Prenatal nicotine exposure alters pulmonary function in newborn rhesus monkeys.

Epidemiological studies have shown that offspring of women who smoke during pregnancy have abnormal lung function and associated higher incidences of lower respiratory disorders. The recent identification of nicotinic acetylcholine receptors (nAChR) in fetal lung suggests that the direct interaction between nicotine and nAChR in fetal lung may underlie the postnatal pulmonary abnormalities seen in such infants. This hypothesis was tested in monkeys to determine if maternal nicotine exposure would produce changes in lung mechanics in newborn monkeys similar to those observed in human infants whose mothers smoked during pregnancy. Timed pregnant rhesus monkeys were infused with either nicotine (1.5 mg/kg/d, n = 7) or saline (n = 7) using subcutaneous osmotic pumps from Day 26 to 160 of gestation. On Day 160 of pregnancy (term = 165 d), fetuses were delivered by C-section, and the following day were subjected to pulmonary function testing. After testing, animals were sacrificed, and lungs weighed and fixed. Lung weight and fixed lung volume decreased (16% and 14%, respectively) significantly following in utero nicotine exposure. Peak tidal expiratory flow, FEV(0.2), mean mid-expiratory flow, forced expiratory volume at peak expiratory flow (FEV(PEF)), and FEV(PEF)/FVC% were significantly lower in newborns exposed to nicotine during gestation. Absolute and specific pulmonary resistance increased significantly whereas absolute and specific dynamic compliance remained unchanged in prenatally nicotine-treated pups. These changes in pulmonary function are strikingly similar to the changes observed in offspring of human smokers. This suggests that the interaction of nicotine with nAChR in developing lung is responsible for the altered pulmonary mechanics observed in human infants whose mothers smoked during pregnancy.

[1]  V. Baste,et al.  Maternal smoking and birthweight: effect modification of period, maternal age and paternal smoking , 2000, Acta obstetricia et gynecologica Scandinavica.

[2]  D. Sherrill,et al.  Parental factors affecting respiratory function during the first year of life , 2000, Pediatric pulmonology.

[3]  Edward B Rappaport,et al.  environmental tobacco smoke exposure and childhood lung function , 2022 .

[4]  A. Maus,et al.  Neuronal nicotinic receptors in non-neuronal cells: new mediators of tobacco toxicity? , 2000, European journal of pharmacology.

[5]  R. Gray,et al.  Maternal cigarette smoking during pregnancy and infant ponderal index at birth in the Swedish Medical Birth Register, 1991-1992. , 2000, American journal of public health.

[6]  D. Holtzman,et al.  Trends in pregnancy-related smoking rates in the United States, 1987-1996. , 2000, JAMA.

[7]  H. Sekhon,et al.  Prenatal nicotine increases pulmonary alpha7 nicotinic receptor expression and alters fetal lung development in monkeys. , 1999, The Journal of clinical investigation.

[8]  J. Stocks,et al.  Impaired airway function and wheezing in infancy: the influence of maternal smoking and a genetic predisposition to asthma. , 1999, American journal of respiratory and critical care medicine.

[9]  A. Milner,et al.  Effects of smoking in pregnancy on neonatal lung function , 1999, Archives of disease in childhood. Fetal and neonatal edition.

[10]  C. Rodeck,et al.  Maternal tobacco exposure and cotinine levels in fetal fluids in the first half of pregnancy. , 1999, Obstetrics and gynecology.

[11]  E. Albuquerque,et al.  Human and rodent bronchial epithelial cells express functional nicotinic acetylcholine receptors. , 1998, Molecular pharmacology.

[12]  P. Robinson,et al.  Maternal cigarette smoking is associated with increased inner airway wall thickness in children who die from sudden infant death syndrome. , 1998, American journal of respiratory and critical care medicine.

[13]  J. Stocks,et al.  Respiratory function among preterm infants whose mothers smoked during pregnancy. , 1998, American journal of respiratory and critical care medicine.

[14]  A. McConnachie,et al.  Permanent effects of maternal smoking on offsprings' lung function , 1998, The Lancet.

[15]  D. Warburton,et al.  Nicotine stimulates branching and expression of SP-A and SP-C mRNAs in embryonic mouse lung culture. , 1998, American journal of physiology. Lung cellular and molecular physiology.

[16]  S. Grando,et al.  Nicotine enhances expression of the alpha 3, alpha 4, alpha 5, and alpha 7 nicotinic receptors modulating calcium metabolism and regulating adhesion and motility of respiratory epithelial cells. , 1997, Research communications in molecular pathology and pharmacology.

[17]  K. Carlsen,et al.  In utero exposure to cigarette smoking influences lung function at birth. , 1997, The European respiratory journal.

