The mammalian uterus is essential for reproduction because it sustains the fertilized ovum, provides an environment suitable for implantation and nurtures the conceptus during early embryonic development and throughout gestation. Our broad objective is to study the interaction between the developing conceptus and the uterine endometrium and to determine the regulatory role of steroid-induced endometrial proteins on maternal/conceptus interactions in the non-human primate. Specifically this proposal seeks to; 1) utilize immunological and molecular probes to determine the hormonal regulation of an estrogen-induced protein (M 33,000; pI 7.6) and a basic protein (M 40,000) induced by progesterone, 2) develop ovulation induction protocols in baboons in order to obtain a sufficient number of pre-implantation conceptuses, and to also evaluate whether exogenous hormones alter endometrial secretory activity, 3) biochemically and immunologically identify changes in conceptus secretory activity prior to, and during the process of implantation, 4) characterize the alterations in tissue specific gene expression of an insulin-like growth factor binding protein during conceptus attachment and implantation, and 5) determine the interaction between insulin-like growth factors and their binding proteins in the uterus during the menstrual cycle and early pregnancy. Morphological changes will be assessed by light and electron microscopy and the localization of tissue-specific, hormonally regulated proteins will be accomplished by immunocytochemistry. Secretory activity will be monitored by analyzing organ culture media containing radioactively labelled proteins on 1 and 2 dimensional polyacrylamide gels followed by fluorography. Synthesis will be confirmed by immunological analysis of the media by immunoprecipitation and Western blots. CDNA probes to hormonally regulated proteins of interest will be used to study regulation at the molecular levels by analysis of RNA on dot and Northern blots and in-situ hybridization. The ultimate goal of these studies is to identify the biological significance of conceptus and endometrial proteins in ensuring successful implantation and pregnancy. The data from the proposed studies should provide basic information on the physiology of the primate uterus and help improve our knowledge relating to implantation. These studies should be helpful to clinicians as they attempt to deal knowledgeably with the full spectrum of the reproductive process, namely conception, infertility and contraction.
