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MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice
The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate sperm...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764304/ https://www.ncbi.nlm.nih.gov/pubmed/29324782 http://dx.doi.org/10.1371/journal.pone.0190800 |
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author | Shawki, Hossam H. Oishi, Hisashi Usui, Toshiaki Kitadate, Yu Basha, Walaa A. Abdellatif, Ahmed M. Hasegawa, Kazunori Okada, Risa Mochida, Keiji El-Shemy, Hany A. Muratani, Masafumi Ogura, Atsuo Yoshida, Shosei Takahashi, Satoru |
author_facet | Shawki, Hossam H. Oishi, Hisashi Usui, Toshiaki Kitadate, Yu Basha, Walaa A. Abdellatif, Ahmed M. Hasegawa, Kazunori Okada, Risa Mochida, Keiji El-Shemy, Hany A. Muratani, Masafumi Ogura, Atsuo Yoshida, Shosei Takahashi, Satoru |
author_sort | Shawki, Hossam H. |
collection | PubMed |
description | The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate spermatogenesis. However, its exact localization and function remain unclear. Here, we localized MAFB expression in embryonic and adult testes and analyzed its gene function using Mafb-deficient mice. We found that MAFB and c-MAF are the only large MAF transcription factors expressed in testes, while MAFA and NRL are not. MAFB was localized in Leydig and Sertoli cells at embryonic day (E) 18.5 but in Leydig cells, Sertoli cells, and pachytene spermatocytes in adults. Mafb-deficient testes at E18.5 showed fully formed seminiferous tubules with no abnormal structure or differences in testicular somatic cell numbers compared with those of control wild-type mice. Additionally, the expression levels of genes related to development and function of testicular cells were unchanged between genotypes. In adults, the expression of MAFB in Sertoli cells was shown to be stage specific and induced by RA. By generating Mafb(fl/fl) CAG-CreER(™) (Mafb-cKO) mice, in which Cre recombinase was activated upon tamoxifen treatment, we found that the neonatal cKO mice died shortly upon Mafb deletion, but adult cKO mice were alive upon deletion. Adult cKO mice were fertile, and spermatogenesis maintenance was normal, as indicated by histological analysis, hormone levels, and germ cell stage-specific markers. Moreover, there were no differences in the proportion of seminiferous stages between cKO mice and controls. However, RNA-Seq analysis of cKO Sertoli cells revealed that the down-regulated genes were related to immune function and phagocytosis activity but not spermatogenesis. In conclusion, we found that MAFB is dispensable for fetal testis morphogenesis and spermatogenesis maintenance in adult mice, despite the significant gene expression in different cell types, but MAFB might be critical for phagocytosis activity of Sertoli cells. |
format | Online Article Text |
id | pubmed-5764304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57643042018-01-23 MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice Shawki, Hossam H. Oishi, Hisashi Usui, Toshiaki Kitadate, Yu Basha, Walaa A. Abdellatif, Ahmed M. Hasegawa, Kazunori Okada, Risa Mochida, Keiji El-Shemy, Hany A. Muratani, Masafumi Ogura, Atsuo Yoshida, Shosei Takahashi, Satoru PLoS One Research Article The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate spermatogenesis. However, its exact localization and function remain unclear. Here, we localized MAFB expression in embryonic and adult testes and analyzed its gene function using Mafb-deficient mice. We found that MAFB and c-MAF are the only large MAF transcription factors expressed in testes, while MAFA and NRL are not. MAFB was localized in Leydig and Sertoli cells at embryonic day (E) 18.5 but in Leydig cells, Sertoli cells, and pachytene spermatocytes in adults. Mafb-deficient testes at E18.5 showed fully formed seminiferous tubules with no abnormal structure or differences in testicular somatic cell numbers compared with those of control wild-type mice. Additionally, the expression levels of genes related to development and function of testicular cells were unchanged between genotypes. In adults, the expression of MAFB in Sertoli cells was shown to be stage specific and induced by RA. By generating Mafb(fl/fl) CAG-CreER(™) (Mafb-cKO) mice, in which Cre recombinase was activated upon tamoxifen treatment, we found that the neonatal cKO mice died shortly upon Mafb deletion, but adult cKO mice were alive upon deletion. Adult cKO mice were fertile, and spermatogenesis maintenance was normal, as indicated by histological analysis, hormone levels, and germ cell stage-specific markers. Moreover, there were no differences in the proportion of seminiferous stages between cKO mice and controls. However, RNA-Seq analysis of cKO Sertoli cells revealed that the down-regulated genes were related to immune function and phagocytosis activity but not spermatogenesis. In conclusion, we found that MAFB is dispensable for fetal testis morphogenesis and spermatogenesis maintenance in adult mice, despite the significant gene expression in different cell types, but MAFB might be critical for phagocytosis activity of Sertoli cells. Public Library of Science 2018-01-11 /pmc/articles/PMC5764304/ /pubmed/29324782 http://dx.doi.org/10.1371/journal.pone.0190800 Text en © 2018 Shawki et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Shawki, Hossam H. Oishi, Hisashi Usui, Toshiaki Kitadate, Yu Basha, Walaa A. Abdellatif, Ahmed M. Hasegawa, Kazunori Okada, Risa Mochida, Keiji El-Shemy, Hany A. Muratani, Masafumi Ogura, Atsuo Yoshida, Shosei Takahashi, Satoru MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice |
title | MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice |
title_full | MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice |
title_fullStr | MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice |
title_full_unstemmed | MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice |
title_short | MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice |
title_sort | mafb is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764304/ https://www.ncbi.nlm.nih.gov/pubmed/29324782 http://dx.doi.org/10.1371/journal.pone.0190800 |
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