NOTCH1 gain of function in germ cells causes failure of spermatogenesis in male mice.

NOTCH1 is a member of the NOTCH receptor family, a group of single-pass trans-membrane receptors. NOTCH signaling is highly conserved in evolution and mediates communication between adjacent cells. NOTCH receptors have been implicated in cell fate determination, as well as maintenance and differenti...

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Autores principales:	Zaohua Huang, Bryan Rivas, Alexander I Agoulnik
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c722dd7a843e4332a18d8406fe9749bf
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spelling	oai:doaj.org-article:c722dd7a843e4332a18d8406fe9749bf2021-11-18T09:01:54ZNOTCH1 gain of function in germ cells causes failure of spermatogenesis in male mice.1932-620310.1371/journal.pone.0071213https://doaj.org/article/c722dd7a843e4332a18d8406fe9749bf2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936265/?tool=EBIhttps://doaj.org/toc/1932-6203NOTCH1 is a member of the NOTCH receptor family, a group of single-pass trans-membrane receptors. NOTCH signaling is highly conserved in evolution and mediates communication between adjacent cells. NOTCH receptors have been implicated in cell fate determination, as well as maintenance and differentiation of stem cells. In the mammalian testis expression of NOTCH1 in somatic and germ cells has been demonstrated, however its role in spermatogenesis was not clear. To study the significance of NOTCH1 in germ cells, we applied a cre/loxP approach in mice to induce NOTCH1 gain- or loss-of function specifically in male germ cells. Using a Stra8-icre transgene we produced mice with conditional activation of the NOTCH1 intracellular domain (NICD) in germ cells. Spermatogenesis in these mutants was progressively affected with age, resulting in decreased testis weight and sperm count. Analysis of downstream target genes of NOTCH1 signaling showed an increased expression of Hes5, with a reduction of the spermatogonial differentiation marker, Neurog3 expression in the mutant testis. Apoptosis was significantly increased in mouse germ cells with the corresponding elevation of pro-apoptotic Trp53 and Trp63 genes' expression. We also showed that the conditional germ cell-specific ablation of Notch1 had no effect on spermatogenesis or male fertility. Our data suggest the importance of NOTCH signaling regulation in male germ cells for their survival and differentiation.Zaohua HuangBryan RivasAlexander I AgoulnikPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e71213 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zaohua Huang Bryan Rivas Alexander I Agoulnik NOTCH1 gain of function in germ cells causes failure of spermatogenesis in male mice.
description	NOTCH1 is a member of the NOTCH receptor family, a group of single-pass trans-membrane receptors. NOTCH signaling is highly conserved in evolution and mediates communication between adjacent cells. NOTCH receptors have been implicated in cell fate determination, as well as maintenance and differentiation of stem cells. In the mammalian testis expression of NOTCH1 in somatic and germ cells has been demonstrated, however its role in spermatogenesis was not clear. To study the significance of NOTCH1 in germ cells, we applied a cre/loxP approach in mice to induce NOTCH1 gain- or loss-of function specifically in male germ cells. Using a Stra8-icre transgene we produced mice with conditional activation of the NOTCH1 intracellular domain (NICD) in germ cells. Spermatogenesis in these mutants was progressively affected with age, resulting in decreased testis weight and sperm count. Analysis of downstream target genes of NOTCH1 signaling showed an increased expression of Hes5, with a reduction of the spermatogonial differentiation marker, Neurog3 expression in the mutant testis. Apoptosis was significantly increased in mouse germ cells with the corresponding elevation of pro-apoptotic Trp53 and Trp63 genes' expression. We also showed that the conditional germ cell-specific ablation of Notch1 had no effect on spermatogenesis or male fertility. Our data suggest the importance of NOTCH signaling regulation in male germ cells for their survival and differentiation.
format	article
author	Zaohua Huang Bryan Rivas Alexander I Agoulnik
author_facet	Zaohua Huang Bryan Rivas Alexander I Agoulnik
author_sort	Zaohua Huang
title	NOTCH1 gain of function in germ cells causes failure of spermatogenesis in male mice.
title_short	NOTCH1 gain of function in germ cells causes failure of spermatogenesis in male mice.
title_full	NOTCH1 gain of function in germ cells causes failure of spermatogenesis in male mice.
title_fullStr	NOTCH1 gain of function in germ cells causes failure of spermatogenesis in male mice.
title_full_unstemmed	NOTCH1 gain of function in germ cells causes failure of spermatogenesis in male mice.
title_sort	notch1 gain of function in germ cells causes failure of spermatogenesis in male mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c722dd7a843e4332a18d8406fe9749bf
work_keys_str_mv	AT zaohuahuang notch1gainoffunctioningermcellscausesfailureofspermatogenesisinmalemice AT bryanrivas notch1gainoffunctioningermcellscausesfailureofspermatogenesisinmalemice AT alexanderiagoulnik notch1gainoffunctioningermcellscausesfailureofspermatogenesisinmalemice
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NOTCH1 gain of function in germ cells causes failure of spermatogenesis in male mice.

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