Successful embryonic development within the female reproductive tract requires the generation of a specialized maternal structure, the decidua. Decidual cells are located at the interface separating invading trophoblast cells from the maternal environment and represent the initial maternal response and adaptation to intrauterine embryonic development. Decidual cells contribute to the establishment and maintenance of pregnancy through their production of secretory products related to anterior pituitary prolactin (PRL). Failure of normal decidual cell maturation may result in early pregnancy loss, uncontrolled trophoblast cell growth and invasion, immunologic rejection of the embryo, embryonic growth retardation or embryonic/fetal death. The overall objective of this research is to understand the involvement of the decidual cell signaling system in the establishment and maintenance of pregnancy. The proposal focuses on decidual signals related to pituitary PRL. This hormone has been implicated in directing the early changes in ovarian and uterine function required for the establishment of pregnancy. Our understanding of the role of this hormone in the establishment of pregnancy has been hindered because an animal model has not been adequately developed. We propose to remedy this situation by establishing the rat as a model for the study of decidual cell signaling.
Specific aims for this proposal include: 1) generation and characterization of recombinant decidual PRL-related protein (dPRP), 2) examination of the distribution of the dPRP in decidual tissues, 3) examination of the biological actions of the dPRP, and 4) characterization of the control of dPRP gene expression. The experiments are directed toward evaluating the nature of the signaling between the decidua and the corpus luteum and between the decidua and the developing placenta. The experimentation utilizes molecular biology, protein chemistry, immunochemistry, and various cell biology and cell culture techniques. The investigation promises to further our understanding of cellular and molecular processes involved in the establishment of pregnancy and our understanding of the chemistry and biology of an important class of regulatory hormones, PRLs. Availability of this knowledge will make possible the development of therapeutic strategies for effectively controlling the establishment of pregnancy.
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