E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice

In the mammalian testes, Sertoli cells are the only somatic cells in the seminiferous tubules that provide structural, nutritional and regulatory support for developing spermatogenic cells. Sertoli cells only proliferate during the fetal and neonatal periods and enter a quiescent state after puberty...

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Main Authors: Rong-Ge Yan, Qi-Lin Yang, Qi-En Yang
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Animals
Subjects:
Online Access:https://www.mdpi.com/2076-2615/10/9/1691
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author Rong-Ge Yan
Qi-Lin Yang
Qi-En Yang
author_facet Rong-Ge Yan
Qi-Lin Yang
Qi-En Yang
author_sort Rong-Ge Yan
collection DOAJ
description In the mammalian testes, Sertoli cells are the only somatic cells in the seminiferous tubules that provide structural, nutritional and regulatory support for developing spermatogenic cells. Sertoli cells only proliferate during the fetal and neonatal periods and enter a quiescent state after puberty. Functional evidences suggest that the size of Sertoli cell population determines sperm production and fertility. However, factors that direct Sertoli cell proliferation and maturation are not fully understood. Transcription factor E4F1 is a multifunctional protein that serves essential roles in cell fate decisions and because it interacts with pRB, a master regulator of Sertoli cell function, we hypothesized that E4F1 may have a functional role in Sertoli cells. <i>E4f1</i> mRNA was present in murine testis and immunohistochemical staining confirmed that E4F1 was enriched in mature Sertoli cells. We generated a conditional knockout mouse model using <i>Amh-cre</i> and <i>E4f1<sup>flox/flox</sup></i> lines to study E4F1 fucntion in Sertoli cells and the results showed that <i>E4f1</i> deletion caused a significant reduction in testis size and fertility. Further analyses revealed that meiosis progression and spermiogenesis were normal, however, Sertoli cell proliferation was impaired and germ cell apoptosis was elevated in the testis of <i>E4f1</i> conditional knockout mice. On the basis of these findings, we concluded that E4F1 was expressed in murine Sertoli cells and served important functions in regulating Sertoli cell proliferation and fertility.
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spelling doaj.art-ae99f059886046c082065d2ac2cd8c792023-11-20T14:17:11ZengMDPI AGAnimals2076-26152020-09-01109169110.3390/ani10091691E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in MiceRong-Ge Yan0Qi-Lin Yang1Qi-En Yang2Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810000, ChinaDepartment of Veterinary Sciences, Qinghai Vocational Technical College of Animal Husbandry and Veterinary, Xining 810016, ChinaKey Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810000, ChinaIn the mammalian testes, Sertoli cells are the only somatic cells in the seminiferous tubules that provide structural, nutritional and regulatory support for developing spermatogenic cells. Sertoli cells only proliferate during the fetal and neonatal periods and enter a quiescent state after puberty. Functional evidences suggest that the size of Sertoli cell population determines sperm production and fertility. However, factors that direct Sertoli cell proliferation and maturation are not fully understood. Transcription factor E4F1 is a multifunctional protein that serves essential roles in cell fate decisions and because it interacts with pRB, a master regulator of Sertoli cell function, we hypothesized that E4F1 may have a functional role in Sertoli cells. <i>E4f1</i> mRNA was present in murine testis and immunohistochemical staining confirmed that E4F1 was enriched in mature Sertoli cells. We generated a conditional knockout mouse model using <i>Amh-cre</i> and <i>E4f1<sup>flox/flox</sup></i> lines to study E4F1 fucntion in Sertoli cells and the results showed that <i>E4f1</i> deletion caused a significant reduction in testis size and fertility. Further analyses revealed that meiosis progression and spermiogenesis were normal, however, Sertoli cell proliferation was impaired and germ cell apoptosis was elevated in the testis of <i>E4f1</i> conditional knockout mice. On the basis of these findings, we concluded that E4F1 was expressed in murine Sertoli cells and served important functions in regulating Sertoli cell proliferation and fertility.https://www.mdpi.com/2076-2615/10/9/1691E4F1sertoli cellsspermatogenesisproliferationfertility
spellingShingle Rong-Ge Yan
Qi-Lin Yang
Qi-En Yang
E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice
Animals
E4F1
sertoli cells
spermatogenesis
proliferation
fertility
title E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice
title_full E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice
title_fullStr E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice
title_full_unstemmed E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice
title_short E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice
title_sort e4 transcription factor 1 e4f1 regulates sertoli cell proliferation and fertility in mice
topic E4F1
sertoli cells
spermatogenesis
proliferation
fertility
url https://www.mdpi.com/2076-2615/10/9/1691
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