, Volume 57, Issue 1, pp 60–71 | Cite as

Effects of cigarette smoke exposure during suckling on food intake, fat mass, hormones, and biochemical profile of young and adult female rats

  • Patricia Cristina LisboaEmail author
  • Patricia Novaes Soares
  • Thamara Cherem Peixoto
  • Janaine Cavalcanti Carvalho
  • Camila Calvino
  • Vanessa Silva Tavares Rodrigues
  • Dayse Nascimento Bernardino
  • Viviane Younes-Rapozo
  • Alex Christian Manhães
  • Elaine de Oliveira
  • Egberto Gaspar de Moura
Original Article



Children from smoking mothers have a higher risk of developing obesity and associated comorbidities later in life. Different experimental models have been used to assess the mechanisms involved with this increased risk. Using a rat model of neonatal nicotine exposure via implantation of osmotic minipumps in lactating dams, we have previously shown marked sexual dimorphisms regarding metabolic and endocrine outcomes in the adult progeny. Considering that more than four thousand substances are found in tobacco smoke besides nicotine, we then studied a rat model of neonatal tobacco smoke exposure: adult male offspring had hyperphagia, obesity, hyperglycemia, hypertriglyceridemia, secondary hyperthyroidism and lower adrenal hormones. Since litters were culled to include only males and since sexual dimorphisms had already been identified in the nicotine exposure model, here we also evaluated the effects of tobacco smoke exposure during lactation on females.


Wistar rat dams and their pups were separated into two groups of 8 litters each: SMOKE (4 cigarettes per day, from postnatal day 3 to 21) and CONTROL (filtered air). Offspring of both sexes were euthanized at PN21 and PN180.


Changes in male offspring corroborated previous data. At weaning, females showed lower body mass gain and serum triglycerides, but no alterations in visceral fat and hormones. At adulthood, females had higher body mass, hyperphagia, central obesity, hyperleptinemia, hypercholesterolemia, hypercorticosteronemia, but no change in serum TSH and T3, and adrenal catecholamine


Sexual dimorphisms were observed in several parameters, thus indicating that metabolic and hormonal changes due to smoke exposure during development are sex-dependent.


Cigarette smoke Lactation Adipose tissue Hormones, Female rats 



All authors are grateful to Mrs. Fabiana Gallaulckydio, Miss Monica Moura and Mr Ulisses Siqueira for technical assistance.


This study was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Supplementary material

