Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Divisions of Critical Care and Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
J Physiol. 2019 May;597(10):2639-2650. doi: 10.1113/JP277775. Epub 2019 Apr 19.
Obstructive sleep apnoea (OSA) is a chronic condition characterized by intermittent hypoxia that induces oxidative stress and inflammation leading to cardiovascular disease. Women can develop OSA during late pregnancy, which is associated with adverse maternal and fetal outcomes. However, the effects of OSA throughout pregnancy on fetoplacental outcomes are unknown. Using a mouse model of intermittent hypoxia, we evaluated main uterine artery function, spiral artery remodelling, circulating angiogenic and anti-angiogenic factors, and placental hypoxia and oxidative stress at gestational day 14.5 in pregnant mice. Gestational intermittent hypoxia increased placental weight but decreased fetal weight, impaired uterine artery function, increased circulating angiogenic and anti-angiogenic factors, and induced placental hypoxia and oxidative stress, but had no impact on spiral artery remodelling. Our results suggest that pregnant women experiencing OSA during pregnancy could be at risk of maternal and fetal complications.
Obstructive sleep apnoea (OSA) is characterized by chronic intermittent hypoxia (IH) and is associated with increased inflammation, oxidative stress and endothelial dysfunction. OSA is a common sleep disorder and remains under-diagnosed; it can increase the risk of adverse maternal and fetal outcomes in pregnant women. We investigated the effects of gestational IH (GIH) on uterine artery function, spiral artery remodelling and placental circulating angiogenic and anti-angiogenic factors in pregnant female mice. WT C57BL/6 mice (8 weeks) were exposed to either GIH ( 12%) or intermittent air ( 21%) for 14.5 days of gestation. Exposure to GIH reduced fetal weight but increased placental weight. GIH dams had higher plasma levels of oxidative stress (8-isoprostane) and inflammatory markers (tumour necrosis factor-α). GIH significantly reduced uterine artery function as indicated by reduced endothelium-dependent vasodilatation and enhanced vasoconstriction. Plasma levels of placental angiogenic and anti-angiogenic markers (soluble fms-like tyrosine kinase-1, soluble endoglin, angiogenic placental growth factor-2 and vascular endothelial growth factor) were higher in pregnant mice exposed to GIH. There was no evidence of impaired spiral artery remodelling based on immunostaining with α-smooth muscle actin and cytokeratin-7, and also by measurements of lumen area. Immunostaining for markers of hypoxia (pimonidazole) and oxidative stress (4-hydroxynonenal) were higher in mice exposed to GIH. Our data show that GIH adversely affects uterine vascular function and may be a mechanism by which gestational OSA leads to adverse maternal and fetal outcomes.
阻塞性睡眠呼吸暂停（OSA）是一种以间歇性缺氧为特征的慢性疾病，可导致氧化应激和炎症，从而引发心血管疾病。女性在妊娠晚期可能会出现 OSA，这与不良的母婴结局有关。然而，OSA 在整个妊娠期间对胎-胎盘结局的影响尚不清楚。本研究使用间歇性低氧的小鼠模型，评估了妊娠 14.5 天时母体子宫动脉功能、螺旋动脉重塑、循环血管生成和抗血管生成因子以及胎盘缺氧和氧化应激。妊娠期间歇性低氧增加了胎盘重量，降低了胎儿体重，损害了子宫动脉功能，增加了循环血管生成和抗血管生成因子，并诱导了胎盘缺氧和氧化应激，但对螺旋动脉重塑没有影响。我们的研究结果表明，妊娠期间患有 OSA 的孕妇可能有发生母婴并发症的风险。
阻塞性睡眠呼吸暂停（OSA）的特征是慢性间歇性缺氧（IH），与炎症、氧化应激和内皮功能障碍增加有关。OSA 是一种常见的睡眠障碍，但仍未得到充分诊断；它会增加孕妇不良母婴结局的风险。本研究旨在探讨妊娠期 IH（GIH）对妊娠雌性小鼠子宫动脉功能、螺旋动脉重塑以及胎盘循环血管生成和抗血管生成因子的影响。WT C57BL/6 小鼠（8 周龄）接受 GIH（12%）或间歇性空气（21%）暴露 14.5 天。GIH 暴露降低了胎儿体重，但增加了胎盘重量。GIH 孕鼠的血浆氧化应激（8-异前列腺素）和炎症标志物（肿瘤坏死因子-α）水平升高。GIH 显著降低了子宫动脉功能，表现为内皮依赖性血管舒张功能降低和血管收缩增强。GIH 暴露的妊娠小鼠的胎盘血管生成和抗血管生成标志物（可溶性 fms 样酪氨酸激酶-1、可溶性内皮因子、血管生成胎盘生长因子-2 和血管内皮生长因子）水平升高。根据α-平滑肌肌动蛋白和细胞角蛋白-7免疫染色以及管腔面积测量，没有证据表明螺旋动脉重塑受损。GIH 暴露的小鼠中缺氧标志物（匹莫硝唑）和氧化应激标志物（4-羟基壬烯醛）的免疫染色增加。我们的数据表明，GIH 对子宫血管功能有不良影响，这可能是妊娠期 OSA 导致不良母婴结局的机制之一。
