LncRNA-SNX17 Promotes HTR-8/SVneo Proliferation and Invasion Through miR-517a/IGF-1 in the Placenta of Diabetic Macrosomia.

Gestational diabetes mellitus (GDM) has become a worldwide problem in recent years. Macrosomia, a primary consequence of GDM, has short-term and life-long consequences in the offspring of mothers with GDM. Our previous study showed that miR-517a was dysregulated in placenta and plasma of fetal growth restriction through inhibiting invasion of trophoblast and might be closely related with the regulation of birth weight by the placenta. To further investigate the mechanism of miR-517a, we conducted genome-wide microarray profile of lncRNAs. lncRNA-SNX17 was found to be significantly upregulated in the placenta of diabetic macrosomia by qRT-PCR, and the expression of miR-517a and IGF-1 were measured by qRT-PCR and Western blot. Interestingly, significant inverse correlations of the miR-517a with both lncRNA-SNX17 and IGF-1 expression were revealed in the placenta of diabetic macrosomia. Bioinformatic prediction also revealed that both lncRNA-SNX17 and IGF-1 possessed binding sites for miR-517a, which were then confirmed by luciferase report assay. LncRNA-SNX17 overexpression reduced the expression of miR-517a and increased the IGF-1 expression in HTR-8/SVneo human trophoblast cell line and thus enhanced the proliferation of HTR-8/SVneo. The enhancement of HTR-8/SVneo proliferation by lncRNA-SXN17 could be nullified by co-transfection of miR-517a mimics. The data suggested that lncRNA-SNX17 might promote the trophoblast proliferation through miR-517a/IGF-1 pathway and might play a role in the placentation of diabetic macrosomia.

Borderline subclinical hypothyroidism during first trimester of pregnancy in euthyroid patients with recurrent spontaneous abortion / 中华内分泌代谢杂志

Objective:To explore the risk factors of borderline subclinical hypothyroidism during first trimester of pregnancy in euthyroid patients with recurrent spontaneous abortion history.Methods:Among the 3 794 outpatients in the Sixth Obstetric Clinic of Shengjing Hospital of China Medical University from July 2017 to July 2019, 302 patients with recurrent spontaneous abortion and euthyroid function before pregnancy were selected after excluding those with abnormality in anatomy, coagulation, genetics, endocrine, infection, and immunology aspects through a systematic etiological screen. Exclusion of 62 patients with pre-pregnancy thyroid stimulating hormone (TSH) above 2.5 mIU/L, 240 recurrent spontaneous abortion patients were finally included. Borderline subclinical hypothyroidism is defined as the level of TSH higher than 2.5 mIU/L but less than the upper limit of pregnancy specific reference range during the first trimester. Among these 240 recurrent spontaneous abortion patients, 84 had borderline subclinical hypothyroidism and 156 were not. After analyzing the history, clinical and laboratory examination results of the two groups of patients, univariate analysis and multivariate logistic regression analysis were applied, to analyze and screen the high-risk factors of borderline subclinical hypothyroidism. Collinear diagnosis of regression analysis and correlation analysis were used to find out the if further relationships among the high-risk factors existed.Results:Univariate analysis suggested that conception method, pre-pregnancy TSH level, anti-nuclear antibody (ANA), lupus anticoagulant (LAC), and anti-β2 glycoprotein 1 (β2GP1) antibody were the potential high-risk factors ( P<0.1). Multivariate logistic regression analysis showed that pre-pregnancy TSH level>1.5 mIU/L ( OR=5.241, 95% CI 2.659-10.330), ANA positive ( OR=3.614, 95% CI 1.866-7.000), anti-β2GP1 antibody positive ( OR=3.415, 95% CI 1.176-9.917), and LAC positive ( OR=2.785, 95% CI 1.024-7.573) were independent risk factors of borderline subclinical hypothyroidism ( P<0.05 or P<0.01). No significant collinearity was found among the factors in the collinearity diagnosis. Except for the thyroid peroxidase antibody and thyroglobulin antibody ( P<0.01), no significant correlation was found among the non-organ-specific antibodies (NOSAs) and antithyroid antibodies. Conclusion:The level of pre-pregnancy TSH and NOSAs before pregnancy are the most important risk factors of borderline subclinical hypothyroidism during first trimester of pregnancy of euthyroid patients with recurrent spontaneous abortion history.