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Updated: Jan 14, 2026
Author Spotlight: Modeling an Aspect of Preeclampsia in Female Mice Using Hypoxic Human Placenta-Derived Small Extracellular Vesicles
Published on: January 26, 2024
Exogenous hydrogen sulfide ameliorates hypoxia-induced trophoblast dysfunction by modulating cellular energy
Jiahui Chen1, Jing Huai1, Ruilin Guo1
1Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China; Beijing Key Laboratory of Maternal Fetal Medicine of Gestational Diabetes Mellitus, China.
Introduction:
Preeclampsia (PE) is characterized by abnormal trophoblast energy metabolism. Hydrogen sulfide (H2S), a key signaling molecule, modulates cellular energy, but its role in PE is unclear. This study investigated the role of H2S in PE pathogenesis by examining its effect on trophoblast energy metabolism.
Methods:
Expression of H2S synthases, cystathiononine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE), was measured in placental tissues from pregnancies. HTR-8 trophoblasts were subjected to cobalt chloride (CoCl2) induced hypoxia and siRNA-mediated knockdown of CBS or CSE. The effects of H2S donor sodium hydrosulfide (NaHS) on cell proliferation, migration, invasion, and key energy metabolism pathways were assessed.
Results:
The expression of H2S synthase was significantly reduced in the placentas of pregnant women with PE. In HTR-8 cells, CoCl2 treatment decreased the expression of CBS and CSE; diminished mitochondrial respiratory function, glycolytic function, and glutamine metabolic ability; and inhibited the proliferation, migration, and invasion abilities of the cells. These alterations could be reversed by NaHS. Silencing of CBS or CSE phenocopied the effects of hypoxia, and these deficits were also rescued by NaHS.
Discussion:
H2S dysregulation associates with hypoxic trophoblast energy metabolism impairment. Exogenous H2S potentially rescues these deficits in vitro, suggesting a therapeutic avenue for PE. This study is limited by its in vitro design, which demonstrates a strong association but does not establish a causal relationship in vivo. The use of a chemical hypoxia model may not fully replicate the complex pathophysiology of preeclampsia.
