Maternal Particulate Matter Exposure Impairs Lung Health and Is Associated with Mitochondrial Damage.

Baoming Wang,Cristan Herbert,Kin Fai Ho,Hui Chen,Ayad G Anwer,Paul S Foster,Bradford J Smith,Bin Jalaludin,Sonia Saad,Hai Guo,Brian G Oliver,David G Chapman,Jiayan Liao,Gerard Li,Paul S Thomas,Yik-Lung Chan

doi:10.3390/antiox10071029

Abstract

Relatively little is known about the transgenerational effects of chronic maternal exposure to low-level traffic-related air pollution (TRAP) on the offspring lung health, nor are the effects of removing such exposure before pregnancy. Female BALB/c mice were exposed to PM2.5 (PM2.5, 5 µg/day) for 6 weeks before mating and during gestation and lactation; in a subgroup, PM was removed when mating started to model mothers moving to cleaner areas during pregnancy to protect their unborn child (Pre-exposure). Lung pathology was characterised in both dams and offspring. A subcohort of female offspring was also exposed to ovalbumin to model allergic airways disease. PM2.5 and Pre-exposure dams exhibited airways hyper-responsiveness (AHR) with mucus hypersecretion, increased mitochondrial reactive oxygen species (ROS) and mitochondrial dysfunction in the lungs. Female offspring from PM2.5 and Pre-exposure dams displayed AHR with increased lung inflammation and mitochondrial ROS production, while males only displayed increased lung inflammation. After the ovalbumin challenge, AHR was increased in female offspring from PM2.5 dams compared with those from control dams. Using an in vitro model, the mitochondria-targeted antioxidant MitoQ reversed mitochondrial dysfunction by PM stimulation, suggesting that the lung pathology in offspring is driven by dysfunctional mitochondria. In conclusion, chronic exposure to low doses of PM2.5 exerted transgenerational impairment on lung health.

Highlights

The World Health Organization reported that more than 91% of people are living in areas with air pollution [1]
There were no significant differences in the mitophagy fusion marker optic atrophy 1 (Opa1) level between the groups, an increasing trend can be found after particulate matter (PM) exposure (Figure 4G)
For the first time, we show that even the inhalation of low dose PM during pregnancy can cause adverse lung health outcomes in female and male offspring reflected by chronic lung inflammation and female offspring had intrinsic airway hyper-responsiveness and an enhanced response to allergic airways disease

Summary

Introduction

The World Health Organization reported that more than 91% of people are living in areas with air pollution [1]. Urbanisation has resulted in traffic-related air pollution (TRAP). The complex composition of TRAP results in more severe impacts on human health than other airborne pollutants [2]. Oxidants can damage the mitochondria, resulting in the imbalance between the removal of damaged mitochondria and re-generation from the undamaged mitochondrial fragment. These processes are mediated through mitochondrial fission (separating damaged and healthy fragments) and fusion (combining healthy fragments), which is called mitophagy that is essential to maintain mitochondrial homeostasis. Our previous studies have confirmed the close relationship between organ pathology and mitochondrial dysfunction [11]

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Methods

Conclusion