Biochanin-A attenuates DHEA-induced polycystic ovary syndrome via upregulation of GDF9 and BMP15 signaling in vivo

Life Sci. 2023 Aug 1:326:121795. doi: 10.1016/j.lfs.2023.121795. Epub 2023 May 23.

Abstract

Aims: Phytoestrogens can act as natural estrogens owing to their structural similarity to human estrogens. Biochanin-A (BCA) is a well-studied phytoestrogen with a wide variety of pharmacological activities, whereas not reported in the most frequently encountered endocrinopathy called polycystic ovary syndrome (PCOS) in women.

Purpose: This study aimed to investigate the therapeutic effect of BCA on dehydroepiandrosterone (DHEA) induced PCOS in mice.

Main methods: Thirty-six female C57BL6/J mice were divided into six groups: sesame oil, DHEA-induced PCOS, DHEA + BCA (10 mg/kg/day), DHEA + BCA (20 mg/kg/day), DHEA + BCA (40 mg/kg/day), and metformin (50 mg/kg/day).

Key findings: The results showed a decrease in obesity, elevated lipid parameters, restoration of hormonal imbalances (testosterone, progesterone, estradiol, adiponectin, insulin, luteinizing hormone, and follicle-stimulating hormone), estrus irregular cyclicity, and pathological changes in the ovary, fat pad, and liver.

Significance: In conclusion, BCA supplementation inhibited the over secretion of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and upregulated TGFβ superfamily markers such as GDF9, BMP15, TGFβR1, and BMPR2 in the ovarian milieu of PCOS mice. Furthermore, BCA reversed insulin resistance by increasing circulating adiponectin levels through a negative correlation with insulin levels. Our results indicate that BCA attenuated DHEA-induced PCOS ovarian derangements, which could be mediated by the TGFβ superfamily signaling pathway via GDF9 and BMP15 and associated receptors as first evidenced in this study.

Keywords: Biochanin-A; DHEA; GDF-9; Phytoestrogens; Polycystic ovary syndrome.

MeSH terms

  • Adiponectin / metabolism
  • Animals
  • Bone Morphogenetic Protein 15 / genetics
  • Bone Morphogenetic Protein 15 / metabolism
  • Dehydroepiandrosterone / therapeutic use
  • Estrogens / therapeutic use
  • Female
  • Growth Differentiation Factor 9 / genetics
  • Growth Differentiation Factor 9 / metabolism
  • Insulin / metabolism
  • Mice
  • Polycystic Ovary Syndrome* / chemically induced
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / metabolism
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation

Substances

  • Adiponectin
  • Bone Morphogenetic Protein 15
  • Dehydroepiandrosterone
  • Estrogens
  • Growth Differentiation Factor 9
  • Insulin
  • Transforming Growth Factor beta