Hypothalamic DNA methylation in rats with dihydrotestosterone-induced polycystic ovary syndrome: effects of

Peng Cui1, Tong Ma1, Amin Tamadon1

  • 1Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, 200032, China.

Experimental Physiology
|September 12, 2018
PubMed

Insights

Hypothalamic DNA methylation is implicated in polycystic ovary syndrome (PCOS) development and electro-acupuncture (EA) treatment response. EA reduced DNA methylation and altered gene expression in PCOS-like rats, suggesting a key epigenetic role.

Area of Science:

  • Reproductive Endocrinology
  • Epigenetics
  • Neuroendocrinology

Background:

  • Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with unclear etiology.
  • Epigenetic mechanisms, particularly DNA methylation, are increasingly studied in PCOS pathogenesis.
  • The role of hypothalamic DNA methylation in PCOS and its modulation by treatments like electro-acupuncture (EA) remains largely unexplored.

Purpose of the Study:

  • To investigate the role of hypothalamic DNA methylation in the development of PCOS.
  • To explore how EA treatment affects hypothalamic DNA methylation in a PCOS rat model.
  • To identify specific genes whose methylation patterns are altered in PCOS and by EA treatment.

Main Methods:

  • Utilized a 5α-dihydrotestosterone-induced PCOS-like rat model.
  • Administered EA treatment to a subset of PCOS rats.
  • Analyzed reproductive, metabolic, and behavioral phenotypes.
  • Quantified global DNA methylation and expression of DNA methyltransferases (DNMTs).
  • Performed pyrosequencing to assess methylation at specific CpG sites in candidate genes (Plcg1, Camk2b, Esr2, Pgr, Ar).

Main Results:

  • PCOS rats exhibited reproductive, metabolic, and behavioral abnormalities.
  • EA treatment improved reproductive function, reduced body weight, and ameliorated depressive behaviors.
  • Global DNA methylation and DNMT expression were elevated in PCOS rats; EA decreased global methylation and DNMT3b expression.
  • Differential methylation of candidate genes (Plcg1, Camk2b, Esr2, Pgr, Ar) was observed in PCOS and PCOS+EA groups.

Conclusions:

  • Hypothalamic DNA methylation is potentially involved in PCOS development.
  • EA treatment influences hypothalamic DNA methylation patterns in PCOS rats.
  • These findings highlight DNA methylation as a key epigenetic mechanism in PCOS and a potential target for EA therapy.

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