Ascorbic Acid and Alpha-Tocopherol Contribute to the Therapy of Polycystic Ovarian Syndrome in Mouse Models

Reprod Sci. 2021 Jan;28(1):102-120. doi: 10.1007/s43032-020-00273-9. Epub 2020 Jul 28.

Abstract

Polycystic ovary syndrome (PCOS) affects up to 10% of women within reproductive ages and has been a cause of infertility and poor quality of life. Alteration in the oxidant-antioxidant profile occurs in PCOS. This study, therefore, investigates the contribution of ascorbic acid (AA) and alpha-tocopherol(ATE) on different PCOS parameters. The mifepristone and letrozole models were used, and young mature female mice were randomly assigned to groups of six per group. On PCOS induction with either mifepristone or letrozole, mice were administered AA and ATE at doses ranging from 10-1000mg/kg to 0.1-1000 mg/kg in the respective models. Vaginal cytology, body weights, and temperature, as well as blood glucose, testosterone, and insulin levels, were measured. Total antioxidant capacity and malondialdehyde levels were analyzed. Determination of gene expression of some reactive oxygen species and histomorphological analysis on the ovaries and uteri were performed. At the end of the experiments, AA and ATE restored reproductive cycling, with AA being more effective. AA and ATE increased fasting blood glucose but had no significant effect on serum insulin levels. AA decreased testosterone levels, but ATE caused slight increases. AA and ATE both increased total antioxidant capacity and decreased malondialdehyde levels. AA and ATE also slightly upregulated the mRNA expressions of catalase, superoxide dismutase, and heme oxygenase 1 mainly. AA and ATE also decreased ovarian weight and mostly resolved cysts in the ovaries and congestion in the uterus. This study has shown that AA and ATE are beneficial in the therapy of PCOS.

Keywords: Estrous; Estrus; Letrozole; Mifepristone; Polycystic ovarian syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Disease Models, Animal
  • Estrous Cycle / drug effects
  • Estrous Cycle / metabolism
  • Female
  • Insulin / blood
  • Mice
  • Ovary / drug effects*
  • Ovary / metabolism
  • Ovary / pathology
  • Ovary / physiopathology
  • Oxidative Stress / drug effects*
  • Polycystic Ovary Syndrome / drug therapy*
  • Polycystic Ovary Syndrome / metabolism
  • Polycystic Ovary Syndrome / pathology
  • Polycystic Ovary Syndrome / physiopathology
  • Testosterone / blood
  • Uterus / drug effects*
  • Uterus / metabolism
  • Uterus / pathology
  • Uterus / physiopathology
  • alpha-Tocopherol / pharmacology*

Substances

  • Antioxidants
  • Blood Glucose
  • Insulin
  • Testosterone
  • alpha-Tocopherol
  • Ascorbic Acid