Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.lfs.2021.119198 http://hdl.handle.net/11449/210108 |
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 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. |
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Repositório Institucional da UNESP |
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2946 |
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Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostateProstateTestosteroneDevelopmentFGF10ShhSmooth muscle layerThe 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.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)Univ Fed Goias, Dept Histol Embryol & Cell Biol, Av Esperanca S-N,Campus Samambaia, BR-74690900 Goiania, Go, BrazilSao Paulo State Univ, Dept Biol, R Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, BrazilSao Paulo State Univ, Dept Biol, R Cristovao Colombo 2265, BR-15054000 Sao Jose Do Rio Preto, SP, BrazilFundacao de Amparo a Pesquisa do Estado de Goias-Brazil (FAPEG): 08/2018CNPq: 422302/2018-0CAPES: 001Elsevier B.V.Universidade Federal de Goiás (UFG)Universidade Estadual Paulista (Unesp)Manso, Luana AraujoMalmann Medeiros, Barbara CostaRodrigues, Giovanna AmaralRamos, Jordana GomesMarques, Mara RubiaTaboga, Sebastiao Roberto [UNESP]Alcantara dos Santos, Fernanda CristinaBiancardi, Manoel Francisco2021-06-25T12:39:57Z2021-06-25T12:39:57Z2021-04-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10http://dx.doi.org/10.1016/j.lfs.2021.119198Life Sciences. Oxford: Pergamon-elsevier Science Ltd, v. 271, 10 p., 2021.0024-3205http://hdl.handle.net/11449/21010810.1016/j.lfs.2021.119198WOS:000626600400033Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengLife Sciencesinfo:eu-repo/semantics/openAccess2021-10-23T20:11:15Zoai:repositorio.unesp.br:11449/210108Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:05:57.010828Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate |
title |
Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate |
spellingShingle |
Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate Manso, Luana Araujo Prostate Testosterone Development FGF10 Shh Smooth muscle layer |
title_short |
Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate |
title_full |
Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate |
title_fullStr |
Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate |
title_full_unstemmed |
Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate |
title_sort |
Testosterone exposure in prenatal life disrupts epithelial nuclear morphology, smooth muscle layer pattern, and FGF10 and Shh expression in prostate |
author |
Manso, Luana Araujo |
author_facet |
Manso, Luana Araujo Malmann Medeiros, Barbara Costa Rodrigues, Giovanna Amaral Ramos, Jordana Gomes Marques, Mara Rubia Taboga, Sebastiao Roberto [UNESP] Alcantara dos Santos, Fernanda Cristina Biancardi, Manoel Francisco |
author_role |
author |
author2 |
Malmann Medeiros, Barbara Costa Rodrigues, Giovanna Amaral Ramos, Jordana Gomes Marques, Mara Rubia Taboga, Sebastiao Roberto [UNESP] Alcantara dos Santos, Fernanda Cristina Biancardi, Manoel Francisco |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Federal de Goiás (UFG) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Manso, Luana Araujo Malmann Medeiros, Barbara Costa Rodrigues, Giovanna Amaral Ramos, Jordana Gomes Marques, Mara Rubia Taboga, Sebastiao Roberto [UNESP] Alcantara dos Santos, Fernanda Cristina Biancardi, Manoel Francisco |
dc.subject.por.fl_str_mv |
Prostate Testosterone Development FGF10 Shh Smooth muscle layer |
topic |
Prostate Testosterone Development FGF10 Shh Smooth muscle layer |
description |
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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T12:39:57Z 2021-06-25T12:39:57Z 2021-04-15 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.lfs.2021.119198 Life Sciences. Oxford: Pergamon-elsevier Science Ltd, v. 271, 10 p., 2021. 0024-3205 http://hdl.handle.net/11449/210108 10.1016/j.lfs.2021.119198 WOS:000626600400033 |
url |
http://dx.doi.org/10.1016/j.lfs.2021.119198 http://hdl.handle.net/11449/210108 |
identifier_str_mv |
Life Sciences. Oxford: Pergamon-elsevier Science Ltd, v. 271, 10 p., 2021. 0024-3205 10.1016/j.lfs.2021.119198 WOS:000626600400033 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Life Sciences |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
10 |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129018875084800 |