Hydrogen sulfide promotes migration of trophoblast cells by a Rho GTPase mediated actin cytoskeleton reorganization

Sunil Kumar Gupta; Sankat Mochan; Pallavi Arora; Neerja Rani; Kalpana Luthra; Sadanand Dwivedi; Neerja Bhatla; Pallavi Kshetrapal; Renu Dhingra

doi:10.1016/j.placenta.2023.09.004

Hydrogen sulfide promotes migration of trophoblast cells by a Rho GTPase mediated actin cytoskeleton reorganization

Placenta. 2023 Oct:142:135-146. doi: 10.1016/j.placenta.2023.09.004. Epub 2023 Sep 15.

Authors

Sunil Kumar Gupta¹, Sankat Mochan¹, Pallavi Arora¹, Neerja Rani¹, Kalpana Luthra², Sadanand Dwivedi³, Neerja Bhatla⁴, Pallavi Kshetrapal⁵, Renu Dhingra⁶

Affiliations

¹ Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
² Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
³ Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
⁴ Department of Obstetrics and Gynaecology, All India Institute of Medical Sciences, New Delhi, India.
⁵ Maternal & Child Health, Translational Health Science and Technology Institute, Faridabad, Haryana, India. Electronic address: pallavi.kshetrapal@thsti.res.in.
⁶ Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. Electronic address: renudhingraaiims@aiims.edu.

PMID: 37774537
DOI: 10.1016/j.placenta.2023.09.004

Abstract

Introduction: 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(H₂S)/Rho GTPase Rac1 axis. This novel role of H₂S and its downstream processes have not yet been studied in the development and function of the placental trophoblast cells.

Methods: 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 H₂S was investigated in a first trimester placental cell line.

Results: H₂S promoted the migration of trophoblast cells in a Rho GTPase dependent manner mediated by actin cytoskeleton reorganization. The reduced levels of H₂S 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 H₂S expression with the use of NaHS as a H₂S donor.

Discussion: Exogenous H₂S increases the migratory potential of the placental cells in culture conditions and also post hypoxia/reoxygenation injury. H₂S 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.