Enhancement of placental inflammation by Dibutyl Phthalate.

Abstract

Recent studies suggest that women with high exposures to dibutyl phthalate (DBP) are at increased risk for preterm birth, a condition associated with aberrant inflammation in the placenta often caused by subclinical infections. Placental inflammation is also a risk factor for neurodevelopmental disorders whose risk may also be enhanced by DBP. It is unclear, however, if DBP enhances placental inflammation. Therefore, we studied the effects of DBP on the production of biomarkers of placental inflammation and neurodevelopment under basal conditions and a setting of mild infection. Placental explant cultures established from women undergoing elective caesarean delivery were treated with DBP with and without co-stimulation by 107 CFU/mL heat-killed E. coli for 24 h at 37 °C. Conditioned medium was harvested and concentrations of IL-1β, TNF-α, IL-10, HO-1 and BDNF, a biomarker for neurodevelopment, were quantified. DBP significantly enhanced IL-6 production in basal cultures but had no significant on the other biomarkers quantified. Both TNF-α and IL-1β production was enhanced by DBP for cultures co-stimulated with E. coli. Although marginal enhancement of IL-6, and IL-10 were observed for bacteria co-treated cultures, results were either non-monotonic or only approached statistical significance. HO-1 production tended to be reduced at the highest concentration of DBP tested and BDNF production was reduced by DBP in a dose-dependent manner for bacteria-stimulated cultures. These results suggest that DBP enhances basal IL-6 production but has little or no effect on other biomarkers studied. However, DBP enhances IL-1β and TNF-α production but reduces BDNF production by bacteria-stimulated cultures.

• Authors: Aisha Manna Alsubaie, Yuko Arita, Matthew Atwater, Ali Mahfuz, Morgan R Peltier
• Journal: Journal of reproductive immunology (J Reprod Immunol) Vol. 147 Pg. 103368 (Sep 2021) ISSN: 1872-7603 [Electronic] Ireland
• PMID: 34461555 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Brain-Derived Neurotrophic Factor
• Environmental Pollutants
• IL1B protein, human
• IL6 protein, human
• Interleukin-1beta
• Interleukin-6
• TNF protein, human
• Tumor Necrosis Factor-alpha
• Dibutyl Phthalate
• BDNF protein, human

Topics

• Brain-Derived Neurotrophic Factor (metabolism)
• Dibutyl Phthalate (toxicity)
• Environmental Pollutants (toxicity)
• Female
• Gene Expression Regulation (drug effects, immunology)
• Humans
• Inflammation (chemically induced, immunology, pathology)
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Placenta (drug effects, immunology, metabolism, pathology)
• Pregnancy
• Pregnancy Complications, Infectious (chemically induced, immunology, microbiology, pathology)
• Primary Cell Culture (methods)
• Tumor Necrosis Factor-alpha (metabolism)