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Effect of Nicotine Exposure During Pregnancy and Lactation on Maternal, Fetal, and Postnatal Rat IGF-II Profile

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Abstract

Smoking during pregnancy has been shown to result in an increased risk of low birth weight. However, the mechanisms underlying this association are poorly understood. The insulin-like growth factor (IGF) system plays a critical role in the regulation of feto-placental growth and development, and abnormal processing of proIGF-II may alter its biological function. Our goal was to investigate the effects of exposure to nicotine on maternal, fetal, and neonatal IGF-II processing. Nulliparous female Wistar rats were randomly assigned to receive saline (vehicle) or nicotine bitartrate (1 mg·kg−1·d−1). After mating, dams were euthanized at embryonic days 15, 18, and 21, and fetal body weight was recorded. Serum (fetal and maternal) was collected for determination of the IGF-II profile by Western blot analysis. Nicotine exposure prevented the decrease in maternal IGF-II processing seen in controls with advancing gestation. However, there was no influence of nicotine on fetal levels of IGF-II. Postnatally (postnatal day [PND] 21), pups exposed to nicotine in utero had decreased levels of big IGF-II. Our results show, for the first time, that nicotine exposure prevents the decrease of IGF-II processing in the maternal compartment. This may represent a compensatory mechanism allowing the mother to counteract the negative influence of nicotine on fetal growth and development. Our postnatal findings of suppressed IGF-II may help explain some of the long-term health complications seen in individuals exposed to smoking in utero.

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References

  1. Andres RL, Day MC. Perinatal complications associated with maternal tobacco use. Semin Neonatol. 2000;5(3):231–241.

    Article  CAS  Google Scholar 

  2. Robinson JS, Moore VM, Owens JA, McMillen IC. Origins of fetal growth restriction. Eur J Obstet Gynecol Reprod Biol. 2000;92(1):13–19.

    Article  CAS  Google Scholar 

  3. Wideroe M, Vik T, Jacobsen G, Bakketeig LS. Does maternal smoking during pregnancy cause childhood overweight? Pae-diatr Perinat Epidemiol. 2003;17(2): 171–179.

    Article  Google Scholar 

  4. Swauger JE, Steichen TJ, Murphy PA, Kinsler S. An analysis of the mainstream smoke chemistry of samples of the U.S. cigarette market acquired between 1995 and 2000. Regul Tox-icol Pharmacol. 2002;35(2 pt 1):142–156.

    Article  CAS  Google Scholar 

  5. Diekmann J, Biefel C, Rustemeier K. Analysis of cigarette mainstream smoke for 1,1-dimethylhydrazine and vinyl acetate by gas chromatography-mass spectrometry. J Chromatogr Sci. 2002;40(9):509–514.

    Article  CAS  Google Scholar 

  6. DeChiara TM, Robertson EJ, Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell. 1991;64(4):849–859.

    Article  Google Scholar 

  7. Baker J, Liu JP, Robertson EJ, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell. 1993;75(1):73–82.

    Article  CAS  Google Scholar 

  8. Allan GJ, Flint DJ, Patel K. Insulin-like growth factor axis during embryonic development. Reproduction. 2001;122(1): 31–39.

    Article  CAS  Google Scholar 

  9. Nayak NR, Giudice LC. Comparative biology of the IGF system in endometrium, decidua, and placenta, and clinical implications for foetal growth and implantation disorders. Placenta. 2003;24(4):281–296.

    Article  CAS  Google Scholar 

  10. Fowden AL. The insulin-like growth factors and feto-placental growth. Placenta. 2003;24(8–9):803–812.

    Article  CAS  Google Scholar 

  11. Smith GC, Stenhouse EJ, Crossley JA, Aitken DA, Cameron AD, Connor JM. Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrau-terine growth restriction, premature birth, preeclampsia, and stillbirth. J Clin Endocrinol Metab. 2002;87(4):1762–1767.

