Inflammation. It is a word usually associated with illness and infection but is actually a crucial step in mammalian pregnancy. During pregnancy, a fertilized egg, or blastocyst, must attach itself to the wall of the uterus. Inflammation is necessary for this implantation to take place, yet it is also an indication of the body’s attempt to reject the blastocyst as a foreign object since it carries unfamiliar paternal genetic information. In fact, implantation failure is the cause of 75 percent of failed pregnancies in humans. So why does this seemingly paradoxical inflammation occur at all?
Researchers at Yale, led by Dr. Günter Wagner of the Department of Ecology and Evolutionary Biology, have found evidence showing that this inflammatory response to embryo attachment is an evolutionary remnant from the very first mammals that gave birth to live young. Humans are eutherians, an infraclass of mammals characterized by the development of a placenta in the uterus, which provides nourishment to the fetus during pregnancy. In eutherians, the uterus eventually switches to an anti-inflammatory state after embryo attachment in order to allow pregnancy to continue. Marsupials, another infraclass of mammals that gives birth to live young, also develop placentas, but instead give birth soon after inflammation and embryo attachment. Since reproduction in marsupials shares many similarities to that of monotremes, the infraclass of mammals characterized by egg-laying, researchers in Wagner’s lab hoped that studying marsupial pregnancies would offer insight into the reproductive processes of the first mammals to give birth to live young. By extension, they also sought to understand the process from which eutherian pregnancy likely evolved.
In order to do this, researchers in Dr. Wagner’s lab used the grey short-tailed opossum, Monodelphis domestica, as a model to study changes in gene expression during marsupial pregnancy. After identifying some key proteins that are expressed at distinct points during the marsupial reproductive process (before pregnancy, before embryo attachment, and after embryo attachment), researchers compared this pattern of gene expression to that of eutherian pregnancies and found many similarities. This was done largely through transcriptomic analysis, the study of RNA transcripts in a cell or tissue of interest, and polymerase chain reaction (PCR), an alternative way to quantify gene expression.
Dr. Wagner foresees the greatest implications of his research being the development and improvement of assisted reproductive technologies. One of the most common complications of in vitro fertilization, for example, is implantation failure after the embryo is introduced to the uterus. Scientists have discovered that scratching of the inner lining of the uterus induces inflammation, dramatically increasing implantation rates. “You can try to understand things by taking it apart, which is the normal way of how experimental biologists go about,” Wagner said, “but if the things are really complicated, it becomes more and more difficult to understand how they work. In this context, it can be really advantageous to know how the thing was put together.”