Title: Uterine Adaptation to Successful Pregnancy in Human; Compromised Decidualization in Sporadic Miscarriage and Ectopic Pregnancy

Speaker:LecturerKaiyu Kubota (Department of Obstetrics and Gynecology, Tokyo Medical University, Japan)

Time: 9:30-12:00 am, December 9th, 2018

Venue: Room No. 4143, Building 4, North Campus, College of Veterinary Medicine

Abstract:

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.

A Brief Introduction to the Speaker:

Dr. Kaiyu Kubota graduated and acquired his Ph.D degree from Kyushu University, Japan in 2010. From 2016 to the present, He was a lecturer of Department of Obstetrics and Gynecology, Tokyo Medical University. Dr. Kubota is a rising star of reproductive physiologist in Japan, whose research interest focusing on early embryonic development through uterine implantation and placentation utilizing biochemical, cellular, and molecular approaches both in vivo and in vitro, as well as hormonal regulation of female estrous cyclicity, and pathophysiology of maternal pancreatic adaptation and gestational diabetes. Dr. Kubota published more than 20 papers in international academic journals, such as PNAS, Endocrinology, Journal of Biological Chemistry, Journal of Reproduction and Development.

All the teachers and students are welcome to attend this seminar.

College of Veterinary Medicine

December 5th, 2018