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Expression and correlation of SMAD2/3 and Th1/Th2/Th17 cytokines in embryonic tissues of idiopathic recurrent miscarriage

Year: 2026

Type: article

Abstract: BACKGROUND: Recurrent miscarriage (RM), the loss of 2 or more consecutive pregnancies before 28 weeks' gestation, has become increasingly common in recent years, imposing significant physical and psychological burdens on affected women. Despite comprehensive evaluation, approx. 40-50% of RM cases remain unexplained and are therefore classified as idiopathic. OBJECTIVES: This study aimed to investigate the expression of SMAD2 and SMAD3 and characterize Th1, Th2 and Th17 cytokine profiles in placental villous tissues from women with idiopathic RM. MATERIAL AND METHODS: Forty-nine women with idiopathic RM in early pregnancy and 41 gestational age-matched women with normal pregnancies (NP) were recruited at Shanxi Maternal and Child Health Hospital (Taiyuan, China) . Following informed consent, placental villous tissues were obtained via ultrasound-guided vacuum aspiration, rinsed in saline and stored at -80°C. Total RNA was extracted from each sample, and SMAD2 and SMAD3 mRNA levels were quantified using real-time quantitative PCR (qPCR) using the 2-ΔΔCq method. Parallelly, tissue homogenates were assayed with enzyme-linked immunosorbent assay (ELISA) for Th1 cytokines (interleukin (IL)-2, intereron gamma (IFN-γ), tumor necrosis factor alpha (TNF-α)), Th2 cytokine (IL-10), and Th17 cytokines (IL-6, IL-17). Spearman's rank correlation was used to evaluate associations between SMAD2/3 expression and cytokine concentrations. All statistical analyses were performed in IBM SPSS v. 27.0, with two-tailed p < 0.05 denoting significance. RESULTS: The qPCR analysis demonstrated that SMAD2 mRNA levels in villous tissues were significantly higher in the RM group than in NP controls (p < 0.05). Consistent with this, ELISA revealed a marked increase in IL-6 concentration (p < 0.05) alongside significant reductions in IL-2, IL-10, TNF-α, and IFN-γ levels in RM samples vs NP (all p < 0.05). Spearman correlation analysis showed that SMAD2 expression was inversely correlated with IFN-γ (ρ < 0, p < 0.05), while SMAD3 expression was negatively associated with both IL-2 and IFN-γ levels (ρ < 0, p < 0.05). CONCLUSIONS: SMAD2/3 can affect the expression of Th1 and Th17 cytokines, which may in turn affect normal embryonic development.

Source: Advances in Clinical and Experimental Medicine

DOI: 10.17219/acem/203971