Stem Cell Finding Could Expand Women's Lifetime Supply of Eggs
SUNDAY Feb. 26, 2012 -- Researchers report that they've isolated stem cells from adult human ovaries that can mature into eggs that may be capable of fertilization.
The lab findings, which upend longstanding scientific theory, could potentially lead to new reproductive technologies and possibly extend the years of a woman's fertility.
It was long believed that women were born with a lifetime supply of eggs, which was depleted by menopause. But a growing body of research -- including a new paper from Massachusetts General Hospital -- suggests egg production may continue into adulthood. The study is published in the March issue of Nature Medicine.
"Fifty years of thinking, in every aspect of experiments, of interpreting the results, and of the clinical management of ovarian function and fertility in women was dictated by one simple belief that turns out to be incorrect," said lead study author Jonathan Tilly, director of the hospital's Vincent Center for Reproductive Biology. "That belief was the egg cell pool endowed at birth is a fixed entity that cannot be renewed."
Dr. Avner Hershlag, chief of the Center for Human Reproduction at North Shore-LIJ Health System in Manhasset, N.Y., said the study is "exciting" but emphasized the work is still very preliminary.
"This is experimental," Hershlag said. "This is a beginning of perhaps something that could bring in new opportunities, but it's going to be a long time in my estimation until clinically we'll be able to actually have human eggs created from stem cells that make babies."
The same team at Mass General caused a stir in 2004 when it published a paper in Nature reporting that female mice retain the ability to make new egg cells well into adulthood.
In both mice and humans, the vast majority of egg cells die through a process called programmed cell death, or apoptosis, the body's way of eliminating unneeded or damaged cells. For humans, that process is dramatic. Female fetuses have about 6 to 7 million eggs at about 20 weeks' gestation, a little more than 1 million at birth, and about 300,000 by puberty.
Studying mice egg cells and follicles, the tiny sacs in which stem cells become eggs, the Mass General researchers discovered something that didn't make mathematical sense.
Most prior research had focused on counting the healthy eggs in the ovaries, and then made assumptions about how many had died from that, Tilly said. But his lab looked at it the opposite way and focused on cell death.
"We found far too many eggs were dying than could be accounted for by the net change in the healthy egg pool," Tilly said. "We reasoned that maybe the field had missed something." They wondered if stem, or precursor cells, were repopulating the ovaries with new eggs.
Initially, the findings were met with skepticism, according to the study authors, but subsequent research bolstered the conclusions.
Those included a 2009 study from a team in China, published in Nature Cell Biology, that isolated, purified and cultured egg stem cells from adult mice, and subsequently introduced them into mice ovaries that were rendered infertile. The infertile mice eventually produced mature oocytes that were fertilized and developed into healthy baby mice.
Studies showing that women had the same capacity as mice were lacking, however.
In this study, Tilly's team used tissue from Japanese women in their 20s and 30s with gender identity disorder, who had their ovaries removed as part of gender reassignment surgery.
The researchers isolated the egg precursor cells and inserted into them a gene from a jellyfish that glows green, then inserted the treated cells into biopsied human ovarian tissue. They then transplanted the human tissue into mice. The green fluorescence allowed researchers to see that the stem cells generated new egg cells.
Tilly said the process makes evolutionary sense. "If you look at this from an evolutionary perspective, males have sperm stem cells that continually make sperm. Because species propagation is so important, we want to make sure it's the best sperm, so don't want sperm sitting around for 60 years waiting to get used," he said. It makes no sense from an evolutionary perspective that "females will be born with all the eggs they will have and let them sit there," he noted.
Hershlag, meanwhile, said much remains to be overcome.
"Ultimately, in our field only one thing counts," he said, "and that is if you can make an egg that can make a healthy baby."
The U.S. National Library of Medicine has more on how human embryos develop.
Posted: February 2012