Cortisol inhibits CSF2 and CSF3 via DNA methylation and inhibits invasion in first-trimester trophoblast cells
| Autor: | Elizabeth Witte, Devin McGee, Jason G. Knott, Kavita Narang, Karen Racicot, Arianna L. Smith |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Hydrocortisone Immunology Article Cell Line Epigenesis Genetic Andrology 03 medical and health sciences 0302 clinical medicine Pregnancy Granulocyte Colony-Stimulating Factor medicine Immunology and Allergy Humans Epigenetics reproductive and urinary physiology Matrigel 030219 obstetrics & reproductive medicine biology Chemistry Pregnancy Outcome Obstetrics and Gynecology Trophoblast Placentation Granulocyte-Macrophage Colony-Stimulating Factor Methylation DNA Methylation Trophoblasts Abortion Spontaneous Pregnancy Trimester First 030104 developmental biology Histone medicine.anatomical_structure Reproductive Medicine embryonic structures DNA methylation biology.protein Female Chromatin immunoprecipitation Stress Psychological |
| Popis: | Problem Heightened maternal stress affects trophoblast function and increases risk for adverse pregnancy outcomes. Methods of Study Studies were performed using the first-trimester trophoblast cell line, Sw.71. Cytokines were quantified using qPCR and ELISA. Epigenetic regulation of cytokines was characterized by inhibiting histone deacetylation (1 μmol/L suberoylanilide hydroxamic acid [SAHA]) or methylation (5 μmol/L 5-azacytidine), or with chromatin immunoprecipitation (ChIP) with a pan-acetyl histone-3 antibody. Invasion assays used Matrigel chambers. Results Cortisol inhibited expression of CSF2 (GM-CSF) and CSF3 (G-CSF) in trophoblast cells. Cortisol-associated inhibition was dependent on DNA methylation and was not affected by acetylation. There was also a modest decrease in trophoblast invasion, not dependent on loss of CSFs. Conclusion In first-trimester trophoblast cells, the physiological glucocorticoid, cortisol, inhibited two cytokines with roles in placental development and decreased trophoblast invasion. Cortisol-associated changes in trophoblast function could increase the risk for immune-mediated abortion or other adverse pregnancy outcomes. |
| Databáze: | OpenAIRE |
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