Poinsignon Léa, Chissey Audrey, Ajjaji Ayoub, Hernandez Isabelle, Vignaud Marie-Leone, Ferecatu Ioana, Fournier Thierry, Beaudeux Jean-Louis, Zerrad-Saadi Amal
Université Paris-Cité, Inserm, 3PHM, F-75006, Paris, France.
Université Paris-Cité, Inserm, 3PHM, F-75006, Paris, France; Service Biochimie, AP-HP, Hôpital Necker Enfants Malades, F-75006, Paris, France.
Arch Biochem Biophys. 2023 Nov;749:109787. doi: 10.1016/j.abb.2023.109787. Epub 2023 Oct 21.
The placenta is an essential organ for fetal development. During the first trimester, it undergoes dramatic changes as it develops in an environment poor in oxygen (around 2-3%). From about 10 gestational weeks, oxygen levels increase to 8% in the intervillous chamber. These changes are accompanied by modulation of the activity of NADPH oxidase, a major source of production of reactive oxygen species in the first trimester of pregnancy. The NOX complex is composed of seven different proteins (NOX1-5 and DUOX1-2) whose placental involvements during physiological and pathological pregnancies are largely unknown. The aim of the study was to produce a cartography of NOX family proteins, in terms of RNA, protein expression, and localization during physiological pregnancy and in the case of preeclampsia (PE), in a cohort of early-onset PE (n = 11) and late-onset PE (n = 7) cases. NOX family proteins were mainly expressed in trophoblastic cells (NOX4-5, DUOX1) and modulated during physiological pregnancy. NOX4 underwent an unexpected and hitherto unreported nuclear translocation at term. In the case of PE, two groups stood out: NOX1-3, superoxide producers, were down-regulated (p < 0.05) while NOX4-DUOX1, hydrogen peroxide producers, were up-regulated (p < 0.05), compared to the control group. Mapping of placental NOX will constitute a reference and guide for future investigations concerning its involvement in the pathophysiology of PE.
胎盘是胎儿发育的重要器官。在孕早期，它在低氧环境（约2%-3%）中发育时会经历显著变化。从妊娠约10周起，绒毛间隙的氧水平升至8%。这些变化伴随着NADPH氧化酶活性的调节，NADPH氧化酶是妊娠早期活性氧产生的主要来源。NOX复合物由七种不同蛋白质（NOX1-5和DUOX1-2）组成，其在生理和病理妊娠期间在胎盘中的作用在很大程度上尚不清楚。本研究的目的是绘制一份NOX家族蛋白图谱，涉及RNA、蛋白表达以及在生理妊娠期间和子痫前期（PE）情况下的定位，研究对象为一组早发型PE（n = 11）和晚发型PE（n = 7）病例。NOX家族蛋白主要在滋养层细胞中表达（NOX4-5、DUOX1），并在生理妊娠期间受到调节。足月时，NOX4发生了意想不到且迄今未报道的核转位。在PE病例中，有两组表现突出：与对照组相比，超氧化物产生者NOX1-3下调（p < 0.05），而过氧化氢产生者NOX4-DUOX1上调（p < 0.05）。胎盘NOX图谱将为未来关于其参与PE病理生理学的研究提供参考和指导。
