Title

Gestational Exposure to Sidestream (Secondhand) Cigarette Smoke Promotes Transgenerational Epigenetic Transmission of Exacerbated Allergic Asthma and Bronchopulmonary Dysplasia

Authors

S. P. Singh, Lovelace Respiratory Research Institute
Hitendra S. Chand, Lovelace Respiratory Research Institute; Herbert Wertheim College of Medicine, Florida International UniversityFollow
R. J. Langley, Lovelace Respiratory Research Institute; University of Southern Alabama
N. Mishra, Lovelace Respiratory Research Institute
T. Barrett, Lovelace Respiratory Research Institute
K. Rudolph, Lovelace Respiratory Research Institute
C. Tellez, Lovelace Respiratory Research Institute
P. T. Filipczak, Lovelace Respiratory Research Institute
S. Belinsky, Lovelace Respiratory Research Institute
Al Saeed, University of New Mexico Medical Center
A. Sheybani, University of New Mexico Medical Center
V. Exil, University of New Mexico Medical Center
H. Agarwal, University of New Mexico Medical Center
V. K. Sighaye, Johns Hopkins University
T. Sussan, Johns Hopkins University
S. Biswal, Johns Hopkins University
M. Sopori, Lovelace Respiratory Research Institute

Date of this Version

5-15-2017

Document Type

Article

Abstract

Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice. Recently, perinatal nicotine injections in rats were reported to induce peroxisome proliferator-activated receptor γ-dependent transgenerational transmission of asthma. Herein, we show that first generation and second generation progeny from gestationally SS-exposed mice exhibit exacerbated AA and BPD that is not dependent on the decrease in peroxisome proliferator-activated receptor γ levels. Lungs from these mice show strong eosinophilic infiltration, excessive Th2 polarization, marked airway hyperresponsiveness, alveolar simplification, decreased lung compliance, and decreased lung angiogenesis. At the molecular level, these changes are associated with increased RUNX3 expression, alveolar cell apoptosis, and the antiangiogenic factor GAX, and decreased expression of HIF-1α and proangiogenic factors NF-κB and VEGFR2 in the 7-d first generation and second generation lungs. Moreover, the lungs from these mice exhibit lower levels of microRNA (miR)-130a and increased levels of miR-16 and miR-221. These miRs regulate HIF-1α-regulated apoptotic, angiogenic, and immune pathways. Thus the intergenerational effects of gestational SS involve epigenetic regulation of HIF-1α through specific miRs contributing to increased incidence of AA and BPD in the progenies.

Comments

Originally published in the Journal of Immunology.

Pubmed Accepted Manuscript

Identifier

FIDC008353

Recommended Citation

Singh, S. P.; Chand, Hitendra S.; Langley, R. J.; Mishra, N.; Barrett, T.; Rudolph, K.; Tellez, C.; Filipczak, P. T.; Belinsky, S.; Saeed, Al; Sheybani, A.; Exil, V.; Agarwal, H.; Sighaye, V. K.; Sussan, T.; Biswal, S.; and Sopori, M., "Gestational Exposure to Sidestream (Secondhand) Cigarette Smoke Promotes Transgenerational Epigenetic Transmission of Exacerbated Allergic Asthma and Bronchopulmonary Dysplasia" (2017). HWCOM Faculty Publications. 175.
https://digitalcommons.fiu.edu/com_facpub/175