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NETosis Markers in Pregnancy: Effects Differ According to Histone Subtypes
Sylvie Bouvier1,2,3, Mathieu Fortier1, Laura Vincent1
1Department of Haematology, University Hospital, Nîmes, France.
Thrombosis and Haemostasis
|January 10, 2021
Summary
Increased nucleosomes in complicated pregnancies impair trophoblast function, potentially linking thrombosis risk and pregnancy issues. Low-molecular-weight heparin showed a restorative effect.
Area of Science:
- Immunology
- Reproductive Biology
- Thrombosis Research
Background:
- NETosis, an innate immune response, involves neutrophils releasing DNA-histone complexes, activating coagulation and increasing thrombosis risk.
- Pregnancy, especially complicated cases, features heightened neutrophil activation and thrombotic risk.
- Increased circulating nucleosomes, specifically nucleosome-bound histones, are observed in complicated pregnancies.
Purpose of the Study:
- Quantify nucleosome-bound histones in normal versus complicated pregnancies.
- Investigate the impact of histones on extravillous trophoblast function.
- Explore potential therapeutic interventions for histone-mediated pregnancy complications.
Main Methods:
- Quantification of circulating nucleosome-bound histones (H3 and H4 variants) in pregnant individuals.
- In vitro assays using extravillous trophoblast cell line (HTR-8/SVNeo) to assess histone effects on migration, invasion, and apoptosis.
- Treatment of cells with recombinant histones and therapeutic agents (enoxaparin, aspirin).
Main Results:
- Circulating nucleosome-bound histones H3 and H4 were elevated in complicated pregnancies.
- Recombinant histones H2B, H3, and H4 inhibited trophoblast migration; H3 also inhibited invasion.
- Histones H3 and H4 induced trophoblast apoptosis, an effect partially reversed by enoxaparin but not aspirin.
Conclusions:
- Elevated circulating nucleosome-bound histones in complicated pregnancies negatively impact trophoblast migration, invasion, and induce apoptosis.
- Histones may mediate the link between thrombosis risk and pregnancy complications.
- Enoxaparin demonstrates potential in mitigating histone-induced negative effects on trophoblasts.
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