Clinical significance and mechanistic role of Hsa_circ_0005075 in recurrent spontaneous abortion: Regulation of trophoblast proliferation and invasion through the Wnt/β-catenin pathway

• Serum hsa_circ_0005075 is significantly elevated in patients with Recurrent Spontaneous Abortion (RSA). • Hsa_circ_0005075 exhibits high diagnostic value (AUC = 0.820) for distinguishing RSA patients from healthy controls. • Overexpression of hsa_circ_0005075 suppresses trophoblast cell proliferation, invasion, and cell cycle progression while promoting apoptosis. • Hsa_circ_0005075 exerts its functional effects by inhibiting the activation of the Wnt/β-catenin signaling pathway. • Targeting hsa_circ_0005075 may represent a novel diagnostic and therapeutic strategy for RSA. Given the current lack of diagnostic markers with high sensitivity and specificity, the diagnosis and treatment of Recurrent Spontaneous Abortion (RSA) have always presented significant difficulties. To analyze the relationship between hsa_circ_0005075 and RSA and conduct a preliminary exploration of its mechanism. Fifty-eight RSA patients admitted to the studied hospital from March 2022 to January 2024 (research group) and 52 normal pregnant women (control group) were selected as the research subjects. Peripheral blood hsa_circ_0005075 expression was detected to determine the difference between the two groups. In addition, the evaluation value of hsa_circ_0005075 for RSA, miscarriage, and adverse pregnancy outcomes was analyzed through Receiver Operating Characteristic (ROC) curves. Furthermore, human placental Trophoblast Cells (TBCs) HTR8/SVneowere purchased and transfected with abnormal hsa_circ_0005075 expression sequences to identify changes in HTR8/SVneoproliferation, invasion, and apoptosis, and alterations in Wnt/β-catenin pathway expression. hsa_circ_0005075 was higher in the research group than in the control group (4.00 ± 0.93 vs. 2.78 ± 0.94, p < 0.05). ROC curves indicated the excellent diagnostic effect of hsa_circ_0005075 on the occurrence of RSA (Area Under Curve [AUC = 0.820]), miscarriage (AUC = 0.744), and adverse pregnancy outcomes (AUC = 0.726). In vitro, increasing hsa_circ_0005075 inhibited HTR8/SVneogrowth, decreased cell clones and cell invasion number, increased apoptosis, shortened the G0/G1 phase, and activated the Wnt/β-catenin pathway; the opposite results were observed after silencing hsa_circ_0005075 expression. Mechanistically, gain and loss-of-function experiments revealed that hsa_circ_0005075 acts as a negative regulator of trophoblast proliferation, invasion, and cell cycle progression, and induces apoptosis by suppressing the Wnt/β-catenin signaling pathway. The present findings identify hsa_circ_0005075 as a promising circulating biomarker for RSA and demonstrate that it contributes to RSA pathogenesis by impairing trophoblast function through inhibition of the Wnt/β-catenin pathway, suggesting its potential as a therapeutic target.