Prenatal genistein exposure in rats affects pubertal onset and serum reproductive hormone levels in male offsprings via the hypothalamic-pituitary-gonadal axis

Genistein, an abundant phytoestrogen found in soy and soy products, can cross the placental barrier. However, impacts of prenatal genistein on male offspring reproductive development are unclear. Here, pregnant Sprague-Dawley rats were exposed to genistein at 1, 10, and 20 mg/kg·bw/day from gestational day 0-17. Medium- and high-dose prenatal genistein delayed pubertal onset in male offspring by 2-3 days, reduced body weight, increased the testis-to-body weight ratio and shortened anogenital distance. Testicular histology revealed disorganized seminiferous tubules and reduced germ cell numbers. At pubertal onset, serum levels of gonadotropin-releasing hormone, follicle-stimulating hormone, luteinizing hormone and estradiol were increased in medium- and high-dose groups, while at postnatal day 49, serum level of testosterone was decreased. Real-Time quantitative PCR revealed reduced transcription of Kiss1 and Esr1, and elevated transcription of Gnrh1 in hypothalamus; reduced transcription of Esr1, Gnrhr, Fshb and Lhb in pituitary; and elevated transcription of Esr2, Lhcgr, Cyp11a1 and Inhba in testes. Immunohistochemistry and Western-blot analyses showed dysregulated protein expression of KISS1, GnRHR, and FSHR. In conclusion, prenatal genistein exposure in rats delays pubertal onset in male offspring by affecting hypothalamic-pituitary-gonadal axis, highlighting potential transgenerational impacts of prenatal phytoestrogen on pubertal and reproductive development of male offspring.