Female infertility to be studied under research grant

Women suffering from infertility may one day have answers for why they cannot become pregnant, thanks to fertility studies currently being conducted on mice.

H. Jade Lim, Ph.D., assistant professor of obstetrics and gynecology, has received a five-year, $1 million grant from the National Institute of Child Health and Human Development to examine the role of a specific protein in the success or failure of early mouse pregnancy.

In the first days of pregnancy, a fertilized egg, called a zygote, is free-floating in the uterus. It must attach, or implant, to the uterine wall for the pregnancy to proceed.

“About 25 percent of women suffer from miscarriage before or around the time of implantation, sometimes even without knowing it,” Lim said.

In both humans and mice, a complex interaction of factors contributes to the success or failure of implantation. In previous mouse studies, Lim’s team found that the enzyme cyclooxygenase-2 (COX-2) plays a crucial role in pregnancy; without it, failures occur in ovulation and fertilization, as well as in the implantation process. COX-2 produces many prostaglandins, and among these prostacyclin turned out to be crucial during implantation.

The current grant builds on these previous studies and seeks to determine the role of a protein called peroxisome proliferator-activator receptor delta (PPARd), which acts as a prostacyclin receptor downstream to COX-2.

“PPARd is a transcription factor, which means it can activate a lot of genes,” Lim said. “We are interested in identifying the kinds of genes that are turned on by PPARd during the process of implantation.”

Although a lack of COX-2 leads to problems with implantation in mice, the role of this pathway in humans requires further investigation. COX-2 is associated with arthritis and some cancers, and medications designed to treat these diseases contain substances that prevent the production of COX-2.

Therefore, it is important for women taking these drugs who also are attempting to become pregnant to know if the COX-2 signaling pathway is indeed necessary for successful implantation in humans as well, Lim said.