Impact of Secondhand Smoke and E-Cigarette Exposure on Placental Apoptotic and Growth-Regulatory Proteins in Mouse Pregnancy

Abstract

Apoptosis is critical in placental development, and its dysregulation is linked to pregnancy complications such as intrauterine growth restriction (IUGR) and preeclampsia (PE). Environmental exposures, particularly secondhand smoke (SHS) and e-cigarettes (eCigs), may contribute to placental dysfunction through apoptotic pathways. This study examined the effects of SHS and eCig exposure on placental apoptosis and growth-regulatory proteins in a murine model. C57BL/6 pregnant mice were exposed to SHS or eCigs at two critical gestational time points: early trophoblast invasion (E12.5 to E18.5) and established invasion (E14.5 to E18.5). Placental tissues were collected and analyzed for pro-apoptotic and anti-apoptotic markers, heat shock proteins, insulin-like growth factor-binding proteins (IGFBPs), and growth regulators. SHS exposure increased pro-apoptotic markers (BAD, Fas/FasL) and decreased mitochondrial function markers (cytochrome c), indicating compromised cellular survival. Both SHS and eCig exposure reduced anti-apoptotic markers (BCL-2, HSP27, survivin) and growth regulators (IGF-1, IGFBPs). SHS and eCig exposure create a pro-apoptotic environment in the placenta, potentially impairing fetal development through altered apoptotic and growth-regulatory pathways. These findings underscore the risks of environmental exposures during pregnancy, highlighting the need for strategies to minimize maternal exposure to SHS and eCigs.

Keywords: apoptosis; e-cigarettes; placenta; pregnancy; secondhand smoke.

Figure 1

Pro-apoptotic markers BAD, cytochrome c, and Fas/FasL during SHS or eCig treatment. Pro-apoptotic mediators were determined in treated animals, and the results were compared to the controls. Protein expression levels of BAD (A), Cyto C (B), and (C) FAS/FASL were differently regulated by the length and type of treatment compared to the controls. Significant differences are noted as p ≤ 0.05.

Figure 2

Anti-apoptotic markers BCL-2, cIAP-2, HSP27, HSP70, Survivin, and XIAP during SHS or eCig treatment. Anti-apoptotic mediators were determined in the treated animals, and the results were compared to the controls. Protein expression levels of BCL-2 (A), cIAP-2 (B), HSP27 (C), HSP70 (D), Survivin (E), and XIAP (F) were differently regulated by the length and type of treatment when compared to the controls. Significant differences are noted as p ≤ 0.05.

Figure 3

IGFBP growth regulation markers IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4, IGFBP-5, and IGFBP-6 during SHS or eCig treatment. IGFBP growth regulation mediators were determined in the treated animals compared to the controls. Protein expression levels of IGFBP-1 (A), IGFBP-2 (B), IGFBP-3 (C), IGFBP-4 (D), IGFBP-5 (E), and IGFBP-6 (F) were differently regulated by the length and type of treatment when compared with the controls. Significant differences are noted as p ≤ 0.05.

Figure 4

Cell cycle and growth inhibition markers p27 and IGF-1 during SHS or eCig treatment. Cell cycle and growth inhibition mediators were determined in the treated animals, and the results were compared to the controls. Protein expression levels of p271 (A) and IGF-1 (B) were differently regulated by the length and type of treatment when compared to the controls. Significant differences are noted as p ≤ 0.05.