{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The chorionic gonadotropin β‐subunit gene CGB5 encodes one of the major protein components of the heterodimeric human chorionic gonadotropin (hCG) hormone that is secreted by placental trophoblasts. Its product is essential for early pregnancy establishment and maintenance by supporting embryo implantation, trophoblast differentiation, and modulation of maternal immune and apoptotic responses. Variations in the gene – whether due to genetic polymorphisms, missense mutations, or epigenetic alterations – can alter the assembly, secretion, and downstream signaling activity of hCG. For example, certain promoter variants and missense mutations in CGB5 may decrease or modify hCG dimer formation yet, in some instances, trigger compensatory receptor signaling; such alterations have been associated with changes in risks for recurrent miscarriage and other adverse pregnancy outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its canonical reproductive functions, aberrant or ectopic expression of CGB5 has been reported in several malignancies. Elevated levels of hCGβ derived from CGB5 have been linked to tumor initiation, growth, invasion, and poor prognosis in cancers such as breast, ovarian, testicular, and gastric cancer, suggesting that hCGβ may act as a paracrine or autocrine growth modulator in these tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, regulation of CGB5 expression is complex. Transcriptional repressors such as MTA3 have been shown to bind directly to the promoter regions of hCG β‐subunit genes, thereby influencing trophoblast differentiation and the balance of cell lineage markers; dysregulation in this control mechanism has been implicated in pregnancy complications like preeclampsia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In some contexts, autoantibodies directed against CGB5 have also been identified and may serve as biomarkers for recurrent glomerular disorders post‐transplantation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings emphasize that CGB5 is not only central to normal placental and reproductive function through its role in hCG production but that its dysregulation can contribute to a spectrum of clinical conditions ranging from adverse pregnancy outcomes to oncogenic processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kristiina Rull, Liina Nagirnaja, Veli-Matti Ulander, et al. 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