Clinical and pathological characteristics of gestational diabetes mellitus with different insulin resistance.

AIMS: To elucidate the clinical and pathological characteristics of gestational diabetes mellitus (GDM) with high and low insulin resistance. METHODS: In total, 1393 GDM and 1001 non-GDM singleton deliveries were included in this study. Insulin resistance subtypes were classified according to the HOMA2-IR value. Clinical data were analyzed using SPSS 26.0. Placenta samples were collected for pathological analysis. RESULTS: Maternal age and fasting glucose were identified as independent risk factors for GDM with high insulin resistance (p < 0.01), while fasting glucose was the sole risk factor for GDM with low insulin resistance (p < 0.001). Fetal distress was associated with both of GDM subtypes (both p < 0.01), while anemia, fetal growth restriction, large for gestational age and intrahepatic cholestasis in pregnancy were related to specific GDM insulin resistance subtype. In addition, GDM with high insulin resistance showed an increase of syncytial knots with down-regulation of PI3K/AKT signaling, while GDM with low insulin resistance showed normal syncytial knot counts and up-regulation of PI3K/AKT signaling. CONCLUSIONS: Our findings provide novel perspectives to the clinical and pathological comprehensions of GDM with high and low insulin resistance, which might facilitate the mechanism study of GDM and its precision pregnancy management.

The Role of Osteocalcin in Placental Function in Gestational Diabetes Mellitus.

Evidence for the role of osteocalcin in glucose metabolism is increasing. The aim of this study was to examine the associations between osteocalcin and gestational diabetes mellitus. Thirteen discovery study subjects and 76 reduplication study subjects were recruited from the Maternal and Child Health Hospital Guangxi Zhuang Autonomous Region from May 2018 to August 2018. Total osteocalcin and biochemical indices of maternal serum and umbilical vein serum were analyzed. Placental tissue samples were used for transcriptome sequencing. For the discovery study subjects, the total osteocalcin concentration in umbilical vein serum was significantly higher than that in maternal serum and umbilical artery serum (55.32 ng/mL ± 17.37 vs. 12.06 ng/mL ± 5.42 [P < 0.001] vs. 38.31 ng/mL ± 11.52 [P < 0.01]), suggesting that trophoblasts may synthesize osteocalcin. In a reduplication subject study, the gestational diabetes mellitus group had lower umbilical vein serum total osteocalcin (51.46 ng/mL ± 24.29 vs. 67.00 ng/mL ± 25.33, P = 0.008), lower adiponectin (1099.72 µg/L ± 102.65 vs. 1235.85 µg/L ± 94.63, P < 0.001). Spearman's correlation analysis showed that umbilical vein serum total osteocalcin levels were closely correlated with leptin (r = -0.456, P = 0.007). A coexpression model of the placental RNA sequence was constructed. Two modules were correlated with osteocalcin, and the Gene ontology pathways of these modules were rich in glucose and lipid metabolism. In conclusion, the placenta may synthesize osteocalcin by itself, and a lower osteocalcin level in umbilical vein serum is associated with gestational diabetes mellitus.

The expression and biological function of chemokine CXCL12 and receptor CXCR4/CXCR7 in placenta accreta spectrum disorders.

OBJECTIVES: Investigation of mechanism related to excessive invasion of trophoblast cells in placenta accreta spectrum disorders (PAS) provides more strategies and ideas for clinical diagnosis and treatment. MATERIALS AND METHODS: Blood and placental samples were collected from included patients. The distribution and expression of CXCL12, CXCR4 and CXCR7 proteins in the paraffin of placental tissue in the included cases were analysed, and we analyse the downstream pathways or key proteins involved in cell invasion. RESULTS: Firstly, our results determined that CXCL12 and CXCR4/CXCR7 were increased in extravillous trophoblastic cell (CXCL12: P < .001; CXCR4: P < .001; CXCR7: P < .001), and the expression levels were closely related to the invasion depth of trophoblastic cells. Secondly, CXCL12 has the potential to become a biochemical indicator of PAS since the high expression of placental trophoblast CXCL12 may be an important source of blood CXCL12. Using lentivirus-mediated RNA interference and overexpression assay, it was found that both chemokine CXCL12 and receptor CXCR4/CXCR7 are associated with regulation of trophoblast cell proliferation, migration and invasion. Further results proved that through the activating the phosphorylation and increasing the expression of MLC and AKT proteins in the Rho/rock, PI3K/AKT signalling pathway, CXCL12, CXCR4 and CXCR7 could up-regulate the expression of RhoA, Rac1 and Cdc42 proteins to promote the migration and invasion of extravillous trophoblastic cell and ultimately formate the placenta accrete compare to the normal placenta. CONCLUSIONS: Our research proved that trophoblasts may contribute to a PAS-associated increase in CXCL12 levels in maternal blood. CXCL12 is not only associated with biological roles of PAS, but may also be potential for prediction of PAS.