Evidence for a conserved role of retinoic acid in urodele amphibian meiosis onset

Abstract

Pleurodeles waltl is a urodele amphibian displaying a ZZ/ZW genetic mode of sex determination. Gonad differentiation can later be modulated by hormone treatment. To investigate germ cell differentiation, we analyzed the expression of the meiosis marker PwDmc1 and show that germ cells enter meiosis in late larval life in females, and 2 months after metamorphosis in males. Organotypic cultures of gonad-mesonephros complexes demonstrated that retinoic acid triggers meiosis entry in P. waltl. In vivo analyses of both PwRaldh2 and PwCyp26b1 expressions, the enzymes required for RA synthesis and degradation respectively, indicate that meiosis onset depends on PwCyp26b1 repression in the gonad during normal or steroid-induced sex-reversed development. Taken together, our results show that RA-dependent meiosis entry could be a conserved mechanism of germ cell differentiation in vertebrates and provide evidence for crosstalk between steroid and RA signaling in the course of sex differentiation. Developmental Dynamics 238:1389 -1397, 2009.

Sex determination in mammalian germ cells: extrinsic versus intrinsic factors

“…Evidence is mounting that RA may trigger entry into meiosis not just in mouse and rat, as detailed above, but also in chickens (Smith et al 2008) and amphibians (Wallacides et al 2009). Although a role for RA in initiating meiosis in humans has not been demonstrated so far, an anterior site of meiosis initiation -originating near the rete ovarii which connects the gonad and mesonephros -is observed in many mammalian species including humans (Byskov 1975, Bendsen et al 2006.…”

Regulation of germ cell meiosis in the fetal ovary

“…RA metabolism has also been studied in chickens: here RALDH2 appears the predominant RA synthesising enzyme that triggers expression of Stra8 prior to meiotic entry (Nekrasova et al, 2011;Smith et al, 2008;Yu et al, 2012). Ovarian and testicular cultures of an amphibian species, Pleurodeles waltl, with RA have also highlighted a conserved role for RAdependent meiosis in vertebrates (Wallacides et al, 2009). Unlike the situation in the developing ovary, testicular germ cells initiate meiosis just prior to puberty, which in rodents occurs within 1-2 weeks postnatally.…”

Sex Reversal in Amphibians

“…In Silurana (Xenopus) tropicalis , testis differentiation seems to occur along an antero-posterior gradient [El Jamil et al, 2008]. Meiosis entry is not observed until after metamorphosis [Wallacides et al, 2009]. At this time, in a cyst, all germ cells enter meiosis and progress along the different phases simultaneously .…”

“…In Pleurodeles waltl , retinoic acid has been shown to be involved in regulation of meiotic entry, with retinoic acid being able to trigger meiosis entry of male germ cells prior to metamorphosis [Wallacides et al, 2009]. Oocytes are arrested at the diplotene stage of prophase of the first meiotic division.…”