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

J Biochem Mol Toxicol. 2022 Sep;36(9):e23120. doi: 10.1002/jbt.23120. Epub 2022 Jun 7.

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.

Keywords: bisphenol A; estrus cycle; granulosa cells; oxidative stress; resveratrol.

MeSH terms

  • Animals
  • Antidotes
  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Apoptosis
  • Autophagy
  • Benzhydryl Compounds / toxicity
  • Estradiol / pharmacology
  • Estrus
  • Female
  • Humans
  • Male
  • Mice
  • Oxidative Stress
  • Phenols
  • Plasticizers / pharmacology
  • Progesterone* / pharmacology
  • Reactive Oxygen Species
  • Resveratrol / pharmacology

Substances

  • Antidotes
  • Antioxidants
  • Benzhydryl Compounds
  • Phenols
  • Plasticizers
  • Reactive Oxygen Species
  • Progesterone
  • Estradiol
  • bisphenol A
  • Resveratrol