Sex-specific differences in fetal germ cell apoptosis induced by ionizing radiation

Area of Science:

• Reproductive biology
• Developmental biology
• Radiation biology

Background:

• Male human fetal germ cells are highly radiosensitive, with apoptosis dependent on p53 activation.
• Previous studies showed male germ cell apoptosis initiated at 0.1 Gy and prevented by pifithrin alpha (a p53 inhibitor).

Purpose of the Study:

• Investigate the radiosensitivity of early female and male fetal proliferating germ cells.
• Compare the response of male and female germ cells to ionizing radiation (IR).

Main Methods:

• Irradiation of human fetal germ cells in organ culture.
• Assessment of gamma H2AX foci, p53 accumulation, and apoptosis.
• Use of p53 inhibitor (pifithrin alpha) and knockout mouse models (p53, p63).

Main Results:

• Both male and female fetal germ cells showed similar gamma H2AX foci after IR.
• Oogonia apoptosis occurred only at high IR doses (≥1.5 Gy) and was p53-independent.
• p53 accumulated in irradiated male germ cells but not female germ cells.
• p53 or p63 knockout improved male germ cell survival post-IR, but did not affect female germ cell survival.

Conclusions:

• Pre-meiotic male and female fetal germ cells exhibit distinct responses to irradiation.
• Oogonia are less sensitive to genotoxic stress and undergo p53-independent apoptosis.