Retinoid Signaling Determines Germ Cell Fate in Mice

Abstract

Germ cells in the mouse embryo can develop as oocytes or spermatogonia, depending on molecular cues that have not been identified. We found that retinoic acid, produced by mesonephroi of both sexes, causes germ cells in the ovary to enter meiosis and initiate oogenesis. Meiosis is retarded in the fetal testis by the action of the retinoid-degrading enzyme CYP26B1, ultimately leading to spermatogenesis. In testes of Cyp26b1-knockout mouse embryos, germ cells enter meiosis precociously, as if in a normal ovary. Thus, precise regulation of retinoid levels during fetal gonad development provides the molecular control mechanism that specifies germ cell fate.

Transcriptome analysis of differentiating spermatogonia stimulated with kit ligand

“…the transition from type B spermatogonia to primary spermatocytes, even though it has been reported that mouse germ cells cocultured with the 15-P1 cell line, expressing the transmembrane form of KL, can undergo transmeiotic progression in culture, whereas the soluble form of KL was reported to antagonize this effect (Vincent et al, 1998). Up to now, the only agent which has been postulated to have a (direct or indirect) role in the induction of meiotic entry is all-trans retinoic acid (ATRA) (van Pelt and de Rooij, 1991;Bowles et al, 2006;Koubova et al, 2006). Interestingly, Wang and Culty (2007) have recently found that ATRA stimulates kit expression in prepuberal spermatogonia.…”

Genetics of germ cell development

“…104 In prenatal males, the cytochrome P450 enzyme CYP26B1 degrades retinoic acid, preventing induction of Stra8. 105,106 Nanos2 is specifically expressed in fetal male germ cells and also functions as a meiotic inhibitor. 107,108 Postnatally, Cyp26b1 is repressed in male gonads, and male spermatogenic precursors gain the ability to respond to retinoic acid and to express Stra8, and they begin to initiate meiosis in regular waves.…”

“…107,108 Postnatally, Cyp26b1 is repressed in male gonads, and male spermatogenic precursors gain the ability to respond to retinoic acid and to express Stra8, and they begin to initiate meiosis in regular waves. 103,105,106 Germ cell sex determination and meiotic entry are therefore temporally coordinated in mammals and are frequently conflated, with initiation of meiosis at E13.5 considered equivalent to female specification, although transcriptional profiling of male and female germ cells at E12.5 points to a moderate amount of sex-specific transcription a day prior to female meiotic initiation. 109 The question of whether meiotic initiation and specification of female sex in fetal germ cells are identical processes, or are simply closely related, remains unresolved.…”

Biological analysis of endocrine-disrupting chemicals in animal meats from the Pearl River Delta, China

“…Chronic exposure to the ligand of PPAR induces development of cancers in livers of both rats and mice (Reddy et al, 1980(Reddy et al, , 1976Rao and Reddy 1987;Pyper et al, 2010), whereas elevated concentrations of glucocorticoids in blood might lead to insulin resistance and diabetes (Chrousos and Kino, 2009;Longui and Faria, 2009;Barnes, 2010). EDCs with retinoic acid-like activities can interfere with embryonic development and differentiation of secondary characteristics of males (Bowles et al, 2006;Bowles and Koopman, 2007). Dioxins the most toxic anthropogenic pollutants are also linked to disorders of developmental and reproduction (Hotchkiss et al, 2008;Bruner-Tran and Osteen, 2010).…”