Nicotine-induced Genetic and Epigenetic Modifications in Primary Human Amniotic Fluid Stem Cells

Overview

Journal Curr Pharm Des

Publisher Bentham Science Publishers

Date 2024 Jun 13

PMID 38867535

Authors

Prabin Upadhyaya

Cristina Milillo

Annalisa Bruno

Federico Anaclerio

Carlotta Buccolini

Anastasia DellElice

Ilaria Angilletta

Marco Gatta

Patrizia Ballerini

Ivana Antonucci

Affiliations

Soon will be listed here.

Abstract

Background: Smoking during pregnancy has been linked to adverse health outcomes in offspring, but the underlying mechanisms are not fully understood. To date, the effect of maternal smoking has been tested in primary tissues and animal models, but the scarcity of human tissues limits experimental studies. Evidence regarding smoking-related molecular alteration and gene expression profiles in stem cells is still lacking.

Methods: We developed a cell culture model of human amniotic fluid stem cells (hAFSCs) of nicotine (NIC) exposure to examine the impact of maternal smoking on epigenetic alterations of the fetus.

Results: NIC 0.1 μM (equivalent to "light" smoking, i.e., 5 cigarettes/day) did not significantly affect cell viability; however, significant alterations in DNA methylation and N6-methyladenosine (m6A) RNA methylation in hAFSCs occurred. These epigenetic changes may influence the gene expression and function of hAFSCs. Furthermore, NIC exposure caused time-dependent alterations of the expression of pluripotency genes and cell surface markers, suggesting enhanced cell stemness and impaired differentiation potential. Furthermore, NICtreated cells showed reduced mRNA levels of key adipogenic markers and hypomethylation of the promoter region of the imprinted gene during adipogenic differentiation, potentially suppressing adipo/lipogenesis. Differential expression of 16 miRNAs, with predicted target genes involved in various metabolic pathways and linked to pathological conditions, including cognitive delay and fetal growth retardation, has been detected.

Conclusion: Our findings highlight multi-level effects of NIC on hAFSCs, including epigenetic modifications, altered gene expression, and impaired cellular differentiation, which may contribute to long-term consequences of smoking in pregnancy and its potential impact on offspring health and development.

References

Jha P, Ranson M, Nguyen S, Yach D . Estimates of global and regional smoking prevalence in 1995, by age and sex. Am J Public Health. 2002; 92(6):1002-6. PMC: 1447501. DOI: 10.2105/ajph.92.6.1002. View

Storr C, Cheng H, Alonso J, Angermeyer M, Bruffaerts R, de Girolamo G . Smoking estimates from around the world: data from the first 17 participating countries in the World Mental Health Survey Consortium. Tob Control. 2009; 19(1):65-74. PMC: 4124902. DOI: 10.1136/tc.2009.032474. View

Drake P, Driscoll A, Mathews T . Cigarette Smoking During Pregnancy: United States, 2016. NCHS Data Brief. 2018; (305):1-8. View

Djordjevic M, Doran K . Nicotine content and delivery across tobacco products. Handb Exp Pharmacol. 2009; (192):61-82. DOI: 10.1007/978-3-540-69248-5_3. View

Goniewicz M, Kuma T, Gawron M, Knysak J, Kosmider L . Nicotine levels in electronic cigarettes. Nicotine Tob Res. 2012; 15(1):158-66. DOI: 10.1093/ntr/nts103. View

Ino T . Maternal smoking during pregnancy and offspring obesity: meta-analysis. Pediatr Int. 2009; 52(1):94-9. DOI: 10.1111/j.1442-200X.2009.02883.x. View

Hackshaw A, Rodeck C, Boniface S . Maternal smoking in pregnancy and birth defects: a systematic review based on 173 687 malformed cases and 11.7 million controls. Hum Reprod Update. 2011; 17(5):589-604. PMC: 3156888. DOI: 10.1093/humupd/dmr022. View

Lindblad F, Hjern A . ADHD after fetal exposure to maternal smoking. Nicotine Tob Res. 2010; 12(4):408-15. DOI: 10.1093/ntr/ntq017. View

Svanes C, Sunyer J, Plana E, Dharmage S, Heinrich J, Jarvis D . Early life origins of chronic obstructive pulmonary disease. Thorax. 2009; 65(1):14-20. DOI: 10.1136/thx.2008.112136. View

10.

Martino D, Prescott S . Epigenetics and prenatal influences on asthma and allergic airways disease. Chest. 2011; 139(3):640-647. DOI: 10.1378/chest.10-1800. View

11.

Somm E, Schwitzgebel V, Vauthay D, Camm E, Chen C, Giacobino J . Prenatal nicotine exposure alters early pancreatic islet and adipose tissue development with consequences on the control of body weight and glucose metabolism later in life. Endocrinology. 2008; 149(12):6289-99. DOI: 10.1210/en.2008-0361. View

12.

Knopik V, Maccani M, Francazio S, McGeary J . The epigenetics of maternal cigarette smoking during pregnancy and effects on child development. Dev Psychopathol. 2012; 24(4):1377-90. PMC: 3581096. DOI: 10.1017/S0954579412000776. View

13.

Joubert B, Haberg S, Bell D, Nilsen R, Vollset S, Midttun O . Maternal smoking and DNA methylation in newborns: in utero effect or epigenetic inheritance?. Cancer Epidemiol Biomarkers Prev. 2014; 23(6):1007-17. PMC: 4140220. DOI: 10.1158/1055-9965.EPI-13-1256. View

14.

Joubert B, Haberg S, Nilsen R, Wang X, Vollset S, Murphy S . 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect. 2012; 120(10):1425-31. PMC: 3491949. DOI: 10.1289/ehp.1205412. View

15.

Maccani M, Avissar-Whiting M, Banister C, McGonnigal B, Padbury J, Marsit C . Maternal cigarette smoking during pregnancy is associated with downregulation of miR-16, miR-21, and miR-146a in the placenta. Epigenetics. 2010; 5(7):583-9. PMC: 2974801. DOI: 10.4161/epi.5.7.12762. View

16.

Maccani M, Knopik V . Cigarette smoke exposure-associated alterations to non-coding RNA. Front Genet. 2012; 3:53. PMC: 3321413. DOI: 10.3389/fgene.2012.00053. View

17.

Izzotti A, Calin G, Arrigo P, Steele V, Croce C, De Flora S . Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J. 2008; 23(3):806-12. PMC: 2653990. DOI: 10.1096/fj.08-121384. View

18.

Wang C, Yang G, Wang Z, Liu C, Li T, Lai Z . Role of perivascular adipose tissue in nicotine‑induced endothelial cell inflammatory responses. Mol Med Rep. 2016; 14(6):5713-5718. DOI: 10.3892/mmr.2016.5934. View

19.

Nguyen T, Li G, Chen H, Cranfield C, McGrath K, Gorrie C . Maternal E-Cigarette Exposure Results in Cognitive and Epigenetic Alterations in Offspring in a Mouse Model. Chem Res Toxicol. 2018; 31(7):601-611. DOI: 10.1021/acs.chemrestox.8b00084. View

20.

Kirschneck C, Maurer M, Wolf M, Reicheneder C, Proff P . Regular nicotine intake increased tooth movement velocity, osteoclastogenesis and orthodontically induced dental root resorptions in a rat model. Int J Oral Sci. 2017; 9(3):174-184. PMC: 5709548. DOI: 10.1038/ijos.2017.34. View