Mammalian egg cells are each surrounded by a blanket of cells known as the ovarian follicle. Scientists knew follicles released molecules that controlled the development of egg cells until they are ready for fertilization. Now researchers discover that egg cells actually unexpectedly regulate follicle release of these maturation chemicals, shedding light on mammal fertility, as shown in research detailed this week in the Proceedings of the National Academy of Sciences.
Developing egg cells, known as oocytes, undergo the process of meiosis like all sex cells, dividing their chromosomes in half. Oocytes have to stall meiosis until a surge of hormones from the pituitary gland starts ovulation.
For decades, scientists knew that somatic cells in the follicle were controlling the arrest of meiosis. They do so via the natriuretic peptide C/natriuretic peptide receptor 2 (NPPC/NPR2) system — when the protein NPPC activates the receptor NPR2, the receptor generates cyclic guanosine monophosphate (cGMP), which sustains meiotic arrest. High levels of the chemical hypoxanthine in follicular fluid may also possibly be linked with meiotic arrest.
Both the NPPC/NPR2 system and hypoxanthine require the activity of the enzyme inosine monophosphate dehydrogenase (IMPDH). This enzyme is needed to produce cGMP and to rescue hypoxanthine from a process that would normally demolish it.
“Up until about 1990, it was thought the oocyte was simply a recipient of the largesse of the surrounding somatic cells — that the cells surrounding the oocyte acted like nurses, taking care of the screaming little baby in the middle of the follicle,” says researcher John Eppig, a reproductive biologist at the Jackson Laboratory in Bar Harbor, Maine. “Then researchers began to get clues this was not a one-way street — that the oocyte was participating in regulating important activity that affected the development of the oocyte itself.”
Now researchers find that molecules from the oocyte regulate IMPDH and NPR2. They also boost cGMP in cumulus cells, a cluster of cells that surround the oocyte in the follicle.
“It’s an interesting bidirectional communication here — the follicle controls the oocyte because the oocyte tells the follicle to,” Eppig says.
This research could open new avenues into treating infertility.
“Are there any cases of infertility that exist among women that can be attributed to failures of the interaction between somatic cells and oocytes? We don’t know the answer to that question yet,” Eppig says. “There are still so many unexplained cases of infertility.”