The protective effects of resveratrol pretreatment in cyclophosphamide-induced rat ovarian injury: an vivo study

Gynecol Endocrinol. 2021 Oct;37(10):914-919. doi: 10.1080/09513590.2021.1885643. Epub 2021 Feb 17.

Abstract

Objectives: To explore whether resveratrol (Res) pretreatment could exert a protective effect on cyclophosphamide (Cy) induced ovarian toxicity in a rat model.

Methods: Twenty-four female 7-week old Sprague-Dawley rats were randomly divided into four groups: Con, administered with vehicle solutions; Cy, treated with Cy; Res + Cy, treated with Cy + Res combined; Res, treated with Res. After 21 d of treatments, the rats were euthanized and blood samples were collected to evaluate the levels of anti-Müllerian hormone (AMH). The Ovaries were processed for immunohistochemical and western blotting.

Results: Cy-treat caused the decrease of body weights and ovarian weight. AMH was lower in Cy group, whereas AMH levels were similar among other groups. Histomorphology showed a large number of primordial follicles were activated in Cy groups, whereas the primordial follicles were inhibited in the Res and Res + Cy groups. The expressions of Sirt1, Foxo3a were up-regulated and p53, Caspase-3, and Bax were down-regulated in Res + Cy and Res groups (p < .05).

Conclusions: Res can prevent the primordial follicle activation and decrease apoptosis induced by Cy. Res may be an effective protection for ovarian function during chemotherapy, which means a new nonsurgical application for protection of ovarian reserve.

Keywords: Resveratrol; apoptosis; cyclophosphamide; follicle; ovary; toxicology.

MeSH terms

  • Animals
  • Anti-Mullerian Hormone / blood
  • Antineoplastic Agents, Alkylating / toxicity*
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / toxicity*
  • Female
  • Fertility Preservation
  • Forkhead Box Protein O3 / analysis
  • Ovarian Diseases / chemically induced*
  • Ovarian Diseases / pathology
  • Ovarian Diseases / prevention & control
  • Ovary / chemistry
  • Ovary / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol / administration & dosage*
  • Sirtuin 1 / analysis
  • Tumor Suppressor Protein p53 / analysis

Substances

  • Antineoplastic Agents, Alkylating
  • FOXO3 protein, rat
  • Forkhead Box Protein O3
  • Tp53 protein, rat
  • Tumor Suppressor Protein p53
  • Anti-Mullerian Hormone
  • Cyclophosphamide
  • Sirt1 protein, rat
  • Sirtuin 1
  • Resveratrol