The Effects of Maternal Smoking on Pregnancy and Offspring: Possible Role for EGF?

Hamed Janbazacyabar,Thea Leusink-Muis,Ingrid Van Ark,Marthe Van Daal,Saskia Braber,Jeroen Van Bergenhenegouwen,Gert Folkerts,Johan Garssen

doi:10.3389/fcell.2021.680902

Abstract

Cigarette smoke exposure during pregnancy and lactation is associated with adverse pregnancy outcomes. Here, we investigated the effects of maternal smoke exposure on pregnancy and offspring immunity and explored whether, epidermal growth factor (EGF), an important growth-promoting factor in human colostrum and milk, might be a possible missing link in maternal smoke exposure and changes in infants’ immune responses. Pregnant BALB/c mice were exposed to either cigarette smoke or air during gestation and lactation, and effects on pulmonary inflammation in dams and immune responses in offspring were examined. Maternal smoke exposure increased airway hyperresponsiveness and accumulation of inflammatory cells in the lungs of pregnant dams compared to non-pregnant dams. The E-cadherin protein expression was reduced in mammary glands of cigarette smoke-exposed pregnant dams. EGF levels were higher in mammary glands and serum of smoke-exposed pregnant dams compared to air-exposed pregnant dams. Offspring from cigarette smoke-exposed dams exhibited elevated levels of IL-17A, MCP-1, IL-22, and IL-13 in anti-CD3 stimulated spleen cell culture supernatants. EGF levels were also increased in serum of offspring from smoke-exposed dams. A positive correlation was observed between serum EGF levels and neutrophil numbers in bronchoalveolar lavage fluid of the dams. Interestingly, IL-17A, MCP-1, IL-22, IL13, and IFN-γ levels in anti-CD3 stimulated spleen cell culture supernatants of male pups also showed a positive correlation with EGF serum levels. In summary, our results reveal that maternal smoke exposure predisposes dams to exacerbated airway inflammation and offspring to exacerbated immune responses and both phenomena are associated with elevated EGF concentrations.

Highlights

Smoking cigarettes throughout pregnancy is one of the most important preventable causes of adverse pregnancy outcomes (Hofhuis et al, 2003; Rauschert et al, 2019)
Cigarette smoking during pregnancy and lactation has been linked to several adverse pregnancy outcomes, smoking during pregnancy is still a prevalent behavior in many countries (Lange et al, 2018; Kondracki, 2019)
To the best of our knowledge, there is no literature available examining the effect of maternal smoking on susceptibility to lung injury during pregnancy

Summary

Introduction

Smoking cigarettes throughout pregnancy is one of the most important preventable causes of adverse pregnancy outcomes (Hofhuis et al, 2003; Rauschert et al, 2019). In addition to the local pulmonary injury, CS has far-reaching consequences on systemic immune responses, directly causing alterations in the innate and adaptive host defense, such as elevated white blood cell counts, and increased C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen levels (Bermudez et al, 2002; Sopori, 2002; Helmersson et al, 2005; Wannamethee et al, 2005; Mehta et al, 2008) Both in vivo and in vitro studies have shown that maternal smoking is associated with substantial changes in the placental morphology (Asmussen, 1977; Kawashima et al, 2014), which lead to impairment of the placental barrier (Demir et al, 1994). Results even indicated that CS components with a low molecular weight and high water solubility can cross the placental barrier and cause fetal injury (Sabra et al, 2017)

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