| Objective:The purpose of this study was to investigate the role of abnormal thyroid hormone metabolism and transport of placental villus in spontaneous abortion in early pregnancy,and to provide theoretical basis for the etiology of spontaneous abortion patients.Methods:From July 2019 to July 2020,45 early pregnant women who planned to undergo induced abortion in the operation room of the Department of Gynecology outpatient clinic of the First Affiliated Hospital of Anhui Medical University were selected as the research subjects.There were 20 cases of voluntary terminations of pregnancy named ETP group and 25 cases of spontaneous abortion named SA group,and the villus tissues of induced abortion in ETP group and SA group were collected respectively.The differences in gestation days,age and thyroid hormone levels（TSH,T3,T4）between ETP group and SA group were compared.The number and proportion of Ki67 positive cells and TUNEL positive cells in total cells in each field were detected by immunohistochemical assay,so as to compare the proliferation and apoptosis of placental villus trophoblast cells in the two groups.The number of CD34 positive blood vessels,the number of VEGF positive cells and the rate of positive cells in each field were detected by immunohistochemistry,so as to compare the angiogenesis in the placental villi of the two groups.The expression levels of TTR protein and m RNA were determined by immunohistochemistry and RT-PCR,so as to compare the expression of TTR in the placental villi of the two groups.In order to compare the transport and metabolism of thyroid hormone in placental villi of ETP group and SA group,the expression levels of thyroid hormone transporter（MCT8 and OATP1A1）,deiodinase（Dio2 and Dio3）and thyroid hormone receptor（THRα and THRβ）protein and m RNA were detected in ETP group and SA group,respectively.The m RNA expression levels of thyroid hormone transporters（MCT8 and OATP1A1）,deiodinase（Dio2 and Dio3）and thyroid hormone receptor（THRα and THRβ）were detected by RT-PCR.In order to further investigate the expression of thyroid hormone receptors（THRα and THRβ）in the placental villi of ETP and SA groups,the expression levels of thyroid hormone receptors（THRα and THRβ）protein levels were detected by immunohistochemistry.In order to further study the expression of Dio2 in the placental villi of ETP and SA groups,immunofluorescence assay and Western Blot assay were used to detect the expression level of Dio2 protein.Result:1.There were no statistically significant differences between ETP group and SA group in gestation days,age and thyroid hormone levels（TSH,T3,T4）（P>0.05）,indicating that the experimental results of the two groups were comparable to some extent.2.Immunohistochemical results showed that compared with ETP group,the number and rate of Ki67 positive cells in placental villi under each visual field in SA group were significantly lower（P<0.01）,indicating that the proliferation of trophoblast cells in placental villi in SA group was significantly reduced.Compared with ETP group,the number and rate of TUNEL positive cells in placental villi per visual field in SA group were significantly increased（P<0.01）,indicating that the apoptosis of trophoblast cells in placental villi in SA group was significantly increased.The above results showed that the proliferation and apoptosis of placental villus trophoblast cells in SA patients were significantly reduced.3.Immunohistochemical results showed that compared with ETP group,the number of CD34 positive blood vessels in placental villi per visual field in SA group was significantly decreased（P<0.01）.Compared with ETP group,the number and rate of positive VEGF cells in placental villus per field of vision in SA group were decreased（P<0.05）.These results indicated that placental villus angiogenesis was significantly reduced in SA patients.4.Immunohistochemistry and RT-PCR results showed that compared with ETP group,the expression level of TTR protein and TTR m RNA in placental villi in SA group was decreased（P<0.05）.These results indicate that TTR expression in placental villi is down-regulated in SA patients.5.In terms of thyroid hormone transporters（MCT8 and OATP1A1）: RT-PCR results showed that,compared with ETP group,there was no statistical significance in the expression levels of Thyroid hormone transporters（MCT8 and OATP1A1）in placental villi of SA group（P>0.05）.In terms of deiodinase（Dio2 and Dio3）: RT-PCR results showed that compared with ETP group,the m RNA levels of deiodinase（Dio2 and Dio3）in placental villi in SA group were significantly down-regulated（P<0.01;P<0.05）;Immunofluorescence test results showed that the fluorescence intensity of Dio2 in placental villi in SA group was lower than that in ETP group.Western Blot results showed that compared with ETP group,the expression level of Dio2 protein in placental villi in SA group was significantly down-regulated（P<0.01）.In terms of thyroid hormone receptors（THRα and THRβ）,RT-PCR results showed that compared with ETP group,the expression level of THRα m RNA in placental villi in SA group was significantly decreased（P<0.05）,but there was no statistical significance in THRβm RNA expression level（P>0.05）.Immunohistochemical results showed that compared with ETP group,the expression level of THRα protein in placental villi in SA group was decreased（P<0.05）,but there was no significant difference in THRβ protein expression level（P>0.05）.The above results indicated that the expressions of Dio2,Dio3 and THRα involved in thyroid hormone transport and metabolism in placental villi of SA patients were down-regulated,while MCT8,OATP1A1 and THRβ were not significantly changed.Conclusion:Abnormal placental villus thyroid hormone metabolism and transport in early pregnancy lead to the proliferation and apoptosis disorder of placental trophoblast cells,abnormal angiogenesis at the maternal-fetal interface,resulting in placental formation and development disorder,and inducing the occurrence of placenta-related adverse pregnancy outcomes,such as early spontaneous abortion,preeclampsia,IUGR and so on. |
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