Animal scientists and physicians team up to treat polycystic ovary disease

Feb. 20, 2007

A long established team of researchers trying to cure polycystic ovary syndrome in women has recently hit upon some major discoveries.

In one finding, published in the journal Reproductive Toxicology, University of Wisconsin-Madison researchers David Abbott and Daniel Dumesic report that the drug pioglitazone improves insulin action and normalizes menstrual cycles in a majority of female rhesus monkeys with PCOS. This work done at the Wisconsin National Primate Research Center is key, the scientists say, because it proves the importance of using this species as a successful model for treating PCOS in women.

"We hear from physicians all the time that knowledge gained from the nonhuman primate is helping them to better understand the disorder in their patients," Abbott said.

PCOS is the leading cause of infertility in women and can present a variety of additional life-disrupting symptoms, including diabetes, irregular menstrual cycles, abdominal obesity, excess body hair, and depression. Women—and monkeys—with PCOS typically show a cluster of small follicles under the surface of the ovaries, giving the syndrome its other name, "ring of pearls" syndrome. Given a 6.6% estimated prevalence of PCOS in reproductive-aged women in the United States—at least 4 million affected women—the annual economic burden of PCOS is at least $4.37 billion. Of that total, $1.35 billion and $0.53 billion are for treating menstrual dysfunction and infertility, respectively. And that doesn’t even take into consideration the greater frequency of pregnancy-related complications, including gestational diabetes, preeclampsia and miscarriage.

Pioglitazone, pronounced "pie-o-glitta-zone", is used to treat Type II diabetes. The drug is also being researched as a possible treatment for Parkinson’s disease at the Primate Center. Taken orally, it has anti-inflammatory properties, protects against oxidative stress, and has no major side effects.

Abbott and Dumesic, both Primate Center and School of Medicine and Public Health Ob/Gyn researchers, also reported in the Journal of Clinical Endocrinology and Metabolism last month a new finding of abnormal gene expression in eggs obtained from PCOS women undergoing in vitro fertilization (IVF). Again, this work was closely linked to their monkey studies.

Abbott and Dumesic together discovered the fetal origins of PCOS in the 1990s, namely that female rhesus monkeys exposed to testosterone excess during fetal life developed PCOS in adulthood. In this decade, they found that involving the now-adult PCOS monkeys in IVF caused them to produce abnormal eggs.

Having gained these key insights into compromised PCOS fertility from the development of their nonhuman primate model, Dumesic and Abbott then initiated a collaborative study with Jennifer Wood in the Department of Animal Science at the University of Nebraska in Lincoln, and Jerome Strauss III in the Department of Ob/Gyn at the Virginia Commonwealth University in Richmond.

The new team this year investigated whether abnormal gene expression in the eggs of women with PCOS might be what is contributing to their infertility. In the Journal of Clinical Endocrinology and Metabolism paper, the collaborative team, led by Wood and Dumesic, show that eggs obtained from women with PCOS who underwent IVF treatment demonstrated abnormal gene expression that could contribute to poor pregnancy outcome. The findings are particularly relevant since a subset of the abnormally expressed genes is responsible for chromosome alignment during egg maturation, fertilization and early embryo development. The eggs were otherwise indistinguishable from those of normal women. The gene findings also provided the team with insight into potential therapeutic strategies that may normalize aberrant egg development in PCOS women and thus improve pregnancy outcome.

References:

Zhou R, Bruns CM, Bird IM, Kemnitz JW, Goodfriend TL, Dumesic DA, Abbott DH. Pioglitazone improves insulin action and normalizes menstrual cycles in a majority of prenatally androgenized female rhesus monkeys. Reprod Toxicol. 2007 Jan 14; [Epub ahead of print]

Wood JR, Dumesic DA, Abbott DH, Strauss JF 3rd. Molecular abnormalities in oocytes from women with polycystic ovary syndrome revealed by microarray analysis. J Clin Endocrinol Metab. 2007 Feb;92(2):705-13. Epub 2006 Dec 5.

For more information, contact:
(608) 263-3583
(608) 263-1217

J. Lenon