Department of Obstetrics and Gynecology, Aichi Medical University School of Medicine, Nagakute, Japan.
J Matern Fetal Neonatal Med. 2021 Feb;34(3):353-359. doi: 10.1080/14767058.2019.1608175. Epub 2019 May 2.
This study aimed to investigate the etiology and pathology of preeclampsia (PE), a two-stage disorder involving uteroplacental dysfunction resulting from abnormal implantation and placentation, and gestational hypertension (GH), for which maternal organic vascular disorder is often an underlying factor. We assessed concentrations of oxygen free radicals (d-ROMs), maternal angiogenic factor (PlGF), and antiangiogenic factor (sFlt-1), placental hypoxic changes, oxidative DNA damage, and maternal organic vascular disorders in 23 women with PE (PE group), 13 with GH (GH group), and 16 with uncomplicated pregnancies (normal group). Intima-media thickness (IMT) of the carotid artery was assessed as a proxy for maternal organ vascular disorder. Immunohistochemical analysis was performed to measure the proportion of placental trophoblast cell nuclei staining positive for hypoxia-inducible factor-1α (HIF-1α), which reflects hypoxic changes, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), which reflects oxidative DNA damage. Maternal serum d-ROM concentrations were significantly increased in both GH and PE groups relative to the normal group. Maternal serum d-ROM concentrations were significantly increased in both GH and PE groups relative to the normal group. Maternal serum sFlt-1 concentrations, ratio of sFlt-1/PlGF, and proportions of HIF-1α-positive nuclei and 8-OHdG-positive nuclei were significantly higher in the PE group compared to GH and normal groups. IMT was significantly greater in GH and PE groups compared to the normal group, and was higher in the GH group compared to the PE group. Our findings suggest that placental hypoxic changes and oxidative DNA damage are severe in patients with PE and accompanied by an increase in antiangiogenic factors. Moreover, maternal organ vascular disorder was more severe in patients with GH compared to those with PE, as assessed by IMT. PE is a two-stage disorder that involves uteroplacental dysfunction, and organic vascular disorder underlies GH.
本研究旨在探讨子痫前期（PE）和妊娠高血压（GH）的病因和病理学。PE 是一种两阶段疾病，涉及胎盘功能障碍，其病因是异常的着床和胎盘形成；GH 常由母体血管病变引起。我们评估了 23 例 PE 患者（PE 组）、13 例 GH 患者（GH 组）和 16 例正常妊娠患者（正常组）的氧自由基（d-ROMs）、母源性血管生成因子（PlGF）和血管生成抑制因子（sFlt-1）浓度、胎盘缺氧变化、氧化 DNA 损伤和母体血管病变。颈动脉内-中膜厚度（IMT）作为母体器官血管病变的替代指标进行评估。采用免疫组织化学分析方法测量胎盘滋养细胞细胞核缺氧诱导因子-1α（HIF-1α）阳性比例，反映缺氧变化，以及 8-羟基-2'-脱氧鸟苷（8-OHdG），反映氧化 DNA 损伤。与正常组相比，GH 组和 PE 组的母体血清 d-ROM 浓度均显著升高。与 GH 组和正常组相比，PE 组的母体血清 sFlt-1 浓度、sFlt-1/PlGF 比值、HIF-1α 阳性核和 8-OHdG 阳性核的比例均显著升高。与正常组相比，GH 组和 PE 组的 IMT 显著增加，且 GH 组高于 PE 组。我们的研究结果表明，PE 患者的胎盘缺氧变化和氧化 DNA 损伤严重，并伴有抗血管生成因子的增加。此外，与 PE 患者相比，GH 患者的母体器官血管病变更为严重，可通过 IMT 评估。PE 是一种两阶段疾病，涉及胎盘功能障碍，GH 的病因是血管病变。