12020_2017_1320_MOESM1_ESM.docx (111 kb)
Supplementary Information


  1. 1.
    M. Bastien, P. Poirier, I. Lemieux, J.P. Després, Overview of epidemiology and contribution of obesity to cardiovascular disease. Prog. Cardiovasc. Dis. 56, 369–381 (2014)CrossRefGoogle Scholar
  2. 2.
    M. Ng, T. Fleming, M. Robinson, B. Thomson, N. Graetz, C. Margono, E.C. Mullany, S. Biryukov, C. Abbafati, S.F. Abera et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384, 766–781 (2014)CrossRefGoogle Scholar
  3. 3.
    D.J. Barker, The developmental origins of adult disease. Eur. J. Epidemiol. 18, 733–736 (2003)CrossRefGoogle Scholar
  4. 4.
    P.D. Gluckman, M.A. Hanson, Developmental plasticity and human disease: research directions. J. Intern. Med. 261, 461–471 (2007)CrossRefGoogle Scholar
  5. 5.
    E.G. De Moura, P.C. Lisboa, M.C. Passos, Neonatal programming of neuroimmunomodulation-role of adipocytokines and neuropeptides. Neuroimmunomodulation 15, 176–188 (2008)CrossRefGoogle Scholar
  6. 6.
    R. von Kries, A.M. Toschke, B. Koletzko, W. Slikker, Jr. Maternal smoking during pregnancy and childhood obesity. Am. J. Epidemiol. 156(10), 954–961 (2002)CrossRefGoogle Scholar
  7. 7.
    M. Wideroe, T. Vik, G. Jacobsen, L.S. Bakketeig, Does maternal smoking during pregnancy cause childhood overweight? Paediatr. Perinat. Epidemiol. 17, 422 (2003)CrossRefGoogle Scholar
  8. 8.
    S.Y. Hill, S. Shen, Locke, J. Wellman, E. Rickin, L. Lowers, Offspring from families at high risk for alcohol dependence: increased body mass index in association with prenatal exposure to cigarettes but not alcohol. Psychiatry Res. 35(3), 203–216 (2005)CrossRefGoogle Scholar
  9. 9.
    M.Z. Goldani, L.S.B. Haeffner, M. Agranonik, M.A. Barbieri, H. Bettiol, A.A.M. Silva, Do early life factors influence body mass index in adolescents? Braz. J. Med. Biol. Res. 40, 1231–1236 (2007)CrossRefGoogle Scholar
  10. 10.
    C.M. McBride, P.L. Pirie, Postpartum smoking relapse. Addict. Behav. 15, 165–168 (1990)CrossRefGoogle Scholar
  11. 11.
    C. Meernik, A.O. Goldstein, A critical review of smoking, cessation, relapse and emerging research in pregnancy and post-partum. Br. Med. Bull. 114(1), 135–146 (2015). doi: 10.1093/bmb/ldv016 CrossRefPubMedGoogle Scholar
  12. 12.
    S. Orton, T. Coleman, S. Lewis, S. Cooper, L.L. Jones, “I was a full time proper smoker”: a qualitative exploration of smoking in the home after childbirth among women who relapse postpartum. PLoS One 11(6), e0157525 (2016). doi: 10.1371/journal.pone.0157525 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    K.I. Pollak, L.J. Fish, P. Lyna, B.L. Peterson, E.R. Myers, X. Gao, G.K. Swamy, A. Brown Johnson, P. Whitecar, A.K. Bilheimer, P.K. Pletsch, Efficacy of a nurse-delivered intervention to prevent and delay postpartum return to smoking: the quit for two trial. Nicot. Tob. Res. 18(10), 1960–1966 (2016)CrossRefGoogle Scholar
  14. 14.
    E. de Oliveira, E.G. Moura, A.P. Santos-Silva, C.R. Pinheiro, N.S. Lima, J.F. Nogueira-Neto, A.L. Nunes-Freitas, Y. Abreu-Villaça, M.C.F. Passos, P.C. Lisboa, Neonatal nicotine exposure causes insulin and leptin resistance and inhibits hypothalamic leptin signaling in adult rats offspring. J. Endocrinol. 206, 55–63 (2010)CrossRefGoogle Scholar
  15. 15.
