{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPregnancy-specific beta-1-glycoprotein 1 (PSG1) plays a critical role during early pregnancy, with evidence pointing to its involvement in implantation and early embryonic development. Messenger RNAs of PSG1 have been detected in mature spermatozoa and may be selectively retained in the zygote, suggesting an early developmental function. In addition, first trimester levels of PSG1 (also referred to as SP1) have been studied as biomarkers for pregnancies with adverse outcomes, and altered PSG1 levels have been associated with conditions such as preeclampsia and hypertensive profiles in pregnancy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in early gestation, PSG1 exhibits potent proangiogenic and immunomodulatory properties. It has been shown to induce transforming growth factor–β1 (TGFB1) and vascular endothelial growth factor A (VEGFA), promoting endothelial tube formation, an activity that is at least partly mediated by its interaction with cell surface glycosaminoglycans. In immunological contexts, PSG1 drives alternative activation of monocytes/macrophages—increasing arginase activity while diminishing nitric oxide production—and enhances regulatory T cell responses by stimulating FOXP3 expression. Furthermore, PSG1 engages in carbohydrate-dependent interactions with lectins such as galectin-1 and other members of the galectin family, which may protect these molecules from oxidative inactivation and fine-tune additional immune responses. Recent findings also indicate that PSG1 can modulate the replicative potential of T cells by down-regulating hTERT expression, thereby contributing to the development of maternal immune tolerance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its well‐documented roles at the fetomaternal interface, PSG1 is implicated in several pathological conditions outside of normal pregnancy. Elevated expression of PSG1 has been detected in certain tumors—including squamous cell carcinomas, colonic adenocarcinomas, and gastric cancers—suggesting a potential role in tumor biology and progression. Moreover, PSG1 has been associated with chemoresistance in estrogen receptor–negative breast cancer cells through TGFB-related pathways, and its ectopic expression in nonplacental tissues such as the gastrointestinal tract and even in aging skin fibroblasts highlights its broader relevance as both a biomarker and a modulator of cellular processes across diverse biological systems."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Conrado Avendaño, Anahí Franchi, Estella Jones, et al. 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