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

Abstract

Meiotic initiation of germ cells at 13.5 dpc (days post-coitus) indicates female sex determination in mice. Recent studies reveal that mesonephroi-derived retinoic acid (RA) is the key signal for induction of meiosis. However, whether the mesonephroi is dispensable for meiosis is unclear and the role of the ovary in this meiotic process remains to be clarified. This study provides data that RA derived from fetal ovaries is sufficient to induce germ cell meiosis in a fetal ovary culture system. When fetal ovaries were collected from 11.5 to 13.5 dpc fetuses, isolated and cultured in vitro, germ cells enter meiosis in the absence of mesonephroi. To exclude RA sourcing from mesonephroi, 11.5 dpc urogenital ridges (UGRs; mesonephroi and ovary complexes) were treated with diethylaminobenzaldehyde (DEAB) to block retinaldehyde dehydrogenase (RALDH) activity in the mesonephros and the ovary. Meiosis occurred when DEAB was withdrawn and the mesonephros was removed 2 days later. Furthermore, RALDH1, rather than RALDH2, serves as the major RA synthetase in UGRs from 12.5 to 15.5 dpc. DEAB treatment to the ovary alone was able to block germ cell meiotic entry. We also found that exogenously supplied RA dose-dependently reduced germ cell numbers in ovaries by accelerating the entry into meiosis. These results suggest that ovary-derived RA is responsible for meiosis initiation.

Cyclic AMP in oocytes controls meiotic prophase I and primordial folliculogenesis in the perinatal mouse ovary

“…We used a SYCP3 antibody to identify the chromosomal axial elements at meiosis prophase I, as described previously (Mu et al, 2013). Combined staining for SYCP1 and SYCP3 was used to determine whether SYCP1 disassembly occurred.…”

“…Western blot analyses were conducted as described previously (Mu et al, 2013). Briefly, total proteins were extracted in WIP (CellChip Beijing Biotechnology Company) according to the manufacturer's protocol.…”

The Effect of Isotretinoin on Ovarian Reserve Based on Hormonal Parameters, Ovarian Volume, and Antral Follicle Count in Women with Acne

“…Conversely, Mu et al [17] concluded that RA derived from the ovary is important for germ cell meiosis initiation and that the level of RA in the ovary influences the size of the primordial pool. Considering the importance of meiosis for female fertility, RA self-sufficiency may be a more reliable and conservative strategy than ovary dependence on another organ.…”

From Sex Determination to Initial Folliculogenesis in Mammalian Ovaries: Morphogenetic Waves along the Anteroposterior and Dorsoventral Axes

“…However, Aldh1a2/1a3 -null ovaries show proper meiotic induction of female germ cells [Kumar et al, 2011]. Moreover, ALDH1A1 is expressed in germ cells of female mice from E12.5 to E15.5 [Mu et al, 2013], and the expression of the Aldh1a2 ortholog has been reported in human gonads [Childs et al, 2011] and other vertebrate species [Smith et al, 2008;Piprek et al, 2013]. Therefore, it remains unclear whether the anteriorposterior pattern of meiotic initiation is regulated by diffusible RA signals [Griswold et al, 2012] or by intrinsic factors such as the RA receptors [Gely-Pernot et al, 2012;Minkina et al, 2014;Ikami et al, 2015] and epigenetic regulators upstream of Stra8 , such as polycomb repressive complex 1 (PRC1) [Yokobayashi et al, 2013].…”