By Ryan Flinn - Sun Feb 26 18:00:00 GMT 2012

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.

Woman have a fixed number of eggs from birth that are depleted by the time of menopause. The finding, published today in the journal Nature Medicine, challenges the belief that their ovaries can't make make more. The research was led by Jonathan Tilly, director of Massachusetts General Hospital’s Vincent Center for Reproductive Biology.

Tilly discovered in 2004 that ovarian stem cells in mice create new eggs, or oocytes, in a manner that's 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 when a woman’s ovaries stop functioning, Tilly said in a telephone interview.

“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. “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 1950’s, scientists thought that ovarian stem cells capable of producing new eggs are only active during fetal development.

Ovarian Stem Cells

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.

“This paper essentially opens the door to the ability to control oocyte development in human ovaries,” Tilly said.

About 10 percent of women of child-bearing age in the U.S., or 6.1 million, have difficulty getting pregnant or staying pregnant, according to the Centers for Disease Control and Prevention. Most cases of female infertility are caused by problems with ovulation, hormone imbalance or age.

Infertility Treatments

Infertility in women is now treated through drugs, surgery, artificial insemination or assisted reproductive technology, in which the woman’s eggs are mixed with sperm outside the body, then reinserted.

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. Still, “there’s a long way to go before this has real practical applications,” he said.

“I’ve spent 35 years of my life studying egg cells and this is a cell that is at least as complicated as a neuron in the brain, if not more,” Albertini said in an interview. “You will need to establish reproducibility from one lab to the next, and hopefully others will be able to confirm his work and extend it, make it into something that will make us confident that the cells are safe to use and we could actually use them to repopulate an egg-depleted ovary.”

New Therapies

The research is opening other therapeutic avenues in fertility treatment, Tilly said.

His 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.

“The problem we face with IVF is we don’t have many eggs to work with,” he said. “These cells are renewable. If we are successful -- and it’s a big if -- in generating functioning eggs from these cells, we can generate as many eggs as we need to on a per patient basis.”

Tilly is also collaborating with researchers at the University of Edinburgh in the U.K. to determine whether the oocytes can be developed into fully mature human eggs for fertilizing. The U.S bans creating or fertilizing embryos for experimental purposes, he said.

A company Tilly co-founded, Boston-based OvaScience Inc., has licensed the technology for potential commercial applications.

To contact the reporter on this story: Ryan Flinn in San Francisco at rflinn@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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Ovarian Stem Cells Produce Eggs in Method That May Aid Fertility Therapy

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