Hypoxic Preconditioning Enhances Cellular Viability and Migratory Ability: Role of DANCR/miR-656-3p/HIF-1α Axis in Placental Mesenchymal Stem Cells.

Preeclampsia (PE) is a common complication of pregnancy characterized by new-onset hypertension, albuminuria, or end-stage organ dysfunction, which is seriously harmful to maternal and infant health. Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from extraembryonic mesoderm. They have the potential for self-renewal, multidirectional differentiation, immunomodulation, and tissue regeneration. Several in vivo and in vitro experiments have confirmed that MSCs can delay the pathological progression of PE and improve maternal and fetal outcomes. However, the major limitations in the application of MSCs are their low-survival rates in ischemic and hypoxic disease areas after transplantation and their low rate of successful migration to the diseased regions. Therefore, enhancing cell viability and migration ability of MSCs in both ischemic and anoxic environments is important. This study aimed to investigate the effects of hypoxic preconditioning on the viability and migration ability of placental mesenchymal stem cells (PMSCs) and their underlying mechanisms. In this study, we found that hypoxic preconditioning enhanced the viability and migration ability of PMSCs, increased the expression of DANCR and hypoxia-inducible factor-1α (HIF-1α), and decreased the expression of miR-656-3p in PMSCs. Inhibiting the expression of HIF-1α and DACNR in PMSCs under hypoxia can inhibit the promotive effect of hypoxic preconditioning on viability and migration ability. In addition, RNA pull down and double luciferase assays confirmed that miR-656-3p could directly bind to DANCR and HIF-1α. In conclusion, our study showed that hypoxia could promote the viability and migration ability of PMSCs through the DANCR/miR-656-3p/HIF-1α axis.

Risk factors for abnormal glucose metabolism in pregnant women with a history of gestational diabetes mellitus / 中华围产医学杂志

Objective:To study the risk factors for abnormal glucose metabolism in pregnant women with a history of gestational diabetes mellitus (GDM).Methods:A retrospective analysis was performed on pregnant women who had two consecutive deliveries and were was complicated by GDM in the previous pregnancy at the First Affiliated Hospital of Sun Yat-sen University from January 2011 to May 2019. Clinical data of both pregnancies were collected, including general information, fasting blood glucose in early pregnancy and 75 g oral glucose tolerance test (OGTT) results, glycosylated hemoglobin A1c and blood lipid profile at 24-28 gestational weeks. The incidence and risk factors of abnormal glucose metabolism in these cases during the present pregnancy were analyzed. Analysis of variance, Kruskal-Wallis test, SNK- q or LSD- t-test, and Chi-square test were used for data analysis. Single-factor logistic regression analysis was used to analyze the high-risk factors, and multifactor logistic regression analysis was performed to fit the model. Variable collinearity diagnosis was performed using the coldiag2 command. Results:(1) A total of 455 cases were enrolled in the study. According to the fasting glucose level in the first trimester and the OGTT results in the present pregnancy, they were divided into three groups: normal OGTT group ( n=240), GDM group ( n=189), and pre-gestational diabetes mellitus group (PGDM, n=26). The incidence of abnormal glucose metabolism in these patients during the present pregnancy was 47.2% (215/455). (2) Those with a history of GDM had higher pre-pregnancy weight, lower weight gain, higher cesarean section rate, smaller gestational age at delivery, and higher neonatal birth weight in the present pregnancy than those in the previous pregnancy [(55.6±8.5) vs (53.3±7.9) kg, t=-4.059; (11.2±4.2) vs (12.5±4.4) kg, t=4.435; 47.9% (218/455) vs 33.0% (150/455), χ2=20.481; (38.6±1.3) vs (38.8±1.3) weeks, t=2.288; (3 177±463) and (3 114±460) g, t=-2.044; all P<0.05]. (3) In the PGDM group, the 2-h plasma glucose level after 75 g OGTT was higher than that in the previous pregnancy [(11.4±1.1) vs (9.9±1.7) mmol/L, t=-3.299, P=0.002]. (4) In the present pregnancy, the PGDM group had the highest fasting blood glucose in early pregnancy, followed by the GDM group and the normal OGTT group [4.6 mmol/L (4.2-7.6 mmol/L), 4.3 mmol/L (4.0-4.6 mmol/L) and 4.1 mmol/L (3.8-4.4 mmol/L), χ2=34.498, P<0.001]. The PGDM group had the least postpartum weight retention, followed by the normal OGTT group and the GDM group [(1.2±3.9), (1.6±3.9), and (2.6±4.9) kg, F=3.086, P<0.05]. (5) Multivariate logistic regression analysis showed postpartum weight retention and the 1-h and 2-h plasma glucose levels after 75 g OGTT in the previous pregnancy were independent risk factors for abnormal glucose metabolism in pregnant women with a history of GDM (postpartum weight retention: OR=1.054, 95% CI: 1.005-1.106; 1-h plasma glucose: OR=1.284, 95% CI: 1.087-1.516; 2-h plasma glucose: OR=1.272, 95% CI: 1.071-1.511). Conclusions:The incidence of abnormal glucose metabolism is higher in subsequent pregnancy in women with GDM history, which may be related to various factors, such as postpartum weight retention and plasma glucose after 75 g OGTT in the previous pregnancy.

Postpartum follow-up and management of gestational diabetes mellitus: comments on relevant issues in American College of Obstetricians and Gynecologists (ACOG) and America Diabetes Association (ADA) guidelines in 2018 / 中华围产医学杂志

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance of variable severity with onset or first recognition during pregnancy.Short-and long-term effects of GDM on both mother and child depend on the severity of the condition and blood sugar level.Currently,relatively standardized guidance on management of GDM in China has greatly improved maternal and infant outcomes.Moreover,standardized postpartum management and monitoring are also essential for the prevention of long-term complications in this population.The guidelines issued by America Diabetes Association (ADA) and American College of Obstetricians and Gynecologists (ACOG) in 2018 recommended that GDM patients should be followed up at 4-12 weeks postpartum for a 75 g oral glucose tolerance test.For those who is normal at the first postpartum follow up,it is necessary to have their blood glucose tested once every 1-3 years.However,for those who is abnormal,medication should also be initiated when necessary in addition to more frequent follow-ups and nutritional intervention and physical exercise.