Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia; Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan.
Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia.
Placenta. 2023 Jul;138:1-9. doi: 10.1016/j.placenta.2023.04.012. Epub 2023 Apr 18.
Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is important for saturated phosphatidylcholine (Sat-PC) production in the lung. Sat-PC is a critical component of pulmonary surfactant, which maintains low alveolar surface tension, facilitating respiration. Previous studies have reported an association between maternal and fetal LPCAT1 levels and neonatal lung function. Using a sheep model of pregnancy, we investigated a potential correlation between glucocorticoid-induced lung maturation and LPCAT1 mRNA and/or protein levels in the fetal lung, the placenta, the fetal plasma, and the maternal plasma.
Eighty seven single pregnant ewes received maternal intramuscular injections of betamethasone. A sub-group of five animals had both maternal and fetal catheters installed to allow for sequential sampling from both plasma compartments. Lambs were surgically delivered under terminal anaesthesia between 2 and 8 days after initial ANS treatment, at a gestational age of 121-123 days. Lambs were ventilated for 30 min to determine functional lung maturation before being euthanized for necropsy and sample collection. Fetal lung, placenta, and fetal and maternal plasma samples were used to analyse LPCAT1 gene expression and protein levels.
The expression of LPCAT1 mRNA in the fetal lung was significantly corelated to Sat-PC levels at 8 days (R = 0.23, p < 0.001) and lung maturation status overall (gas exchange efficiency as determined by measurements of lamb PaCO during ventilation, R = 0.20, p < 0.001). Similarly, fetal lung LPCAT1 mRNA was also significantly correlated with the individual durability of ANS effects on fetal lung maturation (R = 0.20, p < 0.001). Although ANS therapy altered LPCAT1 mRNA expression in the placenta, observed changes were independent of fetal lung maturation outcomes. Neither maternal nor fetal plasma LPCAT1 levels were changed by ANS therapy over the period, including in analysis of serial maternal and fetal samples from chronically catheterised animals.
LPCAT1 expression in the fetal lung was associated with the durability of glucocorticoid effects on fetal lung maturation. However, LPCAT1 expression in the placenta, the fetal plasma, and the maternal plasma was neither associated with, nor predictive of fetal lung maturation after glucocorticoid treatment in a sheep model of pregnancy.
溶血磷脂酰胆碱酰基转移酶 1（LPCAT1）对于肺部饱和磷脂酰胆碱（Sat-PC）的产生很重要。Sat-PC 是肺表面活性剂的关键组成部分，可维持低肺泡表面张力，促进呼吸。先前的研究报告了母胎 LPCAT1 水平与新生儿肺功能之间的关联。本研究使用妊娠绵羊模型，研究了糖皮质激素诱导的肺成熟与胎儿肺、胎盘、胎儿血浆和母体血浆中 LPCAT1mRNA 和/或蛋白水平之间的潜在相关性。
87 只单胎妊娠母羊接受了肌内注射倍他米松。5 只动物的子组安装了母胎导管，以便从两个血浆隔室进行顺序取样。羊在初次 ANS 处理后 2-8 天，在妊娠 121-123 天时进行手术分娩，处于终末麻醉下。羔羊进行通气 30 分钟以确定功能肺成熟度，然后安乐死进行尸检和样本采集。使用胎儿肺、胎盘以及胎儿和母体血浆样本来分析 LPCAT1 基因表达和蛋白水平。
胎儿肺 LPCAT1mRNA 的表达与 8 天时的 Sat-PC 水平（R=0.23，p<0.001）和总体肺成熟度显著相关（通气期间羔羊 PaCO2 的测量确定的气体交换效率，R=0.20，p<0.001）。同样，胎儿肺 LPCAT1mRNA 也与 ANS 对胎儿肺成熟的影响的个体持续时间显著相关（R=0.20，p<0.001）。尽管 ANS 治疗改变了胎盘的 LPCAT1mRNA 表达，但观察到的变化与胎儿肺成熟结局无关。在这段时间内，包括对慢性置管动物进行的母体和胎儿样本的系列分析，母体和胎儿血浆中的 LPCAT1 水平均未因 ANS 治疗而改变。
胎儿肺中的 LPCAT1 表达与糖皮质激素对胎儿肺成熟的持续时间有关。然而，在妊娠绵羊模型中，胎盘、胎儿血浆和母体血浆中的 LPCAT1 表达与糖皮质激素治疗后的胎儿肺成熟既无关联，也不能预测胎儿肺成熟。
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