In the fifth week of pregnancy, a female fetus will develop a small structure called the genital ridge (which will evolve into the ovaries), colonized by special cells called primordial germ cells. Multiplying rapidly, these early cells eventually become eggs. About half way through the pregnancy there are about 7 million of these so-called primitive eggs. Their frenetic multiplication tapers off and actually declines down to 2-3 million eggs by the time of birth, the point at which scientists have assumed that a female has developed all the eggs that she will ever have.
Strangely, in competition with this process of germ cell multiplication, there is a remarkable course of cell death, which begins at about 16 weeks into gestation and continues unrelentingly until all the eggs are gone (typically when a woman is in her early 50's). From the many millions of eggs at the time of birth, the reserve reduces to about 400,000 by puberty. During her lifetime, a woman will ovulate between three and four hundred eggs total. The rest die and are reabsorbed by the ovaries.
The reasons behind this early cell death have remained a mystery. But the facts are staggering. Before a girl even ovulates her first egg (at puberty), she has lost an average of 340 eggs per day since birth. After puberty, the rate averages out at about 25 per day. The rate of depletion then doubles at about age 37, ensuring that the egg supply is exhausted by the early 50’s. Evolutionary biologists have assumed that this is nature's way of stopping a woman from having more babies than she can raise.
Now this entire foundation of knowledge regarding female egg production and depletion is in question. A recent paper by Johnson et al., (Nature, March11th 2004, Vol. 428, pp. 145-150) has opened up new doors for a drastic revision of the biological theory behind female egg production, and thus her fertility.
The research comes from the laboratory of Jonathan Tilly, an established and highly respected developmental biologist at Harvard Medical School. By studying mice, the researchers determined that germ cells persist after birth; and such stem cells give rise to new eggs throughout a mouse's life. In a remarkably simple experiment, researchers quantified the rate of egg depletion in the mouse ovaries, and determined that the rate should have exhausted the egg supply much earlier. Yet an unidentified replenishment was taking place. Mice are normally fertile for about a year, but Tilly found that their egg supply would be exhausted in just 2 weeks if it were not somehow being replenished.
Tilly is confident that these same results will be found with human ovaries, despite significant differences in egg biology between the two species. If he is correct, many new therapies could evolve to preserve fertility and stave off menopause in omen. The germ cells for example, might be easier to preserve (freeze) than eggs, and women under-going ovarian irradiation as part of cancer treatment, which destroys eggs, could have their ovaries repopulated. Also, since the ovary creates estrogen-producing granulosa cells to surround each new egg, germ cell transplants could reverse the hormone withdrawal effects of menopause.
A tremendous amount of research will have to take place over many years before any of this conjecture starts to take shape. Meanwhile, one has to be cautious in assuming that human eggs behave like those of mice, because significant differences exist. Mouse eggs, for example, do not display the same age-related problems, such as increased rate of genetic abnormalities and decreased embryo implantation, which are evident in the eggs of older women. But the prospect of a replenishing egg supply is very exciting and provides hope for those of us trying to preserve fertility.