The mammalian uterus is essential for reproduction because it maintains the fertilized ovum, provides an environment suitable for implantation and sustains the conceptus during early embryonic development and throughout gestation. One of the factors that may be critical to these early events in the normal reproductive process are the specific substances synthesized by the endometrial glands within the uterus and subsequently released into the uterine lumen. The morphology and the secretory activity of the uterine endometrium are regulated by the cyclic changes in ovarian steroids during the menstrual cycle. The objectives of this study are 1) to identify and purify the specific secretory substances synthesized and released by the uterine endometrium, 2) to prepare antibodies against these components and immunologically demonstrate their presence in uterine fluid, culture media and tissue processed for histology, 3) to study the hormonal control of the synthesis and release of these substances, and 4) to ultimately determine their biological function. To accomplish these goals we have proposed comparative morphological and biochemical studies of the tissues and fluids of both the human and baboon uterus. Uterine fluids will be obtained from both humans and baboons using a specially designed flushing cannula. Uterine flushings from baboons will be collected on alternate days of the cycle during the menstrual cycle and artificially induced cycles in ovariectomized animals. Uterine flushings from humans will be obtained on the day of scheduled surgery and prior to obtaining an endometrial biopsy. Endometrial tissue obtained either by biopsy (humans) or at hysterectomy (baboons) will then be minced and placed in organ culture in the presence of radioactively labelled amino acids and sugars under defined conditions for 24 hours. Flushings, culture media and tissue homogenates will be analyzed by one- and two-dimensional gel electrophoresis followed by fluorography where appropriate, to identify uterine specific proteins. Various chromatographic procedures will be utilized to further identify and purify these uterine specific proteins. Morphological differences in secretory granules and secretory cells during the normal menstrual cycle and artificially induced cycles will be assessed by transmission electron microscopy. These studies would enable me to identify the hormonal control of synthesis and release of uterine specific product(s), which is prerequisite for future studies relating to biological functions. This data should provide basic information on the physiology of the primate uterus and should be helpful to clinicians as they attempt to deal knowledgeably with uterine factors in infertility, and as they attempt to improve the success rate during ovulation induction, in vitro fertilization and embryo transfer.
