Prostaglandins and female reproductive function

前列腺素与女性生殖功能

• 批准号: 44276-2011
• 负责人: Fortier, Michel
• 金额: $ 3.42万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=475021
• 关键词: Prostaglandins; female; reproductive; function

Endocrinology of female reproduction is the general research program conducted in my laboratory. Recognition and establishment of pregnancy in ruminants (cattle) is the most important component and has been funded by NSERC GDP for 26 years. Prostaglandins are key regulators of female reproductive function and particularly involved in the communication between the uterus and the ovary to regulate the duration of the estrous cycle. We have proposed that PGE2 and PGF2a rather than PGF2a alone determines luteolysis or maintenance of the CL at the time of recognition of pregnancy. In the present grant cycle, we will confirm the role of our newly identified PGF synthase AKR1B1, its regulation and feed-back interaction with PGE synthases to effect a tight control of the PGE/PGF ratio. We will study the transit of PGs across cell membranes and tissues through the 2 class of PG transporters SLCO and ABCC proteins using polarized endometrial epithelial cell cultures and its involvement during recognition of pregnancy. While native PGE2 and PGF2a will be assayed by our validated EIA assay, analysis of local vs. systemic inactivation of prostaglandins by PGDH will rely on a newly developed LC/MS system to analyze simultaneously the presence of up to 12 PG metabolites in cell culture medium, blood and uterine tissues. The results obtained with cell cultures will be validated using endometrial explants conditioned in vivo. The validated techniques used in our planned research include qRT-PCR, IHC, Western blotting, culture of polarized epithelial cells on membrane inserts, siRNA, and transient transfection of selected genes.

女性生殖内分泌学是我实验室进行的一般研究项目。反刍动物（牛）妊娠的识别和建立是最重要的组成部分，26年来一直由NSERC GDP资助。前列腺素是女性生殖功能的关键调节剂，特别是参与子宫和卵巢之间的通信，以调节发情周期的持续时间。我们提出，PGE 2和PGF 2a，而不是PGF 2a单独决定黄体溶解或维持CL时，承认怀孕。在本资助周期中，我们将确认我们新鉴定的PGF合酶AKR 1B 1的作用，其调节和与PGE脱氢酶的反馈相互作用，以实现对PGE/PGF比率的严格控制。我们将使用极化的子宫内膜上皮细胞培养物研究PG通过2类PG转运蛋白SLCO和ABCC蛋白跨越细胞膜和组织的转运及其在识别妊娠期间的参与。虽然天然PGE 2和PGF 2a将通过我们经验证的EIA测定法进行测定，但通过PGDH进行的局部与系统性伊兰定失活分析将依赖于新开发的LC/MS系统，以同时分析细胞培养基、血液和子宫组织中多达12种PG代谢物的存在。将使用体内调理的子宫内膜外植体验证细胞培养物获得的结果。在我们计划的研究中使用的经验证的技术包括qRT-PCR、IHC、Western印迹、在膜插入物上培养极化上皮细胞、siRNA和所选基因的瞬时转染。