Embryonic Exposure to Cigarette Smoke Extract Impedes Skeletal Development and Evokes Craniofacial Defects in Zebrafish

Abstract

Exposure to cigarette smoke represents the largest source of preventable death and disease in the United States. This may be in part due to the nature of the delayed harmful effects as well as the lack of awareness of the scope of harm presented by these products. The presence of “light” versions further clouds the harmful effects of tobacco products. While active smoking in expectant mothers may be reduced by educational and outreach campaigns, exposure to secondhand smoke is often involuntary yet may harm the developing embryo. In this study, we show that the main component of secondhand smoke, sidestream cigarette smoke, from several brands, including harm-reduction versions, triggered unsuccessful hatching at 3 dpf and reduced overall survival at 6 dpf in developing zebrafish. At non-lethal concentrations, craniofacial defects with different severity based on the cigarette smoke extract were noted by 6 dpf. All tested products, including harm-reduction products, significantly impacted cartilage formation and/or bone mineralization in zebrafish embryos, independent of whether the bones/cartilage formed from the mesoderm or neural crest. Together, these results in a model system often used to detect embryonic malformations imply that exposure of a woman to secondhand smoke while pregnant may lead to mineralization issues in the skeleton of her newborn, ultimately adding a direct in utero association to the increased fracture risk observed in children of mothers exposed to cigarette smoke.

Perturbations in Osteogenic Cell Fate Following Exposure to Constituents Present in Tobacco: A Combinatorial Study

“…An alternative explanation might be that nicotine needs to be metabolized to exert its toxic functions, similar to B(a)A. In line with this notion is a recent study that identified craniofacial defects in developing zebrafish upon nicotine exposure [ 90 ], a phenotype similar to that identified by us in zebrafish upon exposure to aqueous smoke extracts [ 18 ]. These facts may help to resolve the discrepancy between its contradicting cytotoxicity results and explain why cell viabilities were maintained throughout all tested concentrations in both the adult fibroblast and the immature, unspecified stem cells.…”

“…Bones are often hypomineralized, as evidenced by lower bone mineral density and bone mineral content, for example, in the head; consequently, the risk of fracture following minor injuries is increased [ 14 , 15 , 16 , 17 ]. We have recently been able to model these human epidemiological phenotypes in developing zebrafish, which exhibited hypomineralization in multiple bones, alterations to cartilage architecture, and spinal deformations in response to tobacco exposure [ 18 ].…”

Zebrafish (Danio rerio) as a Model for the Study of Developmental and Cardiovascular Toxicity of Electronic Cigarettes

“…They reveal developmental abnormalities, reduced survival rates, and adverse behavioral effects [ 59 , 60 ], providing insights into nicotine-related diseases, craniofacial defects, and behavioral impacts. This underscores their potential in studying the health risks associated with e-cigarette usage [ 61 , 62 ].…”

Integrated mRNA- and miRNA-sequencing analyses unveil the underlying mechanism of tobacco pollutant-induced developmental toxicity in zebrafish embryos

“…Therefore, pertinent studies exclusively examining a single component fall short of representing the global effects of tobacco pollutant exposure on embryos [16]. Moreover, although studies using tobacco pollutant mixture have been conducted, most have focused on visible embryonic developmental toxicity, such as malformations, with a limited exploration into the speci c molecular mechanisms involved in these processes [17,18]. Therefore, studying possible underlying molecular mechanisms and the overall effects of tobacco smoke exposure on embryonic development can address the limitations of existing studies and help in the formulation of new and effective preventive measures during pregnancy.…”