Bone marrow could hold key to turning back clock on fertility

STEM cells that are made in the bone marrow of women could provide their ovaries with fresh eggs to extend fertility and postpone the menopause, according to research that could revolutionise reproductive medicine.

Scientists have discovered that bone marrow produces primitive cells that can be summoned by the ovaries to replenish their egg supplies, challenging the theory that women are born with their life's supply of eggs. A study using female mice indicated that it may be possible to exploit this natural process in women who are infertile because of their age or cancer treatment.

Preliminary tests have established that these egg-precursor cells exist in human bone marrow and blood. Drugs that encourage the cells to migrate to the ovary could be used to restock a 40-year-old woman's declining supply of eggs.

Professor Jonathan Tilly, of the Massachusetts General Hospital in Boston, who led the research, said: "We may be ushering in a new era in the clinical management of female infertility and menopause. This could lead to new treatment approaches, based not on drugs but on regenerative medicine through adult stem cells."

For almost a century, biologists have believed that female mammals are born with all the eggs they will ever have. The follicles or sacs in which the eggs mature gradually die off or are ovulated, until the supply is exhausted.

Last year, however, Professor Tilly discovered that mouse ovaries appeared to be restocking themselves with new follicles in adulthood. His latest study, which is published today in the journal Cell, corroborates these findings and indicates from where these new egg follicles may have come.

Experiments on mice indicated that follicle precursors, called germ cells, which were thought to develop only in embryos, are being made by bone marrow and transported through the blood to the ovaries in response to an unidentified hormonal signal. The chemical markers of germ cells have also been found in human bone marrow and blood.

Professor Tilly said: These results not only confirm last year's findings that the old dogma is wrong, they also show we need to think more broadly about female reproduction.

"We found that every germ cell marker we could think of was expressed in the bone marrow. Everyone had missed finding female germline stem cells because they are not in the ovaries, where everyone would have looked for them."

To check that the germ cells were moving to the ovaries and forming fresh follicles, Professor Tilly ran experiments with two different sets of mice. One set had been sterilised by chemotherapy, while the other was genetically sterile.

He then took bone marrow from another set of mice, which had an added jellyfish gene that made their cells produce a green fluorescent protein, and transplanted it into the sterile animals. After two months, the ovaries of the sterile mice were again teeming with eggs. Some of these eggs glowed with the green protein, proving that they had come from the transplanted marrow. If further experiments confirm that the regenerated follicles are normal and capable of being fertilised, the process could possibly be used to restore or enhance fertility in humans.

Professor Tilly said that the ovary seems to be part of a three-part system. Germ cells are made by bone marrow, they then travel through the bloodstream to the ovary where they mature fully.

Further results suggested that the ovary sends a chemical signal to summon new germ cells when they are needed to replenish the supply of eggs. The nature of the signal has not been identified, but the scientists have ruled out the two main female hormones, oestrogen and progesterone. If the signal can be identified, it may be possible to trigger it artificially, tricking the bone marrow into sending extra germ cells to the ovaries to build up their supply of eggs. Another possibility is that germ cells could be matured in the laboratory, providing a source of eggs for use in therapeutic cloning.

Professor Tilly said that the results could explain why some women who are left infertile by chemotherapy occasionally regain their ovarian function and even conceive after receiving bone marrow transplants.

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