Ovarian stem cells used to produce eggs

Stem cells taken from human ovaries can produce normal, healthy eggs, scientists demonstrated for the first time in an experiment that may lead to new methods to help infertile women.

The finding challenges a belief that women have a fixed number of eggs, or oocytes, from birth that are depleted by the time of menopause, and that their ovaries can't make more. The research, led by Jonathan Tilly, director of the Vincent Center for Reproductive Biology, part of the Harvard University-affiliated Massachusetts General Hospital, is published in the journal Nature Medicine.

In 2004, Tilly discovered that ovarian stem cells in mice can create new eggs, similar to how stem cells in male testes produce sperm throughout a man's life. The latest study proves the same is true in human ovaries, and may point to new ways to overcome infertility or preserve fertility by delaying the time when a woman's ovaries stop functioning, he said.

"The 50-year-old belief in our field wasn't actually based on data proving it was impossible, or not ongoing, it was simply an assumption made because there was no evidence indicating otherwise," Tilly said in a telephone interview. "We have human cells that can produce new oocytes." A female is most endowed with oocytes as a fetus, when she has about 7 million. That number that drops to 1 million by birth, and around 300,000 by puberty. By menopause, the number is zero. Since the 1950s, scientists thought that ovarian stem cells capable of producing new eggs are only active during fetal development.

In the study, healthy ovaries were obtained from consenting patients undergoing sex reassignment surgery. The researchers were able to identify ovarian stem cells because they express a rare protein that's only seen in reproductive cells.

The stem cells from the ovaries were injected into human ovarian tissue that was then grafted under the skin of mice, which provided the blood supply that enabled the cells to grow. Within two weeks, early stage human follicles with oocytes had begun to form.

The study offers "a new model system for understanding the human egg cell," according to David F. Albertini, director of the Center for Reproductive Services and professor in the department of molecular and integrative physiology at Kansas University.

Tilly's team is exploring the development of a bank for ovarian stem cells, which can be cryogenically frozen and thawed without damage, unlike human oocytes. The researchers are also working to identify hormones and other growth factors for accelerating the production of eggs from human ovarian stem cells and ways to improve in vitro fertilization.