The ventromedial hypothalamic nucleus responds differentially to genistein exposure during development in male and female rats in the long term

Genistein may act as an endocrine disruptor due to its structural similarity to estradiol. Exposure to genistein during development has been shown to alter neuromorphology and G protein-coupled estrogen receptor (GPER) expression in the arcuate nucleus in adult rats. In this study, we investigated the long-term effects of genistein exposure in the ventromedial nucleus of the hypothalamus (VMH) during the second week of life. Rats of both sexes were injected daily (s.c.) from postnatal day 6-13, with the following treatments: I) corn oil vehicle (control group); II) 10 μg/g of genistein (G10); and III) 50 μg/g of genistein (G50). Morphometric analyses of the VMH in Nissl-stained and GPER-immunostained brain sections were performed at P90 using ImageJ software. In males, the low dose of genistein provoked a significant increase of GPER-ir neurons in the dorsomedial, central and ventrolateral subdivisions and in the medial division, as well as in the total VMH, while in females no effects in GPER-ir neurons were observed. In females, the high dose of genistein produced a significant decrease of Nissl-stained neurons in the ventrolateral subdivision and medial division, but no effect was detected in males. Early exposure to genistein may differentially alter the VMH in the long-term depending on the sex, dose, and subdivision studied.