| Objective: To explore the mechanism of missed abortion,the concentrations of serum human chorionic gonadotropin-?(?-hCG),progesterone,Insulin-like growth factor-1(IGF-1)and the expression levels of genes and proteins of IGF-1,IGF-1R,PI3K/AKT signaling pathway and apoptosis-related factors in villous tissues were measured.Methods: From May 1,2018 to April 30,2019,we collected the peripheral blood samples and villous tissues from the missed abortion patients and the normal early pregnant women who had terminated pregnancy by artificial abortion due to the unintended pregnancy in Lanzhou maternal and child health care hospital and Jingning county maternal and child health care hospital,and set up a specimen bank,of which 12 pairs of serum and villous tissues samples were selected for detection and analysis.All subjects were in the same age group,at the same gestational week,and had no history of exposure to occupational hazards.(1)Detection of ?-hCG and progesterone in serum by radioimmunoassay.(2)The level of IGF-1 in serum was detected by ELISA.(3)HE staining was used to observe the pathological morphology of villous tissues.(4)The expression levels of IGF-1,IGF-1R,PI3K/AKT signaling pathway related genes PI3 K,AKT mRNA and apoptosis related genes Bad,Bax,Bcl-2,Cyt c,Caspase 3 mRNA in villous tissues were detected by qRT-PCR.(5)Wes was used to detect the expression levels of IGF-1,IGF-1R and PI3K/AKT signaling pathway related proteins PI3 K,p-PI3 K,AKT,p-AKT and apoptosis proteins Bad,p-Bad,Bax,Bcl-2,Cyt c,Caspase 3.Results:(1)Serum ?-hCG and progesterone levels: The levels of ?-hCG and progesterone in the serum of the missed abortion group was lower than that of the normal early pregnancy group(P < 0.05);(2)Level of IGF-1 in serum: The level of IGF-1 in the serum of missed abortion group was lower than that of normal early pregnancy group(P < 0.05);(3)The correlation analysis of IGF-1 level with ?-hCG and progesterone in serum: In normal early pregnancy group,IGF-1 was positively correlated with ?-hCG(r=0.735,P < 0.01);In the missed abortion group,IGF-1 was positively correlated with ?-hCG(r=0.646,P < 0.05)and progesterone(r=0.588,P < 0.05);(4)Pathological morphology of villous tissues: Under the light microscope,the number of villi cells in the missed abortion group was reduced,and the inner trophoblasts and outer trophoblasts were significantly reduced,and the syncytiotrophoblast layer became thinner.The cells arranged intermittently,the lumen of villi became small or even without obvious lumen;(5)Detection results of IGF-1 and IGF-1R in villous tissues: Compared with the normal early pregnancy group,the expression levels of IGF-1 and IGF-1R mRNA in the villous tissues of the missed abortion group were reduced(P < 0.05),and the expression level of IGF-1 protein in the villous tissues was reduced(P < 0.05);(6)PI3K/AKT signaling pathway detection results: Compared with the normal early pregnancy group,the expression levels of PI3 K and AKT mRNA in the villous tissues of the missed abortion group were decreased(P < 0.05);The expression levels of PI3 K,p-PI3 K,AKT,p-AKT proteins in the villous tissues of the missed abortion group were decreased(P < 0.05),and the ratio of p-AKT/AKT was decreased(P < 0.05);(7)The detection results of apoptosis related factors: Compared with the normal early pregnancy group,the expression levels of Bcl-2 mRNA in the villous tissues of the missed abortion group was decreased(P < 0.05),Bax,Bad,Cyt c and Caspase 3 mRNA were increased(P < 0.05),the ratio of Bax/Bcl-2 was increased(P < 0.05);Compared with the normal early pregnancy group,the expression levels of Bcl-2 and p-Bad proteins in the villous tissues of the missed abortion group were decreased(P < 0.05),the expression levels of Bad,Cyt c and Caspase 3 proteins were increased(P < 0.05),the ratio of p-Bad/Bad was decreased(P < 0.05),and the ratio of Bax/Bcl-2 was increased(P < 0.05).Conclusions: The levels of IGF-1 in serum and villous tissues of missed abortion patients were decreased,PI3K/AKT signaling pathway may be inhibit,mitochondrial apoptosis pathway was activated,the apoptosis of trophoblast cells was increased,and the secretory function of ?-hCG and progesterone was decreased,which may be the important mechanism leading to fetal growth arrest. |
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