"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 Dr. Diego Castrillon, assistant professor of pathology and senior author of the study.
He further said the findings were a result of an animal study, "at the molecular level, ovarian biology is very similar in mice and humans."
Dr. Castrillon expressed hopes that his findings might eventually pave the way for clinicians to test whether an infertile woman had problems with a specific gene, allowing for improved diagnostic tests and tailored therapy in future.
In mammals, the ovaries go through a developmental stage after birth in which egg cells become nestled in dormant nests called primordial follicles. Later in development, the follicles become activated by a process that researchers do not fully understand, and at puberty, egg cells begin being released for fertilization.
Normally, follicles are activated on a staggered schedule, so an ovary contains follicles at many different stages of development, according to the background information in the study report appearing in the journal Genetics.
During the course of study, the researchers devoted their focus to a gene called Foxo3, which controls follicle activation.
In female mice genetically engineered to lack Foxo3, the follicles are normal at birth, but later become activated all at the same time.
Dr. Castrillon says that this coordinated maturation indicated that the genes controlling follicle growth were all turned on at the same time, making it easier to detect them.
The researchers employed a method known as expression profiling to identify the active genes, and found 348 genes that were active in ovaries in the mice lacking Foxo3 but not in other tissues, indicating that they could function specifically in follicle growth.
They also found that some of the genes were already known to be involved in infertility, which helped validate the experimental method.
Dr. Castrillon, however, claimed that most of the genes that his team had found were previously unknown.
He also said that a small number of specific genes out of the 348 identified by them were found to be active in the early development of the human ovary.
In their future research, the researchers will study how these genes communicate with each other to control follicle development, and what is their contribution to female infertility.