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Published on: September 7, 2016
Neonatal genistein exposure disrupts ovarian and uterine development in the mouse by inhibiting cellular
Guoyun Wu1, Quanwei Wei1, Debing Yu1
1College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
Abstract:
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.
Insights
Neonatal exposure to genistein from soy formula disrupts ovarian and uterine development in mice, potentially impacting fertility and reproductive health. Further research into isoflavone-rich diets is recommended.
Area of Science:
- Reproductive Biology
- Developmental Toxicology
- Endocrinology
Background:
- Soy-based formulas are rich in genistein, an isoflavone with estrogenic and tyrosine kinase inhibitory properties.
- Genistein's effects on cellular proliferation and development are known, but its long-term impact on ovarian and uterine development requires further investigation.
Purpose of the Study:
- To investigate the acute and chronic effects of neonatal genistein exposure on ovarian and uterine development in mice.
Main Methods:
- Neonatal mice (postnatal day 1) received daily subcutaneous injections of genistein (100 mg/kg) for 10 days.
- Ovaries and uteri were collected on days 10, 21, and 90 for histological evaluation.
- Proliferating cell activity was assessed using the Ki67 marker.
Main Results:
- Genistein induced multi-oocyte follicles and delayed primordial follicle assembly in ovaries.
- Uterine cavity and wall areas were significantly enlarged, with disrupted stroma-myometrium regularity.
- Genistein inhibited proliferative activity (reduced Ki67-positive nuclei) in ovarian and uterine tissues.
- Adult mice exposed to neonatal genistein showed ovarian abnormalities, including lack of corpora lutea, cystic follicles, and theca hypertrophy.
Conclusions:
- Neonatal genistein exposure adversely affects ovarian and uterine development in mice, leading to reproductive abnormalities.
- The findings suggest a need for closer examination of isoflavone-rich diets, including soy-based infant formulas and livestock feed, due to potential health implications.
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