scholarly journals Meiosis occurs normally in the fetal ovary of mice lacking all retinoic acid receptors

2020 ◽  
Vol 6 (21) ◽  
pp. eaaz1139
Author(s):  
Nadège Vernet ◽  
Diana Condrea ◽  
Chloé Mayere ◽  
Betty Féret ◽  
Muriel Klopfenstein ◽  
...  

Gametes are generated through a specialized cell differentiation process, meiosis, which, in ovaries of most mammals, is initiated during fetal life. All-trans retinoic acid (ATRA) is considered as the molecular signal triggering meiosis initiation. In the present study, we analyzed female fetuses ubiquitously lacking all ATRA nuclear receptors (RAR), obtained through a tamoxifen-inducible cre recombinase-mediated gene targeting approach. Unexpectedly, mutant oocytes robustly expressed meiotic genes, including the meiotic gatekeeper STRA8. In addition, ovaries from mutant fetuses grafted into adult recipient females yielded offspring bearing null alleles for all Rar genes. Thus, our results show that RAR are fully dispensable for meiotic initiation, as well as for the production of functional oocytes. Assuming that the effects of ATRA all rely on RAR, our study goes against the current model according to which meiosis is triggered by endogenous ATRA in the developing ovary. It therefore revives the search for the meiosis-inducing substance.

2019 ◽  
Author(s):  
Nadège Vernet ◽  
Manuel Mark ◽  
Diana Condrea ◽  
Betty Féret ◽  
Muriel Klopfenstein ◽  
...  

AbstractGametes are generated through a specialized cell differentiation process, meiosis which, in most mammals, is initiated in ovaries during fetal life. It is widely admitted that all-trans retinoic acid (ATRA) is the molecular signal triggering meiosis initiation in mouse female germ cells, but a genetic approach in which ATRA synthesis is impaired disputes this proposal. In the present study, we investigated the contribution of endogenous ATRA to meiosis by analyzing fetuses lacking all RARs ubiquitously, obtained through a tamoxifen-inducible cre recombinase-mediated gene targeting approach. Efficient ablation of RAR-coding genes was assessed by the multiple congenital abnormalities displayed by the mutant fetuses. Unexpectedly, their germ cells robustly expressed STRA8, REC8, SYCP1 and SYCP3, showing that RAR are actually dispensable up to the zygotene stage of meiotic prophase I. Thus our study goes against the current model according to which meiosis is triggered by endogenous ATRA in the developing ovary and revives the identification of the meiosis-preventing substance synthesized by CYP26B1 in the fetal testis.


2012 ◽  
Vol 351 (2) ◽  
pp. 306-316 ◽  
Author(s):  
Brenda J. Mengeling ◽  
Michael L. Goodson ◽  
William Bourguet ◽  
Martin L. Privalsky

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 267-282 ◽  
Author(s):  
E. Ruberte ◽  
V. Friederich ◽  
P. Chambon ◽  
G. Morriss-Kay

We have studied the transcript distribution of the retinoic acid receptors (RARs) and the cytoplasmic retinoid binding proteins during embryonic development of the mouse nervous system. Of the three retinoic acid receptors, only RAR-gamma was not expressed in developing neural structures. RAR-beta and RAR-alpha both showed rostral limits of expression in the medulla oblongata equivalent to their patterns of expression in the neuroepithelium of the early hindbrain neural tube. Within their expression domains in the spinal cord and brain, RAR-alpha was ubiquitously expressed, whereas RAR-beta transcripts showed very specific patterns of expression, suggesting that this receptor is involved in mediating retinoic acid-induced gene expression in relation to the development of specific neural structures or pathways. The cytoplasmic binding proteins, cellular retinoic acid binding proteins type I and II (CRABP I and CRABP II) and cellular retinol binding protein type I (CRBP I), were widely distributed in developing neural structures. Their differential spatiotemporal patterns of expression suggest that fine regional control of availability of retinoic acid (RA) to the nuclear receptors plays an important role in organization and differentiation of the nervous system. For instance, expression of CRABP I in the migrating cells that give rise to the olivary and pontine nuclei, which develop abnormally in conditions of retinoid excess, is consistent with observations from a variety of other systems indicating that CRABP I limits the access of RA to the nuclear receptors in normal physiological conditions. Similarly, expression of CRBP I in the choroid plexuses, which develop abnormally in conditions of vitamin A deficiency, is consistent with observations indicating that this binding protein mediates the synthesis of RA in tissues requiring high levels of RA for their normal developmental programme. RAR-beta and CRABP II, which are both RA-inducible, were coexpressed with CRBP I in the choroid plexus and in many other sites, perhaps reflecting the fact that all three genes are RA-inducible. The function of CRABP II is not well understood; its domains of expression showed overlaps with both CRABP I and CRBP I.


1994 ◽  
Vol 57 (3) ◽  
pp. 195-203 ◽  
Author(s):  
Agnès Bloch-Zupan ◽  
Didier Décimo ◽  
Maria Loriot ◽  
Manuel P. Mark ◽  
Jean Victor Ruch

1992 ◽  
Vol 89 (6) ◽  
pp. 2321-2325 ◽  
Author(s):  
B. Blumberg ◽  
D. J. Mangelsdorf ◽  
J. A. Dyck ◽  
D. A. Bittner ◽  
R. M. Evans ◽  
...  

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