    C.R. Pinheiro, E. Oliveira, I.H. Trevenzoli, A.C. Manhães, A.P. Santos-Silva, V. Younes-Rappozo, S. Claudio-Neto, A.C. Santana, C.C.A. Nascimento-Saba, E.G. Moura, P.C. Lisboa, Developmental plasticity in adrenal function and leptin production primed by nicotine exposure during lactation: gender differences in rats. Horm Metab Res 43, 1–9 (2011)CrossRefGoogle Scholar
  16. 16.
    P.C. Lisboa, E. de Oliveira, A.C. Manhães, A.P. Santos-Silva, C.R. Pinheiro, V. Younes-Rapozo, L.C. Faustino, T.M. Ortiga-Carvalho, E.G. Moura, Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny. J. Endocrinol. 224(3), 315–325 (2015). doi: 10.1530/JOE-14-0473 CrossRefPubMedGoogle Scholar
  17. 17.
    C.R. Pinheiro, E.G. Moura, A.C. Manhães, M.C. Fraga, S. Claudio-Neto, V. Younes-Rapozo, A.P. Santos-Silva, B.M. Lotufo, E. Oliveira, P.C. Lisboa, Maternal nicotine exposure during lactation alters food preference, anxiety-like behavior and the brain dopaminergic reward system in the adult rat offspring. Physiol. Behav. 149, 131–141 (2015b)CrossRefGoogle Scholar
  18. 18.
    A.P. Santos-Silva, E. Oliveira, C.R. Pinheiro, A.C. Santana, C.C. Nascimento-Saba, Y. Abreu-Villaça, E.G. Moura, P.C. Lisboa, Endocrine effects of tobacco smoke exposure during lactation in weaned and adult male offspring. J. Endocrinol. 218, 13–24 (2013)CrossRefGoogle Scholar
  19. 19.
    C.R. Pinheiro, E.G. Moura, A.C. Manhães, M.C. Fraga, S. Claudio-Neto, Y. Abreu-Villaça, E. Oliveira, P.C. Lisboa, Concurrent maternal and pup postnatal tobacco smoke exposure in wistar rats changes food preference and dopaminergic reward system parameters in the adult male offspring. Neuroscience 301, 178–192 (2015a)CrossRefGoogle Scholar
  20. 20.
    M.C.F. Passos, C.F. Ramos, E.G. Moura, Short and long term effects of malnutrition in rats during lactation on the body weight of offspring. Nutr. Res. 20(11), 1603–1612 (2000)CrossRefGoogle Scholar
  21. 21.
    A.P. Santos-Silva, E. Oliveira, C.R. Pinheiro, A.L. Nunes-Freitas, Y. Abreu-Villaça, A.C. Santana, C.C. Nascimento-Saba, J.F. Nogueira-Neto, A.M. Reis, E.G. Moura, P.C. Lisboa, Effects of maternal tobacco smoke exposure during lactation on nutritional and hormonal profiles in mothers and offspring. J. Endocrinol. 209, 1–11 (2011)CrossRefGoogle Scholar
  22. 22.
    B. Eskenazi, J.J. Bergmann, Passive and active maternal smoking during pregnancy, as measured by serum cotinine, and postnatal smoke exposure. I. Effects on physical growth at age 5 years. Am. J. Epidemiol. 142(9), 10–18 (1995)CrossRefGoogle Scholar
  23. 23.
    E.P. Conceição, E.G. Moura, I.H. Trevenzoli, N. Peixoto-Silva, C.R. Pinheiro, V. Younes-Rapozo, E. Oliveira, P.C. Lisboa, Neonatal overfeeding causes higher adrenal catecholamine content and basal secretion and liver dysfunction in adult rats. Eur. J. Nutr. 52(4), 1393–1404 (2013). doi: 10.1007/s00394-012-0448-8 CrossRefPubMedGoogle Scholar
  24. 24.
    K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4), 402–8 (2001)CrossRefGoogle Scholar
  25. 25.
    G.E. Mott, D.S. Lewis, H.C. McGill Jr., Programming of cholesterol metabolism by breast or formula feeding. Ciba. Found. Symp. 156, 56–66 (1991)PubMedGoogle Scholar
  26. 26.
    M.E. Symonds, Integration of physiological and molecular mechanisms of the developmental origins of adult disease: new concepts and insights. Proc. Nutr. Soc. 66, 442–450 (2007)CrossRefGoogle Scholar
  27. 27.
    E. Oliveira, E. Moura, A. Santos-Silva, A. Fagundes, A. Rios, Y. Abreu-Villaca, J.F. Nogueira-Neto, M.C.F. Passos, P.C. Lisboa, Short and long-term effects of maternal nicotine exposure during lactation on body adiposity, lipid profile and thyroid function of rat offspring. J. Endocrinol. 202(3), 397–405 (2009)CrossRefGoogle Scholar
