Objective: To investigate the relationship between maternal circulating serum toll like receptor 1(TLR-1), TLR-2, TLR-4, TLR-6 levels and premature rupture of membranes(PROM) or subclinical chorioamnionitis. Methods: 520 PROM pregnant women(PROM group), including 249 term(tPROM group) pregnant women and 271 preterm(pPROM group) pregnant women, were enrolled from January 2019 to December 2019 in our hospital. In addition, 50 term and 50 preterm pregnant women with normal delivery were selected into control group. Serum samples at admission and fresh fetal membranes after delivery were collected. The serum levels of TLR-1,-2,-4,-6 were detected by ELISA; mRNA and protein expressions of TLR-1,-2,-4,-6 in fetal membranes were detected by qRT-PCR and immunohistochemistry. According to the histopathological examination, the diagnosis of subclinical chorioamnionitis was performed in PROM pregnant women. Results: Compared with the control group, the levels of TLR-2 and TLR-4 in serum or fetal membranes were significantly increased in PROM group(P<0.05). The serum levels of TLR-1,-2,-4,-6 were positively correlated with the relative expression of TLRs mRNA in fetal membranes(P<0.001). According to the histopathological diagnosis, 53 cases(21.29%) in tPROM group and 116 cases(42.80%) in pPROM group had subclinical chorioamnionitis. Compared with the pregnant women without subclinical chorioamnionitis, the serum levels of TLR-2 and TLR-4 in tRPOM or pPROM pregnant women with subclinical chorioamnionitis were significantly higher(P<0.05). Multivariate logistic regression analysis showed that the increased serum TLR-2 and TLR-4 were the independent risk factors of subclinical chorioamnionitis(P<0.05). The area under ROC curve of serum TLR-2 and TLR-4 for predicting subclinical chorioamnionitis in tPROM or pPROM pregnant women were 0.657(95% CI:0.579-0.743), 0.668 (95% CI:0.584-0.759) and 0.793 (95% CI:0.711-0.918), 0.813 (95% CI:0.725-0.942), respectively. Conclusion: The increase of serum TLR-2 and TLR-4 levels is related with PROM or subclinical chorioamnionitis, which mainly reflects the activation of TLR-2 and TLR-4 in fetal membranes of PROM pregnant women. The detection of serum TLR-2 and TLR-4 levels has an early predictive value for PROM complicated with subclinical chorioamnionitis.
 STRAUSS J F,ROMERO R,GOMEZ-LOPEZ N,et al.Spontaneous preterm birth:advances toward the discovery of genetic predisposition[J].Am J Obstet Gynecol,2018,218(3):294-314.
 TRIANTAFILOU M,DE GLANVILLE B,ABOKLAISH A F,et al. Synergic activation of toll-like receptor (TLR) 2/6 and 9 in response to ureaplasma parvum & urealyticum in human amniotic epithelial cells[J].PLoS One,2013,8(4):e61199.
 张晓杰.妇产科病理学[M]. 北京:人民卫生出版社,2013:245-246.
 MENON R,RICHARDSON L S. Preterm prelabor rupture of the membranes:a disease of the fetal membranes[J].Semin Perinatol,2017,41(7):409-419.
 KIM J S,KIM Y R,YANG C S. Latest comprehensive knowledge of the crosstalk between TLR signaling and mycobacteria and the antigens driving the process[J].J Microbiol Biotechnol,2019,29(10):1506-1521.
 BAHIA W,SOLTANI I,HADDAD A,et al. Links between SNPs in TLR-2 and TLR-4 and idiopathic recurrent pregnancy loss[J].Br J Biomed Sci,2020,77(2):64-68.
 WUJCICKA W,WILCZYNSKI J,NOWAKOWSKA D,et al. Genetic alterations within TLR genes in development of Toxoplasma gondii infection among Polish pregnant women[J].Adv Med Sci,2017,62(2):216-222.
 BOUVIER D,FOREST J C,BLANCHON L,et al. Risk factors and outcomes of preterm premature rupture of membranes in a cohort of 6968 pregnant women prospectively recruited[J].J Clin Med,2019,8(11):1987.
 ABRAHAMS V M,POTTER J A,BHAT G,et al. Bacterial modulation of human fetal membrane Toll-like receptor expression[J].Am J Reprod Immunol,2013,69(1):33-40.