    Article  CAS  Google Scholar 

  12. Hudgins WR, Hampton B, Burgess WH, Perdue JF. The identification of O-glycosylated precursors of insulin-like growth factor II. J Biol Chem. 1992;267(12):8153–8160.

    CAS  PubMed  Google Scholar 

  13. Qiu Q, Basak A, Mbikay M, Tsang B, Gruslin A. Role of proIGF-II processing by proprotein convertase 4 in human placental development. Proc Natl Acad Sci USA. 2005;102(31):11047–11052.

    Article  CAS  Google Scholar 

  14. Qiu Q, Jiang JY, Bell M, Tsang BK, Gruslin A. Activation of endoproteolytic processing of insulin-like growth factor-II in fetal, early postnatal, and pregnant rats and persistence of circulating levels in postnatal life. Endocrinology. 2007;148(10): 4803–4811.

    Article  CAS  Google Scholar 

  15. Holloway AC, Kellenberger LD, Petrik JJ. Fetal and neonatal exposure to nicotine disrupts ovarian function and fertility in adult female rats. Endocrine. 2006;30(2):213–216.

    Article  CAS  Google Scholar 

  16. George L, Granath F, Johansson AL, Cnattingius S. Self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy. Acta Obstet Gynecol Scand. 2006;85(11):1331–1337.

    Article  CAS  Google Scholar 

  17. Haddow JE, Knight GJ, Palomaki GE, Kloza EM, Wald NJ. Cigarette consumption and serum cotinine in relation to birthweight. Br J Obstet Gynaecol. 1987;94(7):678–681.

    Article  CAS  Google Scholar 

  18. Newman MB, Shytle RD, Sanberg PR. Locomotor behavioral effects of prenatal and postnatal nicotine exposure in rat offspring. Behav Pharmacol. 1999;10(6–7):699–706.

    Article  CAS  Google Scholar 

  19. Holloway AC, Lim GE, Petrik JJ, Foster WG, Morrison KM, Gerstein HC. 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. 2005;48(12):2661–2666.

    Article  CAS  Google Scholar 

  20. Sferruzzi-Perri AN, Owens JA, Standen P, et al. Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term. Am J Physiol Endocrinol Metab. 2007;292(3):E668–E76.

    Article  CAS  Google Scholar 

  21. Sferruzzi-Perri AN, Owens JA, Pringle KG, Robinson JS, Roberts CT. Maternal insulin-like growth factors-I and -II act via different pathways to promote fetal growth. Endocrinology. 2006;147(7):3344–3355.

    Article  CAS  Google Scholar 

  22. Roberts CT, Owens JA, Sferruzzi-Perri AN. Distinct actions of insulin-like growth factors (IGFs) on placental development and fetal growth: lessons from mice and guinea pigs. Placenta. 2008;29(suppl A):S42–S47.

    Article  Google Scholar 

  23. Trollmann R, Klingmuller K, Schild RL, Rascher W, Dotsch J. Differential gene expression of somatotrophic and growth factors in response to in vivo hypoxia in human placenta. Am JObstet Gynecol. 2007;197(6):601–606.

    Google Scholar 

  24. Mao C, Yuan X, Cui Y, et al. Prenatal exposure to nicotine with associated in utero hypoxia decreased fetal brain muscarinic mRNA in the rat. Brain Res. 2008;1189:43–50.

    Article  CAS  Google Scholar 

  25. Yildiz D, Liu YS, Ercal N, Armstrong DW. Comparison of pure nicotine- and smokeless tobacco extract-induced toxicities and oxidative stress. Arch Environ Contam Toxicol. 1999;37(4):434–439.

    Article  CAS  Google Scholar 

  26. Swami S, Suryakar AN, Katkam RV, Kumbar KM. Absorption of nicotine induces oxidative stress among bidi workers. Indian J Public Health. 2006;50(4):231–235.

    CAS  PubMed  Google Scholar 

  27. Constancia M, Angiolini E, Sandovici I, et al. Adaptation of nutrient supply to fetal demand in the mouse involves interaction between the Igf2 gene and placental transporter systems. Proc Natl Acad Sci U S A. 2005;102(52):19219–19224.

    Article  CAS  Google Scholar 

  28. Pringle PJ, Geary MP, Rodeck CH, Kingdom JC, Kayamba-Kay’s S, Hindmarsh PC. The influence of cigarette smoking on antenatal growth, birth size, and the insulin-like growth factor axis. J Clin Endocrinol Metab. 2005;90(5):2556–2562.

    Article  CAS  Google Scholar 

  29. Bruin JE, Gerstein HC, Morrison KM, Holloway AC. Increased pancreatic beta-cell apoptosis following fetal and neonatal exposure to nicotine is mediated via the mitochondria. Toxicol Sci. 2008;103(2):362–370.

    Article  CAS  Google Scholar 

  30. Petrik J, Arany E, McDonald TJ, Hill DJ. Apoptosis in the pancreatic islet cells of the neonatal rat is associated with a reduced expression of insulin-like growth factor II that may act as a survival factor. Endocrinology. 1998;139(6):2994–3004.

    Article  CAS  Google Scholar 

  31. Petrik J, Reusens B, Arany E, et al. A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II. Endocrinology. 1999;140(10):4861–4873.

    Article  CAS  Google Scholar 

  32. Sandhu MS, Gibson JM, Heald AH, Dunger DB, Wareham NJ. Low circulating IGF-II concentrations predict weight gain and obesity in humans. Diabetes. 2003;52(6):1403–1408.

    Article  CAS  Google Scholar 

  33. Bergmann KE, Bergmann RL, Von KR, et al. Early determinants of childhood overweight and adiposity in a birth cohort study: role of breast-feeding. Int JObes Relat Metab Disord. 2003;27(2):162–172.

    Article  CAS  Google Scholar 

  34. Toschke AM, Koletzko B, Slikker W Jr, Hermann M, Von KR. Childhood obesity is associated with maternal smoking in pregnancy. Eur J Pediatr. 2002;161(8):445–448.

    Article  CAS  Google Scholar 

  35. Vik T, Jacobsen G, Vatten L, Bakketeig LS. Pre- and postnatal growth in children of women who smoked in pregnancy. Early Hum Dev. 1996;45(3):245–255.

    Article  CAS  Google Scholar 

  36. Von KR, Toschke AM, Koletzko B, Slikker W Jr. Maternal smoking during pregnancy and childhood obesity. Am J Epidemiol. 2002;156(10):954–961.

    Article  Google Scholar 

  37. Oken E, Huh SY, Taveras EM, Rich-Edwards JW, Gillman MW. Associations of maternal prenatal smoking with child adiposity and blood pressure. Obes Res. 2005;13(11): 2021–2028.

    Article  Google Scholar 

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Authors and Affiliations

  1. Division Maternal-Fetal Medicine, Department OBS-GYN and Newborn Care, The Ottawa Hospital University of Ottawa, Room 8420, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada

    Andrée Gruslin MD

  2. Chronic Disease Program, Ottawa Health Research Institute, Ottawa, Ontario, Canada

    Andrée Gruslin MD, Michael Bell BSc & Qing Qiu MD

  3. Reproductive Biology Division, Department of Obstetrics & Gynecology, McMaster University, Ontario, Hamilton, Canada

    Carolyn E. Cesta BSc, Maria A. Petre BSc & Alison C. Holloway PhD

Authors
  1. Andrée Gruslin MD
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  2. Carolyn E. Cesta BSc
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  3. Michael Bell BSc
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  4. Qing Qiu MD
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  5. Maria A. Petre BSc
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  6. Alison C. Holloway PhD
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Correspondence to Andrée Gruslin MD.

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Gruslin, A., Cesta, C.E., Bell, M. et al. Effect of Nicotine Exposure During Pregnancy and Lactation on Maternal, Fetal, and Postnatal Rat IGF-II Profile. Reprod. Sci. 16, 875–882 (2009). https://doi.org/10.1177/1933719109337038

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  • DOI: https://doi.org/10.1177/1933719109337038

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