Respiratory Immunology Division, Lovelace Respiratory Research Institute, Albuquerque, NM, United States.
Department of Immunology and Nanomedicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, United States.
Front Immunol. 2020 Jul 28;11:1628. doi: 10.3389/fimmu.2020.01628. eCollection 2020.
Gestational cigarette smoke (CS) impairs lung angiogenesis and alveolarization, promoting transgenerational development of asthma and bronchopulmonary dysplasia (BPD). Hydrogen sulfide (HS), a proangiogenic, pro-alveolarization, and anti-asthmatic gasotransmitter is synthesized by cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and mercaptopyruvate sulfur transferase (3MST). Determine if gestational CS exposure affected the expression of HS synthesizing enzymes in the mouse lung and human placenta. Mice were exposed throughout gestational period to secondhand CS (SS) at approximating the dose of CS received by a pregnant woman sitting in a smoking bar for 3 h/days during pregnancy. Lungs from 7-days old control and SS-exposed pups and human placenta from mothers who were either non-smokers or smokers during pregnancy were analyzed for expression of the enzymes. Mouse lungs and human placentas were examined for the expression of CSE, CBS, and 3MST by immunohistochemical staining, qRT-PCR and/or Western blot (WB) analyses. Compared to controls, mouse lung exposed gestationally to SS had significantly lower levels of CSE, CBS, and 3MST. Moreover, the SS-induced suppression of CSE and CBS in F1 lungs was transmitted to the F2 generation without significant change in the magnitude of the suppression. These changes were associated with impaired epithelial-mesenchymal transition (EMT)-a process required for normal lung angiogenesis and alveolarization. Additionally, the placentas from mothers who smoked during pregnancy, expressed significantly lower levels of CSE, CBS, and 3MST, and the effects were partially moderated by quitting smoking during the first trimester. Lung HS synthesizing enzymes are downregulated by gestational CS and the effects are transmitted to F2 progeny. Smoking during pregnancy decreases HS synthesizing enzymes is human placentas, which may correlate with the increased risk of asthma/BPD in children.
妊娠期间吸烟会损害肺部血管生成和肺泡化，促进哮喘和支气管肺发育不良（BPD）的跨代发生。硫化氢（HS）是一种促血管生成、促肺泡化和抗哮喘的气体递质，由胱硫醚-γ-裂解酶（CSE）、胱硫醚-β-合酶（CBS）和巯基丙酮酸硫转移酶（3MST）合成。本研究旨在确定妊娠期间吸烟是否会影响小鼠肺部和人胎盘中 HS 合成酶的表达。将小鼠在整个妊娠期暴露于二手烟（SS）中，其剂量近似于孕妇在怀孕期间每天坐在吸烟吧中 3 小时所接受的 CS 剂量。分析 7 天大的对照组和 SS 暴露组幼鼠的肺部以及妊娠期间不吸烟或吸烟的母亲的胎盘的酶表达情况。通过免疫组织化学染色、qRT-PCR 和/或 Western blot（WB）分析检测小鼠肺部和人胎盘的 CSE、CBS 和 3MST 表达情况。与对照组相比，妊娠期间暴露于 SS 的小鼠肺部的 CSE、CBS 和 3MST 水平明显降低。此外，SS 诱导的 F1 肺部 CSE 和 CBS 抑制作用传递到 F2 代，而抑制作用的幅度没有显著变化。这些变化与上皮-间充质转化（EMT）受损有关，这是正常肺部血管生成和肺泡化所必需的过程。此外，妊娠期间吸烟的母亲的胎盘表达的 CSE、CBS 和 3MST 水平明显降低，而在孕早期戒烟可部分缓解这些变化。妊娠期间吸烟会下调肺部 HS 合成酶，且这种影响可传递至 F2 代。母亲在妊娠期间吸烟会降低人胎盘中的 HS 合成酶，这可能与儿童哮喘/BPD 风险增加有关。
