The research proposed here represents an attempt to utilize genetic and biochemical approaches to study maternal-fetal interactions. We have focussed our efforts on adenosine deaminase (ADA) a key enzyme in purine metabolism, which is expressed in two overlapping phases during gestation in mice. In the first phase, ADA enzyme activity increases over one- hundred fold in the antimesometrial decidua daring the early postimplantation stages of gestation and by 9 days postcoitum is a major gene product of this maternal tissue. The second phase of ADA expression is associated with the development of the chorioallantoic placenta where high concentrations of ADA are present until term. Major goals of the proposed research are to identify and characterize the genetic signaling pathways that target high level expression of ADA to the maternal cells of the antimesometrial decidua and the fetal derived trophoblasts of the chorioallantoic placenta. Additional major goals are to determine the physiological role for ADA in decidual cells of the uterine stroma and in trophoblasts of the chorioallantoic placenta. Overall, the proposed research should lead to a better understanding of the genetic control and biological function of ADA in maternal-fetal interactions. Furthermore, the ADA gene regulatory signals identified as a result of research proposed here will make it possible to use transgenic mouse technologies to genetically target high level expression of any desired gene to the antimesometrial decidua and/or chorioallantoic placenta, thereby providing significant new investigative opportunities in maternal-fetal biology.
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