Researchers Identify Gene with Possible Link to Infertility in Mice

The steps involved with conception and pregnancy are delicate and complex – particularly the process of folliculogenesis. In females, fertility is dependant on the growth of a follicle, a structure that ultimately transforms to release a mature egg.

In an ordinary cycle, one follicle, known as the dominant follicle, matures to release an egg, while the rest of the eggs produced in that cycle will die. Disruption at any stage in the development of the follicle can prevent this maturation and impair fertility, as well as alter the production of hormones in the ovaries.

In the study, published online in the Oct. 1 issue of the journal Biology of Reproduction, researchers used a mouse model to examine the role of a gene known as Smad-3 in the early stages of follicular growth to better understand the molecular mechanisms that could influence fertility. Specifically, they looked at the signaling pathways involved in the follicles’ response to follicle stimulating hormone, or FSH. FSH is one of the most important hormones involved in fertility and is responsible for helping a woman’s body develop a mature egg.

The team, led by principal investigator Elizabeth McGee, M.D., associate professor of obstetrics and gynecology in the VCU School of Medicine, reported that female mice missing the Smad-3 gene did not experience normal ovulation and were infertile because there is a reduced ability of the follicle to respond to FSH stimulation. Further, the team concluded that Smad-3 regulates follicle growth and an important family of proteins that are essential for follicle development.

“Learning precisely how the FSH receptor is regulated is an important step in understanding the subtle defects in signal transduction that can interfere with follicle development and female fertility and could lead to new types of fertility treatments,” said McGee, who is director of reproductive endocrinology and infertility at the VCU Medical Center.

This work was supported by a grant from the National Institutes of Health.

About VCU and the VCU Medical Center: Virginia Commonwealth University is the largest university in Virginia with national and international rankings in sponsored research. Located on two downtown campuses in Richmond, VCU enrolls 32,000 students in 205 certificate and degree programs in the arts, sciences and humanities. Sixty-five of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 15 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation’s leading academic medical centers.