Rätsep Matthew T, Hickman Andrew F, Croy B Anne
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Placenta. 2016 Dec;48 Suppl 1:S40-S46. doi: 10.1016/j.placenta.2016.02.001. Epub 2016 Feb 6.
Preeclampsia (PE) is a significant gestational disorder affecting 3-5% of all human pregnancies. In many PE pregnancies, maternal plasma is deficient in placental growth factor (PGF), a placentally-produced angiokine. Beyond immediate fetal risks associated with acute termination of the pregnancy, offspring of PE pregnancies (PE-F1) have higher long-term risks for hypertension, stroke, and cognitive impairment compared to F1s from uncomplicated pregnancies. At present, mechanisms that explain PE-F1 gains in postpartum risks are poorly understood. Our laboratory found that mice genetically-deleted for Pgf have altered fetal and adult brain vascular development. This is accompanied by sexually dimorphic alterations in anatomic structure in the adult Pgf brain and impaired cognitive functions. We hypothesize that cerebrovascular and neurological aberrations occur in fetuses exposed to the progressive development of PE and that these brain changes impair cognitive functioning, enhance risk for stroke, elevate severity of stroke, and lead to worse stroke outcomes. These brain and placental outcomes may be linked to down-regulated PGF gene expression in early pre-implantation embryos, prior to gastrulation. This review explores our hypothesis that there are mechanistic links between low PGF detection in maternal plasma prodromal to PE, PE, and altered brain vascular, structural, and functional development amongst PE-F1s. We also include a summary of preliminary outcomes from a pilot study of 7-10 year old children that is the first to report magnetic resonance imaging, magnetic resonance angiography, and functional brain region assessment by eye movement control studies in PE-F1s.
子痫前期（PE）是一种严重的妊娠疾病，影响着3%至5%的人类妊娠。在许多患子痫前期的妊娠中，母体血浆中缺乏胎盘生长因子（PGF），这是一种由胎盘产生的血管生成素。除了与妊娠急性终止相关的直接胎儿风险外，子痫前期妊娠的后代（PE-F1）与正常妊娠的F1相比，患高血压、中风和认知障碍的长期风险更高。目前，解释PE-F1产后风险增加的机制尚不清楚。我们实验室发现，基因敲除Pgf的小鼠的胎儿和成年大脑血管发育发生了改变。这伴随着成年Pgf大脑解剖结构的性别差异改变和认知功能受损。我们假设，暴露于子痫前期进展过程中的胎儿会出现脑血管和神经异常，这些大脑变化会损害认知功能，增加中风风险，提高中风严重程度，并导致更差的中风预后。这些大脑和胎盘的结果可能与原肠胚形成前早期植入前胚胎中PGF基因表达下调有关。本综述探讨了我们的假设，即子痫前期前驱期母体血浆中低PGF检测、子痫前期与子痫前期后代（PE-F1）大脑血管、结构和功能发育改变之间存在机制联系。我们还总结了一项针对7至10岁儿童的试点研究的初步结果，该研究首次报告了对子痫前期后代（PE-F1）进行磁共振成像、磁共振血管造影以及通过眼动控制研究进行功能性脑区评估的结果。
