Sex determination in mammalian germ cells: extrinsic versus intrinsic factors

Abstract

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.

Molecular signatures to define spermatogenic cells in common marmoset (Callithrix jacchus)

“…In contrast, another pluripotencydetermining factor, NANOG, was expressed exclusively in marmoset ES cells and testis. Among the germ cell marker genes, PRDM1, DPPA3 (STELLA), and IFITM3, which are expressed predominantly during the PGC stages in mouse development (Ohinata et al 2008, Bowles & Koopman 2010, displayed significant expression in marmoset testis. Indeed, these genes were only expressed at faint or undetectable levels in mouse testis (Fig.…”

“…Indeed, in the current study, we identified the following expression profiles that distinguish marmoset testis from mouse testis: POU5F1K/NANOGC/PRDM1C/DPPA3C/IFITM3C /ZP1C in marmoset and Pou5f1C/NanogK/Prdm1K /Dppa3K/Ifitm3K/ZP1K in mouse (Figs 1 and 2). Compared with mouse, marmoset testis tended to express genes whose homologs in mouse are known as typical markers at an earlier developmental stage, as shown by the expression of the migratory PGC markers NANOG, PRDM1, DPPA3, and IFITM3 (Ohinata et al 2008, Bowles & Koopman 2010. A recent report also demonstrated that prepubertal human spermatogonia exhibit an expression profile similar to that of mouse gonocytes (Wu et al 2009).…”

“…In mammals, the initial germ cells (primordial germ cells, PGCs) are specified in pluripotent epiblasts and then migrate toward the genital ridge during embryogenesis. Even though the migratory PGCs are sexually bipotent, their gender is determined by surrounding environment in the genital ridge (Bowles & Koopman 2010). In males, the stem cell-based system continuously produces spermatogenic cells that proceed to spermiogenesis after birth (Ehmcke et al 2006, Hermann et al 2010; however, in the case of higher primates and humans, the process of spermatogenesis only initiates during adolescence.…”

The role of non-coding RNAs in male sex determination and differentiation

“…In an ovary, PGCs enter the first meiotic prophase, while in a testis they enter mitotic arrest (Bullejos & Koopman 2004, Western et al 2008. XX and XY germ cells were believed to not be sexually dimorphic until this differentiation process is initiated by their surrounding cells, testicular or ovarian somatic cells (Bowles & Koopman 2010). This view has been challenged by two reports demonstrating sexually dimorphic gene expression in PGCs long before initiation of meiosis in an ovary and mitotic arrest in a testis.…”

Comparative molecular portraits of human unfertilized oocytes and primordial germ cells at 10 weeks of gestation

“…Cytological analysis in mice and human suggests that both female and male PGCs are equally capable of entering meiosis (12 dpc in mice and 10 weeks in humans) and that the decision of cell fate of germ cells, either meiosis or mitosis takes place in the gonad (McLaren and Southee, 1997;Suzuki and Saga, 2008;Bowles and Koopman, 2010). It is still unknown and controversial whether entry into meiosis is induced in the female gonad or whether it is intrinsically programmed in both male and female PGCs and inhibited in the male gonad and permissive in the female gonad, or whether it is due to a combination of regulatory factors.…”