Sexual Dimorphism in Mouse Metanephroi Exposed to 17β-Estradiol in vitro

Abstract

17β-Estradiol, the most potent circulating estrogen, has been shown to greatly impact on the development and formation of tissues of the urogenital tract. The adult kidney has previously been shown to be highly responsive to 17β-estradiol stimulation. However, the direct effect of 17β-estradiol on kidney development remains unclear. Aim: To investigate the direct effect of 17β-estradiol on male and female metanephric kidney development. Methods: Whole embryonic-day-12.5 (E12.5) C57Bl/6 male and female mouse metanephroi were cultured in the presence of varying concentrations of 17β-estradiol (0.1–5.0 nM) for 72 h. Metanephric development was assessed using immunofluorescence labeling techniques. The real-time polymerase chain reaction was used to investigate estrogen receptor-α (ERα), glial-cell-line-derived neurotrophic factor (GDNF) and its associated receptor cRET, transforming growth factor-β (TGFβ1), TGFβ2 and TGFβ3 mRNA expression levels. Results:ERα was present in developing metanephroi at E12.5; however, ERβ was absent. No significant sex difference in ERα mRNA expression was observed. Significant increases in the number of ureteric branch points, terminal tips and developing glomeruli were observed in female metanephroi cultured in the presence of 1.0 and 5.0 nM 17β-estradiol. Conversely, no significant effect was observed in male metanephroi cultured with 17β-estradiol. GDNF and cRET mRNA expression was increased in both male and female metanephroi, whilst TGFβ1 and TGFβ2 mRNA expression was decreased following culture in the presence of 17β-estradiol. Conclusion: This study is the first to establish that the mouse metanephros displays a sexual dimorphism in response to specific concentrations of estrogens.