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

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. Lactational genistein exposure accelerates vaginal opening, increases hypothalamic GnRH secretion, enhances kisspeptin receptor expression, and elevates blood levels of GnRH, luteinizing hormone, and follicle‐stimulating hormone in female rats.