The role of sex chromosomes in mammalian germ cell differentiation: can the germ cells carrying X and Y chromosomes differentiate into fertile oocytes?

Abstract

The sexual differentiation of germ cells into spermatozoa or oocytes is strictly regulated by their gonadal environment, testis or ovary, which is determined by the presence or absence of the Y chromosome, respectively. Hence, in normal mammalian development, male germ cells differentiate in the presence of X and Y chromosomes, and female germ cells do so in the presence of two X chromosomes. However, gonadal sex reversal occurs in humans as well as in other mammalian species, and the resultant XX males and XY females can lead healthy lives, except for a complete or partial loss of fertility. Germ cells carrying an abnormal set of sex chromosomes are efficiently eliminated by multilayered surveillance mechanisms in the testis, and also, though more variably, in the ovary. Studying the molecular basis for sex-specific responses to a set of sex chromosomes during gametogenesis will promote our understanding of meiotic processes contributing to the evolution of sex determining mechanisms. This review discusses the fate of germ cells carrying various sex chromosomal compositions in mouse models, the limitation of which may be overcome by recent successes in the differentiation of functional germ cells from embryonic stem cells under experimental conditions.

Figure 1

Sexual differentiation of germ cells. ICM: innercell mass; ESC: embryonic stem cells; EpiC: epiblast cells; PGC: primordial germ cells; MPI: meiotic prophase I.

Figure 2

Pairing of sex chromosomes at the pachytene stage of meiotic prophase I. Microspread ovarian or testicular cells were immunostained with human autoantibody CREST (red), with specific antibodies against SCP3 (red) and γH2AX (green), and counterstained with DAPI (blue). The merged image (top) is followed by γH2AX signals alone (middle) and red signals of SCP3 and CREST alone (bottom). (a) A pachytene oocyte nucleus collected from an XX fetal ovary at 18.5 dpc. 20 sets of homologous chromosomes including the XX pair are fully synapsed. No γH2AX signals are seen. (b) A pachytene oocyte nucleus collected from a B6.Y^TIR fetal ovary at 18.5 dpc. The short Y chromosome is apart from the single X chromosome, the latter of which is covered by a γH2AX domain, a characteristic of unsynapsed chromosome. Nineteen autosomal pairs are fully synapsed without γH2AX signals. (c) A pachytene spermatocyte nucleus collected from a B6.Y^TIR adult testis. The X and Y chromosomes are partially synapsed at their pseudoautosomal regions and covered by a γH2AX domain, named XY or sex body. Nineteen autosomal pairs are fully synapsed.