Pregnancy-specific glycoproteins: Complex gene families regulating maternal-fetal interactions

The pregnancy-specific glycoproteins (PSGs) are the most abundant trophoblastic proteins in maternal blood during human pregnancy and they appear to be exclusive to species with hemochorial placentation. There are ten protein-coding human PSG genes (PSG1 - PSG9, PSG11) and also multiple PSG genes in non-human primates, rodents and bats. Several studies indicate that PSGs have immunoregulatory, pro-angiogenic, and anti-platelet functions. Some PSGs have been shown to bind different moieties on the surface of cells, including the tetraspanin CD9, hepa-ran sulphate, and specific integrins. Recently, PSG1 was shown to associate with and activate the anti-inflammatory cytokines transforming growth factor (TGF)-β1 and TGF-β2 making PSG1 one of the few known biological activators of these important cytokines. TGF-βs regulate many biological processes essential for pregnancy success including trophoblast invasion and proliferation, angio-genesis, extracellular matrix formation and tolerance to the fetal semi-allograft. As summarized in this review, progress has been made in recent years towards a better understanding of the functions of these proteins which were originally described in the early 1970s, but more research will likely contribute to demonstrate their importance for a successful pregnancy.