Women’s infertility may be due to genetic uptick in male hormones

If an ovarian cell carries a certain genetic variant it could spell an excess of androgens much like testosterone in women with polycystic ovary syndrome (PCOS), making it more difficult for them to conceive. This revelation could eventually lead to a diagnostic test and treatment, according to an announcement yesterday from the National Institutes of Health (NIH).

PCOS affects an estimated 5 to 7 percent of women in their reproductive years and with the diagnosis comes a list of possible comorbidities including type 2 diabetes, heart disease and high blood pressure, as well as cosmetic effects such as excess body hair and acne.

“PCOS is a major cause of female infertility and is associated with other serious health problems,” said Louis V. De Paolo, PhD, chief of fertility and infertility research at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, in a statement. “In identifying this gene, the study authors have uncovered a promising new lead in the long search for more effective ways to diagnose and treat the condition, and perhaps, to one day prevent it from even occurring.”

The Eunice Kennedy Shriver National Institute of Child Health and Human Development bankrolled the study and M. McAllister, PhD, a professor of pathology, obstetrics and gynecology, and cellular and molecular physiology in the Penn State College of Medicine, Hershey, Pa., and colleagues published their findings in the Proceedings of the National Academy of Sciences earlier this year.

The gene, called DENND1A, is housed in theca cells and given the responsibility of providing all the genetic information needed to produce a protein within these cells that will then line the inside surface of the follicle. The researchers suggested that PCOS arises out of a network of genetic links and perhaps environmental exposure. This is supported by previous genome-wide studies of women.

The researchers developed live theca cells from PCOS patients in the lab and then compared these with theca cells from women with PCOS and high levels of the variant DENNDA1A.V2. As a result of further experiments, they were able to reproduce the conditions needed for DENNDA1A.V2 to overproduce these androgens. This variant is also present in other reproductive organs such as the testes, and can be found in a form of adrenal cancer cells. Urine samples revealed higher messenger RNA for DENNDA1A.V2 in those women with PCOS than controls.

“PCOS is often difficult to diagnose, especially in adolescents,” added McAllister. “The fact that DENND1A.V2 is present in urine opens up the possibility that it might provide the basis for a test to screen for PCOS.”

Futher genetic testing is needing to fully elucidate the connection between PCOS and infertility before a diagnostic test could be made available for clinical use.