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Humboldt Field Research Institute

Posted February 23, 1999

Ovarian Cell Study Focuses on Causes of Female Infertility

It's an old and simple question: where do babies come from? In a series of experiments with ovarian cells and hormones, a University of Maine biologist and her colleagues are finding new answers that could shed light on some of the causes and possible treatments of female infertility.

Holly Lavoie, assistant professor in the Department of Biological Sciences, studies the complex interaction of the hormones, ovarian cells and genetic processes that are necessary for successful pregnancy. Lavoie received her Ph.D. at the Medical College of Virginia in 1994 in physiology and before coming to Maine in 1998, she conducted post-doctoral research in reproductive endocrinology at the University of Virginia.

Lavoie also teaches undergraduate biology courses such as Endocrinology, Anatomy and Physiology.

Her research focuses on the production of progesterone, a hormone which is as important to pregnancy as food is to life. “If a woman ovulates and the egg is fertilized by sperm, the dividing embryo wants to implant into the uterus. Without progesterone, that won't happen. Progesterone helps maintain the uterine lining so an embryo can implant,” she explains.

The ovary takes center stage in Lavoie's research because it makes progesterone. After ovulation, the ovarian cells which nourish an egg early in the menstrual cycle shift into another gear to make the critical hormone. This process of change is called differentiation, and infertility can occur if these cells fail to differentiate properly. Problems in this process are linked to at least two forms of infertility, polycystic ovarian syndrome and luteal phase defect.

Scientists do not know how many women experience these conditions, but they are related to other types of infertility and possibly to other health problems as well. For example, many women with polycystic ovarian syndrome experience insulin resistance. In fact, the ovary produces an important protein known as insulin-like growth factor one, nicknamed IGF-1, which has already been shown by Lavoie and many of her colleagues to be one of the keys to proper cell differentiation.

“The ovary goes through phases where it's developing exponentially. Masses of cells are differentiating. So many things in the ovary have to happen at the right time,” says Lavoie. “If this ability to make progesterone is blocked, the uterine lining will shed. The embryo will abort. This is pretty much true in all mammals.”

The ovary is not the only actor in the drama. The pituitary gland plays an important role by producing hormones which ovarian cells use to differentiate. Through her research, Lavoie wants to know how growth factors and hormones produced by both the ovary and the pituitary pave the way for the production of progesterone.

“If we can make a breakthrough in the proteins that are regulated by the ovarian growth factors and how they interact with the proteins regulated by pituitary hormones, then we will have a made a big step in understanding how the ovary differentiates. It's pretty exciting,” she says.

Since human ovaries are not available for research purposes, Lavoie relies on an animal that might seem an unlikely substitute, the pig. It turns out that porcine and human ovaries produce progesterone in a similar fashion.

Maine, however, is not known as a pig producing state, and to get enough pig ovaries for her work, Lavoie travels to a meat packing plant in Moncton, New Brunswick. In slaughter houses, ovaries are considered waste products. Lavoie takes ice chests to the plant and collects up to 100 ovaries at a time as pigs are being butchered.

Back in her lab in Murray Hall, Lavoie isolates ovarian cells and cultures them in order to get what she really wants, the nuclear proteins and RNA.

“I look for proteins that are known to bind certain DNA sequences. Pituitary hormones and ovarian growth factors stimulate proteins to bind to the DNA and turn on genes regulating cell differentiation. Although some of the proteins are known, most are not. So we do a scan. And when you do a scan, you get tons of stuff that supposedly binds to these proteins.

“Whether it's true for the ovarian cell is a different story. That's a very important point. We're trying to say that the ovary regulates this DNA sequence, this gene, in a different way from other cells in the body,” she says.

Lavoie and her colleagues at the University of Virginia Health Sciences Center published two articles in the January, 1999 issue of Endocrinology. The articles describe their work on the hormones and genetic factors that affect the ability of ovarian cells to make progesterone.

Last October, Lavoie submitted a grant proposal for $529,920 to the National Institutes of Health, Ovarian LDL Receptor and StAR Gene Regulation. A decision on that proposal is due this Spring.

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