Role of oxygen in fetoplacental endothelial responses: hypoxia, physiological normoxia, or hyperoxia?
- 作者列表："Zhou C","Zou QY","Jiang YZ","Zheng J
:During pregnancy, placental vascular growth, which is essential for supporting the rapidly growing fetus, is associated with marked elevations in blood flow. These vascular changes take place under chronic physiological low O2 (less than 2-8% O2 in human; chronic physiological normoxia, CPN) throughout pregnancy. O2 level below CPN pertinent to the placenta results in placental hypoxia. Such hypoxia can cause severe endothelial dysfunction, which is associated with adverse pregnancy outcomes (e.g., preeclampsia) and high risk of adult-onset cardiovascular diseases in children born to these pregnancy complications. However, our current knowledge about the mechanisms underlying fetoplacental endothelial function is derived primarily from cell models established under atmospheric O2 (~21% O2 at sea level, hyperoxia). Recent evidence has shown that fetoplacental endothelial cells cultured under CPN have distinct gene expression profiles and cellular responses compared with cells cultured under chronic hyperoxia. These data indicate the critical roles of CPN in programming fetal endothelial function and prompt us to re-examine the mechanisms governing fetoplacental endothelial function under CPN. Better understanding these mechanisms will facilitate us to develop preventive and therapeutic strategies for endothelial dysfunction-associated diseases (e.g., preeclampsia). This review will provide a brief summary on the impacts of CPN on endothelial function and its underlying mechanisms with a focus on fetoplacental endothelial cells.
: 在怀孕期间，胎盘血管生长 (对于支持快速生长的胎儿至关重要) 与血流量的显着升高有关。这些血管变化在整个怀孕期间在慢性生理低O2 (人类小于2-8% O2; 慢性生理常氧，CPN) 下发生。O2水平低于与胎盘相关的CPN导致胎盘缺氧。这种缺氧可导致严重的内皮功能障碍，这与不良妊娠结局 (例如，先兆子痫) 和这些妊娠并发症所生儿童的成年发病心血管疾病的高风险相关。然而，我们目前对胎儿胎盘内皮功能机制的了解主要来自在大气O2 (海平面约21% O2，高氧) 下建立的细胞模型。最近的证据表明，与在慢性高氧下培养的细胞相比，在CPN下培养的胎儿胎盘内皮细胞具有不同的基因表达谱和细胞反应。这些数据表明CPN在编程胎儿内皮功能中的关键作用，并提示我们重新审视CPN下控制胎儿胎盘内皮功能的机制。更好地理解这些机制将有助于我们开发内皮功能障碍相关疾病 (例如，先兆子痫) 的预防和治疗策略。本文就CPN对内皮细胞功能的影响及其机制作一综述。
METHODS::Background: The exact cause of preeclampsia remains unknown. The past decade has seen an ongoing debate on the relative importance of primipaternity versus prolonged birth/pregnancy interval.Aims: The aim of the current study was to analyze these two major potential risk factors in a high risk population in the Northern suburbs of Adelaide; a socioeconomically disadvantaged area characterized by instable relationships and overall poor health and lifestyle.Methods: A retrospective cohort study was performed on all multigravid women birthing at the Lyell McEwin Hospital, Adelaide, from July 2011 to August 2012; 2003 patients were included in this analysis. Basic demographic data, previous pregnancy outcomes, paternity, and birth and pregnancy intervals were recorded.Results: Women with a previously normal pregnancy had a significantly increased risk of developing preeclampsia in subsequent pregnancy with a new paternity (OR: 2.27 [p = .015]). Increasing birth and pregnancy intervals were associated with a significantly increased risk of developing preeclampsia in later pregnancies, with OR 1.39 at 3 years (p = .042) and OR 2.05 at 4 years (p = .002).Conclusions: The results of this study indicate that both prolonged birth interval and primipaternity are independent risk factors for preeclampsia in multigravidae.
METHODS::Introduction: Philadelphia-negative myeloproliferative neoplasms (MPNs) greatly increase the risk of maternal and fetal complications during pregnancy. Currently, international agreements regarding the management of these women are lacking.Patients and methods: Our study aimed to assess the current management and outcomes of MPN pregnancies in a French cohort. We retrospectively analyzed 27 pregnancies in women with MPNs that were associated with a specific mutation. Nineteen pregnancies in nine women with essential thrombocythemia and eight pregnancies in five women with polycythemia vera were identified.Results: Our study showed 70% live births, but only 30% uneventful pregnancies. Fetal complications were mainly early spontaneous abortions (22%), fetal growth restriction (15%), and premature delivery (15%). Maternal issues were divided between thrombosis (15%) and hemorrhages (11%). High rates of preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome (15%) were reported. Uterine artery Doppler was performed in 70% pregnancies. Abnormal Doppler results were found in 43% pregnancies. Pregnancies with high platelet counts and packed cell volume remaining static or increasing ended with fetal death and utero-placental dysfunction. According to expert consensus, most of the pregnancies (67%) could be stratified in the high risk group and had a bad obstetrical outcome, with 50% standard-risk pregnancies versus 22% high-risk pregnancies that were uneventful. Higher risk pregnancies were prescribed heparin and/or interferon α in 72%.Conclusions: The prognosis of these pregnancies remains very bad and may be improved by a more effective collaboration between specialists as well as a therapeutic intensification including heparin and interferon α.
METHODS::Purpose: The challenge to obtain improved predictive tools, able to identify women destined to develop preeclampsia (PE), is raising the interest of researchers for the attractive chance to allow for timely initiation of prophylactic therapy, appropriate antenatal surveillance, and better-targeted research into preventive interventions. We aimed to gather all the evidence reported up to now in scientific literature relating to all prediction tests for PE.Materials and methods: We searched articles on conventional literature platforms from January 1952 to August 2016, using the terms "preeclampsia," "gestational preeclampsia," and "gestational hypertensive disorders" combined with "predictive test" and "risk assessment." Abstracts/titles identified by the search were screened by three investigators.Results: The search identified 203 citations, of which 154 potentially relevant after the initial evaluation. Among these studies, 20 full articles were excluded, therefore, 134 primary studies met the criteria for inclusion and were analyzed.Conclusions: Current evidence suggests that a combination of several features may provide the best predictive accuracy for the identification of PE. Large-scale, multicenter, multiethnic, prospective trials are required to propose an ideal combination of markers for routine screening.