Retinoids and spermatogenesis: Lessons from mutant mice lacking the plasma retinol binding protein

Ghyselinck, Norbert B.; Vernet, Nadège; Dennefeld, Christine; Giese, Norbert; Nau, Heinz; Chambon, Pierre; Viville, Stéphane; Mark, Manuel

doi:10.1002/dvdy.20795

Cited by 75 publications

(76 citation statements)

References 75 publications

(136 reference statements)

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“…2 H and K). It must be stressed that spermatogenesis can resume in Rbp4-null males if vitamin A is restored in the diet or if RA is administered (24). These results indicate that RA-activated RARA in SC is able to drive the initial transition from Aal to A1 spermatogonia, but not the following ones and suggest that RA needs to act elsewhere in the seminiferous epithelium to induce subsequent cycles of spermatogenesis.…”

Section: Resultsmentioning

confidence: 91%

“…According to our study, it is now conceivable that the signal committing gonocytes to differentiation as A1 spermatogonia relies on RA-activated RARA in SC. However, undifferentiated spermatogonia also rely on RA as attested by the requirement of retinol (or RA) to resume spermatogenesis in VAD adult males (3,24). The Aal-to-A1 transitions during all but the first wave of spermatogenesis may depend on RAR-dependent signals distinct from those controlled by RARA in SC for commitment of gonocytes.…”

Section: Resultsmentioning

confidence: 99%

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Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis

Raverdeau

Gély-Pernot

Féret

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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201

253

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Direct evidence for a role of endogenous retinoic acid (RA), the active metabolite of vitamin A in the initial differentiation and meiotic entry of spermatogonia, and thus in the initiation of spermatogenesis is still lacking. RA is synthesized by dedicated enzymes, the retinaldehyde dehydrogenases (RALDH), and binds to and activates nuclear RA receptors (RARA, RARB, and RARG) either within the RA-synthesizing cells or in the neighboring cells. In the present study, we have used a combination of somatic genetic ablations and pharmacological approaches in vivo to show that during the first, prepubertal, spermatogenic cycle ( i ) RALDH-dependent synthesis of RA by Sertoli cells (SC), the supporting cells of the germ cell (GC) lineage, is indispensable to initiate differentiation of A aligned into A1 spermatogonia; ( ii ) RARA in SC mediates the effects of RA, possibly through activating Mafb expression, a gene whose Drosophila homolog is mandatory to GC differentiation; ( iii ) RA synthesized by premeiotic spermatocytes cell autonomously induces meiotic initiation through controlling the RAR-dependent expression of Stra8 . Furthermore, we show that RA of SC origin is no longer necessary for the subsequent spermatogenic cycles but essential to spermiation. Altogether, our data establish that the effects of RA in vivo on spermatogonia differentiation are indirect, via SC, but direct on meiotic initiation in spermatocytes, supporting thereby the notion that, contrary to the situation in the female, RA is necessary to induce meiosis in the male.

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Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis

Raverdeau

Gély-Pernot

Féret

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

201

253

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“…7,8 RA functions inside the nucleus recognising two different classes of retinoid receptors. Both classes (RARs and RXRs) consist of three types of receptors, α, β and γ, encoded by distinct genes 9 and transduce RA signal by binding directly to retinoic acid responsive elements (RARE). During post-natal development, each RAR is detected predominantly in a specific cell type of the seminiferous epithelium: RAR α in Sertoli cells, RAR β in round spermatids and RAR γ in A spermatogonia.…”

Section: Introductionmentioning

confidence: 99%

ATRA and KL promote differentiation toward the meiotic program of male germ cells.

Pellegrini¹,

Filipponi²,

Gori³

et al. 2008

Cell Cycle

112

144

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While it is known that Retinoic Acid (RA) induces meiosis in mouse female fetal gonads, the mechanisms which regulate this process during spermatogenesis are poorly understood. We show that the All trans RA derivative (ATRA) and Kit Ligand (KL) increase meiotic entry of postnatal mouse spermatogonia in vitro without synergism. Competence to enter meiosis is reached by spermatogonia only at the stage in which they undergo Kit-dependent divisions. Besides increasing Kit expression in spermatogonia, ATRA also upregulates KL expression in Sertoli cells. Both ATRA and KL increase the expression of Stimulated by Retinoic Acid Gene 8 and Dmc1, an early meiotic marker. A specific Kit tyrosine kinase inhibitor prevents the increase in the number of meiotic cells induced by both the two factors, suggesting that they converge on common Kit-dependent signalling pathways. Meiotic entry induced by ATRA and KL is independent from their ability to affect germ cell viability, and is mediated by the activation of PI3K and MAPK pathways through Kit autophosphorylation. ATRA-induced phosphorylation of the two downstream kinases is mediated by a non-genomic mechanism.These data suggest that RA may control the timing of meiosis by influencing both the somatic and the germ cell compartment of the postnatal testis through the activation of the KL/Kit system.

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“…An opportunity to explore this question experimentally arises from recent studies of Stra8 (Stimulated by retinoic acid gene 8), a vertebrate-specific gene that encodes a cytoplasmic protein and whose expression is induced by retinoic acid (6)(7)(8)(9)(10)(11). Our laboratory previously reported that, in female mice, Stra8 is expressed in embryonic ovarian germ cells shortly before they enter meiotic prophase (12).…”

mentioning

confidence: 99%

Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice

Anderson

Baltus²,

Roepers-Gajadien³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

544

539

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In eukaryotes, diploid cells give rise to haploid cells via meiosis, a program of two cell divisions preceded by one round of DNA replication. Although key molecular components of the meiotic apparatus are highly conserved among eukaryotes, the mechanisms responsible for initiating the meiotic program have diverged substantially among eukaryotes. This raises a related question in animals with two distinct sexes: Within a given species, are similar or different mechanisms of meiotic initiation used in the male and female germ lines? In mammals, this question is underscored by dramatic differences in the timing of meiotic initiation in males and females. Stra8 is a vertebrate-specific, cytoplasmic factor expressed by germ cells in response to retinoic acid. We previously demonstrated that Stra8 gene function is required for meiotic initiation in mouse embryonic ovaries. Here we report that, on an inbred C57BL/6 genetic background, the same factor is also required for meiotic initiation in germ cells of juvenile mouse testes. In juvenile C57BL/6 males lacking Stra8 gene function, the early mitotic development of germ cells appears to be undisturbed. However, these cells then fail to undergo the morphological changes that define meiotic prophase, and they do not display the molecular hallmarks of meiotic chromosome cohesion, synapsis and recombination. We conclude that, in mice, Stra8 regulates meiotic initiation in both spermatogenesis and oogenesis. Taken together with previous observations, our present findings indicate that, in both the male and female germ lines, meiosis is initiated through retinoic acid induction of Stra8. meiosis ͉ spermatocyte

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Retinoids and spermatogenesis: Lessons from mutant mice lacking the plasma retinol binding protein

Cited by 75 publications

References 75 publications

Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis

Retinoic acid induces Sertoli cell paracrine signals for spermatogonia differentiation but cell autonomously drives spermatocyte meiosis

ATRA and KL promote differentiation toward the meiotic program of male germ cells.

Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice

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