Chronic Exposure to Flavored Tobacco Aerosols Induces Inflammation and Hepatic Mitochondrial Impairment in Pregnant Versus Non-Pregnant Mouse Cohorts

This study was conducted to investigate the impact of Virginia tobacco (VT), Menthol (MT), and sham aerosols on both normal and pathological responses in pregnant and non-pregnant mouse groups. Aerosol vaping exposure and body weight analysis were evaluated in pregnant and non-pregnant cohorts and compared with controls exposed to sham aerosols in each group. We assessed pulmonary inflammation using the Bronchoalveolar Lavage Fluid (BALF) total cell count, total protein, and lactate dehydrogenase (LDH) activity. In addition, we measured hepatic triglyceride levels and lipogenic genes in the liver, such as Scd1, Fasn, Srebp1c1, and the estrogen receptor (Esr1), via RT-qPCR and Western blot analysis. Liver fibrosis was assessed via histopathology and mitochondrial functional assays, and serum cytokines were measured in each group. In pregnant mice exposed to VT, pulmonary inflammation, increased cell counts and protein content, and no change in lactate dehydrogenase activity in Bronchoalveolar Lavage Fluid (BALF) were observed compared with non-pregnant mice. VT exposure appeared to cause direct adverse health outcomes leading to increased expression of liver lipogenic genes, such as Scd1, Fasn, Srebp1c, and estrogen receptors. Maternal liver lipid equilibrium was disrupted upon VT exposure. Vaping either VT or MT significantly reduced mitochondrial oxidative function in the livers of pregnant mice but not in those of non-pregnant mice. This study’s findings suggest that pregnancy may be associated with distinct immunological responses to VT and MT exposure. VT exposure was associated with altered hepatic lipogenic gene expression, suggesting potential metabolic effects on the maternal liver, whereas MT exposure was associated with liver structural changes and fibrosis-related outcomes.