative stress-related genes and p-p65, p-IκBα in offspring mice. While N-acetylcysteine (NAC) pretreatment abolished the increases of apoptosis, reactive oxygen species (ROS), p-p65 and p-IκBα levels in ovarian granulosa COV434 cells induced by PM2.5 exposure. These findings reveal that maternal exposure to PM2.5 decreases the initial size of primordial follicle pool, and impairs ovarian follicular development in offspring mice. Our data suggest that this involves the activation of the PI3K/AKT/FoxO3a pathway and the ROS-dependent NF-κB pathway. Our study implicates a link between maternal PM2.5 exposure and ovarian reserve in offspring, and improves our understanding of the effects of PM2.5 on reproductive health. [Display omitted] • Maternal PM2.5 exposure reduces ovarian reserve. • Maternal PM2.5 exposure accelerates primordial follicle activation through the PI3K/AKT/FoxO3a pathway. • Maternal PM2.5 exposure induces follicular atresia through ROS-dependent NF-κB pathway. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of tanshinone II A ( Tan II A) on the intermittent high glucose (IHG)- induced oxidative stress and apoptosis of Schwann cells (SCs) in suckling rat. Methods Cultured SCs of newborn suckling rats were randomized into several groups including control (con, 5.6 mmol/L glucose), stable high glucose (HG, 50 mmol/L glucose), IHG (5.6 and 50.0 mmol/L glucoseper 8 h alternative), osmotic control, ALA (500 µmol/L) and IHG in the presence of 0.1, 1.0, 10.0 µmol/L Tan II A. Apoptosis rate, oxidative stress level, expression of apoptosis related proteins and the mRNA in the cells were detected. Results (1) The percentages of apoptotic cells exposed to HG ((34.57± 2.45)%) and IHG ((40.17±2.33)%) were significantly higher than that in control group ((4.74±0.26)%). Furthermore, apoptosis rate of IHG was much higher than that of HG (t=3.70,P<0.01). (2) ROS and 8-OHdG levels increased significantly in the IHG group compared with those in control and HG groups (F=73.44, 194.21, P<0.01). IHG exposure up-regulated expression of bax protein and mRNA (F=66.78, 126.69, both P<0.01), while down-regulating expression of bcl-2 protein and mRNA (F=151.88,54.99,both P<0.01). In addition, IHG increased activities of caspase-3 and (poly(ADP-ribose) polymerase, PARP) (129% ,18% , 139% ,56% ,all P<0.01). (3) Treatment with 1.0 µmol/L and 10.0 µmol/L of Tan IIA inhibited IHG-enhanced ROS production and 8-OHdG levels (t=3.50-6.47,P<0.05). Bax protein and mRNA (t=3.59-5.39,P<0.01), PARP and caspase-3 activation (42%,61%,13%,34%,all P<0.01), and SC apoptosis (t= 12.39, 21.26, P<0.01)were decreased with Tan µ A, too. Conclusions Tan µ A decreases IHG-induced apoptosis via reducing oxidative stressin SCs of newborn suckling rats. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) therapy for tissue repair is limited by low survival of cells transplanted in the recipient sites after spinal cord injury (SCI). Here, we investigated the effects of a calpain inhibitor (MDL28170) on BMSCs survival by a rat model of spinal cord injury in vitro and in vivo. Conditioned medium from hypoxia injured VSC4.1 motor neurons (Hypoxia-CM) were collected to mimic the micro-environment of injured spinal cord. Tunicamycin was also applied to induce endoplasmic reticulum (ER) stress in BMSCs. The CCK-8 assay, LDH leakage assay and flow cytometer assay demonstrated that MDL28170 could enhance BMSCs survival in response to Hypoxia-CM and tunicamycin. Moreover, MDL28170 significantly enhanced GFP-positive BMSCs survival in vivo after transplantation into the contused spinal cord of SCI rats. The protective effects of MDL28170 on BMSCs survival may inhibit the activation of calpain and the downstream ER stress-induced apoptosis. The present results suggested for the first time that MDL28170 with BMSCs transplant helped to rescue cells in injured spinal cord by modulating the ER stress-induced apoptosis. The calpain inhibitor, MDL28170 may have the promising new strategies for promoting the survival of transplanted BMSCs on cell-based regenerative medicine. [ABSTRACT FROM AUTHOR]