Pigs help study of links between polycystic ovary syndrome, obesity, cardiovascular disease and diabetes

Despite the exaggerated, wrinkly snout and long, coarse, spiky hair reminiscent of the 1980s television space alien ALF, some very special swine are helping researchers at Purdue and Indiana universities understand human infertility, diabetes and cardiovascular disease.

In addition to their odd appearance, these Ossabaw pigs are predisposed to metabolic syndrome. The disease includes a host of health problems, including obesity, insulin resistance leading to Type 2 (mellitus/adult-onset diabetes), hypertension, artery-clogging bad cholesterol and triglycerides, and abnormally high blood clotting. Many of these same features are characteristic of polycystic ovary syndrome, an illness that leads to infertility in 5 percent to 10 percent of reproductive-age women.

Rebecca Krisher, a Purdue developmental and reproductive biologist, is studying the Ossabaws to determine if they also embody all of the metabolic and reproductive aspects of polycystic ovary syndrome (PCOS). If further research confirms the preliminary finding that this swine breed exhibits PCOS, it could lead to a cure for that type of infertility and related diseases, Krisher said.

Currently there is no research model for polycystic ovary syndrome, and the IU/Purdue Ossabaw herd is the only breeding group of this species, which scientists rescued from a South Carolina coastal island.

Krisher's colleagues at Indiana University Medical School, led by Michael Sturek, are studying links between polycystic ovary syndrome, obesity, cardiovascular disease and diabetes.

"PCOS is one of the leading causes of infertility in women, and it's exacerbated by obesity, which is rampant in this country," Krisher said. "Women with PCOS often have metabolic syndrome and obesity, so they are seven times more likely to have cardiovascular disease than a healthy female.

"If we could figure out how to successfully cure PCOS, then not only could we alleviate a common form of infertility, but we also may be able to prevent cardiovascular disease in many women."

Eighteen reproductively mature female pigs will be used in the study. The animals will be divided into two treatment groups. One group will include nine Ossabaw pigs fed a normal swine diet. The other group will have nine Ossabaw pigs fed an unlimited high-fat and high-sugar diet.

The researchers will study all aspects of PCOS-induced infertility, including hormones and metabolism, egg viability and development, and ovary cycles.

"Two or three times a week, using ultrasound, we'll look at the ovaries of reproductively mature pigs to check follicle growth and development and see if they become cystic," Krisher said.

The pigs' estrus cycle will be monitored as one way to determine if the animals are experiencing PCOS, since one syndrome characteristic is very irregular cycle lengths. In addition, egg quality will be studied by using sperm from male Ossabaws for in vitro fertilization.

"Ossabaw pigs are such good models for human diseases because they can exhibit all these metabolic and cardiovascular abnormalities due to their diet," Krisher said. "If it turns out they characterize PCOS also, that will be a bonus."

After the initial study of reproductive hormone metabolism, Purdue and IU researchers will study the Ossabaws' reproductive systems in more detail. They also will further investigate cardiovascular functioning and metabolism of such energy-related hormones as leptin and adiponectin associated with obesity and diabetes. The researchers already know that diabetes changes muscle condition. In turn, diabetic condition is worsened because the muscle can't use as much energy, a process that normally would lower glucose levels and mitigate diabetes processes.

This research is part of the Center for Comparative Medicine, a collaborative effort among IU Medical School and Purdue's Department of Animal Sciences and School of Veterinary Medicine. The Indiana University/Purdue University Collaboration in Biomedical Research Pilot Grant Program- 2nd Round (CBR2) is providing funding for this study.