scholarly journals Meiosis Initiates In The Fetal Ovary Of Mice Lacking All Retinoic Acid Receptor Isotypes

2019 ◽  
Author(s):  
Nadège Vernet ◽  
Manuel Mark ◽  
Diana Condrea ◽  
Betty Féret ◽  
Muriel Klopfenstein ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Germ Cells ◽  
Congenital Abnormalities ◽  
Retinoic Acid Receptor ◽  
Current Model ◽  
Fetal Life ◽  
Genetic Approach ◽  
Molecular Signal ◽  
Fetal Ovary ◽  
Multiple Congenital Abnormalities

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.

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 ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Current Model ◽  
Retinoic Acid Receptors ◽  
Null Alleles ◽  
Fetal Life ◽  
Adult Recipient ◽  
Molecular Signal ◽  
Fetal Ovary ◽  
Meiotic Initiation

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.

scholarly journals Identification of regulatory elements required for Stra8 expression, in fetal ovarian germ cells of the mouse

Development ◽  
2021 ◽  
pp. dev.194977
Author(s):  
Chun-Wei Feng ◽  
Guillaume Burnet ◽  
Cassy M. Spiller ◽  
Fiona Ka Man Cheung ◽  
Kallayanee Chawengsaksophak ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Germ Cells ◽  
Regulatory Element ◽  
Regulatory Elements ◽  
Egfp Expression ◽  
Spatiotemporal Regulation ◽  
Targeted Mutation ◽  
Fetal Ovary

In mice, the entry of germ cells into meiosis critically depends on the expression of stimulated by retinoic acid gene 8 (Stra8). Stra8 is expressed specifically in pre-meiotic germ cells of females and males, at fetal and postnatal stages respectively, but the mechanistic details of its spatiotemporal regulation are yet to be defined. In particular, there has been considerable debate regarding whether retinoic acid is required, in vivo, to initiate Stra8 expression in the mouse fetal ovary. We show that the distinctive anterior-to-posterior pattern of Stra8 initiation, characteristic of germ cells in the fetal ovary, is faithfully recapitulated when 2.9 kb of the Stra8 promoter is used to drive eGFP expression. Using in vitro transfection assays of cut-down and mutant constructs we identified two functional retinoic acid responsive elements (RAREs) within this 2.9 kb regulatory element. We also show that the transcription factor DMRT1 enhances Stra8 expression, but only in the presence of RA and the most proximal RARE. Finally, we used CRISPR/Cas9-mediated targeted mutation studies to demonstrate that both RAREs are required for optimal Stra8 expression levels, in vivo.

Retinoic Acid Receptor Alpha in Germ Cells Is Important for the Organization of Germ Cell Layers in the Seminiferous Tubules.

2011 ◽  
Vol 85 (Suppl_1) ◽  
pp. 584-584
Author(s):  
Sze Ming Law ◽  
Kylie J. Nelson ◽  
Kelsey E. Brooks ◽  
Hui Li ◽  
William D. Willis ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Germ Cell ◽  
Germ Cells ◽  
Retinoic Acid Receptor ◽  
Seminiferous Tubules ◽  
Retinoic Acid Receptor Alpha ◽  
Acid Receptor ◽  
Receptor Alpha ◽  
Cell Layers

Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants

Development ◽  
1994 ◽  
Vol 120 (10) ◽  
pp. 2723-2748 ◽  
Author(s):  
D. Lohnes ◽  
M. Mark ◽  
C. Mendelsohn ◽  
P. Dolle ◽  
A. Dierich ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Vitamin A ◽  
Congenital Malformations ◽  
Double Mutant ◽  
Congenital Abnormalities ◽  
Retinoic Acid Receptor ◽  
Retinoic Acid Receptors ◽  
Acid Receptor ◽  
Null Mutants

Numerous congenital malformations have been observed in fetuses of vitamin A-deficient (VAD) dams [Wilson, J. G., Roth, C. B., Warkany, J., (1953), Am. J. Anat. 92, 189–217]. Previous studies of retinoic acid receptor (RAR) mutant mice have not revealed any of these malformations [Li, E., Sucov, H. M., Lee, K.-F., Evans, R. M., Jaenisch, R. (1993) Proc. Natl. Acad. Sci. USA 90, 1590–1594; Lohnes, D., Kastner, P., Dierich, A., Mark, M., LeMeur, M., Chambon, P. (1993) Cell 73, 643–658; Lufkin, T., Lohnes, D., Mark, M., Dierich, A., Gorry, P., Gaub, M. P., Lemeur, M., Chambon, P. (1993) Proc. Natl. Acad. Sci. USA 90, 7225–7229; Mendelsohn, C., Mark, M., Dolle, P., Dierich, A., Gaub, M.P., Krust, A., Lampron, C., Chambon, P. (1994a) Dev. Biol. in press], suggesting either that there is a considerable functional redundancy among members of the RAR family during ontogenesis or that the RARs are not essential transducers of the retinoid signal in vivo. In order to discriminate between these possibilities, we have generated a series of RAR compound null mutants. These RAR double mutants invariably died either in utero or shortly after birth and presented a number of congenital abnormalities, which are reported in this and in the accompanying study. We describe here multiple eye abnormalities which are found in various RAR double mutant fetuses and are similar to those previously seen in VAD fetuses. Interestingly, we found further abnormalities not previously reported in VAD fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential Functions of Retinoic Acid Receptor A in Sertoli Cells and Germ Cells During Spermatogenesis

