14 DAY TRIAL // A woman is a complex universe. So complex, that 350 genes combine to allow her to become a mother. This is the number of genes found by a team at UT Southwestern Medical Center to be connected to female fertility, a breakthrough in the investigation of woman infertility.
"This study gives us a way to begin to understand the causes of female infertility. It gives us a much more complete list of candidate genes to explore. Before, we didn't even know where to look." said senior author Dr. Diego Castrillon, assistant professor of pathology and specialist in the diagnosis of infertility and other diseases of women.
Even if the research was made on lab mice, "at the molecular level, ovarian biology is very similar in mice and humans. These discoveries might lead the way to eventually allowing clinicians to test whether an infertile woman has problems with a specific gene, allowing for improved diagnostic tests and tailored therapy in the future," said Castrillon.
"About 13 % of women suffer from infertility, with the most common cause being dysfunction of the ovary. Researchers suspected genetic links in many cases," he added.
In the mammals' ovaries, following the birth, the egg cells are dormant, located in nests named primordial follicles. At puberty, the follicles mature and are activated through a scarcely understood process, when egg cells (ovules) start to be released for fertilization. Follicle activation was known to be induced by a gene dubbed Foxo3.
Normally, follicles are scheduled for activation, so that an ovary has follicles at various developmental stages. When the researchers engineered female mice to lack Foxo3, the result was that the follicles, normal at birth, later were activated all at the same moment. Genes controlling follicle development turned active at the same time, and through the method of expression profiling, the researchers detected them.
348 genes were found to be active only in ovaries of the mutated mice, but not in other organs, pointing to the fact that their encoded proteins (enzymes) were involved specifically in follicle development. "Some of the genes the researchers found were already known to be involved in infertility, which helped validate the experimental method. Most, however, were previously unknown," said Castrillon.
Some of these genes, randomly selected, were checked in human ovaries, and were found to be active in the ovary's early development. "Future work will focus on finding out how these genes communicate with each other to control follicle development, and study their contribution to female infertility", Castrillon added.