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PSGs are produced by placental trophoblasts and secreted into the maternal bloodstream at high levels where they may regulate maternal immune and vascular functions through receptor binding and modulation of cytokine and chemokine expression and activity. PSGs may have autocrine and paracrine functions in the placental bed, and PSGs can activate soluble and extracellular matrix bound TGF-\u03b2, with potentially diverse effects on multiple cell types. PSGs are also found at high levels in the maternal circulation, at least in human, where they may have endocrine functions. In a non-reproductive context, PSGs are expressed in the gastrointestinal tract and their deregulation may be associated with colorectal cancer and other diseases. Like many placental hormones, PSGs are encoded by multigene families and they have an unusual phylogenetic distribution, being found predominantly in species with hemochorial placentation, with the notable exception of the horse in which PSG-like proteins are expressed in the endometrial cups of the epitheliochorial placenta. The evolution and expansion of PSG gene families appear to be a highly active process, with significant changes in gene numbers and protein domain structures in different mammalian lineages and reports of extensive copy number variation at the human locus. Against this apparent diversification, the available evidence indicates extensive conservation of PSG functions in multiple species. These observations are consistent with maternal\u2013fetal conflict underpinning the evolution of PSGs.<\/jats:p>","DOI":"10.1530\/rep-21-0390","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T12:52:44Z","timestamp":1641819164000},"page":"R11-R23","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":58,"title":["Pregnancy-specific glycoproteins: evolution, expression, functions and disease associations"],"prefix":"10.1093","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9712-9625","authenticated-orcid":false,"given":"Tom","family":"Moore","sequence":"first","affiliation":[{"name":"School of Biochemistry and Cell Biology , University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Williams","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Cell Biology , University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angeles","family":"Becerra-Rodriguez","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Cell Biology , University College Cork, Cork, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Dunne","sequence":"additional","affiliation":[{"name":"Institute of Food Nutrition and Health , ETH Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Kammerer","sequence":"additional","affiliation":[{"name":"Institute of Immunology , Friedrich-Loeffler-Institut, Greifswald \u2013 Insel Riems, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Dveksler","sequence":"additional","affiliation":[{"name":"Uniformed Services University of the Heath Sciences , Bethesda, Maryland, 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