regulation of bovine endometrial function during the estrous cycle and early pregnacy

卵巢激素雌二醇(E2)和孕酮(P4)控制着子宫细胞的有序生长和分化。这个被发育中的胚胎信号改变的重塑过程，对于着床、胎盘的形成和妊娠的维持是至关重要的。子宫组织不能对卵巢激素或胚胎做出适当的反应会导致胎盘缺陷，这与一系列妊娠障碍有关。这些疾病是孕产妇和围产儿发病率和死亡率的主要原因。这些疾病及其对子宫内膜、P4、E2和胚胎结构的影响也调节其功能；例如，在黄体溶解和分娩期间，前列腺素合成和催产素受体(OTR)。在体内，黄体期产生的P4下调OTR，防止黄体过早溶解。然而，由于P4在体外对OTR的下调是有问题的，所以涉及到P4作用的机制还不清楚。这项拟议工作的第一个主要目标是了解P4在奶牛子宫内膜中的作用机制。不同细胞类型的子宫内膜中多种受体、共激活物和抑制物之间的相互作用将被阐明。第二个研究领域将研究子宫内膜上皮细胞分泌的两种蛋白质MIF和可溶性E-钙粘附素的调节和作用。我之前已经证明，这些蛋白质的分泌是由干扰素-tau刺激的，干扰素-tau是负责维持奶牛怀孕的胚胎信号。据推测，它们在植入前的组织重塑中发挥了作用。这项工作的意义在于它将为P4在子宫内膜中的作用以及着床所必需的胚胎和子宫之间的相互作用提供重要的基础信息。在养牛业，这可能会带来提高怀孕率的方法，这将给加拿大带来巨大的经济利益。这项工作的结果也可能与人类健康相关，并导致更好地理解分娩和减少早期胚胎损失。

The ovarian hormones estradiol (E2) and progesterone (P4) control the ordered growth and differentiation of uterine cells. This remodeling process, which is modified by signals from the developing embryo, is critical for implantation, the formation of the placenta, and maintenance of pregnancy. Failure of uterine tissues to respond appropriately to ovarian hormones or the embryo results in defective placentation, associated with a spectrum of pregnancy disorders. These disorders are a major cause of maternal and perinatal morbidity and mortality.  As well as their effects on the structure of the endometrium, P4, E2 & the embryo also regulate its function; for example, prostaglandin synthesis and the oxytocin receptor (OTR) during luteolysis and parturition. In vivo, the P4 produced during the luteal phase down regulates the OTR and prevents luteolysis from occurring too soon. However, the mechanisms involved in the action of P4 are not understood since downregulation of OTR by P4 in vitro is problematic. The first main objective of the proposed work is to understand the mechanisms of action of P4 in the endometrium of the cow. The interaction between multiple receptors, coactivators, and repressors within the different cell types of the endometrium involved in the regulation of OTR will be elucidated. The second area of research will examine the regulation and the action of two proteins, MIF and soluble E-cadherin, secreted from the endometrial epithelial cells. I have previously shown that secretion of these proteins is stimulated by interferon-tau, the embryonic signal responsible for the maintenance of pregnancy in the cow. It is hypothesized that they play a role in tissue remodeling prior to implantation. The significance of this work is that it will provide important basic information on the action of P4 in the endometrium and on interaction between the embryo and uterus necessary for implantation. In the cattle industry this could lead to ways of improving pregnancy rates, which will be of great economic benefit to Canada. The results of this work could also be relevant to human health and lead to a better understanding of parturition and a decrease in early embryonic loss.