  28. 28.
    W.J. Chen, R.B. Kelly, Effect of prenatal or perinatal nicotine exposure o neonatal thyroid status and offspring growth in rats. Life Sci. 76, 1249–1258 (2005)CrossRefGoogle Scholar
  29. 29.
    Y.J. Gao, A.C. Holloway, Z.H. Zeng, G.E. Lim, J.J. Petrik, W.G. Foster, R.M. Lee, Prenatal exposure to nicotine causes postnatal obesity and altered perivascular adipose tissue function. Obes. Res. 13, 687–692 (2005)CrossRefGoogle Scholar
  30. 30.
    A.C. Holloway, G.E. Lim, J.J. Petrik, W.J. Foster, K.M. Morrison, H.C. Gerstein, Fetal and neonatal exposure to nicotine in Wistar rats results in increased beta cell apoptosis at birth and postnatal endocrine and metabolic changes associated with type 2 diabetes. Diabetologia 48(12), 2661–2666 (2005)CrossRefGoogle Scholar
  31. 31.
    E. Somm, V.M. Schwitzgebel, D.M. Vauthay, E.J. Camm, C.Y. Chen, J.P. Giacobino, S.V. Sizonenko, M.L. Aubert, P.S. Hüppi, Prenatal nicotine exposure alters early pancreatic islet and adipose tissue development with consequences and the control of body weight and glucose metabolism later in life. Endocrinology 149, 6289–6299 (2008)CrossRefGoogle Scholar
  32. 32.
    P. Kokkoris, F.X. Pi-Sunyer, Obesity and endocrine disease. Endocrinol. Metab. Clin. N. Am. 32(4), 895–914 (2003)CrossRefGoogle Scholar
  33. 33.
    M.J. Müller, J. Enderle, A. Bosy-Westphal, Changes in energy expenditure with weight gain and weight loss in humans. Curr. Obes. Rep. 5(4), 413–423 (2016)CrossRefGoogle Scholar
  34. 34.
    R. Vranckx, L. Savu, M. Maya, E.A. Nunez, Characterization of a major development-regulated serum thyroxine-binding globulin in the euthyroid mouse. Biochem. J. 271(2), 373–379 (1990)CrossRefGoogle Scholar
  35. 35.
    L. Bartalena, J. Robbins, Thyroid hormone transport proteins. Clin. Lab. Med. 13(3), 583–98 (1993)CrossRefGoogle Scholar
  36. 36.
    G.A. Heussen, G.J. Schefferlie, M.J. Talsma, H. van Til, M.J. Dohmen, A. Brouwer, G.M. Alink, Effects on thyroid hormone metabolism and depletion of lung vitamin a in rats by airborne particulate matter. J. Toxicol. Environ. Health 38(4), 419–34 (1993)CrossRefGoogle Scholar
  37. 37.
    A. Ishihara, S. Sawatsubashi, K. Yamauchi, Endocrine disrupting chemicals: interference of thyroid hormone binding to transthyretins and to thyroid hormone receptors. Mol. Cell. Endocrinol. 99(1-2), 105–17 (2003)CrossRefGoogle Scholar
  38. 38.
    A.C. Bianco, B.W. Kim, Deiodinases: implications of the local control of thyroid hormone action. J. Clin. Invest. 116, 2571–2579 (2006)CrossRefGoogle Scholar
  39. 39.
    D.L. St Germain, V.A. Galton, A. Hernandez, Minireview: defining the roles of the iodothyronine deiodinases: current concepts and challenges. Endocrinology 150, 1097–1107 (2009)CrossRefGoogle Scholar
  40. 40.
    R.H. Stimson, B.R. Walker, The role and regulation of 11β-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome. Horm. Mol. Biol. Clin. Investig. 15, 37–48 (2013). doi: 10.1515/hmbci-2013-0015 CrossRefPubMedGoogle Scholar
  41. 41.
