PULLMAN, Wash. - A Washington State University researcher will study the oviductal epithelium environment to learn more about poor success and inherent problems associated with assisted reproductive technologies (ART), which are used to treat infertility.
The five-year $1.59 million grant from the National Institutes of Health will focus on studying how the ovarian steroid hormones estrogen and progesterone affect fertility during sperm migration, fertilization, embryo development, and embryo transport within the female reproductive tract.
"Approximately 50-80 million reproductive age couples worldwide suffer from infertility. These couples encounter psychological distress, including low self-esteem, isolation, and depression, emphasizing the need of better understanding of the causes of infertility," said Wipawee "Joy" Winuthayanon, assistant professor in the College of Veterinarian Medicine School of Molecular Biosciences.
ART procedures work by removing eggs from a woman's body to combine with sperm to make an embryo. The embryo is then placed back in the woman's body. ART procedures bypass fallopian tubes when the embryo is inserted into the woman's uterus. Multiple components of the cells in the female reproductive tract work together to provide an optimal microenvironment for gametes and the embryo to establish successful pregnancy. In vitro fertilization (IVF) is the most common and effective type of ART. In the U.S., one percent of all babies are born by ART.
"Critical development of an embryo happens in the fallopian tubes as it moves down to implant into the wall of the uterus. We don't know how estrogen and progesterone in the fallopian tubes affect the cells lining that directly interacts with the embryo. My research will help us better understand how the hormones affect the cells," said Winuthayanon. "I also will be observing changes in the cells lining fallopian tubes during sperm migration, fertilization and embryo development to see if the hormones play a significant role in determining if genes are changed or remain the same."
Winuthayanon will use genetic engineered mouse models to dissect the molecular mechanisms and functional requirement of estrogen and progesterone signals through their classical nuclear receptors. Estrogen binds to its receptor to modulate gene expression within the cell. To understand how the hormones affects the gene expression, Winuthayanon will remove one sex steroid hormone signaling from the models. She will then compare the effect of the deletion of either estrogen or progesterone receptors to see if changes were made to the gene expression.
"If I can understand the fundamental biology of these two hormones in the fallopian tube, I can pinpoint the cause of changes in gene expression that leads to defects in the cell," said Winuthayanon.
Understanding the fundamental knowledge in reproductive biology during early pregnancy will also help determine what factors may play a part in whether an embryo lives or dies. This could potentially lead to targets for contraceptive agents to prevent pregnancy and therapeutic approaches to address infertility.
"My research will identify whether an embryo will die if estrogen or progesterone are not present. If we know exactly what hormone affects what stage of fertilization, we could potentially also use this information to develop contraceptive to prevent fertilization," said Winuthayanon.
