The notion of a biological clock in women arises from the fact that immature egg cells- 'oocytes' - progressively decline in number as females get older, along with a decades-old view that oocytes cannot be renewed in mammals after birth. A recent genetic study tracing the origins of oocytes from the embryonic period throughout adulthood and adds new information to a growing controversy. Scientists from Massachusetts General Hospital and the University of Edinburgh argue that the findings support formation of new eggs during adult life; a topic that has been historically controversial and has sparked considerable debate in recent years.
Eggs are formed from progenitor germ cells that exit the mitotic cycle, thereby ending their ability to proliferate through cell division, and subsequently enter meiosis, a process unique to the formation of eggs and sperm which removes one half of the genetic material from each type of cell prior to fertilization.
While traditional thinking has held that female mammals are born with all of the eggs they will ever have, newer research has demonstrated that adult mouse and human ovaries contain a rare population of progenitor germ cells called oogonial stem cells capable of dividing and generating new oocytes. Researchers traced the number of divisions a cell has undergone with age (its 'depth') and counted the number of times progenitor germ cells divided before becoming oocytes.(1)
If traditional thinking held true, all divisions would have occurred prior to birth, and thus all oocytes would exhibit the same depth regardless of age. However, the opposite was found – eggs showed a progressive increase in depth as the female mice grew older.
In a new assessment of the work by Shapiro and colleagues, reproductive biologists Dori Woods, Evelyn Telfer and Jonathan Tilly conclude that the most plausible explanation for these findings is that progenitor germ cells in ovaries continue to divide throughout reproductive life, resulting in production of new oocytes with greater depth as animals age. (2)
Postnatal oogenesis through ongoing oogonial stem cell (OSC) mitosis explains increasing oocyte depth with age. (a) Following primordial germ cell (PGC) expansion starting at embryonic day 7.5 (e7.5) in the mouse, proliferation of female germ cells (oogonia; pink) ceases at e13.5 concomitant with a 5-day period of germ cell meiotic commitment that drives formation of oocytes (blue); since all oocytes produced during this time are of equivalent “depth”, the production-line hypothesis of postnatal oocyte maturation cannot logically explain increasing oocyte depth as females age. (b) If continued proliferation of OSCs (red) and their subsequent differentiation into oocytes (blue) during postnatal life is superimposed on the production-line hypothesis, the emerging picture is consistent with a progressive increase in oocyte depth in females as they age. Credit: doi:10.1371/journal.pgen.1002848.g001
Although these investigations were performed in mice, there is emerging evidence that oogonial stem cells are also present in the ovaries of reproductive-age women, and these cells possess the capacity, like their mouse counterparts, to generate new oocytes under certain experimental conditions.
Woods and colleagues say that "the recent work of Shapiro and colleagues is one of the first reports to offer experimental data consistent with a role for postnatal oocyte renewal in contributing to the reserve of ovarian follicles available for use in adult females as they age."
(1) Reizel Y, Itzkovitz S, Adar R, Elbaz J, Jinich A, et al. (2012) Cell lineage analysis of the mammalian female germline. PLoS Genet 8: e1002477 doi:10.1371/journal.pgen.1002477.
(2) Citation: Woods DC, Telfer EE, Tilly JL (2012) Oocyte Family Trees: Old Branches or New Stems? PLoS Genet 8(7): e1002848. doi:10.1371/journal.pgen.1002848