Resveratrol improves follicular development of PCOS rats via regulating glycolysis pathway and targeting SIRT1

Syst Biol Reprod Med. 2023 Apr;69(2):153-165. doi: 10.1080/19396368.2022.2125855. Epub 2022 Oct 21.

Abstract

Polycystic ovary syndrome (PCOS) is a disease characterized by metabolic disorders. This study aimed to examine the effects of resveratrol treatment on ovulation in the PCOS rat model. Quantitative real-time PCR and immunohistochemistry were used to determine the mRNA and protein expression levels. TNUEL assay was used to evaluate cell apoptosis in ovary. The metabolites were evaluated by liquid chromatography with tandem mass spectrometry. Resveratrol alleviated disrupted estrous cycle and improved granular cell layers, and reversed the decreased proliferation and increased cell apoptosis of granulosa cells in the ovarian tissues of PCOS rats. Resveratrol restored the changes in the mRNA expression levels in the rate-limiting genes of glycolysis in the PCOS ovary. The expression of lactate dehydrogenase A (LDH-A), pyruvate kinase isozyme M2 (PKM2), and sirtuin 1 (SIRT1) was significantly downregulated in ovarian tissues of the PCOS rats; while the resveratrol treatment significantly increased the expression of LDH-A, PKM2, and SIRT1 in the ovarian tissues of PCOS rats. Collectively, the protective effects of resveratrol in the PCOS rats may be associated with the regulation of glycolysis-related mediators including PKM2, LDH-A, and SIRT1. Resveratrol may represent a good candidate in alleviating the development of PCOS.

Keywords: Polycystic ovary syndrome; SIRT1; glycolysis; ovulation; resveratrol.

MeSH terms

  • Animals
  • Female
  • Granulosa Cells / metabolism
  • Lactate Dehydrogenase 5 / metabolism
  • Lactate Dehydrogenase 5 / pharmacology
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Resveratrol / pharmacology
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Sirtuin 1 / pharmacology

Substances

  • Lactate Dehydrogenase 5
  • Resveratrol
  • RNA, Messenger
  • Sirt1 protein, rat
  • Sirtuin 1