Females are born with all the eggs they will ever have: You learned this in middle school biology, again in high school and maybe even one more time at Hopkins.
Now, however, researchers in Shanghai are challenging this long-held biological doctrine. They claim to have taken newly-created egg cells from an adult mouse ovary, and then implanted them in another mouse that subsequently gave birth to a litter from these cells.
The finding of newly-born egg cells, or oocytes, in addition to the older ones that had been present in the ovary for the mouse's entire life, challenges the long-held belief that all of a mammal's oocytes are already developed before she is born.
If the researchers' finding is correct - and there is substantial uncertainty about the accuracy of the new paper - it will not only represent a major paradigm shift in developmental biology, but might also have implications for infertile women seeking to have children.
The accuracy of this paper, however, is stirring up much debate in the reproductive biology community. Despite many attempts made by different research groups over several decades, no scientist has ever successfully found newborn oocytes in an adult mammalian ovary.
Researchers at the Shanghai Jiao Tong University report in the April issue of Nature Cell Biology that they found the new egg cells indirectly, by scanning the mice's ovaries for vasa homolog, a protein found in germ-line cells.
"Vasa is a protein that acts to control the production of proteins in cells, a process called mRNA translation," Allan Spradling, a researcher at the Carnegie Institution and a professor at Hopkins, said.
By looking for vasa protein along with other cellular markers in the ovary, the Shanghai group reported the presence of both newborn and older oocytes in a mouse ovary.
Spradling expressed reservations about the Shanghai group's use of vasa homolog as a marker for new cells. "It has often been used as a marker to prove a cell is a germ cell. However, it is not specific to stem cells and cannot reveal the developmental stage of a germ cell," he said.
After the researchers found the vasa-producing cells that were assumed to be newborn oocytes, they removed the cells, grew them in cell cultures and marked them with a unique fluorescent tag.
They then injected the vasa-producing cells into the ovaries of mice whose eggs had been removed. It was hoped that these cells would then be fertilized and develop into newborn mice, thus proving that these new oocytes were fully functional eggs.
After mating these mice, the researchers found that some of the offspring contained the fluorescent tag - proof that these infant mice had originated from the vasa-positive germ-line cells.
If true, the findings of this paper challenge biological orthodoxy. However, substantial doubts remain in the scientific community over the validity of these new results.
"The idea has met resistance because the experimental support in the past has been poor, but the work has been published anyway, in some cases against the advice of reviewers, by journals eager for news value," Spradling said.
It's also difficult to assess the clinical implications of these results. If newborn oocytes really are formed in adult ovaries, these cells could be preferentially targeted in fertility treatments. Presumably, these newer cells would be healthier than older oocytes.
However, it is unclear whether these oocytes exist in mice, let alone in humans. Further experimental work is needed before the paper's findings will be supported and accepted by experts.
Spradling and other scientists, are currently unconvinced that this research will lead to new clinical developments.
"The chances that this procedure would lead to fertility in cases where more conventional in vitro fertilization is unsuccessful seems remote at this point," Spradling said.
"The stem cell field already has enough quack therapies being pushed in foreign countries in the absence of any proven clinical benefit. I am concerned this will encourage someone to undertake risky and expensive medical procedures that have no realistic prospect of success," he said.
Until further research is completed, the debate over female germ-line cells will continue.
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