{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRetroviral envelope genes—collectively known as syncytins—have been co‐opted during mammalian evolution to enable the formation of specialized placental structures through cell–cell fusion. In both primates and rodents, independently acquired syncytin genes (syncytin‑1 and syncytin‑2 in humans; syncytin‑A and syncytin‑B in mice) drive the fusion of trophoblasts into multinucleated syncytiotrophoblast layers that form the key barrier at the maternofetal interface, facilitating nutrient exchange and overall placental morphogenesis (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond their fusogenic activity, some syncytins exert immunosuppressive functions that promote maternofetal tolerance. For instance, while human syncytin‑2 and murine syncytin‑B exhibit immunosuppressive properties, their counterparts maintain fusogenicity without directly dampening immune responses. In vivo knockout and inducible gene disruption studies further demonstrate that loss of specific syncytins leads to architectural placental defects, impaired vascular formation, and, in some cases, embryonic lethality—highlighting the nonredundant roles of these genes in placental development (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the mechanistic level, detailed cellular and biochemical assays have unraveled how syncytins mediate cell fusion. The identification of the receptor for mouse syncytin‑A—Ly6e—demonstrates that syncytin–receptor interactions are essential for initiating and regulating trophoblast fusion. Furthermore, studies employing trophoblast stem cell differentiation and fusion inhibition experiments have provided important insights into the structural elements governing fusogenicity and the potential compensatory mechanisms that safeguard placental function when syncytin expression is altered. These findings underscore the evolutionary convergence of retroviral gene capture in shaping the complex molecular machinery of placentation (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anne Dupressoir, Geoffroy Marceau, Cécile Vernochet, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Early patterning of the chorion leads to the trilaminar trophoblast cell structure in the placental labyrinth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.020099"}], "href": "https://doi.org/10.1242/dev.020099"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18448564"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18448564"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Marianne Mangeney, Martial Renard, Géraldine Schlecht-Louf, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Placental syncytins: Genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0707873105"}], "href": "https://doi.org/10.1073/pnas.0707873105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18077339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18077339"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Anne Dupressoir, Cécile Vernochet, Olivia Bawa, et al. 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