Effect of PM10 on pulmonary immune response and fetus development

Highlights

• PM10 was characterized PM10 and instilled intratracheally to male and female mice.

• PM10 induced dose-dependent inflammatory response followed by pathological lesions.

• PM10 exposure seemed to affect to the reproductive toxicity-related endpoints.

• Stillbirth was observed in three mice among eight dams exposed to the maximum dose.

• Expression of hypoxia-related proteins was altered in the lung tissues and cells.

Abstract

Despite numerous reports that ambient particulate matter is a key determinant for human health, toxicity data produced based on physicochemical properties of particulate matters is very lack, suggesting lack of scientific evidence for regulation. In this study, we sampled inhalable particulate matters (PM10) in northern Seoul, Korea. PM10 showed atypical- and fiber-type particles with the average size and the surface charge of 1,598.1 ± 128.7 nm and −27.5 ± 2.8, respectively, and various toxic elements were detected in the water extract. On day 90 after the first pulmonary exposure, total cell number dose-dependently increased in the lungs of both sexes of mice. PM10 induced Th1-dominant immune response with pathological changes in both sexes of mice. Meanwhile, composition of total cells and expression of proteins which functions in cell-to-cell communication showed different trends between sexes. Following, male and female mice were mated to identify effects of PM10 to the next generation. PM10 remained in the lung of dams until day 21 after birth, and the levels of IgA and IgE increased in the blood of dams exposed to the maximum dose compared to control. In addition, the interval between births of fetuses, the number of offspring, the neonatal survival rate (day 4 after birth) and the sex ratio seemed to be affected at the maximum dose, and particularly, all offspring from one dam were stillborn. In addition, expression of HIF-1α protein increased in the lung tissue of dams exposed to PM10, and level of hypoxia-related proteins was notably enhanced in PM10-exposed bronchial epithelial cells compared to control. Taken together, we suggest that inhaled PM10 may induce Th1-shifting immune response in the lung, and that it may affect reproduction (fetus development) by causing lung hypoxia. Additionally, we propose that further study is needed to identify particle-size-dependent effects on development of the next generation.

Introduction

Atmospheric particulate matter (APM) is micro-sized particles suspended in the air, and inhalable APM is largely divided into coarse- (less than 10 μm, known as PM10), fine- (less than 2.5 μm, known as PM2.5) and ultrafine particles (less than 0.1 μm) based on the size (diameter). APM is either emitted directly into the atmosphere (primary pollutants) or formed by the nucleation and condensation of gas phase materials (secondary pollutants) due to natural or human anthropogenic activity (Mukherjee and Agrawal, 2017; Sun et al., 2019). Primary and secondary pollutants are main sources for PM10 and PM2.5, respectively, and thus sources for PM10 are relatively well-known, suggesting it is possible to control emissions. Given that an increase in the exposure to APM was proportional to the increased risk of lung cancer, the International Agency for Research on Cancer (IARC) classified APM as a Group 1 carcinogen (carcinogenic to humans) in 2013. The IARC also concluded that this classification should be applied worldwide without consideration for both the difference in the chemical composition of air pollution and the exposure level. In addition, accumulated evidence has showed that chronic exposure to APM are associated with various types of pulmonary disease including chronic obstruction pulmonary disease, lung fibrosis, and asthma, depending on the complex interaction between inhaled APM and biological composition (Nyberg and Pershagen, 2000; Nadel, 2013; Delfino, 2002; Herbarth et al., 2001; Peden, 2001; Dai et al., 2016; www.epa.gov, 2020). However, toxicological data presented with results on the properties of APM are still not enough, thus it is difficult to set the APM regulation guidelines.

Countries need to maintain an optimum level birth rate to sustain their population, and fertility rate can be affected by many different factors, including wealth, education, home economy, residence, and female labor participation. Meanwhile, the average global birth rate has been continuously falling since records began, and in 2016, it was 18.6 births per 1000 persons, corresponding to about 256 births per minute (www.un.org, 2020). Thus, struggling with a low birth rate has become an important global issue. Particularly, in Korea, the total fertility rate, which indicates the average number of children which a woman will have in her lifetime, has dropped sharply since 2015 (1.239), and it was assessed as 0.92 in 2019 (www.kostat.go.kr, 2020). This low fertility is currently one of the key tasks that the Korean government has to tackle, with the increasing elderly population. In addition, WHO reported that stillbirth rate was 18.4 per 1000 total births worldwide in 2015, and 98 % of these births took place in low (or middle)-income countries such as India, Pakistan, Nigeria, China, and Bangladesh (www.who.int, 2020; Altijani et al., 2018; McClure et al., 2009). In the United States, the number of stillborn babies (23,595) has exceeded the number of infant deaths (23,446) for the first time, and this number showed an increasing trend in both the aged mother than the younger mother and mothers less than 15 years old (www.cdc.gov, 2015). Additionally, the WHO has suggested that pregnancy complications such as high blood pressure and diabetes, infectious diseases such as malaria and syphilis, and lifestyle factors such as obesity and smoking may be among the main causes of stillbirth (www.who.int, 2020). Furthermore, some researchers have proposed that maternal exposure to the increased environmental pollution can result in stillbirths, particularly in the antepartum period and that PM10 is a key risk across the world (Mukherjee and Agrawal, 2017; Smith et al., 2020). In this study, we characterized properties of PM10 and instilled PM10 intratracheally to male and female mice. Then, we identified effects of PM10 on the lung health and reproduction function of parental mice and development of the next generation.