Trophectoderm Production of Hyaluronan: A Perquisite for Blastocyst Attachment in Mice
AWARD NOMINEE

Successful embryo implantation requires the fulfillment of highly synchronized processes at the feto-maternal interface, including blastocyst attachment to the endometrial epithelium followed by its invasion into the uterine wall. Hyaluronan is a major ECM component known to regulate numerous adhesion-associated biological processes in a number of physiological settings. Therefore, we hypothesized that the adhesive properties of hyaluronan facilitate blastocyst attachment in mice. In order to test the role of hyaluronan during attachment, we have generated mouse transgenic blastocysts, in which genes encoding for hyaluronan synthesizing enzymes were deleted by lentiviral incorporation into the embryonic trophectoderm. Transduced embryos were either tested for their attachment competence in vitro, or transferred to foster dams, scanned by MRI, assessed for successful implantation in vivo and analyzed for expression of essential genes for blastocyst attachment in mice, at the day of implantation, E4.5. Histological analysis revealed impaired implantation at E4.5. In addition, flushing of pregnant mice uteri revealed decreased attachment of mutated embryos, a notion that was further supported by decreased attachment rates of mutated blastocysts to human uterine epithelium cells, in vitro. Moreover, trophectoderm expression of ostepontin, an indispensable attachment bio-marker, was decreased in vivo as well as in vitro. Functional MRI inspections revealed decrease in uterine blood vessels permeability, which constitute the immediate response to blastocyst apposition in mice. Taking these observations into account, we suggest that hyaluronan generated by the trophectoderm plays an essential role at the feto-maternal interface, during the attachment of blastocysts to uterine epithelium.