This study provides the first in vivo demonstration that both COX-2 and GM-CSF are up-regulated during critical steps of the establishment of pregnancy in cattle, and that this stimulation can be mimicked by IFN-t treatment. Indeed, the secretion of IFN-t (between d12P-d28P, peaking at d15P-d19P) by uninucleate trophoblastic cells is concomitant with dramatic cellular modifications that happen to both the uterine epithelium and the conceptus. Early attachment in ruminants is divided in three main stages.
The first is characterized by the exponential elongation of the conceptus; the second involves apposition between the trophoblast and the flattened uterine epithelium; and the third is the adhesion stage during which trophoblastic binucleate cells fuse with LE cells to form hybrid syncitia, accounting for 50% of the maternal layer by d24P. The attachment begins in the vicinity of the embryo then spreads throughout, explaining why fusion of trophoblastic and epithelial cells is less advanced at the extremities of the conceptus. Uterine LE is quickly reconstituted after d30P, however, and giant multinucleate cells are absent from d40P. On the basis of results obtained in vitro, it has been proposed that IFN-t stimulates COX-2, PGE2, PGF2a, and GM-CSF in the endometrium.