Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.

Endocrine disruptors (ED) have been incriminated in the current increase of male reproductive alterations. Bisphenol A (BPA) is a widely used weak estrogenic environmental ED and it is debated whether BPA concentrations within the average internal exposure are toxic. In the present study we investig...

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Autores principales:	Thierry N'Tumba-Byn, Delphine Moison, Marlène Lacroix, Charlotte Lecureuil, Laëtitia Lesage, Sophie M Prud'homme, Stéphanie Pozzi-Gaudin, René Frydman, Alexandra Benachi, Gabriel Livera, Virginie Rouiller-Fabre, René Habert
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70776421d15b4928ac8561c42db225cb
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spelling	oai:doaj.org-article:70776421d15b4928ac8561c42db225cb2021-11-18T08:04:50ZDifferential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.1932-620310.1371/journal.pone.0051579https://doaj.org/article/70776421d15b4928ac8561c42db225cb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284716/?tool=EBIhttps://doaj.org/toc/1932-6203Endocrine disruptors (ED) have been incriminated in the current increase of male reproductive alterations. Bisphenol A (BPA) is a widely used weak estrogenic environmental ED and it is debated whether BPA concentrations within the average internal exposure are toxic. In the present study we investigated the effects of 10(-12) to 10(-5) M BPA concentrations on fetal Leydig cell function, as fetal life is a critical period of sensitivity to ED effects on male reproductive function. To this aim, fetal testes from human at 6.5-10.5 gestational weeks (GW) or from rat and mouse at a comparable critical period of development (14.5 days post-coitum (dpc) for rat and 12.5 dpc for mouse) were explanted and cultured using our validated organotypic culture system in the presence or absence of BPA for 1-3 days. BPA concentrations as low as 10(-8) M reduced testosterone secretion by human testes from day 1 of culture onwards, but not by mouse and rat testes where concentrations equal to 10(-5) M BPA were required. Similarly, 10(-8) M BPA reduced INSL3 mRNA levels only in human cultured testes. On the contrary, 10(-5) and 10(-6) M diethylstilbestrol (DES), a classical estrogenic compound, affected testosterone secretion only in rat and mouse testis cultures, but not in human testis cultures. Lastly, contrarily to the DES effect, the negative effect of BPA on testosterone produced by the mouse fetal testis was maintained after invalidation of estrogen receptor α (ERα). In conclusion, these results evidenced i) a deleterious effect of BPA on fetal Leydig cells function in human for concentrations from 10(-8) M upwards, ii) species-specific differences raising concerns about extrapolation of data from rodent studies to human risk assessment, iii) a specific signaling pathway for BPA which differs from the DES one and which does not involve ERα.Thierry N'Tumba-BynDelphine MoisonMarlène LacroixCharlotte LecureuilLaëtitia LesageSophie M Prud'hommeStéphanie Pozzi-GaudinRené FrydmanAlexandra BenachiGabriel LiveraVirginie Rouiller-FabreRené HabertPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51579 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thierry N'Tumba-Byn Delphine Moison Marlène Lacroix Charlotte Lecureuil Laëtitia Lesage Sophie M Prud'homme Stéphanie Pozzi-Gaudin René Frydman Alexandra Benachi Gabriel Livera Virginie Rouiller-Fabre René Habert Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.
description	Endocrine disruptors (ED) have been incriminated in the current increase of male reproductive alterations. Bisphenol A (BPA) is a widely used weak estrogenic environmental ED and it is debated whether BPA concentrations within the average internal exposure are toxic. In the present study we investigated the effects of 10(-12) to 10(-5) M BPA concentrations on fetal Leydig cell function, as fetal life is a critical period of sensitivity to ED effects on male reproductive function. To this aim, fetal testes from human at 6.5-10.5 gestational weeks (GW) or from rat and mouse at a comparable critical period of development (14.5 days post-coitum (dpc) for rat and 12.5 dpc for mouse) were explanted and cultured using our validated organotypic culture system in the presence or absence of BPA for 1-3 days. BPA concentrations as low as 10(-8) M reduced testosterone secretion by human testes from day 1 of culture onwards, but not by mouse and rat testes where concentrations equal to 10(-5) M BPA were required. Similarly, 10(-8) M BPA reduced INSL3 mRNA levels only in human cultured testes. On the contrary, 10(-5) and 10(-6) M diethylstilbestrol (DES), a classical estrogenic compound, affected testosterone secretion only in rat and mouse testis cultures, but not in human testis cultures. Lastly, contrarily to the DES effect, the negative effect of BPA on testosterone produced by the mouse fetal testis was maintained after invalidation of estrogen receptor α (ERα). In conclusion, these results evidenced i) a deleterious effect of BPA on fetal Leydig cells function in human for concentrations from 10(-8) M upwards, ii) species-specific differences raising concerns about extrapolation of data from rodent studies to human risk assessment, iii) a specific signaling pathway for BPA which differs from the DES one and which does not involve ERα.
format	article
author	Thierry N'Tumba-Byn Delphine Moison Marlène Lacroix Charlotte Lecureuil Laëtitia Lesage Sophie M Prud'homme Stéphanie Pozzi-Gaudin René Frydman Alexandra Benachi Gabriel Livera Virginie Rouiller-Fabre René Habert
author_facet	Thierry N'Tumba-Byn Delphine Moison Marlène Lacroix Charlotte Lecureuil Laëtitia Lesage Sophie M Prud'homme Stéphanie Pozzi-Gaudin René Frydman Alexandra Benachi Gabriel Livera Virginie Rouiller-Fabre René Habert
author_sort	Thierry N'Tumba-Byn
title	Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.
title_short	Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.
title_full	Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.
title_fullStr	Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.
title_full_unstemmed	Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.
title_sort	differential effects of bisphenol a and diethylstilbestrol on human, rat and mouse fetal leydig cell function.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/70776421d15b4928ac8561c42db225cb
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Differential effects of bisphenol A and diethylstilbestrol on human, rat and mouse fetal leydig cell function.

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