Immunohistochemical examination of the uteroplacental interface of cows on days 21, 31, 40, and 67 of gestation

What we understand about the early stages of placentation in cattle is based on an elegant series of electron microscopic images that provide exquisite detail but limited appreciation for the microanatomy across the uteroplacental interface. In order to achieve a global perspective on the histology of bovine placentation during critical early stages of gestation, i.e., days 21, 31, 40, and 67, we performed immunohistochemistry to detect cell-specific expression of pregnancy-associated glycoprotein (PAG), cytokeratin, epithelial (E)-cadherin, and serine hydroxymethyltransferase 2 (SHMT2) at the intact uteroplacental interface. Key findings from the immunohistochemical analyses are that there are: (i) PAG-positive cells with a single nucleus within the uterine luminal epithelial (LE) cells; (ii) PAG-positive cells with two nuclei in the LE; (iii) PAG-positive syncytial cells with more than three nuclei in the LE; (iv) LE cells that are dissociated from one another and from the basement membrane in regions of syncytialization within the LE layer; (v) replacement of the mononuclear LE with a multilayer thick population of PAG-positive cells invading into the uterine stroma of caruncles but not into the stroma of intercaruncular endometrium; and (vi) PAG-, E-cadherin-, and SHMT2-positive mononuclear cells at the leading edge of developing cotyledonary villi that eventually represent the majority of the epithelial surface separating caruncular stroma from cotyledonary stroma. Finally, the uteroplacental interface of ruminants is not always uniform across a single cross section of a site of placentation, which allows different conclusions to be made depending on the part of the uteroplacental interface being examined.