Neonatal genistein exposure disrupts ovarian and uterine development in the mouse by inhibiting cellular proliferation

摘要

Soy-based formula contains high concentrations of the isoflavone genistein. Genistein possesses estrogenic and tyrosine kinase inhibitory activity and interferes with cellular proliferation and development. To date, the acute and chronic effects of genistein on ovarian and uterine development have not been fully elucidated. In this study, mice at postnatal day 1 were subcutaneously injected with 100 mg/kg genistein for 10 consecutive days, and then their ovaries and uteri were collected on days 10, 21, and 90. Histological evaluation was performed after hematoxylin and eosin staining. The proliferating activity was indicated by the proliferating indicator protein Ki67. Results showed that the subcutaneous injection of genistein to neonatal mice induced the formation of multi-oocyte follicles and delayed the primordial follicle assembly in the ovaries. Genistein significantly enlarged the cross-sectional area of the uterine cavity and wall and disrupted the regularity between the uterine stroma and myometrium. Genistein exposure inhibited proliferative activity because fewer Ki67-positive nuclei were detected in ovarian and uterine cell populations than in the control. Furthermore, most ovaries from adult mice given neonatal genistein were without corpora lutea, and there appeared to be cystic follicles and hypertrophy of the theca, and cortical and medullary layers. Considering the high concentration of isoflavone in soy-based infant formulas and livestock feed, we suggest that the use of isoflavone-rich diets in humans and livestock receive closer examination.