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

Abstract

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, heparan sulphate, and specific integrins. Recently, PSG1 was shown to associate with and activate the anti-inflammatory cytokines transforming growth factor (TGF)-b1 and TGF-b2 making PSG1 one of the few known biological activators of these important cytokines. TGF-bs regulate many biological processes essential for pregnancy success including trophoblast invasion and proliferation, angiogenesis, 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.

Convergent evolution of pregnancy-specific glycoproteins in human and horse

“…Additional poorly characterized secreted factors are likely to participate in tolerance induction during pregnancy (Trowsdale & Betz 2006). PSGs may represent such factors inducing immunotolerance and thromboregulation, in humans and mice (Moore & Dveksler 2014, Ballesteros et al 2015. Thus, we speculate that equine PSG-like CEACAMs expressed by infiltrating chorionic girdle trophoblast and endometrial cup cells may have a similar function controlling activity of T-cells located at the borders of endometrial cups, and perhaps on peripheral T-cells.…”

“…An anti-platelet activity may be beneficial for endometrial cup function because at the base of endometrial cups, newly formed lymph and blood vessels in the immature capillary bed support constant circulation to support the cups (Antczak et al 2013). In addition, PSGs have been shown to bind other integrins, besides platelet integrin (Moore & Dveksler 2014), and it is possible that this also occurs in the horse. Therefore, a PSG-integrin interaction may have additional yet unknown benefits for the function and/ or survival of endometrial cups.…”

Pregnancy-specific glycoprotein expression in normal gastrointestinal tract and in tumors detected with novel monoclonal antibodies

“…13,33 The function of PSG expression in the GI tract is unknown, but there is increasing evidence that PSGs may have multiple functions in immunoregulation, thromboregulation, and angiogenesis. 34 Consistent with their co-expression, PSGs and CEACAMs both exhibit immunoregulatory functions. 5 An immunoregulatory function for PSGs in the GI tract is also supported by the expression of mouse Psg18 in the follicle-associated epithelium overlaying Peyer's patches in the small intestine, 35 possibly contributing to a tolerogenic response to commensal bacteria and food antigens, or regulating immune responses to pathogens.…”

Mechanisms of maternal tolerance to the fetus: lessons of molecular diplomacy

“…Гликопротеины, специфичные для беременности (PSG), синтезируются в большом количестве трофо-бластом и обладают способностью индуцировать се-крецию TGF-β и IL-10 моноцитами и макрофагами [66]. Пониженные концентрации cуммарных PSG ас-социируют с замедленным ростом плода и преэкламп-сией, а также с внематочной беременностью [67].…”