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. Implantation per se is a complex and poorly understood reproductive process regulated by many factors including the ovarian steroids. It is possible that steroid-specific and/or stage- specific macromolecules play a key role in the establishment and maintenance of pregnancy. Thus, these macromolecules could potentially serve as markers for a uterus that is receptive to the implanting embryo. The overall objective of this proposal is to determine the regulation of previously identified proteins i.e., retinol binding protein (RBP) and insulin-like growth factor binding protein-1 (IGFBP-1), and two additional groups of P and hCG regulated proteins (Mr 40,000 and Mr 27,000-30,000) between days 7 and 14 post-ovulation (PO) in the pregnant and non-pregnant baboon uterus. Since our previous studies have shown that RBP and IGFBP-1 are regulated in a cell - and stage specific manner between 18 and 32 days PO, the proposed studies in the first specific aim will determine the biochemical, immunological and molecular regulation of these uterine proteins during the period of implantation in the baboon. The second specific aim will determine the effects of ovarian hyperstimulation by exogenous hormones and post-ovulatory inhibition of estrogen action on the expression of these macromolecules during implantation. finally, since growth factors are thought to regulate the action of ovarian steroids via paracrine and/or autocrine actions we propose to study the expression of insulin-like factor and epidermal growth factors and their respective receptors during implantation. The ultimate goal of these studies is to identify and biological significance of 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 contraception.
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