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。这种由发育中的胚胎信号修饰的重塑过程对着床、胎盘的形成和妊娠的维持至关重要。子宫组织不能对卵巢激素或胚胎作出适当的反应，导致胎盘缺陷，与一系列妊娠障碍有关。这些疾病是孕产妇和围产期发病率和死亡率的主要原因。除了对子宫内膜结构的影响外，P4、E2和胚胎也调节其功能；例如，在黄体溶解和分娩过程中，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，防止过早发生黄体溶解。然而，P4的作用机制尚不清楚，因为P4在体外下调OTR是有问题的。提出的工作的第一个主要目的是了解P4在奶牛子宫内膜中的作用机制。将阐明不同子宫内膜细胞类型中参与OTR调节的多种受体、共激活因子和抑制因子之间的相互作用。第二个研究领域将检查子宫内膜上皮细胞分泌的两种蛋白质，MIF和可溶性e -钙粘蛋白的调节和作用。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是维持奶牛妊娠的胚胎信号。据推测，它们在植入前的组织重塑中起作用。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需的胚胎与子宫的相互作用提供重要的基础信息。在养牛业中，这可能会导致提高怀孕率的方法，这将为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有关，并有助于更好地了解分娩和减少早期胚胎丢失。

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.