March 10, 2014
Endometriosis Cause And Development Linked To Unstudied Genes
Rebekah Eliason for redOrbit.com – Your Universe Online
A study from Northwestern Medicine has led to a new theory regarding the development and cause of endometriosis. The chronically painful disease, which affects 1 in 10 women, has been linked to two previously unstudied genes.
Matthew Dyson, research assistant professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine, along with Serdar Bulun, MD, chair of obstetrics and gynecology at Feinberg and Northwestern Memorial Hospital, were able to recognize a novel role for a family of key gene regulators found in the uterus.
"Until now, the scientific community was looking for a genetic mutation to explain endometriosis," said Bulun, a member of the Center for Genetic Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "This is the first conclusive demonstration that the disease develops as a result of alterations in the epigenetic landscape and not from classical genetic mutations."
Heather C. Guidone, Surgical Program Director at The Center for Endometriosis Care explains that, “Endometriosis results when tissue similar to that which lines the uterus grows in other areas of the body. The persistent survival of these cells results in chronic pelvic pain, organ dysfunction, infertility and more. Although the cause of the disease has remained unknown on a cellular level, there have been several different models established to explain its development.”
Since endometriosis is only found in menstruating primates, it is likely that the unique evolution of uterine development and menstruation are connected with the disease. Retrograde menstruation, the movement of cells up the fallopian tubes and into the pelvis, has long been considered by scientists as a probable cause of endometriosis. Since most women experience retrograde menstruation at some point, this model fails to explain why only ten percent of women develop the disease. In addition, this theory is insufficient at explaining instances where endometriosis arises independent of menstruation.
Bulun and Dyson theorize that there is an epigenetic switch that allows the expression of the genetic receptor GATA6 instead of GATA2. This results in progesterone resistance leading to development of the disease.
"We believe an overwhelming number of these altered cells reach the lining of the abdominal cavity, survive and grow," Bulun said. "These findings could someday lead to the first noninvasive test for endometriosis."
Bulun hopes that one day clinicians could prevent the disease by placing teenagers predisposed to this epigenetic change on a birth control pill regimen.
In further research, Dyson intends to investigate the epigenetic fingerprint that results from the presence of GATA6 instead of GATA2 and use the information as a potential diagnostic tool since such epigenetic differences are readily detectable.
"These findings have the potential to shift how we view and treat the disease moving forward," Bulun said. This study was published in PLoS Genetics.