报告题目：Uterine Adaptation to Successful Pregnancy in Human; Compromised Decidualization in Sporadic Miscarriage and Ectopic Pregnancy

　　报告人：LecturerKaiyu Kubota（日本东京医科大学久保田海雄讲师）

　　报告时间：2018年12月9日上午9:30-12:00

　　报告地点：北校区动物医学院4号教学楼4143会议室

　　摘要：

　　Human pregnancy is the rather inefficient way of reproduction since approximately seventy percent of all conceptions cannot be reached to the term delivery. Most of the rest lose in the early phase of pregnancy, such as the implantation failure or the early miscarriage. Chromosomal abnormalities are thought to be the major cause of fetal malformations and in that case the abnormal pregnancies might be eliminated on purpose, whereas improper uterine adaptation for either embryonic implantation or fetal development may also be the different cause and very important particularly in cases in which healthy embryos are compromised by impaired uterine surroundings. Here my talk consists of three short topics of our current studies focusing mainly on the uterus to understand the pathophysiology of these early pregnancy complications.

　　1. PGR knockout rats (animal study). Transgenic mice have been the best tool to study gene functions for decades. Recent advance of genome editing technique extends animal species subjected other than mice. Progesterone signaling governs the establishment and maintenance of pregnancy. Therefore we have generated progesterone receptor (PGR) knockout rats to study the uterine adaptation to pregnancy. As similar to the findings from mice with PGR deletion, PGR deficient female rats were infertile due to the lack of the capacity of uterine stromal decidual differentiation. However, inconsistent with the previous theory, these animals have robust estrous cycles.

　　2. KLF5 in early sporadic miscarriage. Accumulated knowledges of decidual essential genes, which is identified from animal studies, prompted us to evaluate the expression levels of these genes in the decidua of women with early sporadic miscarriage. Among them, transcription factor kruppel-like factor 5 (KLF5) expression was significantly lower in the miscarriage-decidua. In in vitro experiments, KLF5 knockdown strongly inhibited human uterine stromal decidualization.

　　3. Embryonic stimuli in ectopic pregnancy. Ectopic pregnancy occurs in about one percent of total pregnancies. More than ninety five percent of them are a tubal pregnancies. In the uterus, uterine stromal cells are decidualized apparently but without local embryonic signaling since embryo implanted at the oviduct. We utilized these decidual specimens to study the uterine genes regulated by local embryonic stimuli. RNA-seq analysis identified numbers of embryo-stimulated genes including interferon stimulated gene 15, which is well known as an embryonic interferon-responsive factor in ruminants.

　　报告人简介：

　　久保田海雄讲师，2010年毕业于日本九州大学，获农学博士学位。2010年-2016年在美国堪萨斯大学医学中心从事博士后研究，2016年至今在东京医科大学妇产科系任讲师职位。久保田讲师是日本动物生殖生理学研究领域的青年科学家，其研究主要集中于早期胚胎发育、胚胎附植以及激素调控雌性生殖周期等方面。截至目前，久保田讲师共在PNAS、Endocrinology、Journal of Biological Chemistry、Journal of Reproduction and Development等国际著名术期刊发表学术研究论文20余篇。

　　欢迎广大师生参加！

　　动物医学院

　　2018年12月5日

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