Relationship between TGF-β1/Smad3 signaling pathway and adverse pregnancy outcomes caused by Toxoplasma gondii infection

OBJECTIVE To explore the relationship between transforming growth factor-β1 (TGF-β1) /Smad3 signaling pathway and adverse pregnancy outcomes of the pregnant women with Toxoplasma gondii infection. METHODS A total of 98 pregnant women who were treated in Shengjing Hospital of China Medical University from Oct 2019 to Oct 2020 were enrolled in the study, 32 of whom had T.gondii infection, and 66 did not have T.gondii infection. The umbilical cord blood specimens and fetal membrane tissues were collected; the expressions of TGF-β1, Smad3 and forkhead box P3 (Foxp3) mRNA were detected by polymerase chain reaction, the percentage of CD₄⁺CD₂₅⁺Foxp3⁺regulatory T cell (Treg) cell in umbilical cord blood was detected by flow cytometry, the expressions of TGF-β1, phosphorylated Smad3 ( P-Smad3) and Foxp3 proteins in placenta were detected by Western blot assay, the levels of serum interleukin-10 (IL-10) and interferon-γ (IFN-γ) were detected by enzyme-linked immunosorbent assay, the IFN-γ/IL-10 was calculated, the levels of above indexes were compared among the groups, and the relationship among the indexes was observed. RESULTS The gestational weeks of the infection group were significantly shorter than those of the control group(P<0.05), the neonatal body weight and placenta of the infection group were significantly lower than those of the control group (P<0.05); the incidence of adverse pregnancy outcomes of the infection group was significantly higher than that of the control group(P<0.05). The expression levels of TGF-β1, P-Smad3, Foxp3 mRNA and their proteins in placenta tissues, percentage of CD₄⁺CD₂₅⁺Foxp3⁺Treg cell in umbilical cord blood and IL-10 were significantly lower in the infection group than in the control group(P<0.05). The levels of serum IFN-γ and IL-10/IFN-γ of the infection group were significantly higher than those of the control group (P<0.05). The percentage of CD₄⁺CD₂₅⁺Foxp3⁺Treg cell in umbilical cord blood of the pregnant women with T.gondii infection was positively correlated with the expression levels of TGF-β1, P-Smad3, Foxp3 mRNA and their proteins in placenta tissues(P<0.05), and it was negatively correlated with the serum IFN-γ/IL-10 level(P<0.05). CONCLUSION The T.gondii infection may lead to the decline of TGF-β1/Smad3 signaling pathway factors and the imbalance of Th1/Th2, disrupt the immune tolerance state of normal pregnancy and increase the risk of adverse pregnancy outcomes.