2007 ◽  
Vol 1120 (1) ◽  
pp. 114-130 ◽  
Author(s):  
T. J. DOYLE ◽  
K. W. BRAUN ◽  
D. J. MCLEAN ◽  
R. W. WRIGHT ◽  
M. D. GRISWOLD ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Retinoic Acid Receptor ◽  
Potential Functions ◽  
Acid Receptor

scholarly journals Retinoic acid synthesis by ALDH1A proteins is dispensable for meiosis initiation in the mouse fetal ovary

2020 ◽  
Vol 6 (21) ◽  
pp. eaaz1261
Author(s):  
Anne-Amandine Chassot ◽  
Morgane Le Rolle ◽  
Geneviève Jolivet ◽  
Isabelle Stevant ◽  
Jean-Marie Guigonis ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Germ Cells ◽  
Gene Deletion ◽  
Ex Vivo ◽  
Acid Synthesis ◽  
Distinct Gene ◽  
Fetal Ovary ◽  
Present View

In mammals, the timing of meiosis entry is regulated by signals from the gonadal environment. All-trans retinoic acid (ATRA) signaling is considered the key pathway that promotes Stra8 (stimulated by retinoic acid 8) expression and, in turn, meiosis entry. This model, however, is debated because it is based on analyzing the effects of exogenous ATRA on ex vivo gonadal cultures, which not accurately reflects the role of endogenous ATRA. Aldh1a1 and Aldh1a2, two retinaldehyde dehydrogenases synthesizing ATRA, are expressed in the mouse ovaries when meiosis initiates. Contrary to the present view, here, we demonstrate that ATRA-responsive cells are scarce in the ovary. Using three distinct gene deletion models for Aldh1a1;Aldh1a2;Aldh1a3, we show that Stra8 expression is independent of ATRA production by ALDH1A proteins and that germ cells progress through meiosis. Together, these data demonstrate that ATRA signaling is dispensable for instructing meiosis initiation in female germ cells.

scholarly journals Sex determination in mammalian germ cells: extrinsic versus intrinsic factors

Reproduction ◽  
2010 ◽  
Vol 139 (6) ◽  
pp. 943-958 ◽  
Author(s):  
Josephine Bowles ◽  
Peter Koopman
Keyword(s):  
Germ Cells ◽  
Critical Time ◽  
Fetal Life ◽  
Extrinsic Factors ◽  
Intrinsic Factors ◽  
Fetal Testis ◽  
Time Period ◽  
Full Complement ◽  
Fetal Ovary ◽  
Male Specific

Mammalian germ cells do not determine their sexual fate based on their XX or XY chromosomal constitution. Instead, sexual fate is dependent on the gonadal environment in which they develop. In a fetal testis, germ cells commit to the spermatogenic programme of development during fetal life, although they do not enter meiosis until puberty. In a fetal ovary, germ cells commit to oogenesis by entering prophase of meiosis I. Although it was believed previously that germ cells are pre-programmed to enter meiosis unless they are actively prevented from doing so, recent results indicate that meiosis is triggered by a signaling molecule, retinoic acid (RA). Meiosis is avoided in the fetal testis because a male-specifically expressed enzyme actively degrades RA during the critical time period. Additional extrinsic factors are likely to influence sexual fate of the germ cells, and in particular, we postulate that an additional male-specific fate-determining factor or factors is involved. The full complement of intrinsic factors that underlie the competence of gonadal germ cells to respond to RA and other extrinsic factors is yet to be defined.

Retinoic acid derived from the fetal ovary initiates meiosis in mouse germ cells

2012 ◽  
Vol 228 (3) ◽  
pp. 627-639 ◽  
Author(s):  
Xinyi Mu ◽  
Jing Wen ◽  
Meng Guo ◽  
Jianwei Wang ◽  
Ge Li ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Germ Cells ◽  
Fetal Ovary

Contribution of retinoic acid receptor signalling to adrenal cortex morphology and functional zonation through modulation of WNT/[beta]-catenin pathway

2017 ◽  
Author(s):  
Zein Rami El ◽  
Amanda J Rickard ◽  
Golib Dzib Jose Felipe ◽  
Benoit Samson-Couterie ◽  
Angelique Rocha ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Adrenal Cortex ◽  
Retinoic Acid Receptor ◽  
Beta Catenin ◽  
Acid Receptor ◽  
Receptor Signalling
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