title: Preconception omega-3 fatty acid supplementation of adult male mice with a history of developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure prevents preterm birth in unexposed female partners.
abstract: We have recently reported that adult male C57BL/6 mice exposed in utero to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) confer an increased risk of preterm birth (PTB) to unexposed females. Risk of PTB was coincident with decreased placental progesterone receptor (Pgr) mRNA expression and increased toll-like receptor 4 (Tlr4) mRNA expression, suggesting that toxicant exposure induced a heightened inflammatory response at the maternal-fetal interface. Since omega-3 fatty acids exhibit anti-inflammatory activity, in this study, we provided TCDD-exposed males a fish oil-enriched diet prior to mating. Although PTB was common in control females mated to TCDD-exposed males on the standard diet, fish oil supplementation of TCDD-exposed males eliminated PTB in unexposed partners. We also determined the influence of preconception, paternal fish oil supplementation on the placental inflammatory response in late pregnancy (E18.5) by examining the expression of Pgr and Tlr4 mRNA as well as the expression of 15-hydroxyprostaglandin dehydrogenase (PGDH). PGDH catabolizes the inflammatory PGE2 to an inactive form; thus, reduced expression of this enzyme would promote tissue inflammation. Compared with control pregnancies, examination of E18.5 placentas arising from TCDD-exposed males on the standard diet revealed a significant increase in Tlr4 mRNA expression corresponding to a reduction in Pgr mRNA and PGDH protein expression. In contrast, fish oil supplementation of toxicant-exposed males led to normalization of placental expression of both Pgr and Tlr4 mRNA and a marked increase in PGDH expression. These studies suggest that a paternal preconception diet that includes omega-3 fatty acids prevents the toxicant-associated increase in the placental inflammatory response at late gestation, preventing PTB.
authors.affiliation: Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, 1161 21st Avenue S, MCN B-1100, Nashville, Tennessee 37232, USA.
authors.forename: Melinda E
authors.initials: ME
authors.lastname: McConaha
authors.forename: Tianbing
authors.initials: T
authors.lastname: Ding
authors.forename: John A
authors.initials: JA
authors.lastname: Lucas
authors.forename: Joe A
authors.initials: JA
authors.lastname: Arosh
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Osteen
authors.forename: Kaylon L
authors.initials: KL
authors.lastname: Bruner-Tran
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D019587:Dietary Supplements; D004785:Environmental Pollutants / Q000633:toxicity*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005395:Fish Oils / Q000627:therapeutic use; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018812:Paternal Exposure; D010920:Placenta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D047928:Premature Birth / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004785:Environmental Pollutants; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D000072317:Polychlorinated Dibenzodioxins; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase