Beck Logan, Kirkham Madison N, Shin Marley, Bikman Benjamin T, Reynolds Paul R, Arroyo Juan A
Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Cells. 2025 Mar 19;14(6):453. doi: 10.3390/cells14060453.
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.
细胞凋亡在胎盘发育中至关重要，其失调与诸如胎儿生长受限（IUGR）和子痫前期（PE）等妊娠并发症有关。环境暴露，尤其是二手烟（SHS）和电子烟（eCigs），可能通过凋亡途径导致胎盘功能障碍。本研究在小鼠模型中考察了SHS和eCig暴露对胎盘细胞凋亡及生长调节蛋白的影响。将C57BL/6怀孕小鼠在两个关键妊娠时间点暴露于SHS或eCigs：早期滋养层侵入期（E12.5至E18.5）和已建立侵入期（E14.5至E18.5）。收集胎盘组织并分析促凋亡和抗凋亡标志物、热休克蛋白、胰岛素样生长因子结合蛋白（IGFBPs）以及生长调节因子。SHS暴露增加了促凋亡标志物（BAD、Fas/FasL）并降低了线粒体功能标志物（细胞色素c），表明细胞存活受到损害。SHS和eCig暴露均降低了抗凋亡标志物（BCL-2、HSP27、生存素）和生长调节因子（IGF-1、IGFBPs）。SHS和eCig暴露在胎盘中营造了一种促凋亡环境，可能通过改变凋亡和生长调节途径损害胎儿发育。这些发现强调了孕期环境暴露的风险，突出了采取策略尽量减少母体接触SHS和eCigs的必要性。