[18]  K. Bauman,et al.  Urinary cotinine and parent history (questionnaire) as indicators of passive smoking and predictors of lower respiratory illness in infants , 1997, Pediatric pulmonology.

[19]  Boyd Rt.  The molecular biology of neuronal nicotinic acetylcholine receptors , 1997 .

[20]  R. Corriveau,et al.  Expression of the Nicotinic Receptor α7 Gene in Tendon and Periosteum During Early Development , 1997 .

[21]  K. Nicolaides,et al.  Perinatal lung function and invasive antenatal procedures. , 1997, Thorax.

[22]  P. Sly,et al.  Effects of maternal smoking during pregnancy and a family history of asthma on respiratory function in newborn infants , 1996, The Lancet.

[23]  V J Carey,et al.  Passive respiratory mechanics in healthy infants. Effects of growth, gender, and smoking. , 1996, American journal of respiratory and critical care medicine.

[24]  I. Tager,et al.  Maternal smoking during pregnancy. Effects on lung function during the first 18 months of life. , 1995, American journal of respiratory and critical care medicine.

[25]  J. A. López-Villanueva,et al.  Influence of negatively and positively charged scattering centers on electron mobility in semiconductor inversion layers: A Monte Carlo study , 1995 .

[26]  W. Thurlbeck,et al.  Pulmonary function alterations after 3 wk of exposure to hypobaria and/or hypoxia in growing rats. , 1995, Journal of applied physiology.

[27]  D. Dockery,et al.  Racial differences in the association between maternal smoking during pregnancy and lung function in children. , 1995, American journal of respiratory and critical care medicine.

[28]  R. Castile,et al.  Effect of maternal smoking during pregnancy on passive respiratory mechanics in early infancy , 1995, Pediatric pulmonology.

[29]  J. Stocks,et al.  The relationship between tPTEF:tE and specific airway conductance in infancy , 1994, Pediatric pulmonology.

[30]  D. Dockery,et al.  Maternal smoking during pregnancy as a predictor of lung function in children. , 1994, American journal of epidemiology.

[31]  F. Speizer,et al.  Lung function, pre- and post-natal smoke exposure, and wheezing in the first year of life. , 1993, The American review of respiratory disease.

[32]  T. Slotkin,et al.  Fetal nicotine exposure alters ontogeny of M1-receptors and their link to G-proteins. , 1993, Neurotoxicology and teratology.

[33]  John Everard Cotes,et al.  Handbook of Pulmonary Drug Therapy , 1993, Thorax.

[34]  E. Levin,et al.  Fetal nicotine exposure ablates the ability of postnatal nicotine challenge to release norepinephrine from rat brain regions. , 1992, Brain research. Developmental brain research.

[35]  F. Speizer,et al.  The effect of maternal smoking during pregnancy on early infant lung function. , 1992, The American review of respiratory disease.

[36]  E. Lieberman,et al.  Association of Intrauterine Cigarette Smoke Exposure With Indices of Fetal Lung Maturation , 1992, Obstetrics and gynecology.

[37]  N. Benowitz,et al.  Selected ion monitoring method for determination of nicotine, cotinine and deuterium-labeled analogs: absence of an isotope effect in the clearance of (S)-nicotine-3',3'-d2 in humans. , 1991, Biological mass spectrometry.

[38]  R. Krell,et al.  A pharmacologic examination of receptors mediating serotonin-induced bronchoconstriction in the anesthetized guinea pig. , 1991, The Journal of pharmacology and experimental therapeutics.

[39]  G H Land,et al.  The effects of maternal smoking on fetal and infant mortality. , 1988, American journal of epidemiology.

[40]  J. Wadsworth,et al.  Maternal smoking during pregnancy and lower respiratory tract illness in early life. , 1987, Archives of disease in childhood.

[41]  L. S. James,et al.  Fetal lung hypoplasia associated with maternal smoking: a morphometric analysis. , 1985, Pediatric research.

[42]  H Nau,et al.  Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers. , 1985, Developmental pharmacology and therapeutics.

[43]  A. Hislop,et al.  The effect of amniocentesis and drainage of amniotic fluid on lung development in Macacafascicularis , 1984, British journal of obstetrics and gynaecology.

[44]  R. L. Wainright.  Change in observed birth weight associated with change in maternal cigarette smoking. , 1983, American journal of epidemiology.

[45]  D. Fergusson,et al.  Parental smoking and respiratory illness in infancy. , 1980, Archives of disease in childhood.

[46]  J. Stocks,et al.  Nasal resistance during infancy. , 1978, Respiration physiology.

[47]  J. Stocks,et al.  Specific airway conductance in relation to postconceptional age during infancy. , 1977, Journal of applied physiology: respiratory, environmental and exercise physiology.