The potential of the human decidua/fetal membrane system as an accessible autocrine/paracrine model will be further explored, in order to elucidate the role of relaxins in the local control of collagenolysis and the rupture of the fetal membranes at parturition. An added challenge is our finding that the second human relaxin gene (H1) is expressed in this system. This will be accomplished by studying the four components of the relaxin system: gene expression, control of secretion, biological effects and receptor distribution. Relaxin H1 and H2 gene expression and the translated products, will be identified in the endometrium/decidua, fetal membranes and placenta with specific riboprobes and antibodies throughout the cycle and pregnancy. The effect on decidual cell relaxin secretion and the mRNA levels for relaxins by a range of decidual and placental hormones will be studied in in vitro. The biological effects of human relaxin H2 on fetal membrane/decidual production of key collagenolytic enzymes and inhibitors will be sought both in vitro and in vivo. Changes in the concentration of relaxin receptors in intrauterine tissues will be studied through the cycle and gestation by quantitative autoradiography and the results related to those from the experiments above. The combined results will provide insights into significant problems, the local control of the accommodation of the fetal membranes to the growing fetus in the last weeks of pregnancy, and the timing of normal spontaneous membrane rupture. These studies will lead to a greater understanding of premature rupture of the fetal membranes, a major cause of premature birth which results in infants with a high incidence of neurodevelopmental impairment.
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