March 10, 2004 -- A surprising finding about female fertility in mice is challenging the notion that women are born with a lifetime's supply of eggs.
Researchers have long believed that female mammals, including mice and humans, were born with a fixed supply of egg-producing follicles in their ovaries. In contrast, most male mammals continuously generate new sperm cells that allow them to reproduce throughout their adult life.
But a new study published in the March 11 issue of Nature shows that female mice continue to produce eggs to replace damaged ones after birth.
Researchers say the discovery indicates that females may share the ability to replenish reproductive cells during life, and if the same process occurs in humans it may also help explain why female fertility declines rapidly after age 30.
Finding Challenges Basic Reproductive Biology Beliefs
Researchers say that the theory that female mammals are born with a fixed supply of eggs stems from studies that showed females develop a finite number of egg-producing follicles in their ovaries during fetal life, as opposed to males who continue to generate sperm-producing cells throughout their lives.
"Although this dogma has persisted for more than 50 years, the present study provides evidence that challenges the validity of this belief, which represents one of the most basic underpinnings of reproductive biology," write researcher Joshua Johnson of Harvard Medical School and colleagues.
Rather than having a fixed supply of egg-producing follicles, the study shows that female mice have a reserve supply of cells that replenish the follicle pool during adolescence as damaged follicles die.
In the study, researchers carefully measured follicle numbers at birth and then tracked their subsequent loss in female mice. They found that adolescent mice had about 2,500-5,000 healthy follicles but the number of dying follicles increased rapidly to up to 1,200 per ovary after adolescence.
Dying follicles degenerate or disappear within a few days, which means that the total number of healthy follicles should have dropped rapidly during this time period. Instead the study showed that in female mice the ovaries contain a population of cells that are required to maintain overall number of follicles for adult life.
Researchers found that the number of healthy follicles actually decreased relatively slowly despite this rapid loss of follicles. That finding shows that healthy egg-producing follicles must be produced somewhere in young mouse ovaries.
To test this theory, researchers treated the young mice with a chemical that kills egg cells and instead found that the mice still produced viable eggs in adulthood.
Researchers say the results show that a reserve of stem cells that form the building blocks for reproductive cells must exist in female mice as they do in male mammals. But more research is needed to determine how they function and what causes them to decline after adolescence.
Implications for Female Fertility
In an editorial that accompanies the study, Allan C. Spradling of the Carnegie Medical Institute Laboratory in Baltimore, Md., says the study raises many interesting and important questions.
For example, the location and the number of these 'reserve' or germ stem cells in females will need to be determined.
In addition, "the question on everyone's lips will be whether there are germline stem cells in the human ovary."
Spradling says these cells might have easily been missed in humans for the same reasons they were missed in mice for so long -- they were thought to be rare.
He says the work also raises "the strong possibility" that the rapid decline in female fertility that occurs after age 30 is caused by the depletion of these 'reserved' cells coupled with an age-related decline in healthy egg-producing follicles.