Cellular events during ovine implantation and impact for gestation.

The establishment of pregnancy in sheep includes elongation of the blastocyst into a filamentous conceptus, pregnancy recognition, production of histotroph, attachment of the conceptus to the endometrium for implantation, and development of synepitheliochorial placentation. These processes are complex, and this review describes some of the molecular events that underlie and support successful pregnancy. The free-floating sheep blastocyst elongates into a filamentous conceptus and metabolizes, or is responsive to, molecules supplied by the endometrium as histotroph. Amongst these molecules are SPP1, glucose and fructose, and arginine that stimulate the MTOR nutrient sensing system. The placental trophectoderm of elongating conceptuses initiate pregnancy recognition and implantation. The mononucleate cells of the trophectoderm secrete IFNT, which acts on the endometrial LE to block increases in estrogen receptor α to preclude oxytocin receptor expression, thereby preventing oxytocin from inducing luteolytic pulses of PGF2α. In addition, IFNT increases expression of IFN stimulated genes in the endometrial stroma, including ISG15, a functional ubiquitin homologue. Implantation is the initial step in placentation, and includes sequential pre-contact, apposition, and adhesion phases. Implantation in sheep includes downregulation of Muc1 and interaction of GLYCAM1, galectin 15 (LGALS15) and SPP1 with lectins and integrins (αvβ3). Sheep have synepitheliochorial placentation in which mononucleate trophectoderm cells fuse to form binucleate cells (BNCs). BNCs migrate and fuse with endometrial LE cells to form trinucleate syncytial cells, and these syncytia enlarge through continued BNC fusion to form syncytial plaques that form the interface between endometrial and placental tissues within the placentome. The placentae of sheep organize into placentomal and interplacentomal regions. In placentomes there is extensive interdigitation of endometrial and placental tissues to provide hemotrophic nutrition to the fetus. In interplacentomal regions there is epitheliochorial attachment of endometrial LE to trophectoderm, mediated through focal adhesion assembly, and areolae that take up histotroph secreted by endometrial GE.