The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation

Abstract Steroidogenic factor 1 (NR5A1) is essential for gonadal development. To study the importance of NR5A1 during early gonadal sex differentiation, we generated Sox9-Cre-Nr5a1 conditional knockout (cKO) mice: Sox9-Cre;Nr5a1 flox/flox and Sox9-Cre;Nr5a1 flox/− mice. Double-immunostaining for NR5...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yayoi Ikeda, Ayako Tagami, Mamiko Maekawa, Akiko Nagai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b57d436cdcb44e22987eecff4e5a9328
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b57d436cdcb44e22987eecff4e5a9328
record_format	dspace
spelling	oai:doaj.org-article:b57d436cdcb44e22987eecff4e5a93282021-12-02T11:35:57ZThe conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation10.1038/s41598-021-84095-y2045-2322https://doaj.org/article/b57d436cdcb44e22987eecff4e5a93282021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84095-yhttps://doaj.org/toc/2045-2322Abstract Steroidogenic factor 1 (NR5A1) is essential for gonadal development. To study the importance of NR5A1 during early gonadal sex differentiation, we generated Sox9-Cre-Nr5a1 conditional knockout (cKO) mice: Sox9-Cre;Nr5a1 flox/flox and Sox9-Cre;Nr5a1 flox/− mice. Double-immunostaining for NR5A1 and AMH revealed silenced NR5A1 in Sertoli cells and reduced AMH+ cells in the gonads of XY Sox9-Cre-Nr5a1 cKO mice between embryonic days 12.5 (E12.5) and E14.5. Double-immunostaining for SOX9 and FOXL2 further indicated an early block in Sertoli cells and ectopic granulosa cell differentiation. The number of cells expressing the Leydig cell marker 3βHSD obviously reduced in the gonads of XY Sox9-Cre;Nr5a1 flox/− but not Sox9-Cre;Nr5a1 flox/flox mice at E15.5. The presence of STRA8+ cells indicated that germ cells entered meiosis in the gonads of XY Sox9-Cre-Nr5a1 cKO mice. The results of qRT-PCR revealed remarkably reduced and elevated levels of testis and ovary markers, respectively, in the gonads of XY Sox9-Cre-Nr5a1 cKO mice at E12.5‒E13.5. These data suggested that the loss of Nr5a1 abrogates the testicular pathway and induces the ectopic ovarian pathway, resulting in postnatal partial/complete male-to-female gonadal sex reversal. Our findings provide evidence for the critical role of NR5A1 in murine gonadal sex determination in vivo.Yayoi IkedaAyako TagamiMamiko MaekawaAkiko NagaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yayoi Ikeda Ayako Tagami Mamiko Maekawa Akiko Nagai The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation
description	Abstract Steroidogenic factor 1 (NR5A1) is essential for gonadal development. To study the importance of NR5A1 during early gonadal sex differentiation, we generated Sox9-Cre-Nr5a1 conditional knockout (cKO) mice: Sox9-Cre;Nr5a1 flox/flox and Sox9-Cre;Nr5a1 flox/− mice. Double-immunostaining for NR5A1 and AMH revealed silenced NR5A1 in Sertoli cells and reduced AMH+ cells in the gonads of XY Sox9-Cre-Nr5a1 cKO mice between embryonic days 12.5 (E12.5) and E14.5. Double-immunostaining for SOX9 and FOXL2 further indicated an early block in Sertoli cells and ectopic granulosa cell differentiation. The number of cells expressing the Leydig cell marker 3βHSD obviously reduced in the gonads of XY Sox9-Cre;Nr5a1 flox/− but not Sox9-Cre;Nr5a1 flox/flox mice at E15.5. The presence of STRA8+ cells indicated that germ cells entered meiosis in the gonads of XY Sox9-Cre-Nr5a1 cKO mice. The results of qRT-PCR revealed remarkably reduced and elevated levels of testis and ovary markers, respectively, in the gonads of XY Sox9-Cre-Nr5a1 cKO mice at E12.5‒E13.5. These data suggested that the loss of Nr5a1 abrogates the testicular pathway and induces the ectopic ovarian pathway, resulting in postnatal partial/complete male-to-female gonadal sex reversal. Our findings provide evidence for the critical role of NR5A1 in murine gonadal sex determination in vivo.
format	article
author	Yayoi Ikeda Ayako Tagami Mamiko Maekawa Akiko Nagai
author_facet	Yayoi Ikeda Ayako Tagami Mamiko Maekawa Akiko Nagai
author_sort	Yayoi Ikeda
title	The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation
title_short	The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation
title_full	The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation
title_fullStr	The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation
title_full_unstemmed	The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation
title_sort	conditional deletion of steroidogenic factor 1 (nr5a1) in sox9-cre mice compromises testis differentiation
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b57d436cdcb44e22987eecff4e5a9328
work_keys_str_mv	AT yayoiikeda theconditionaldeletionofsteroidogenicfactor1nr5a1insox9cremicecompromisestestisdifferentiation AT ayakotagami theconditionaldeletionofsteroidogenicfactor1nr5a1insox9cremicecompromisestestisdifferentiation AT mamikomaekawa theconditionaldeletionofsteroidogenicfactor1nr5a1insox9cremicecompromisestestisdifferentiation AT akikonagai theconditionaldeletionofsteroidogenicfactor1nr5a1insox9cremicecompromisestestisdifferentiation AT yayoiikeda conditionaldeletionofsteroidogenicfactor1nr5a1insox9cremicecompromisestestisdifferentiation AT ayakotagami conditionaldeletionofsteroidogenicfactor1nr5a1insox9cremicecompromisestestisdifferentiation AT mamikomaekawa conditionaldeletionofsteroidogenicfactor1nr5a1insox9cremicecompromisestestisdifferentiation AT akikonagai conditionaldeletionofsteroidogenicfactor1nr5a1insox9cremicecompromisestestisdifferentiation
_version_	1718395840699039744

The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation

Ejemplares similares