Abstract:Objective To assess the relationship between serum sex hormone-binding globulin (SHBG) concentrations and the risk of gestational diabetes mellitus (GDM) in early and midterm pregnancies and the effect of SHBG on the biological behavior of trophoblast cells. Methods During the period from March 2020 to March 2022, 65 GDM patients (case group) and 130 healthy pregnant women (control group) who were in early pregnancy (before 14 weeks) or middle pregnancy (14-28 weeks) were selected as the research objects. Serum SHBG level was measured by ELISA kit. In vitro, the trophoblast cell line HTR-8/SVneo was selected as the research object, which was divided into high glucose (HG) group and control group [normal glucose (NG) group]. HG group cells were transfected with SHBG plasmid or Vector. Cell proliferation, migration and invasion were investigated by cell counting kit, wound healing test and Transwell test. Results Serum SHBG concentrations were significantly higher in the GDM group compared to the control group. Also, pregnant women who subsequently developed GDM showed significantly higher serum SHBG concentrations in early pregnancy than controls. Logistic regression analysis showed an adjusted OR of 2.74(95%CI: 1.17-6.43) for the occurrence of GDM in the lowest tertile of serum SHBG. In addition, the multivariate adjusted OR for GDM was 1.49(95%CI: 1.05-2.12) for each standard deviation reduction in serum SHBG. Compared with the NG group, the HG group showed reduced expression of SHBG in HTR8/SVneo cells, decreased cell viability, and diminished cell migration and invasion. Compared with the HG+Vector group, the expression of SHBG in HTR8/SVneo cells was upregulated, cell viability was increased, and cell migration and invasion were enhanced in the HG+SHBG group. Conclusions The risk of GDM in pregnant women with low serum SHBG concentration increases significantly, and the up-regulation of SHBG promotes the proliferation and migration of trophoblasts in HG background.
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