Gupta Sunil Kumar, Mochan Sankat, Arora Pallavi, Rani Neerja, Luthra Kalpana, Dwivedi Sadanand, Bhatla Neerja, Kshetrapal Pallavi, Dhingra Renu
Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
Placenta. 2023 Oct;142:135-146. doi: 10.1016/j.placenta.2023.09.004. Epub 2023 Sep 15.
Preeclampsia (PE) arises due to defective spiral artery remodelling which may be due to deficient migration of trophoblast cells. Migration of human endothelial cells has been shown to be promoted via Hydrogen sulphide(HS)/Rho GTPase Rac1 axis. This novel role of HS and its downstream processes have not yet been studied in the development and function of the placental trophoblast cells.
Placental tissues were obtained post-delivery from consented preeclamptic and normotensive mothers (n = 60). The protein expression levels of cystathionine-gamma-lyase (CSE) and cystathionine-beta-synthase (CBS) along with its downstream migratory molecules were compared in both the arms. The pro-migratory role of HS was investigated in a first trimester placental cell line.
HS promoted the migration of trophoblast cells in a Rho GTPase dependent manner mediated by actin cytoskeleton reorganization. The reduced levels of HS producing enzymes in the PE placentae along with decreased levels of Rho GTPases (Rac1 and Rho A) corroborate the results of PAG and AOAA treatment in down regulating the Rho GTPases in the in vitro grown placental cultures. Reduction of the migratory potential of trophoblastic cells caused due to hypoxia/reoxygenation was rescued by upregulating the HS expression with the use of NaHS as a HS donor.
Exogenous HS increases the migratory potential of the placental cells in culture conditions and also post hypoxia/reoxygenation injury. HS as a gaso-transmitter holds a great potential as a therapeutic agent. Its long-term effects need to be investigated using model systems (rat/mouse) of PE following it up with clinical regulatory trials.
子痫前期（PE）是由于螺旋动脉重塑缺陷引起的，这可能是由于滋养层细胞迁移不足所致。已有研究表明，硫化氢（HS）/Rho GTPase Rac1轴可促进人内皮细胞的迁移。HS的这一新作用及其下游过程尚未在胎盘滋养层细胞的发育和功能中进行研究。
从同意参与研究的子痫前期和血压正常的母亲（n = 60）产后获取胎盘组织。比较两组中胱硫醚-γ-裂解酶（CSE）和胱硫醚-β-合酶（CBS）及其下游迁移分子的蛋白表达水平。在孕早期胎盘细胞系中研究HS的促迁移作用。
HS以依赖Rho GTPase的方式促进滋养层细胞迁移，该过程由肌动蛋白细胞骨架重组介导。子痫前期胎盘组织中HS生成酶水平降低，同时Rho GTPases（Rac1和Rho A）水平降低，这证实了PAG和AOAA处理在下调体外培养的胎盘细胞中Rho GTPases方面的结果。使用NaHS作为HS供体上调HS表达，可挽救因缺氧/复氧导致的滋养层细胞迁移潜能降低。
外源性HS可增加培养条件下胎盘细胞的迁移潜能，以及缺氧/复氧损伤后的迁移潜能。HS作为一种气体递质，具有作为治疗剂的巨大潜力。需要使用子痫前期的模型系统（大鼠/小鼠）对其长期影响进行研究，随后进行临床监管试验。
