September 20, 2005

Research may help with problem pregnancies

by K.C. Jaehnig


CARBONDALE, Ill. -- A reproductive physiologist from Southern Illinois University Carbondale has received a $1.1 million grant from the National Institutes of Health that will help him look more closely at what happens in a mother's womb shortly after an embryo attaches itself there.

"The uterus has to provide an environment where the embryo can survive and thrive," said Brent M. Bany, an assistant professor in the School of Medicine's Carbondale campus.

"It has always been assumed that the embryo and the uterus do their things independently under some kind of automatic program, but my take is that the embryo takes a more active role in directing the environment that the uterus provides."

Bany focuses on molecular interactions that take place in the brief span between the time the newly conceived embryo implants itself in the uterine wall and the time in which the mature placenta develops. Researchers are beginning to suspect that problems here may trigger later difficulties in pregnancy, such as preeclampsia, a severe form of high blood pressure that sometimes kills both mother and baby.

"Some forms of female infertility may also be linked to abnormalities in these interactions," Bany said.

Based on some earlier work, Bany thinks the embryo may influence, perhaps through hormonal signaling, changes that take place in the uterine lining, or endometrium, after the embryo burrows in. When pregnancy does not occur, that lining breaks down, becoming just so much uterine litter disposed of in monthly periods. But with an embryo attached, the lining develops new blood vessels, while old ones get revamped. Bany also thinks the embryo acts to keep the mother's immune system from rejecting it.

"One of the amazing things about early pregnancy is that a fetus carries maternal and paternal genes," Bany said.

"These genes are made into proteins, so the genes from the father are expressing antigens (a substance that spurs the body to produce antibodies to fight off the invader) that are foreign to the mother. This means the fetus can be considered a somewhat foreign body."

Over the project's next five years, Bany will try to determine whether certain embryonic cells put some of the genes in the endometrium to work on building new blood vessels and remodeling those that already exist there.

"The cells that make up the placenta are all from the fetus, and there's one group of ‘giant cells' that stands out here," Bany said.

"These giant cells are in direct contact with the endometrium. We eventually want to identify molecules that are released from the placenta or fetus that then cause changes in endometrial gene expression (the process that converts a gene's information into proteins inside the cells). My feeling is that molecules secreted from these giant cells will be involved as they are closest to the mother."

Knowledge about how the process normally works will give future researchers studying problem pregnancies a kind of roadmap that will help them pinpoint where things went wrong.

Bany also will study a special kind of white blood cell that plays a key role in the immune system. In a newly pregnant woman, large numbers of these cells flock to the site where the embryo has settled in. There, they change in both appearance and function. Scientists are just beginning to understand what they do there. Current knowledge suggests that these "uterine natural killer cells" appear to have a role in altering blood vessels in the endometrium.

"My twist is that we have found that the conceptus (another word for a young embryo) can control uterine natural killer cell numbers and their development in the uterus, though we don't know exactly how it does that," Bany said.

In conducting his research, Bany will use several kinds of mice, pregnant and not. Early mouse embryos are close in size and behavior to their human counterparts and, like human "test-tube babies," also can be conceived in a lab.

"A human is not a mouse, but there are common changes that occur in mammalian uterine gene expression during early pregnancy," Bany said.

Bany also will grow and study giant cells taken from the part of the mouse embryo that becomes the placenta. In addition, he will examine connective tissue cells extracted from the endometria of mice and eventually perhaps of women who have had hysterectomies.

"We are using a multi-faceted approach in this study," he said.

While knowledge gained from this project may someday help scientists assist infertile women or those with problem pregnancies, Bany stressed that he aimed only to add to the store of knowledge about what happens in early pregnancy.

"We look at basic biological processes in their simplest form without a great deal of attention paid to what it might mean in terms of something like drug development for infertility," he said.

"But usually a big medical breakthrough requires this kind of basic research. You need basic knowledge about biological processes before you can develop a treatment or a drug."

Leading in research, scholarly and creative activities is among the goals of Southern at 150: Building Excellence Through Commitment, the blueprint for the development of the University by the time it celebrates its 150th anniversary in 2019.