The Fetus as a Foreign Object by Yolanda Cruz
Related Links: • Biology Department's Home Page • Yolanda Cruz's Home Page		APRIL 2, 2003--For the past three years, I have been investigating the role of a protein, dubbed Early Pregnancy Factor (EPF), in mammals. EPF ensures that the pregnant mother is physiologically "in sync" with her embryo. Perhaps because humans, like most other mammals, give birth to babies instead of laying eggs that hatch into babies, we do not usually think about how anomalous pregnancy really is as a method of reproduction. Pregnancy violates a body's tenets of immunity; a fetus is by definition an alien tissue within its mother and should be rejected, just as a patient rejects a grafted organ from an incompatible donor. Because a fetus is not entirely maternal in origin (it has a father, and so has the ability to make father-originated proteins, which mark it as "alien"), it's long been thought that some metabolic adjustment occurs during pregnancy to prevent the maternal immune system from rejecting the fetus. In past experiments, my coworkers and I observed that the white blood cells of pregnant mice were somehow disabled from doing their normal job of protecting the mother from "foreign elements." This caused us to hypothesize that a specific protein was playing a role in suppressing the maternal immune system, thus making pregnancy possible.
Cruz holds one of her test subjects, a Brazilian gray oppossum.		Although we know that EPF helps suppress the immune system's regular functions, we do not understand the mechanics behind its action. It has been difficult to evaluate EPF action because pregnancy involves dramatic hormonal changes that alter maternal physiology. What we do know from our research is that EPF almost certainly attaches to the surface of white blood cells, disabling them from their normal task of protecting pregnant mammals from foreign elements. To take our research further, we will need to discover the specific molecule to which EPF binds on white blood cell surfaces. Because my colleagues and I suspect that the hormonal changes that occur during pregnancy generate a "background noise" that can mask EPF action, my students and I use an unusual animal model system for studying EPF. Instead of the more commonly used laboratory mammals, we use laboratory opossums in our work. These marsupial mammals, like their more familiar relatives (kangaroos, koalas, and Tasmanian devils), do not undergo the remarkable hormonal shifts that otherwise characterize pregnancy. We can thus study EPF in these animals without having to deal with the confounding effects of hormonal changes during pregnancy. Using a mammal that does not undergo hormonal changes during pregnancy eliminates the possibility that these hormonal changes are protecting a mother from her fetus during pregnancy. Any chemical changes we note in our test subjects can be attributed to the activity of EPF. We expect our work to have practical applications in the study of immunoregulation--or, how a mammal's immune function adjusts during pregnancy--as well as in the study of contraception and pregnancy detection. Because EPF has been discovered by others to have clinical uses as an immunosuppressant, our work may also have implications for treating autoimmune disorders. For example, EPF has been found to ameliorate the effects of a condition similar to multiple sclerosis in lab rats and mice, without the negative side effects that other drugs can cause. EPF also has been detected in the blood in certain kinds of cancers, so it has possible uses in cancer detection and diagnosis.
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