Combination treatment of recombinant growth differentiation factor-9 and Cetrorelix improves gestational origin of the polycystic ovarian syndrome in female rats

Life Sci. 2023 May 15:321:121638. doi: 10.1016/j.lfs.2023.121638. Epub 2023 Mar 29.

Abstract

Aims: Polycystic ovary syndrome (PCOS) is a hyper-androgenic endocrinopathy prevalent in premenopausal women with no cure available. The current study aimed to investigate the therapeutic effect of recombinant GDF-9 and Cetrorelix on the gestational origin of dehydroepiandrosterone (DHEA) induced PCOS in postnatal pups' delivered to rat dams.

Main methods: The body weight measurement, blood and serum analysis for glucose tolerance, lipid profile, liver enzymes, sex hormones (Testosterone, Estradiol, and Progesterone), estrus cyclicity assessment, histological staining of ovary and liver, molecular markers expressions of pro-inflammatory by qRT-PCR and immuno-histochemistry technique for folliculogenesis genes and histological staining studies of liver and ovary were done.

Key findings: The combinational treatment was found to normalize the biochemical parameters and reduction in the estrus irregularity by altering the sex hormones as well as the glucose metabolism and insulin resistance via HOMA-IR value. Further, molecular markers expression confirmed the pro-inflammatory (IL-1β, TNF-α, and IL-6) and folliculogenesis (GDF-9, BMPR2, and TGF-βR1) genes associated with PCOS were improved by combinational therapy.

Significance: In conclusion, rGDF-9 could be a potential therapeutic agent in combination with Cetrorelix as a better treatment regime for metabolic and reproductive phenotypes in PCOS. However, the effect of rGDF-9 on infertility-associated phenotypes in PCOS needs further evaluation.

Keywords: Anovulation; Cetrorelix; Combinational treatment; Polycystic ovary syndrome; Prenatal; Recombinant GDF-9.

MeSH terms

  • Animals
  • Female
  • Gonadal Steroid Hormones
  • Growth Differentiation Factor 9 / pharmacology
  • Humans
  • Insulin Resistance*
  • Polycystic Ovary Syndrome* / metabolism
  • Rats

Substances

  • cetrorelix
  • Growth Differentiation Factor 9
  • Gonadal Steroid Hormones