Impact of Physiologically Relevant Genistein Exposure at Different Time Windows on Puberty Onset and Neuroendocrine Function in Female Rats

Mol Nutr Food Res. 2022 Dec;66(24):e2200486. doi: 10.1002/mnfr.202200486. Epub 2022 Nov 11.

Abstract

Scope: Puberty timing, critical for adulthood wellbeing, is influenced by the environment, life-style, and diets. However, differential puberty-interfering effects of soy and soy isoflavone are observed in both epidemiological and toxicological studies. Additionally, their impact on neuroendocrine function at various pre-pubertal developmental windows is unclear.

Methods and results: This study investigates the effect of genistein, a typical soy isoflavone, at neonatal, lactational, and post-weaning stages on the time of vaginal opening and determines the levels of neuroendocrine factors in female rats using immunofluorescence, immunochemistry, and enzyme-linked immunosorbent assays. A physiologically relevant dosage (10 mg kg-1 ) is used to resemble human exposure. The results show that genistein exposure at lactational stage significantly accelerates vaginal opening time, marginally increases hypothalamic gonadotropin-releasing hormone (GnRH) secretion, significantly enhances kisspeptin receptor expression, and markedly elevates blood levels of GnRH, luteinizing hormone, and follicle-stimulating hormone, while neonatal and post-weaning exposures do not induce significant alternations.

Conclusion: Lactational stage may be an important window for genistein to impact reproductive development and neuroendocrine regulations.

Keywords: GPR54; GnRH; HPG; isoflavone; vaginal opening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Genistein* / pharmacology
  • Gonadotropin-Releasing Hormone / metabolism
  • Gonadotropin-Releasing Hormone / pharmacology
  • Kisspeptins / metabolism
  • Kisspeptins / pharmacology
  • Luteinizing Hormone / pharmacology
  • Rats
  • Sexual Maturation* / physiology

Substances

  • Genistein
  • Gonadotropin-Releasing Hormone
  • Kisspeptins
  • Luteinizing Hormone