    R.H. Stimson, J. Andersson, R. Andrew, D.N. Redhead, F. Karpe, P.C. Hayes, T. Olsson, B.R. Walker, Cortisol release from adipose tissue by 11β-hydroxysteroid dehydrogenase type 1 in humans. Diabetes 58, 46–53 (2009). doi: 10.2337/db08-0969 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    K.A. Hughes, K.N. Manolopoulos, J. Iqbal, N.L. Cruden, R.H. Stimson, R.M. Reynolds, D.E. Newby, R. Andrew, F. Karpe, B.R. Walker, Recycling between cortisol and cortisone in human splanchnic, subcutaneous adipose, and skeletal muscle tissues in vivo. Diabetes 61(6), 1357–1364 (2012). doi: 10.2337/db11-1345. CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    L.L. Woods, J.R. Ingelfinger, J.R. Nyengaard, R. Rasch, Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr. Res. 49, 460–467 (2001). [PubMed: 11264427]CrossRefGoogle Scholar
  44. 44.
    B.T. Alexander, Placental insufficiency leads to development of hypertension in growth-restricted offspring. Hypertension 41, 457–462 (2003). [PubMed: 12623943]CrossRefGoogle Scholar
  45. 45.
    L.A. Ortiz, A. Quan, F. Zarzar, A. Weinberg, M. Baum, Prenatal dexamethasone programs hypertension and renal injury in the rat. Hypertension 41, 328–34 (2003). [PubMed: 12574103]CrossRefGoogle Scholar
  46. 46.
    L.L. Woods, J.R. Ingelfinger, R. Rasch, Modest maternal protein restriction fails to program adult hypertension in female rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289, R1131–R1136 (2005). [PubMed: 15961538]CrossRefGoogle Scholar
  47. 47.
    A. Stefanidis, S.J. Spencer, Effects of neonatal overfeeding on juvenile and adult feeding and energy expenditure in the rat. PLoS One 7(12), e52130 (2012). doi: 10.1371/journal.pone.0052130 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    N.B. Ojeda, S. Intapad, B.T. Alexander, Sex differences in he developmental programming of hypertension. Acta. Physiol. 210(2), 307–316 (2014). doi: 10.1111/apha.12206 CrossRefGoogle Scholar
  49. 49.
    J.H. Dasinger, B.T. Alexander, Gender differences in developmental programming of cardiovascular diseases. Clin. Sci. 130(5), 337–348 (2016). doi: 10.1042/CS20150611 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    A.L. Kozyrskyj, R. Kalu, P.T. Koleva, S.L. Bridgman, Fetal programming of overweight through the microbiome: boys are disproportionatelyaffected. J. Dev. Orig. Health Dis. 7(1), 25–34 (2016). doi: 10.1017/S2040174415001269 CrossRefPubMedGoogle Scholar
  51. 51.
    C.L. Gibson, B. Coomber, J. Rathbone, Is progesterone a candidate neuroprotective factor for treatment following ischemic stroke? Neuroscientist 15(4), 324–332 (2009). doi: 10.1177/1073858409333069 CrossRefPubMedGoogle Scholar
  52. 52.
    P. Gaignard, M. Fréchou, M. Schumacher, P. Thérond, C. Mattern, A. Slama, R. Guennoun, Progesterone reduces brain mitochondrial dysfunction after transient focal ischemia in male and female mice. J. Cereb. Blood Flow. Metab. 36(3), 562–568 (2016). doi: 10.1177/0271678X15610338 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Patricia Cristina Lisboa
    • 1
    Email author
  • Patricia Novaes Soares
    • 1
  • Thamara Cherem Peixoto
    • 1
  • Janaine Cavalcanti Carvalho
    • 1
  • Camila Calvino
    • 1
  • Vanessa Silva Tavares Rodrigues
    • 1
  • Dayse Nascimento Bernardino
    • 1
  • Viviane Younes-Rapozo
    • 1
  • Alex Christian Manhães
    • 2
  • Elaine de Oliveira
    • 1
  • Egberto Gaspar de Moura
    • 1
  1. 1.Laboratory of Endocrine Physiology, Biology InstituteState University of Rio de JaneiroRio de JaneiroBrazil
  2. 2.Laboratory of Neurophysiology, Biology InstituteState University of Rio de JaneiroRio de JaneiroBrazil

Personalised recommendations