Ovarian Club X and CoGEN in Asia

SpeakerS

Nava DEKEL (Israel)

Nava Dekel earned her PhD degree at Tel Aviv University (1977). After a postdoctoral period at Rockefeller University (1977-1979) and at New York University (1980-1981), she returned to Israel and joined the Weizmann Institute of Science in the Department of Hormone Research, which she headed from 1992-1995. From 2005-2011, she headed the Department of Biological Regulation and was the Director of the Willner Family Center for Vascular Biology. She was promoted to Full Professor and the incumbent of the Philip M. Klutznick Professorial Chair of Developmental Biology in 2003. From 2000 to 2004, she served as President of the Israel Endocrine Society.  Since 2015 she is a Professor Emeritus of the Weizmann Institute and presently serves as the Head of the Institutional Review Board.

Abstract

A New Strategy for Genetic Manipulation Targeted to the Blastocyst Trophectoderm: Possible Practical Application

Mammalian pregnancy is initiated by embryo implantation and followed by decidualization and placental formation. Interestingly, about two-thirds of the abortive pregnancies in humans, are attributed to implantation failure.   Implantation   consists of highly synchronized processes that include apposition of the blastocyst trophoblast cells and   their attachment to the endometrial epithelium, followed by the invasion of the embryo   into the uterine wall. Hyaluronan, a large negatively charged oligosaccharide, is a major ECM component known to regulate adhesion-associated biological processes in a number of physiological settings. We   hypothesized that the adhesive properties of hyaluronan facilitate blastocyst attachment.  To test our hypothesis, we generated mouse transgenic blastocysts, in which the deletion of genes encoding for hyaluronan synthesizing enzymes were exclusively directed to the embryonic trophectoderm. The   genetically manipulated blastocysts were then transferred into uteri of foster mothers. Histological analysis of the uteri of the pregnant mice revealed impaired implantation. Uterine flushing of these mice indicated a decreased embryo   attachment, an observation further supported by a reduced attachment rate of mutated blastocysts to human uterine epithelium cells, in vitro. Functional MRI inspections detected a low permeability of uterine blood vessels, which constitutes   the immediate response to blastocyst apposition. Our findings suggest that hyaluronan plays an essential role at the feto-maternal interface, allowing the attachment of blastocysts to uterine epithelium.  As the placenta is primarily composed of trophoblast cells, trophectoderm-targeted genetic manipulation, practiced by us in the present study, could be further employed for the exploration of the role of specific placental genes in successful pregnancy.