This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The superfamily of UDP-glucuronosyl transferase (UGT) enzymes are critical for the metabolic clearance of most biological substances including chemicals, hormones, dietary drugs and environmental chemicals. They regulate the levels of these compounds by degrading them. We have previously demonstrated that UGTs play an important role in human reproduction. During the first trimester of pregnancy, total UGT activity in the human placenta is equal to or greater than that found in the liver of adults. This incredibly high rate of activity in the placenta suggests that some isoforms in the superfamily play key roles in pregnancy and human development. Two sub-families exist: UGT1A and UGT2B and we have previously demonstrated that UGT2B isoforms are present in relatively low levels and static. On the other hand, UGT1A levels are higher and dynamic during pregnancy. Taken together, these facts strongly support that UGT enzymes, especially those in the UGTA1 subfamily, are important in pregnancy and fetal development. However, their precise role in this process remains unclear. The major goal of this Project is to understand the role of UGT enzymes in normal pregnancy. This will be accomplished by testing UGT levels in normal and abnormal human placentas. We will also determine how UGT alters steroid metabolism in assisted reproductive technologies using the mouse as a model.
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