Offspring sex affects the susceptibility to maternal smoking-induced lung inflammation and the effect of maternal antioxidant supplementation in mice

Baoming Wang,Hui Chen,Shengyu Zhou,Brian G Oliver,Yik Lung Chan,Sonia Saad

doi:10.1186/s12950-020-00253-5

Abstract

BackgroundCigarette smoke exposure (SE) during pregnancy is the largest modifiable risk factor for the development of lung disorders in offspring. We have previously shown that maternal L-Carnitine treatment can reduce the adverse impacts of maternal SE on renal and brain disorders in offspring. Here, we investigated the effect of maternal L-Carnitine supplementation on lung inflammatory pathways, autophagy, and mitophagy markers in the offspring in response to maternal SE.MethodsFemale BALB/c mice (8 weeks) were exposed to cigarette smoke for 6 weeks prior to mating, during gestation and lactation. Some of the SE dams were given L-Carnitine supplementation (1.5 mM in drinking water, SE + LC) during gestation and lactation. Lungs from the offspring were studied at birth and adulthood (13 weeks).ResultsAt birth, in male offspring, there were increased levels of inflammatory markers (phosphorylated(p)-ERK1,2, p-P38 MAPK, p- NF-κB), and inflammasome marker (NLRP3), as well as mitophagy fission marker Drp-1 and autophagosome marker (LC3A/B-II) in the lung. Maternal L-Carnitine supplementation significantly reduced NLRP3 level. In contrast, maternal SE only increased IL1-β in female offspring, which was reversed by maternal L-Carnitine supplementation. At 13 weeks, there was an increase in LC3A/B-II and p- NF-κB in the male SE offspring with reduced p-JNK1,2, which were partially normalised by maternal L-Carnitine treatment. Female offspring were not affected by maternal SE at this age.ConclusionMaternal SE had adverse impacts on the male offspring’s lung, which were partially alleviated by maternal L-Carnitine supplementation. Females seem to be less affected by the adverse effects of maternal SE.

Highlights

Cigarette smoke exposure (SE) during pregnancy is the largest modifiable risk factor for the development of lung disorders in offspring
Our previous murine studies found that the changes in inflammation, oxidative stress, mitophagy, and autophagy have a marked sex difference in the offspring’s brain and kidney following in-utero SE, wherein female offspring are less affected from such adverse effects [13, 14]
Effect of maternal SE on lung p-extracellular signal-regulated kinase (ERK), p-p38, p-Jun N-terminal kinase (JNK), and pNF-κB in the offspring At P1, maternal SE significantly increased the levels of p-ERK1,2 (P < 0.01 vs SHAM, Fig. 1a), p-P38 (P < 0.01 vs SHAM, Fig. 1e) and p-NF-κB (P < 0.01 vs, SHAM, Fig. 1g) in the male offspring

Summary

Introduction

Cigarette smoke exposure (SE) during pregnancy is the largest modifiable risk factor for the development of lung disorders in offspring. We have previously shown that maternal L-Carnitine treatment can reduce the adverse impacts of maternal SE on renal and brain disorders in offspring. We investigated the effect of maternal L-Carnitine supplementation on lung inflammatory pathways, autophagy, and mitophagy markers in the offspring in response to maternal SE. Inutero smoke exposure (SE) reduces lung function in human newborns [4, 5]. The common pathophysiological process includes increased inflammation, oxidative stress, impaired mitochondrial renewal (mitophagy), and cellular self-cleaning mechanism (autophagy) [12]. Our previous murine studies found that the changes in inflammation, oxidative stress, mitophagy, and autophagy have a marked sex difference in the offspring’s brain and kidney following in-utero SE, wherein female offspring are less affected from such adverse effects [13, 14]

Methods

Results

Conclusion