{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPlac1 is an X‐linked gene with trophoblast‐specific expression that is essential for proper placental development and embryonic growth. Experimental models show that ablation of Plac1 leads to placentomegaly, an expanded spongiotrophoblast layer invading the labyrinth, and intrauterine growth restriction, while targeted transgenic expression can partially rescue fetal development—even though placental hyperplasia may persist. These studies also reveal that although Plac1 is predominantly maternally expressed, the paternal allele partially escapes complete X-inactivation, thereby contributing to the regulation of placental growth and overall fetal viability."}, {"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": "\nIn tumor models, Plac1 re‐expression is implicated in promoting cancer cell proliferation and in establishing a tolerogenic tumor microenvironment through modulation of chemokine signaling. For instance, Plac1 knockdown in mammary carcinoma cells decreases proliferation and alters the expression of several immune–inflammatory molecules, suggesting a role in adaptive immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, Plac1 is highly enriched in mouse oocytes, where it localizes to the membrane during meiosis and regulates microvillus organization. Mechanistically, Plac1 activates furin, which in turn triggers IGF-1 receptor signaling and downstream Akt phosphorylation to ensure proper oocyte maturation and chromosomal integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In line with its oncogenic functions, further studies in melanoma have demonstrated that Plac1 can induce anti-cancer immune responses and impede tumor progression, reinforcing its potential as a target for immunotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTogether, these findings establish Plac1 as a multifunctional regulator whose tightly controlled expression is critical in diverse biological contexts—including placental formation, oocyte development, and tumor immunomodulation. The dual roles of Plac1 in facilitating normal gestational processes and in contributing to pathological states underscore the promise of further research into its associated signaling pathways, which may yield novel therapeutic strategies for managing pregnancy complications and certain cancers.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Suzanne M Jackman, Xiaoyuan Kong, Michael E Fant "}, {"type": "b", "children": [{"type": "t", "text": "Plac1 (placenta-specific 1) is essential for normal placental and embryonic development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Reprod Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mrd.22062"}], "href": "https://doi.org/10.1002/mrd.22062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22729990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22729990"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiaoyuan Kong, Suzanne M Jackman, Michael E Fant "}, {"type": "b", "children": [{"type": "t", "text": "Plac1 (placenta-specific 1) is widely expressed during fetal development and is associated with a lethal form of hydrocephalus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Birth Defects Res A Clin Mol Teratol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/bdra.23171"}], "href": "https://doi.org/10.1002/bdra.23171"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24014101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24014101"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Masanaga Muto, Yoshitaka Fujihara, Tomohiro Tobita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lentiviral Vector-Mediated Complementation Restored Fetal Viability but Not Placental Hyperplasia in Plac1-Deficient Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1095/biolreprod.115.133454"}], "href": "https://doi.org/10.1095/biolreprod.115.133454"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26586843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26586843"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yanli Gu, Junhui Wan, Lv Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plac1 Expression Pattern at the Mouse Fetomaternal Interface and Involvement in Trophoblast Differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000484154"}], "href": "https://doi.org/10.1159/000484154"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29055961"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29055961"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hongyan Yuan, Xiaoyi Wang, Chunmei Shi, et al. 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