7 - Is ovarian ageing inexorable?

Summary

Establishment of the follicle reserve

In the eggs of many invertebrate animals, a specific patch of cytoplasm is predetermined for creating germ cells, but mammalian eggs have no equivalent region. Instead, germ cells emerge during a process called epigenesis under the influence of inductive factors from neighbouring cells. Their progenitors are first recognisable in the proximal epiblast of mouse blastocysts shortly after implantation when a tiny cluster of Stella-positive cells is directed to a germ cell fate by BMP4 secreted by the extraembryonic ectoderm. Prdm1 (formerly Blimp1) is a key transcription factor in germ cells that regulates cell fate by repressing the somatic cell programme expressed in neighbouring cells. As germline stem cells (GSCs, also called primordial germ cells) emerge, they acquire alkaline phosphatase activity and migrate along the hind gut towards the gonadal ridge using a combination of morphogenetic movements and amoeboid motion. They express canonical genes, Dazl, c-Kit and Vasa, and undergo epigenetic reprogramming involving global demethylation of DNA (including imprinted genes) and histone modifications to produce a chromatin architecture resembling that of undifferentiated pluripotent stem cells. The life history of human germ cells is less well known but probably similar to rodents, apart from having a much longer schedule: the time to generate follicles from GSCs is several months compared with only 1—2 weeks for rodents. Oogenesis is completed by birth in most species.

Human GSCs have a high nuclear to cytoplasmic ratio and lack notable cytoplasmic specialisation. They continue multiplying after arriving in the ovary and enter meiosis at 2—3 months of gestation, when they are regarded as oocytes.