The Effect Of MICA And Environmental Endocrine Disruptors On Fetal Growth And Preterm Birth

Background and Aim: 1.Preterm birth and low birth weight are the main causes to result in neonatal morbidity and mortality.Previous studies demonstrated that the genetic predisposition and environmental factors played pivotal roles in the pathophysiology of preterm birth and low birth weight.However,few studies established the association between MICA polymorphisms,the environmental endocrine disruptors and preterm birth as well as low birth weight.Methods: 1.By conducting prospective cohort studies,we genotyped the genetic variants in MICA gene from 127 cases and 634 healthy controls.We used logistic and linar regression models to assess the MICA polymorphisms and preterm birth as well as low birth weight,respectively.2.We used different concentrations of TCS and PFOS to treat the JEG3 cells.We detected cell viability by CCK8.The m RNA expression of MICA was detected by RT-PCR.The membrane protein expression of MICA was detected by FACS.The soluble MICA was examined by ELISA.We used the cytotoxic detection kit to determine the lysis role of effect cells on target cells.3.We used different concentrations of TCS to treat the HTR8 cells.The effect of TCS on cell apoptosis was detected by FACS.The effect of TCS exposure on apoptotic protein expressions were detected by western blotting.Results: 1.The case-control study displayed that the AA genotype of rs2256318 in MICA gene was correlated with elevated risk of preterm birth(OR = 6.97,95% CI=2.34-20.74,P = 0.001).In addition,the A allele of rs2256318 was associated with decreased placental weight of neonates(β =-25.331;P = 0.033).2.The A allele of rs117246140 in MICA gene was associated with increased risk of low birth weight(β =-98.94,95% CI =(-186.52,-11.36),P = 0.03).In addition,the GA genotype of rs117246140 was associated with elevated risk of low birth weight(β =-157.8,95%CI=(-256.31,-59.29),P = 0.002).3.TCS and PFOS exposure inhibited cell viability in a dosedependent manner in JEG3 cells.In addition,PFOS treatment decreased MICA m RNA and protein expressions in JEG3 cells.4.Cell apoptosis detection: The FACS assay showed that TCS exposure could increase cell apoptosis in a dose dependent manner.Western blotting demonstrated that TCS treatment could increase protein expressions of Bax,Cyto C,DR5,cleaved caspase-8,cleaved caspase-9,Cleaved caspase-3,PARP,whereas inhibited the expression levels of procaspase-9 and Bcl-2.Additionally,TCS exposure could increase total p53,p-p53(s15),p-p53(s20)and p-p38 protein expressions,whereas transfect p53 si RNA significantly inverse these effects.Conclusion: 1.MICA polymorphism rs2256318 was associated with decreased placental weight and increased risk of preterm birth.2.The variant allele of rs117246140 was associated with decreased neonatal birth weight.3.PFOS exposure could upregulate m RNA expression level of MICA in JEG3 cell line.4.TCS enhances p53-dependent apoptosis involving p38/MAPK signaling pathway in HTR8 cells.