Maternal dietary Docosahexaenoic acid (DHA) supplementation prevents fetal growth restriction and pulmonary fibrosis caused by perinatal inflammation

Abstract

BackgroundEpidemiological data suggest that maternal inflammation contributes to intrauterine growth restriction, preterm birth, and adult‐onset pulmonary diseases. DHA has anti‐inflammatory properties but responsible mechanisms are not defined.ObjectiveWe hypothesized that perinatal inflammation and oxidative stress induce a fibrotic phenotype by EMT induction and that this phenotype can be rescued by dietary DHA administration.MethodsPregnant C3H/HeN mice were injected on E 16 with LPS or saline and placed on control or DHA diets. Pups were exposed to 85% (O2) or RA for 2 weeks than returned to room air (RA). Protein, RNA, histological, and pulmonary function analyses were performed.ResultsLPS/O2 exposure reduced birth weight, decreased alveolarization, impaired pulmonary function, induced inflammation, matrix remodeling, EMT, and collagen deposition. Maternal DHA supplementation attenuated deleterious effects on birth weight, alveolarization, pulmonary mechanics, matrix remodeling, collagen deposition, and EMT in lung tissues of LPS/O2 mice.ConclusionsOur data indicate that pulmonary morbidities at 8 weeks are due to maternal inflammation and neonatal oxidative stress. Perinatal DHA supplementation improves outcome by attenuating fibrotic response and improving alveolarization. These strategies would be straightforward to implement in pregnancy/lactationGrant Funding Source: NIH: LKR R01AT006880, DFG: MV, VE 614/1–1