Retinoic Acid Receptor Alpha Is Essential in Postnatal Sertoli Cells but Not in Germ Cells
Retinoic acid signaling is indispensable for the completion of spermatogenesis. It is known that loss of retinoic acid nuclear receptor alpha (RARA) induces male sterility due to seminiferous epithelium degeneration. Initial genetic studies established that RARA acts in Sertoli cells, but a recent p...
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MDPI AG
2022-03-01
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| author | Diana Condrea Sirine Souali-Crespo Betty Féret Muriel Klopfenstein Sylvain Faisan Manuel Mark Norbert B. Ghyselinck Nadège Vernet |
| author_facet | Diana Condrea Sirine Souali-Crespo Betty Féret Muriel Klopfenstein Sylvain Faisan Manuel Mark Norbert B. Ghyselinck Nadège Vernet |
| author_sort | Diana Condrea |
| collection | DOAJ |
| description | Retinoic acid signaling is indispensable for the completion of spermatogenesis. It is known that loss of retinoic acid nuclear receptor alpha (RARA) induces male sterility due to seminiferous epithelium degeneration. Initial genetic studies established that RARA acts in Sertoli cells, but a recent paper proposed that RARA is also instrumental in germ cells. In the present study, we have re-assessed the function of RARA in germ cells by genetically ablating the <i>Rara</i> gene in spermatogonia and their progenies using a cell-specific conditional mutagenesis approach. We show that loss of <i>Rara</i> in postnatal male germ cells does not alter the histology of the seminiferous epithelium. Furthermore, RARA-deficient germ cells differentiate normally and give rise to normal, living pups. This establishes that RARA plays no crucial role in germ cells. We also tested whether RARA is required in Sertoli cells during the fetal period or after birth. For this purpose, we deleted the <i>Rara</i> gene in Sertoli cells at postnatal day 15 (PN15), i.e., after the onset of the first spermatogenic wave. To do so, we used temporally controlled cell-specific mutagenesis. By comparing the testis phenotypes generated when <i>Rara</i> is lost either at PN15 or at embryonic day 13, we show that RARA exerts all of its functions in Sertoli cells not at the fetal stage but from puberty. |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:44:08Z |
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| series | Cells |
| spelling | doaj.art-c48b394a08f34a128ae0175c1c49bb8c2023-11-23T22:51:50ZengMDPI AGCells2073-44092022-03-0111589110.3390/cells11050891Retinoic Acid Receptor Alpha Is Essential in Postnatal Sertoli Cells but Not in Germ CellsDiana Condrea0Sirine Souali-Crespo1Betty Féret2Muriel Klopfenstein3Sylvain Faisan4Manuel Mark5Norbert B. Ghyselinck6Nadège Vernet7Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Génétique Fonctionnelle et Cancer, Centre National de la Recherche Scientifique (CNRS, UMR7104), Institut National de la Santé et de la Recherche Médicale (INSERM U1258), Université de Strasbourg (UNISTRA), 1 rue Laurent Fries, CEDEX, 67404 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Génétique Fonctionnelle et Cancer, Centre National de la Recherche Scientifique (CNRS, UMR7104), Institut National de la Santé et de la Recherche Médicale (INSERM U1258), Université de Strasbourg (UNISTRA), 1 rue Laurent Fries, CEDEX, 67404 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Génétique Fonctionnelle et Cancer, Centre National de la Recherche Scientifique (CNRS, UMR7104), Institut National de la Santé et de la Recherche Médicale (INSERM U1258), Université de Strasbourg (UNISTRA), 1 rue Laurent Fries, CEDEX, 67404 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Génétique Fonctionnelle et Cancer, Centre National de la Recherche Scientifique (CNRS, UMR7104), Institut National de la Santé et de la Recherche Médicale (INSERM U1258), Université de Strasbourg (UNISTRA), 1 rue Laurent Fries, CEDEX, 67404 Illkirch, FranceICube (UMR 7357), Laboratoire des Sciences de l’Ingénieur, de l’Informatique et de l’Imagerie, UNISTRA, CNRS, 300 Boulevard Sébastien Brant, CEDEX, 67412 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Génétique Fonctionnelle et Cancer, Centre National de la Recherche Scientifique (CNRS, UMR7104), Institut National de la Santé et de la Recherche Médicale (INSERM U1258), Université de Strasbourg (UNISTRA), 1 rue Laurent Fries, CEDEX, 67404 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Génétique Fonctionnelle et Cancer, Centre National de la Recherche Scientifique (CNRS, UMR7104), Institut National de la Santé et de la Recherche Médicale (INSERM U1258), Université de Strasbourg (UNISTRA), 1 rue Laurent Fries, CEDEX, 67404 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Département de Génétique Fonctionnelle et Cancer, Centre National de la Recherche Scientifique (CNRS, UMR7104), Institut National de la Santé et de la Recherche Médicale (INSERM U1258), Université de Strasbourg (UNISTRA), 1 rue Laurent Fries, CEDEX, 67404 Illkirch, FranceRetinoic acid signaling is indispensable for the completion of spermatogenesis. It is known that loss of retinoic acid nuclear receptor alpha (RARA) induces male sterility due to seminiferous epithelium degeneration. Initial genetic studies established that RARA acts in Sertoli cells, but a recent paper proposed that RARA is also instrumental in germ cells. In the present study, we have re-assessed the function of RARA in germ cells by genetically ablating the <i>Rara</i> gene in spermatogonia and their progenies using a cell-specific conditional mutagenesis approach. We show that loss of <i>Rara</i> in postnatal male germ cells does not alter the histology of the seminiferous epithelium. Furthermore, RARA-deficient germ cells differentiate normally and give rise to normal, living pups. This establishes that RARA plays no crucial role in germ cells. We also tested whether RARA is required in Sertoli cells during the fetal period or after birth. For this purpose, we deleted the <i>Rara</i> gene in Sertoli cells at postnatal day 15 (PN15), i.e., after the onset of the first spermatogenic wave. To do so, we used temporally controlled cell-specific mutagenesis. By comparing the testis phenotypes generated when <i>Rara</i> is lost either at PN15 or at embryonic day 13, we show that RARA exerts all of its functions in Sertoli cells not at the fetal stage but from puberty.https://www.mdpi.com/2073-4409/11/5/891anti-RARA antibodies for IHCmouseretinoic acidSertoli cellseminiferous epitheliumSox9-CreERT<sup>2</sup> |
| spellingShingle | Diana Condrea Sirine Souali-Crespo Betty Féret Muriel Klopfenstein Sylvain Faisan Manuel Mark Norbert B. Ghyselinck Nadège Vernet Retinoic Acid Receptor Alpha Is Essential in Postnatal Sertoli Cells but Not in Germ Cells Cells anti-RARA antibodies for IHC mouse retinoic acid Sertoli cell seminiferous epithelium Sox9-CreERT<sup>2</sup> |
| title | Retinoic Acid Receptor Alpha Is Essential in Postnatal Sertoli Cells but Not in Germ Cells |
| title_full | Retinoic Acid Receptor Alpha Is Essential in Postnatal Sertoli Cells but Not in Germ Cells |
| title_fullStr | Retinoic Acid Receptor Alpha Is Essential in Postnatal Sertoli Cells but Not in Germ Cells |
| title_full_unstemmed | Retinoic Acid Receptor Alpha Is Essential in Postnatal Sertoli Cells but Not in Germ Cells |
| title_short | Retinoic Acid Receptor Alpha Is Essential in Postnatal Sertoli Cells but Not in Germ Cells |
| title_sort | retinoic acid receptor alpha is essential in postnatal sertoli cells but not in germ cells |
| topic | anti-RARA antibodies for IHC mouse retinoic acid Sertoli cell seminiferous epithelium Sox9-CreERT<sup>2</sup> |
| url | https://www.mdpi.com/2073-4409/11/5/891 |
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