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Cutting Edge
University of Maine Research on the Frontiers of Science
Progesterone and Pregnancy
Where do babies come from? In a series of experiments with ovarian cells and hormones, a UMaine 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. Her research focuses on progesterone, a hormone 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 says.
After ovulation, the ovarian cells that 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. 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 ability to make progesterone is blocked, the uterine lining will shed. The embryo will abort. This is pretty much true in all mammals."
In addition, 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 made a big step in understanding how the ovary differentiates."
Since human ovaries are not available for research purposes, Lavoie relies on those of pigs. Porcine and human ovaries produce progesterone in a similar fashion. 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.
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.
Detecting Pesticides
Donna Eash, a Ph.D. candidate in the Department of Food Science and Human Nutrition, likes a good challenge. Rock climbing and skiing are two of her current passions. And through her research, she has tackled the intricacies of a demanding new process for detecting pesticides in food and water.
In the past four years, Eash has mastered the techniques of capillary electrophoresis (CE) in collaboration with her advisor, Professor Rodney Bushway.
Eash, a native of the Manchester, N.H. area, became the department's resident expert on the process that is now used in the pharmaceutical, medical and food processing industries. CE offers analytical chemists an alternative to other standard techniques. It uses small sample volumes and avoids toxic organic solvents that can pose a waste disposal problem with other methods.
"The biggest challenge for me has been learning to be patient," she says. "This is relatively new technology, and no one here had used it when the machine arrived four years ago. After the representative from Hewlett Packard set up the machine and gave us the instructions, we had to learn it from the ground up - the theory, the methods, the software, everything."
She admits that on some days, she went home feeling frustrated that the steps she was following weren't working out. "I just had to get over it and come back the next morning and start over," she says.
Eventually, Eash developed and verified new methods to detect hexazinone, known commercially as Velpar, an herbicide which is used in Maine on blueberry barrens and transportation corridors. Velpar has been detected in very low concentrations in drinking water wells and groundwater in Maine.
Other pesticides for which she worked out analytical methods include thiabendazole and malic hydrazide.
Being able to use the latest technology in pesticide detection gives Eash a marketable skill, she says. Her job search includes companies and government agencies, including the FBI, all on the East Coast. Prior to coming to UMaine, she worked as a medical technologist for Concord Hospital in New Hampshire. She received her bachelor's degree from the University of New Hampshire in medical technology, and while she was working full time, she pursued her master's degree in clinical laboratory sciences from the University of Massachusetts-Lowell.
"When I attended UMass-Lowell, I worked on oryzanol levels in rice oil. That sparked my interest in a career in the food industry and sharpened my skills in chromatography," she says. "I was looking at Ph.D. programs around the country, and working with Dr. Bushway was the most attractive option for me. I feel so lucky to have him as an advisor. He has supported my travel to conferences to present the results of my research, and he has always insisted that if I did the work and wrote the paper, my name was first as the author."
Eash has also provided assistance to other faculty and students in the department. For example she worked with a master's student on analyzing levels of tri-poly-phosphate in processed lobsters.
Eash has published her work in four peer reviewed journals: the Journal of Agricultural and Food Chemistry, Journal of High Performance and Liquid Chromatography, Journal of Chromatography, and Journal of the AOAC International.