Developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure of either parent enhances the risk of necrotizing enterocolitis in neonatal mice.

ABSTRACT:

Background

Necrotizing enterocolitis (NEC) is a rare, but potentially fatal intestinal inflammatory condition most often arising in premature infants. Infants provided formula are also at greater risk of developing this disease. Although the majority of formula-fed, preterm infants do not develop NEC, up to 30% of infants with the disease do not survive. Thus, identifying additional, currently unrecognized factors, which may predispose a specific infant to NEC development would be a significant clinical advancement. In this regard, we have previously reported that offspring of female or male mice with a history of developmental exposure to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibit altered sensitivity to inflammatory challenges and are frequently born premature. Herein, we examined the possibility that, compared to unexposed mice (F1_NONE ), developmental TCDD exposure of either parent (maternal, F1M_TCDD , or paternal, F1P_TCDD ) would enhance the risk of NEC in offspring (F2_TCDD mice) in association with supplemental formula feeding.

Methods

Beginning on postnatal day 7, all neonates were randomized to maternal milk only or maternal milk with up to 20 supplemental formula feedings. All pups remained with the Dams and were additionally allowed to nurse ad libitum.

Results

Formula-fed F2_NONE pups rarely developed NEC while this disease was common in formula-fed F2M_TCDD and F2P_TCDD mice. Unexpectedly, 50% of F2M_TCDD pups that were not provided supplemental formula also developed NEC.

Conclusions

Our studies provide evidence that a history of parental TCDD exposure enhances the risk of NEC in offspring and suggest exposure to environmental immunotoxicants such as TCDD may also contribute to this inflammatory disease in humans.

SUBMITTER: Mokshagundam S 

PROVIDER: S-EPMC8274937 | biostudies-literature |

REPOSITORIES: biostudies-literature