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Germ cell sex determination in mammals.

Kocer A, Reichmann J, Best D, Adams IR - Mol. Hum. Reprod. (2009)

Bottom Line: In response to these sex-determining cues, germ cells in female embryos initiate oogenesis and enter meiosis, whereas germ cells in male embryos initiate spermatogenesis and inhibit meiosis until after birth.In addition, we discuss the possibility that some of the reported effects of these factors on germ cell development may be indirect consequences of impairing sexual differentiation of gonadal somatic cells or germ cell survival.Understanding the molecular mechanisms of germ cell sex determination may provide candidate genes for susceptibility to germ cell tumours and infertility in humans.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.

ABSTRACT
One of the major decisions that germ cells make during their development is whether to differentiate into oocytes or sperm. In mice, the germ cells' decision to develop as male or female depends on sex-determining signalling molecules in the embryonic gonadal environment rather than the sex chromosome constitution of the germ cells themselves. In response to these sex-determining cues, germ cells in female embryos initiate oogenesis and enter meiosis, whereas germ cells in male embryos initiate spermatogenesis and inhibit meiosis until after birth. However, it is not clear whether the signalling molecules that mediate germ cell sex determination act in the developing testis or the developing ovary, or what these signalling molecules might be. Here, we review the evidence for the existence of meiosis-inducing and meiosis-preventing substances in the developing gonad, and more recent studies aimed at identifying these molecules in mice. In addition, we discuss the possibility that some of the reported effects of these factors on germ cell development may be indirect consequences of impairing sexual differentiation of gonadal somatic cells or germ cell survival. Understanding the molecular mechanisms of germ cell sex determination may provide candidate genes for susceptibility to germ cell tumours and infertility in humans.

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Developmental timing of germ cell sex determination. Schematic diagram of when germ cells commit to spermatogenesis and oogenesis during mouse embryogenesis. Germ cells are sexually bipotential (green) at 11.5 dpc, and commit to spermatogenesis (blue) between 11.5 and 12.5 dpc in male gonads or to oogenesis (pink) ∼1 day later in female gonads. dpc, days post-coitum.
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GAP008F2: Developmental timing of germ cell sex determination. Schematic diagram of when germ cells commit to spermatogenesis and oogenesis during mouse embryogenesis. Germ cells are sexually bipotential (green) at 11.5 dpc, and commit to spermatogenesis (blue) between 11.5 and 12.5 dpc in male gonads or to oogenesis (pink) ∼1 day later in female gonads. dpc, days post-coitum.

Mentions: The germ cells’ decision to develop as male or female depends on external signals in their surrounding environment rather than the chromosomal sex of the germ cells themselves: XY germ cells can develop as oocytes in female chimaeric embryos and XX germ cells can develop as prospermatogonia in male chimaeric embryos (Ford et al., 1975; Palmer and Burgoyne, 1991). These observations are consistent with the sex-determining activity of the Y chromosome acting only in the supporting cell lineage and the resulting Sertoli cells influencing sexual differentiation of other gonadal cell types through extracellular signals (Palmer and Burgoyne, 1991). The developmental timing of the germ cells’ response to sex-determining signals in the gonad differs between male and female embryos (Fig. 2). Germ cells in XY gonads commit to spermatogenesis between 11.5 and 12.5 dpc (McLaren and Southee, 1997; Chuma and Nakatsuji, 2001; Adams and McLaren, 2002). Thus, germ cells in 11.5 dpc XY gonads can be induced to sex-reverse and initiate meiosis by co-culturing on feeder cells, in embryonic lung tissue, and in female embryonic urogenital ridge tissue (McLaren and Southee, 1997; Chuma and Nakatsuji, 2001; Adams and McLaren, 2002). However, by 12.5 dpc germ cells in XY gonads have responded to the XY gonadal environment, are committed to differentiate along a male pathway and will not sex-reverse or initiate meiosis even when co-cultured in female embryonic urogenital ridge tissue (Adams and McLaren, 2002). Germ cells in XX gonads appear to commit to oogenesis a day later than germ cells in XY gonads commit to spermatogenesis. Thus, germ cells in 12.5 dpc XX gonads can be induced to sex-reverse and differentiate into prospermatogonia by co-culture in male embryonic urogenital ridge tissue, but germ cells in 13.5 dpc XX gonads continue to differentiate as meiotic oocytes in these conditions (Adams and McLaren, 2002).


Germ cell sex determination in mammals.

