RESUMO
The aim of this study was to evaluate whether high levels of exogenous testosterone (T) interfere in prostate morphogenesis. Pregnant females were exposed to subcutaneous injections of T cypionate (500 µg/animal) at gestational days 20 and 22. Male and female pups were euthanized at postnatal days 1 and 15. 15-day-old males had only fibroblast growth factor 10 (FGF10) immunostaining and nuclear form factor altered by the treatment, whereas treated females (T1 and T15) had almost all analyzed parameters changed. T1 females showed an increased anogenital distance (AGD), whereas T15 females had both AGD and ovary weight increased. T1 females had a higher number of epithelial buds emerging from the urethral and vaginal epithelium. We observed ectopic prostatic tissue surrounding the vagina in both T1 and T15 females. Moreover, the ectopic acini of T15 females showed delayed luminal formation, and there was a thickening of the periacinar smooth muscle layer (SML). Finally, FGF10 immunostaining intensity decreased in both T15 male and female prostates. Indeed, Sonic hedgehog (Shh) was upregulated in T15 female prostates, whereas no difference was observed between the male groups. These data showed that exogenous T changed the nuclear morphology of prostate epithelial cells in both males and females. Surprisingly, smooth muscle hyperplasia was also observed in the ectopic female prostate. Moreover, T downregulated FGF10 in both male and female prostates. Interestingly, the results suggest that FGF10 downregulation is mediated by the upregulation of Shh in females. In conclusion, exogenous T disrupts prostate development, particularly, affecting, the female.
Assuntos
Epitélio/metabolismo , Fator 10 de Crescimento de Fibroblastos/biossíntese , Proteínas Hedgehog/biossíntese , Músculo Liso/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Próstata/metabolismo , Testosterona/toxicidade , Animais , Animais Recém-Nascidos , Epitélio/efeitos dos fármacos , Epitélio/patologia , Feminino , Fator 10 de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica no Desenvolvimento , Gerbillinae , Proteínas Hedgehog/genética , Masculino , Músculo Liso/citologia , Músculo Liso/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Próstata/efeitos dos fármacos , Próstata/patologiaRESUMO
The prostate is a mammalian gland that shows a complex process of organogenesis. Here, a morphological study to characterize the organogenesis of the ventral prostate lobe in male gerbils was conducted. The urogenital sinus (UGS) was dissected out and processed for paraffin embedding. Histological sections were subjected to cytochemical, immunofluorescence, immunohistochemical, and three-dimensional reconstruction techniques. We found that the first ventral buds emerged from the ventral urethral epithelium between the days 20 and 21 of prenatal life, reaching the ventral mesenchymal pad and initiating the branching process on the first day of postnatal life. The buds presented a V-shaped elongation, suggesting that the smooth muscle layer (SML) plays an important role during budding events. Indeed, whereas the androgen receptor (AR) was preferentially found in the UGS mesenchyme (UGM), estrogen receptor alpha (ERα) was localized in both the UGM and in the emerging buds. This study characterized the morphological aspects of the budding process in a different rodent from rat and mice, serving as a new model for future studies on developmental biology of the prostate.