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Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis

Sertoli cells are highly polarized testicular supporting cells that simultaneously nurture multiple stages of germ cells during spermatogenesis. Proper localization of polarity protein complexes within Sertoli cells, including those responsible for blood-testis barrier formation, is vital for sperma...

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Detalles Bibliográficos
Autores principales: Heinrich, Anna, Bhandary, Bidur, Potter, Sarah J., Ratner, Nancy, DeFalco, Tony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604081/
https://www.ncbi.nlm.nih.gov/pubmed/34706238
http://dx.doi.org/10.1016/j.celrep.2021.109885
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author Heinrich, Anna
Bhandary, Bidur
Potter, Sarah J.
Ratner, Nancy
DeFalco, Tony
author_facet Heinrich, Anna
Bhandary, Bidur
Potter, Sarah J.
Ratner, Nancy
DeFalco, Tony
author_sort Heinrich, Anna
collection PubMed
description Sertoli cells are highly polarized testicular supporting cells that simultaneously nurture multiple stages of germ cells during spermatogenesis. Proper localization of polarity protein complexes within Sertoli cells, including those responsible for blood-testis barrier formation, is vital for spermatogenesis. However, the mechanisms and developmental timing that underlie Sertoli cell polarity are poorly understood. We investigate this aspect of testicular function by conditionally deleting Cdc42, encoding a Rho GTPase involved in regulating cell polarity, specifically in Sertoli cells. Sertoli Cdc42 deletion leads to increased apoptosis and disrupted polarity of juvenile and adult testes but does not affect fetal and postnatal testicular development. The onset of the first wave of spermatogenesis occurs normally, but it fails to progress past round spermatid stages, and by young adulthood, conditional knockout males exhibit a complete loss of spermatogenic cells. These findings demonstrate that Cdc42 is essential for Sertoli cell polarity and for maintaining steady-state sperm production.
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spelling pubmed-86040812021-11-19 Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis Heinrich, Anna Bhandary, Bidur Potter, Sarah J. Ratner, Nancy DeFalco, Tony Cell Rep Article Sertoli cells are highly polarized testicular supporting cells that simultaneously nurture multiple stages of germ cells during spermatogenesis. Proper localization of polarity protein complexes within Sertoli cells, including those responsible for blood-testis barrier formation, is vital for spermatogenesis. However, the mechanisms and developmental timing that underlie Sertoli cell polarity are poorly understood. We investigate this aspect of testicular function by conditionally deleting Cdc42, encoding a Rho GTPase involved in regulating cell polarity, specifically in Sertoli cells. Sertoli Cdc42 deletion leads to increased apoptosis and disrupted polarity of juvenile and adult testes but does not affect fetal and postnatal testicular development. The onset of the first wave of spermatogenesis occurs normally, but it fails to progress past round spermatid stages, and by young adulthood, conditional knockout males exhibit a complete loss of spermatogenic cells. These findings demonstrate that Cdc42 is essential for Sertoli cell polarity and for maintaining steady-state sperm production. 2021-10-26 /pmc/articles/PMC8604081/ /pubmed/34706238 http://dx.doi.org/10.1016/j.celrep.2021.109885 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ).
spellingShingle Article
Heinrich, Anna
Bhandary, Bidur
Potter, Sarah J.
Ratner, Nancy
DeFalco, Tony
Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis
title Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis
title_full Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis
title_fullStr Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis
title_full_unstemmed Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis
title_short Cdc42 activity in Sertoli cells is essential for maintenance of spermatogenesis
title_sort cdc42 activity in sertoli cells is essential for maintenance of spermatogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604081/
https://www.ncbi.nlm.nih.gov/pubmed/34706238
http://dx.doi.org/10.1016/j.celrep.2021.109885
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