Pepsin-related molecules secreted by trophoblast

The pregnancy-associated glycoproteins (PAGs) were first described as placental antigens of cattle that were also present in the blood serum of the mother after implantation. Molecular cloning studies have shown that they are members of the aspartic proteinase gene family and closely related to the pepsinogens. An enzymatic role seems unlikely, as at least some of them have mutations likely to render them enzymatically inactive. Nevertheless, these molecules have retained the substrate-binding cleft of the pepsins and are expressed abundantly in trophectoderm, particularly in the invasive binucleate cell component. There may be as many as 100 PAG genes in cattle and sheep, many of which are transcribed. PAGs are also products of the placenta of the pig, a species whose progenitors diverged from the ruminants at least 55 million years ago. There is even evidence for PAG-like molecules outside the Artiodactyla. Although their function remains elusive, it seems unlikely that these placentally expressed molecules are simply oddities in view of their long-term evolutionary survival and conspicuous presence at the fetal-maternal interface.