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Development. 2019 Jan 4;146(1). pii: dev170225. doi: 10.1242/dev.170225.

Two functionally redundant sources of retinoic acid secure spermatogonia differentiation in the seminiferous epithelium.

Author information

1
Institut 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, F-67404 Illkirch Cedex, France.
2
Service de Biologie de la Reproduction, Hôpitaux Universitaires de Strasbourg (HUS), France.
3
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA.
4
Institut 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, F-67404 Illkirch Cedex, France manuel.mark@igbmc.fr.

Abstract

In mammals, all-trans retinoic acid (ATRA) is instrumental to spermatogenesis. It is synthesized by two retinaldehyde dehydrogenases (RALDH) present in both Sertoli cells (SCs) and germ cells (GCs). In order to determine the relative contributions of each source of ATRA, we have generated mice lacking all RALDH activities in the seminiferous epithelium (SE). We show that both the SC- and GC-derived sources of ATRA cooperate to initiate and propagate spermatogenetic waves at puberty. In adults, they exert redundant functions and, against all expectations, the GC-derived source does not perform any specific roles despite contributing to two-thirds of the total amount of ATRA present in the testis. The production from SCs is sufficient to maintain the periodic expression of genes in SCs, as well and the cycle and wave of the SE, which account for the steady production of spermatozoa. The production from SCs is also specifically required for spermiation. Importantly, our study shows that spermatogonia differentiation depends upon the ATRA synthesized by RALDH inside the SE, whereas initiation of meiosis and expression of STRA8 by spermatocytes can occur without ATRA.

KEYWORDS:

Aldh8a1 knockout; Immunohistochemistry; Lgals1; Puberty; Spermatogenesis

PMID:
30487180
PMCID:
PMC6340151
DOI:
10.1242/dev.170225
[Indexed for MEDLINE]
Free PMC Article

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