Transplanted stem cells become eggs in sterile mice

Oocyte success raises hopes for infertility treatments

Germline stem cells

EGG-CITING DEVELOPMENT  Germline stem cells (orange circles, left) implanted into a mouse’s ovary move to the edge of the ovary (middle) and begin developing into eggs. By day 6 (right) the cells began making a protein called STRA8 (pointed out with red arrow), one sign that they were starting to turn into eggs.

 C. Wu et al/Molecular Therapy 2017

With an assist, an old mouse might be able to make new eggs.

Sterilized female mice produced healthy babies after receiving a transplant of egg-generating stem cells from another mouse, researchers report online May 18 in Molecular Therapy. If such a procedure worked in humans — still a distant prospect — it could help women with early menopause or chemotherapy-induced infertility to conceive.

These egg-generating cells are germline stem cells — precursors that become either eggs or sperm depending on whether they end up in ovaries or testes. While male germline stem cells differentiate (or become specialized) throughout a man’s life to produce a steady supply of new sperm, a woman’s are believed to differentiate into a stockpile of eggs during a relatively narrow time frame before she’s even born. Some recent studies have begun to question that conventional wisdom, though the idea that germline stem cells could still exist in women after birth is controversial (SN Online: 7/9/12).

“It’s been a debate for many years, whether there were indeed cells in the adult ovary capable of forming new eggs,” says Evelyn Telfer, a reproductive biologist at the University of Edinburgh who wasn’t part of the new study.

If such a population of cells existed, women might be able to produce new eggs later in life. That could offer hope to women whose existing eggs were damaged in some way. Isolating those germline stem cells and coaxing them to become eggs has proven tricky, though. The cells need just the right environmental conditions to turn into eggs.

Scientists have previously shown that isolated germline stem cells from mice can turn into eggs in a petri dish. “The argument is whether these cells will do it in the body normally, or is this a feature of the cells being cultured,” Telfer says.

Developmental biologist Ji Wu and her colleagues at Shanghai Jiao Tong University in China took germline stem cells from the ovaries of a 6-day-old mouse, cultured them in a petri dish, and then transplanted those cells into the ovaries of sterilized adult mice. There, the stem cells gradually moved to a spot just under the ovary’s surface, where they settled down and turned into eggs.

Five to eight weeks after the transplant, Wu and colleagues mated those mice with healthy males. Six of the eight stem cell recipients became pregnant, and went on to deliver healthy baby mice.

The results show that germline stem cells can indeed restore fertility when transplanted into other mice, Wu says. But such a therapy has a long way to go before it could help humans.

It’s also additional evidence that germline stem cells collected after a female mammal is born can still turn into viable eggs, Telfer says. But, she notes, the stem cells were collected from very young mice. “Maybe a cleaner experiment would have been to take them from an adult.”

Editor’s note: This story was updated June 2, 2017, to correct the implication that the researchers analyzed the chromosomes of baby mice. This step occurred at the oocyte stage.

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