Context. The regulation of germ cell proliferation and loss during human ovarian development is poorly understood. This is of particular interest at the time leading up to the formation of primordial follicles, at 18 weeks gestation onwards.

Objective. To identify and quantify germ cell proliferation and apoptosis, and expression of caspases in the human fetal ovary.

Design. Laboratory investigation.

Setting. Research institute.

Methods. Cell proliferation and apoptosis were detected using immunohistochemical localization of phosphorylated histone H3 (phospho-H3) and cleaved caspase 3 respectively. Caspases were also detected by immunoblotting.

Results. The overall proportion of germ cells in mitosis remained constant between 14 and 19 weeks, but showed increasing clustering. Caspases 2, 3, 7, 8 and 9 were detected by immunoblotting. There was a significant increase in germ cell apoptosis. A specimen of 20 weeks gestation showed similar phospho-H3 but markedly lower cleaved caspase 3 expression than earlier gestations. Cleaved caspase 3 was not expressed in oocytes which had formed primordial follicles.

Conclusions. These results indicate that as primordial follicle formation is initiated and progresses, there is an increase in both mitotic activity and apoptosis of those germ cells that have not reached the apparently protective environment of the primordial follicle.