AUTHOR=Suzuki Daisuke , Sasaki Keisuke , Kumamoto Soichiro , Tanaka Keisuke , Ogawa Hidehiko 

TITLE=Dynamic Changes of Gene Expression in Mouse Mural Trophectoderm Regulated by Cdx2 During Implantation

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.945241

DOI=10.3389/fcell.2022.945241

ISSN=2296-634X

ABSTRACT=<p>Implantation of the blastocyst into the uterus is a specific and essential process for mammalian embryonic development. In mice, implantation is initiated from the mural trophectoderm of the blastocyst and the mTE controls implantation progression by acquiring the ability to attach and invade into the endometrium while differentiating into primary trophoblast giant cells. Nevertheless, it remains largely unclear when and how the mTE differentiates and acquires this ability during implantation. Here, by RNA sequencing analysis with the pre- and peri-implantation mTE, we show that the mTE undergoes stage-specific and dynamic changes of gene expression during implantation. We also reveal that the mTE begins down-regulating <italic>Cdx2</italic> and up-regulating differentiation marker genes during the peri-implantation stage. In addition, using trophectoderm (TE) -specific lentiviral vector-mediated gene transduction, we demonstrate that TE-specific <italic>Cdx2</italic> overexpression represses differentiation of the mTE into the primary trophoblast giant cells. Moreover, we reveal that TE-specific <italic>Cdx2</italic> overexpression also represses the up-regulation of cell adhesion- and migration-related genes, including <italic>Slc6a14</italic>, <italic>Slc16a3</italic>, <italic>Itga7</italic>, <italic>Itgav</italic> and <italic>Itgb3</italic>, which are known to regulate migration of trophectoderm cells. In particular, the expression of <italic>Itgb3</italic>, an integrin subunit gene, exhibits high inverse correlation with that of <italic>Cdx2</italic> in the TE. Reflecting the down-regulation of the genes for TE migration, TE-specific <italic>Cdx2</italic> overexpression causes suppression of the blastocyst outgrowth <italic>in vitro</italic> and abnormal progression of implantation <italic>in vivo</italic>. Thus, our results specify the time-course changes of global gene expression in the mTE during implantation and uncover the significance of <italic>Cdx2</italic> down-regulation for implantation progression.</p>