Kocer A, Reichmann J, Best D, Adams IR - Mol. Hum. Reprod. (2009)

Developmental timing of germ cell sex determination. Schematic diagram of when germ cells commit to spermatogenesis and oogenesis during mouse embryogenesis. Germ cells are sexually bipotential (green) at 11.5 dpc, and commit to spermatogenesis (blue) between 11.5 and 12.5 dpc in male gonads or to oogenesis (pink) ∼1 day later in female gonads. dpc, days post-coitum.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2657314&req=5

GAP008F2: Developmental timing of germ cell sex determination. Schematic diagram of when germ cells commit to spermatogenesis and oogenesis during mouse embryogenesis. Germ cells are sexually bipotential (green) at 11.5 dpc, and commit to spermatogenesis (blue) between 11.5 and 12.5 dpc in male gonads or to oogenesis (pink) ∼1 day later in female gonads. dpc, days post-coitum.
Mentions: The germ cells’ decision to develop as male or female depends on external signals in their surrounding environment rather than the chromosomal sex of the germ cells themselves: XY germ cells can develop as oocytes in female chimaeric embryos and XX germ cells can develop as prospermatogonia in male chimaeric embryos (Ford et al., 1975; Palmer and Burgoyne, 1991). These observations are consistent with the sex-determining activity of the Y chromosome acting only in the supporting cell lineage and the resulting Sertoli cells influencing sexual differentiation of other gonadal cell types through extracellular signals (Palmer and Burgoyne, 1991). The developmental timing of the germ cells’ response to sex-determining signals in the gonad differs between male and female embryos (Fig. 2). Germ cells in XY gonads commit to spermatogenesis between 11.5 and 12.5 dpc (McLaren and Southee, 1997; Chuma and Nakatsuji, 2001; Adams and McLaren, 2002). Thus, germ cells in 11.5 dpc XY gonads can be induced to sex-reverse and initiate meiosis by co-culturing on feeder cells, in embryonic lung tissue, and in female embryonic urogenital ridge tissue (McLaren and Southee, 1997; Chuma and Nakatsuji, 2001; Adams and McLaren, 2002). However, by 12.5 dpc germ cells in XY gonads have responded to the XY gonadal environment, are committed to differentiate along a male pathway and will not sex-reverse or initiate meiosis even when co-cultured in female embryonic urogenital ridge tissue (Adams and McLaren, 2002). Germ cells in XX gonads appear to commit to oogenesis a day later than germ cells in XY gonads commit to spermatogenesis. Thus, germ cells in 12.5 dpc XX gonads can be induced to sex-reverse and differentiate into prospermatogonia by co-culture in male embryonic urogenital ridge tissue, but germ cells in 13.5 dpc XX gonads continue to differentiate as meiotic oocytes in these conditions (Adams and McLaren, 2002).

Bottom Line: In response to these sex-determining cues, germ cells in female embryos initiate oogenesis and enter meiosis, whereas germ cells in male embryos initiate spermatogenesis and inhibit meiosis until after birth.In addition, we discuss the possibility that some of the reported effects of these factors on germ cell development may be indirect consequences of impairing sexual differentiation of gonadal somatic cells or germ cell survival.Understanding the molecular mechanisms of germ cell sex determination may provide candidate genes for susceptibility to germ cell tumours and infertility in humans.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.

ABSTRACT
One of the major decisions that germ cells make during their development is whether to differentiate into oocytes or sperm. In mice, the germ cells' decision to develop as male or female depends on sex-determining signalling molecules in the embryonic gonadal environment rather than the sex chromosome constitution of the germ cells themselves. In response to these sex-determining cues, germ cells in female embryos initiate oogenesis and enter meiosis, whereas germ cells in male embryos initiate spermatogenesis and inhibit meiosis until after birth. However, it is not clear whether the signalling molecules that mediate germ cell sex determination act in the developing testis or the developing ovary, or what these signalling molecules might be. Here, we review the evidence for the existence of meiosis-inducing and meiosis-preventing substances in the developing gonad, and more recent studies aimed at identifying these molecules in mice. In addition, we discuss the possibility that some of the reported effects of these factors on germ cell development may be indirect consequences of impairing sexual differentiation of gonadal somatic cells or germ cell survival. Understanding the molecular mechanisms of germ cell sex determination may provide candidate genes for susceptibility to germ cell tumours and infertility in humans.

Show MeSH
Related in: MedlinePlus