Gestational Exposure to Cigarette Smoke Suppresses the Gasotransmitter H2S Biogenesis and the Effects Are Transmitted Transgenerationally

Abstract

Rationale: Gestational cigarette smoke (CS) impairs lung angiogenesis and alveolarization, promoting transgenerational development of asthma and bronchopulmonary dysplasia (BPD). Hydrogen sulfide (H 2 S), a proangiogenic, pro-alveolarization, and anti-asthmatic gasotransmitter is synthesized by cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfur transferase (3MST). Objective: Determine if gestational CS exposure affected the expression of H 2 S synthesizing enzymes in the mouse lung and human placenta. Methods: 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. Measurements: 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. Results: 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. Singh et al. Gestational Smoke Inhibits H 2 S Biogenesis Conclusions: Lung H 2 S synthesizing enzymes are downregulated by gestational CS and the effects are transmitted to F2 progeny. Smoking during pregnancy decreases H 2 S synthesizing enzymes is human placentas, which may correlate with the increased risk of asthma/BPD in children.

Increased Expression of LASI lncRNA Regulates the Cigarette Smoke and COPD Associated Airway Inflammation and Mucous Cell Hyperplasia

“…qRT-PCR was conducted using the Bio-Rad CFX Real-Time PCR detection system. Quantification of the results was performed using the delta-delta (ΔΔ)Ct method and U6 noncoding small nuclear RNA (snRNA) was used as a reference gene for lncRNA expression levels and beta-actin and GAPDH were used for mRNA expression levels as described recently ( 15 ).…”

Disrupted H2S Signaling by Cigarette Smoking and Alcohol Drinking: Evidence from Cellular, Animal, and Clinical Studies

“…A recent study further found that the expressions of three H 2 S-generating genes, including CSE, CBS, and 3MST, were all lower in the placentas from mothers who smoked during pregnancy in comparison with the mothers who never smoked. Quitting smoking during the first trimester of pregnancy could partially improve the expressions of these H 2 S-generating genes in the placentas [ 52 ]. More studies need to be conducted to validate if the downregulated expressions of these H 2 S-generatiang enzymes might be a biomarker for asthma susceptibility in children.…”

“…It was found that mouse lung exposed gestationally to cigarette smoking had significantly lower levels of CSE, CBS, and 3MST in both the F1 and F2 generation. Moreover, the lungs from F1 and F2 progenies displayed with impaired angiogenesis and alveolarization, suggesting that a lower level of H 2 S is correlated with the increased risk of lung disorders [ 52 ].…”