Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate

Autor: Sebastião Roberto Taboga, Mara Rubia Marques, Fernanda C. A. Santos, Luana Araújo Manso, Giovanna Amaral Rodrigues, Manoel F. Biancardi, Barbara Costa Malmann Medeiros, Jordana Gomes Ramos
Přispěvatelé: Universidade Federal de Goiás (UFG), Universidade Estadual Paulista (Unesp)
Rok vydání: 2021
Předmět:
Zdroj: Web of Science
Repositório Institucional da UNESP
Universidade Estadual Paulista (UNESP)
instacron:UNESP
ISSN: 0024-3205
DOI: 10.1016/j.lfs.2021.119198
Popis: Made available in DSpace on 2021-06-25T12:39:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-15 Fundacao de Amparo a Pesquisa do Estado de Goias-Brazil (FAPEG) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 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 mu g/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. Univ Fed Goias, Dept Histol Embryol & Cell Biol, Av Esperanca S-N,Campus Samambaia, BR-74690900 Goiania, Go, Brazil Sao Paulo State Univ, Dept Biol, R Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil Sao Paulo State Univ, Dept Biol, R Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil Fundacao de Amparo a Pesquisa do Estado de Goias-Brazil (FAPEG): 08/2018 CNPq: 422302/2018-0 CAPES: 001
Databáze: OpenAIRE