School of Biomedical Sciences, The University of Queensland, St Lucia, Australia.
Child Health Research Centre, The University of Queensland, South Brisbane, Australia.
Reprod Sci. 2021 May;28(5):1390-1402. doi: 10.1007/s43032-020-00413-1. Epub 2021 Jan 6.
Maternal alcohol consumption during pregnancy results in elevated vulnerability to intrauterine growth restriction, preterm birth, miscarriage, and stillbirth. Many of the detrimental effects of fetal alcohol exposure may be mediated through placental dysfunction; however, the exact mechanisms remain unknown. Here, we aimed to determine the effect of maternal alcohol exposure prior to and during early pregnancy on placental glucocorticoid receptor (GR) isoforms, associated GR regulated genes, and infant outcomes. Participants carrying singleton fetuses (n = 113) were recruited during early pregnancy. Amount and type of alcohol consumed over the last 12 months were obtained at 18 weeks of gestation. The level of drinking was separated into none (0 g/day), low (< 10 g/day), moderate (10-100 g/day), and heavy (> 100 g/day). At delivery, placental weight, infant sex, birthweight, and head circumference were recorded. Placental GR isoforms and genes involved in downstream signalling pathways were quantified. The majority of women (70.8%) consumed alcohol. Of these, most consumed low (48.8%) or moderate (37.5%) amounts. Placental weight was unaffected by alcohol consumption, but infants born to heavy drinkers tended to be lighter at birth. In female, but not male, placentae, maternal alcohol consumption resulted in increased GRαC and decreased GRαD1 cytoplasmic expression. In both female and male placentae, a dampened inflammatory response was evident with maternal alcohol consumption, involving downregulated IL6R and upregulated POU2F2 gene expression, respectively. Maternal alcohol consumption in the months prior to, and/or during early, pregnancy alters placental GR isoform and expression of some inflammatory genes in a sex-specific manner.
母亲在怀孕期间饮酒会导致胎儿易患宫内生长受限、早产、流产和死产。胎儿酒精暴露的许多有害影响可能是通过胎盘功能障碍介导的；然而，确切的机制尚不清楚。在这里，我们旨在确定母亲在怀孕前和怀孕早期饮酒对胎盘糖皮质激素受体 (GR) 同工型、相关 GR 调节基因和婴儿结局的影响。招募了携带单胎胎儿的参与者（n=113）在孕早期进行。在 18 周妊娠时获得过去 12 个月内消耗的酒精量和类型。饮酒量分为零（0g/天）、低（<10g/天）、中（10-100g/天）和高（>100g/天）。分娩时记录胎盘重量、婴儿性别、出生体重和头围。定量分析胎盘 GR 同工型和下游信号通路相关基因。大多数女性（70.8%）饮酒。其中，大多数人低（48.8%）或中等（37.5%）饮酒。饮酒对胎盘重量没有影响，但重度饮酒者的婴儿出生时体重较轻。在女性而非男性胎盘中，母体饮酒导致 GRαC 增加和 GRαD1 细胞质表达减少。在女性和男性胎盘中，母体饮酒导致炎症反应减弱，分别表现为 IL6R 下调和 POU2F2 基因表达上调。母亲在怀孕前几个月和/或怀孕早期饮酒会以性别特异性的方式改变胎盘 GR 同工型和某些炎症基因的表达。
