过量碘诱导绒毛膜滋养层细胞凋亡与早期妊娠稽留流产相关机制研究

Mechanism of excessive iodine-induced apoptosis of chorionic trophoblast cells in relation to missed early miscarriage

目的探讨过量碘诱导绒毛膜滋养层细胞凋亡与早期妊娠稽留流产的相关机制。方法选择2019年9月至2022年9月于天津市中心妇产科医院就诊的孕周≤12周的不明原因早期妊娠稽留流产患者(MA组,n=43)和正常孕妇(对照组,n=64)作为研究对象,采集绒毛组织,进行增殖细胞核抗原Ki67免疫组织化学检测和细胞凋亡检测;采集尿样,进行尿碘含量检测。另用不同剂量碘刺激培养人绒毛膜滋养层细胞株(HTR8/SVneo细胞)24 h,采用细胞计数试剂盒8(CCK8)检测细胞增殖活力,流式细胞术检测细胞凋亡情况。结果(1)对照组尿碘为159.70(114.21,218.73)μg/L,MA组为210.80(143.10,336.70)μg/L,二者比较差异有统计学意义(Z=2.26,P=0.024)。(2)MA组绒毛组织Ki67免疫组织化学染色阳性和强阳性比例明显低于对照组(χ^(2)=37.00,P<0.001)。(3)MA组绒毛组织细胞凋亡率明显高于对照组[(26.24±1.06)%比(2.96±1.97)%,t=92.23,P<0.001]。(4)50、100、300、500μg碘组HTR8/SVneo细胞增殖率均明显低于0μg碘组(均P<0.05),其中500μg碘组低于半数致死量。(5)0、50、500μg碘组细胞凋亡率分别为(8.79±0.12)%、(9.56±0.08)%、(19.86±0.05)%,3组间比较差异有统计学意义(F=7.32,P=0.007);其中,50、500μg碘组均高于0μg碘组,且500μg碘组高于50μg碘组(均P<0.05)。结论早期妊娠稽留流产患者尿碘含量明显增高,过量碘摄入可能导致绒毛膜滋养层细胞的增殖活力下降,细胞凋亡增多。

Objective To investigate the mechanism of excessive iodine-induced apoptosis of chorionic trophoblast cells associated with missed early miscarriage.Methods Patients with unexplained missed early miscarriage≤12 weeks of gestation(MA group,n=43)and normal pregnant women(control group,n=64)who were treated at Tianjin Central Obstetrics and Gynecology Hospital from September 2019 to September 2022 were selected as the study subjects,and villous tissues were collected for proliferating cell nuclear agtigen Ki67 immunohistochemistry and apoptosis assay,while urine samples were collected for urinary iodine content assay.Different doses of iodine were used to stimulate the cultivation of human chorionic trophoblast cell line(HTR8/SVneo)for 24 h.Cell proliferation viability was detected using cell counting kit 8(CCK8),and apoptosis was detected using flow cytometry.Results(1)Urinary iodine values were 159.70(114.21,218.73)μg/L in the control group and 210.80(143.10,336.70)μg/L in the MA group,the difference between the two groups was statistically significant(Z=2.26,P=0.024).(2)The proportion of positive and strong positive Ki67 immunohistochemical staining of the villous tissues in the MA group was significantly lower than that in the control group(χ^(2)=37.00,P<0.001).(3)The apoptosis rate of villous tissue in the MA group was significantly higher than that in the control group[(26.24±1.06)%vs(2.96±1.97)%,t=92.23,P<0.001].(4)The cell proliferation rates of HTR8/SVneo in the 50,100,300 and 500μg iodine groups were significantly lower than that in the 0μg iodine group(P<0.05),with the 500μg iodine group below the median lethal dose(LD 50).(5)The apoptosis rates of 0,50 and 500μg iodine groups were(8.79±0.12)%,(9.56±0.08)%and(19.86±0.05)%,respectively,and the differences among the three groups were statistically significant(F=7.32,P=0.007);in which the 50 and 500μg iodine groups were higher than that of the 0μg iodine group,and the 500μg iodine group was higher than that of the 50μg iodine group(P<0.05).Conclusions Urine iodine content significantly increases in patients with missed early miscarriage.Excessive iodine intake may lead to a decrease in the proliferation viability and an increase in cell apoptosis of chorionic trophoblast cells.