Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model.
Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model.
复制标题
DOI：
10.1095/biolreprod.116.142273
复制
发表时间：
2016-12
影响因子：
3.6
通讯作者：
Telugu BP
中科院分区：
文献类型：
--
作者：
Thompson LP;Pence L;Pinkas G;Song H;Telugu BP
慢性胎盘缺氧是导致先兆子痫和母体高血压的胎盘不适的根本原因之一。慢性缺氧导致滋养层（TB）发育中断、侵入母体蜕膜和母体螺旋动脉重塑。妊娠豚鼠具有与人类相似的特征，如血单绒膜胎盘、绒毛状胎盘、深部结核侵袭和母体动脉重塑，是研究胎盘发育的理想动物模型。我们假设，慢性胎盘缺氧的怀孕豚鼠抑制结核病的侵袭和改变螺旋动脉重塑。将同期交配的妊娠豚鼠从妊娠20天至中期（39-40天）或足月（60-65天）暴露于常氧（NMX）或三种缺氧水平（HPX：16%、12%或10.5%O2）。足月时，HPX（10.5%O2）使母体动脉血压升高（HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3，P < 0.001），胎儿体重降低16.1%（P < 0.05），胎盘绝对和相对重量分别增加10.1%和31.8%（P < 0.05）。在中期，HPX胎盘中TB增殖显著增加，如通过增加的PCNA和KRT 7染色以及升高的ESX 1（TB标记物）基因表达所证实的（P < 0.05）。此外，定量图像分析显示TB细胞对母体血管的侵袭减少。总之，胎盘HPX的这种动物模型鉴定了异常胎盘发育的几个方面，包括TB增殖增加和TB迁移和侵入螺旋动脉减少，其后果与母体高血压和胎儿生长受限相关。
Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O2) from 20 day gestation until midterm (39–40 days) or term (60–65 days). At term, HPX (10.5% O2) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction.