Ovulated egg cells, or oocytes, in adult female mice are not formed from germ cells in the blood or bone marrow.
That's the conclusion of a new study led by investigators at Joslin Diabetes Center and Harvard University. These findings refute a controversial recent study conducted at Massachusetts General Hospital (MGH), which itself contradicted the long-held belief that female mammals are born with a finite number of oocytes that cannot be replenished or regenerated if lost to injury or disease by suggesting that transplanted bone marrow or peripheral blood cells were capable of generating new oocytes in the ovaries of recipient mice.
The Joslin study appears Nature..
"It was a very important study to do," says Amy J. Wagers, Ph.D., Investigator in Developmental and Stem Cell Biology at Joslin Diabetes Center and Assistant Professor of Pathology at Harvard Medical School. "The suggestion that bone marrow cells might represent a previously unappreciated source of cells capable of restoring female fertility had significant implications for patients undergoing chemotherapy, which often leads to sterility, and for individuals donating or receiving bone marrow cells for transplant, as well as for women experiencing premature menopause."
The MGH study reported that transplanted cells from the bone marrow or blood could enter the ovaries of genetically infertile or chemically sterilized female mice and produce new oocytes but didn't study whether those oocytes could be ovulated, or whether bone marrow cells normally migrate to the ovary as part of a normal process of ovary regeneration. The Joslin study's goal was to find out if that was possible.
Joslin study researchers used a parabiotic mouse model in which pairs of mice are joined using a surgical procedure that enables blood vessels to fuse such that the mice develop a common circulatory system. "It's a very useful model," reports Wagers, "because it allows one to track cells that normally circulate in the blood under physiological conditions."
The mice used were almost genetically identical, except that one member of the pair expressed throughout its body green fluorescent protein (GFP), a gene from jellyfish that causes cells expressing it to glow green under certain wavelengths of light. Thus, once the mice were joined, any cells moving through the circulation from the GFP-expressing mouse to its non-fluorescent partner would be identifiable by their green marking, while cells moving from the non-fluorescent partner to the GFP partner would be identifiable by their lack of green fluorescence.
Wagers and the research team used hormones to stimulate ovulation in the parabiotic pairs after they had been joined for six to eight months and examined ovulated oocytes from both mice for the presence of green cells. They found that all of the oocytes in the GFP-expressing partners were green, while none of the oocytes collected from the non-fluorescent partners were green. This demonstrated that the ovulated oocytes had not been produced by cells that arrived in the ovary through the bloodstream.
"We didn't find any oocytes ovulated in the parabiotic mice that would have been derived from circulating cells. Our data argue that circulating cells don't normally contribute to oocytes that are ovulated and therefore available for fertilization," says Wagers.