Resveratrol improves estrus disorder induced by bisphenol A through attenuating oxidative stress, autophagy, and apoptosis

Abstract

Bisphenol A (BPA), as a widely used plasticizer, is easily absorbed by animals and humans. It has certain toxic effects on various tissues, including liver, heart, kidney, testis, and ovary. The toxic effects of BPA on animal reproduction have aroused widespread concern, but its regulatory mechanism and antidote in female animals estrus cycle remain unclear. In this study, the results displayed that BPA destroyed the normal estrus cycle of mice through decreasing the levels of progesterone and estradiol. Furthermore, BPA significantly increased the levels of oxidative stress, autophagy, and apoptosis in ovaries and granulosa cells. Interestingly, we found that the natural antioxidant resveratrol rescued estrus disorder and impaired estradiol secretion, reduced the abnormal reactive oxygen species accumulation, autophagy, and apoptosis in BPA exposed ovarian tissues. Moreover, transmission electron microscopy showed that resveratrol reduced BPA‐induced autophagic vesicles formation and flow cytometry showed that resveratrol inhibited the increase of apoptotic cells induced by BPA on granulosa cells. Therefore, the supplement of resveratrol could restore BPA‐induced estrus disorder by protecting ovarian granulosa cells. Overall, resveratrol is a potential drug to alleviate BPA‐induced estrous cycle disorders and ovarian damage.

The effects of natural products and bioactive ingredients of traditional Chinese medicine on apoptosis of ovarian granulosa cells

“…Resveratrol treatment ameliorated aflatoxin B 1 ‐induced GC apoptosis, this effect was due to the regulation of AKT/PI3K signaling pathway (Zhou et al, 2019). Moreover, a recent study reported that the protective effect of resveratrol on bisphenol A‐induced apoptosis in mice ovaries and GCs, and showed that resveratrol inhibited the expression of cleaved caspase‐9, cleaved caspase‐3, and Bax, increased Bcl‐2 (Jiao et al, 2022). Procyanidin B2 was shown to increase expression of antiapoptotic micoRNA let‐7a to alleviate H 2 O 2 ‐induced upregulation by Fas and caspase‐3 in GCs (Zhang et al, 2019).…”

Resveratrol Protects Rat Ovarian Luteinized Granulosa Cells from H2O2-Induced Dysfunction by Activating Autophagy

“…For instance, Yong et al found that resveratrol attenuated the effects of malathion on inducing autophagy and apoptosis in granulosa cells [ 20 ]. Jiao et al found that resveratrol inhibited autophagy by reducing BPA-induced autophagic vesicle formation in granulosa cells [ 21 ]. However, resveratrol was also found to activate autophagy and mitochondrial biogenesis in oocytes and granulosa cell complexes [ 22 ].…”