2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) enhances placental inflammation

Morgan R. Peltier, Yuko Arita, Natalia G. Klimova, Ellen M. Gurzenda, Hchi Chi Koo, Amitasrigowri Murthy, Veronica Lerner, Nazeeh Hanna

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Preterm birth is a leading cause of perinatal morbidity and mortality that is often associated with ascending infections from the lower genital tract. Recent studies with animal models have suggested that developmental exposure to the environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) can increase the risk of preterm birth in the offspring. How TCDD may modify placental immunity to ascending infections is unclear. Therefore, we studied the effects of TCDD treatment on basal and Escherichia coli-stimulated cytokine production by placental explants. Cultures of second-trimester placentas were treated with up to 40nM TCDD for 72h and then stimulated with 107CFU/ml E. coli for an additional 24h. Concentrations of cytokines and PGE2 were measured in conditioned medium by immunoassay. TCDD exposure increased mRNA levels of IL-1β by unstimulated cultures, but no effects on protein levels of this cytokine were detected. TNF-α production was unaffected by TCDD for unstimulated cultures, but pre-treatment with 40nM TCDD significantly increased E. coli-stimulated TNF-α production. Both basal and bacteria-stimulated PGE2 and COX-2 gene expression were enhanced by TCDD pretreatment. In contrast, production of the anti-inflammatory cytokine, IL-10, was reduced by TCDD pretreatment for both unstimulated and E. coli-stimulated cultures. No effect of TCDD on the viability of the cultures was detected. These results suggest that TCDD exposure may shift immunity to enhance a proinflammatory phenotype at the maternal-fetal interface that could increase the risk of infection-mediated preterm birth.

Original languageEnglish (US)
Pages (from-to)10-20
Number of pages11
JournalJournal of Reproductive Immunology
Volume98
Issue number1-2
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Cytokine
  • Interleukin-10
  • Placenta
  • Preterm birth
  • TCDD

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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