Prostaglandins and the regulation of female reproductuve function

在过去的20年里，NSERC的资助允许开发几种来自不同动物物种子宫的细胞培养模型，以研究胚胎-母体通信过程中局部涉及的机制，特别是关于母体识别妊娠的机制。在不同物种中，子宫内膜细胞最显着和最保守的特性是它们产生特定前列腺素（PG）的能力。单个细胞内PG的产生可以通过性类固醇、滋养层干扰素（IFNtau）、催产素和血小板活化因子（PAF）来调节。在反刍动物中，由子宫内膜上皮细胞产生的PGF 2 β负责破坏黄体并返回周期。另一方面，PGE 2是抗黄体溶解的，并发挥不同的作用，有利于建立怀孕。在识别妊娠时，胚胎必须调节子宫PG的产生，以防止黄体溶解和返回到新的周期。我们已经发现，在上皮细胞中，基础PGF 2 α的产生被催产素刺激，但被IFN τ转换为PGE 2。在过去的五年中，我们已经确定了牛子宫内膜的功能性PGF合酶作为醛糖还原酶AKR 1B 5，一种具有新功能的旧酶。我们也是第一个提出新发现的PG转运蛋白PGT在生殖系统中PG内分泌作用的人。最后，我们发现PG受体在子宫和黄体中的表达与生物合成和转运蛋白的表达模式密切相关。我们的研究结果导致了一个新的模式，在产妇识别怀孕的PG行动的监管。我们希望利用下一个授予期提供一个新的综合观点PG行动在牛生殖系统。我们将使用在不同生理条件下在体内收集的细胞培养物和组织来研究这些系统。 通过EIA分析PG的产生，通过GC/MS-MS分析由sn-6和ω-3脂肪酸产生的全部PG代谢物。通过真实的时间RT-PCR和北方分析进行信使RNA的表达，通过蛋白质印迹和IHC进行蛋白质水平。

Over the last twenty years, NSERC funding allowed to develop several cell culture models derived from the uterus of different animal species to study the mechanisms involved locally during embryo-maternal communication especially with regard to maternal recognition of pregnancy. Across species, the single most remarkable and best conserved property of endometrial cells is their ability to produce specific prostaglandins (PG). PG production within a single cell can be modulated by sex steroids, trophoblastic interferons (IFNtau), oxytocin and platelet activating factor (PAF). In ruminants, PGF2fÑ produced by the endometrial epithelial cells is responsible for the destruction of the corpus luteum and the return to the cycle. On the other hand, PGE2 is antiluteolytic and plays different roles that favor the establishment of pregnancy. At the time of recognition of pregnancy, the embryo must regulate the production of uterine PGs to prevent luteolysis and the return to a new cycle. We have found that in epithelial cells basal PGF2fÑ production was stimulated by oxytocin but switched to PGE2 by IFNtau. Over the last five years, we have identified the functional PGFsynthase of the bovine endometrium as the aldose reductase AKR1B5, an old enzyme with a new function. We have also been the first to propose a role for the newly discovered PG transporter PGT in endocrine action of PGs in the reproductive system. Finally we have shown that the expression of PG receptors in the uterus and corpus luteum closely matches the pattern of expression of biosynthetic and transport proteins. Our findings lead to a new paradigm for the regulation of PG action during maternal recognition of pregnancy. We want to use the next granting period to provide a novel integrated view of PG action in the bovine reproductive system. We will study these systems using cell cultures and tissues collected in vivo under different physiological conditions.  The production of PGs will be analyzed by EIA and the full array of PG metabolites produced from sn-6 and omega-3 fatty acids by GC/MS-MS. Expression of messenger RNA will be done by real time RT-PCR and Northern analysis and protein levels by Western blotting and IHC.