Mother Infant Research Institute, Tufts Medical Center, Boston, MA 02111, USA.
Magee Womens Research Institute, Pittsburgh, PA 15213, USA.
J Clin Endocrinol Metab. 2021 Nov 19;106(12):3526-3535. doi: 10.1210/clinem/dgab571.
An increase in maternal insulin resistance (IR) during pregnancy is essential for normal fetal growth. The mechanisms underlying this adaptation are poorly understood. Placental factors are believed to instigate and maintain these changes, as IR decreases shortly after delivery. Methylation of placental gene loci that are common targets for miRNAs are associated with maternal IR.
We hypothesized that placental miRNAs targeting methylated loci are associated with maternal IR during late pregnancy.
We collected placentas from 132 elective cesarean sections and fasting blood samples at delivery to estimate maternal homeostasis model assessment of insulin resistance (HOMA-IR). Placental miRNA expression was measured via whole genome small-RNA sequencing in a subset of 40 placentas selected by maternal pre-gravid body mass index (BMI) and neonatal adiposity. Five miRNAs correlated with maternal HOMA-IR and previously identified as targeting methylated genes were selected for validation in all 132 placenta samples via RT-qPCR. Multiple regression adjusted for relevant clinical variables.
Median maternal age was 27.5 years, with median pre-pregnancy BMI of 24.7 kg/m2, and median HOMA-IR of 2.9. Among the 5 selected miRNA, maternal HOMA-IR correlated with the placental expression of miRNA-371b-3p (r = 0.25; P = 0.008) and miRNA-3940-3p (r = 0.32; P = 0.0004) across the 132 individuals. After adjustment for confounding variables, placental miRNA-3940-3p expression remained significantly associated with HOMA-IR (β = 0.16; P = 0.03).
Placental miRNA-3940-3p was associated with maternal IR at delivery. This placental miRNA may have an autocrine or paracrine effect-regulating placental genes involved in modulating maternal IR.
妊娠期间母体胰岛素抵抗（IR）的增加对于正常胎儿生长至关重要。这种适应的机制尚不清楚。据信胎盘因素引发并维持这些变化，因为产后 IR 会很快下降。胎盘基因座的甲基化是 miRNA 的常见靶点，与母体 IR 相关。
我们假设针对甲基化基因座的胎盘 miRNA 与妊娠晚期母体 IR 相关。
我们收集了 132 例择期剖宫产的胎盘和分娩时的空腹血样，以估计母体稳态模型评估的胰岛素抵抗（HOMA-IR）。在通过母体孕前体重指数（BMI）和新生儿肥胖选择的 40 个胎盘的亚集中，通过全基因组小 RNA 测序测量胎盘 miRNA 表达。与母体 HOMA-IR 相关且先前被鉴定为靶向甲基化基因的 5 个 miRNA 通过 RT-qPCR 在所有 132 个胎盘样本中进行验证。多变量回归调整了相关临床变量。
中位母体年龄为 27.5 岁，中位孕前 BMI 为 24.7kg/m2，中位 HOMA-IR 为 2.9。在 5 个选定的 miRNA 中，miRNA-371b-3p（r=0.25；P=0.008）和 miRNA-3940-3p（r=0.32；P=0.0004）与 132 名个体的胎盘表达相关。在调整混杂变量后，胎盘 miRNA-3940-3p 的表达仍与 HOMA-IR 显著相关（β=0.16；P=0.03）。
胎盘 miRNA-3940-3p 与分娩时母体 IR 相关。这种胎盘 miRNA 可能具有自分泌或旁分泌作用，调节参与调节母体 IR 的胎盘基因。
