Maternal Nicotine Research Articles

Influence of maternal environmental tobacco smoke exposure assessed by hair nicotine levels on birth weight.

While the perinatal outcomes of active maternal smoking are well documented, results of the effects of environmental tobacco smoke (ETS) exposure during pregnancy are inconsistent. We aimed to examine the effect of ETS exposure, assessed by maternal hair nicotine levels at 35th week of gestation, on birth weight and the risk of small for gestational age (SGA) and low birth weight (LBW). A total of 871 non-smoking healthy pregnant women were recruited by one Korean hospital between 1 October 2006 and 31 July 2007. Hair samples were collected and anthropometric questionnaires administered at 35th week of gestation. The primary outcome was birth weight and secondary outcomes were the risk of babies being SGA and LBW. Log-transformed hair nicotine concentrations were inversely related with birth weight after adjusting for confounding variables (β=-0.077, p=0.037). After stratifying hair nicotine levels by tertiles (T1, low [0.0-0.28 ng/mg]; T2, medium [0.29-0.62 ng/mg]; and T3, high [0.63-5.99 ng/mg]), the mean birth weight in each groups were 3,342 g (T1) 3,296 g (T2) and 3,290 g (T3), respectively. However the difference between groups was not statistically significant by analysis of co-variance (ANCOVA) adjusting for covariates (p=0.062). In logistic regression analysis, the risk of SGA was higher in the T3 (OR=1.59, 95%CI 1.05-2.42) than in the reference group (T1), after controlling for confounding variables. The risk of low birth weight (<2,500 g, LBW) was not significantly higher (OR=1.44, 95%CI 0.95-2.19), but the risk of babies being below 3,000g birth weight was increased in the T3 group (OR=1.53, 95%CI 1.00-2.36) compared with that in the T1 group. Maternal ETS exposure during pregnancy was inversely related with birth weight. The risk of SGA increased in the highest ETS exposure group compared with in the low exposure group. To prevent ETS exposure during pregnancy, more comprehensive tobacco control policies are needed.

Maternal nicotine exposure leads to impaired disulfide bond formation and augmented endoplasmic reticulum stress in the rat placenta.

Maternal nicotine exposure has been associated with many adverse fetal and placental outcomes. Although underlying mechanisms remain elusive, recent studies have identified that augmented endoplasmic reticulum (ER) stress is linked to placental insufficiency. Moreover, ER function depends on proper disulfide bond formation—a partially oxygen-dependent process mediated by protein disulfide isomerase (PDI) and ER oxidoreductases. Given that nicotine compromised placental development in the rat, and placental insufficiency has been associated with poor disulfide bond formation and ER stress, we hypothesized that maternal nicotine exposure leads to both placental ER stress and impaired disulfide bond formation. To test this hypothesis, female Wistar rats received daily subcutaneous injections of either saline (vehicle) or nicotine bitartrate (1 mg/kg) for 14 days prior to mating and during pregnancy. Placentas were harvested on embryonic day 15 for analysis. Protein and mRNA expression of markers involved in ER stress (e.g., phosphorylated eIF2α, Grp78, Atf4, and CHOP), disulfide bond formation (e.g., PDI, QSOX1, VKORC1), hypoxia (Hif1α), and amino acid deprivation (GCN2) were quantified via Western blot and/or Real-time PCR. Maternal nicotine exposure led to increased expression of Grp78, phosphorylated eIF2α, Atf4, and CHOP (p<0.05) in the rat placenta, demonstrating the presence of augmented ER stress. Decreased expression of PDI and QSOX1 (p<0.05) reveal an impaired disulfide bond formation pathway, which may underlie nicotine-induced ER stress. Finally, elevated expression of Hif1α and GCN2 (p<0.05) indicate hypoxia and amino acid deprivation in nicotine-exposed placentas, respectively, which may also cause impaired disulfide bond formation and augmented ER stress. This study is the first to link maternal nicotine exposure with both placental ER stress and disulfide bond impairment in vivo, providing novel insight into the mechanisms underlying nicotine exposure during pregnancy on placental health.

Smoking during Pregnancy Is a Risk Factor for Executive Function Deficits in Preschool-aged Children.

Introduction: Maternal nicotine use during pregnancy has a negative impact on the child. Numerous studies have demonstrated an association between smoking during pregnancy and psychological deficits. This study looks at deficits in executive functioning in preschool-aged children. Methods: The executive functioning of preschool children was assessed by asking parents to complete the parental form of the Behavior Rating Inventory of Executive Functions - Preschool Version (BRIEF-P, German version). The results for preschool children whose mothers had smoked during pregnancy (n = 71) were compared with those of a control group. In a subsample, parental assessments of children of smokers (n = 42) and non-smokers (n = 27) were complemented by the teacher form of the BRIEF-P (German version), which allowed inter-rater agreement (parents vs. preschool teachers) to be assessed. Results: An increased incidence of executive function deficits was noted in the children of smokers, based on parental assessment. Clinically relevant deficits were particularly evident with regard to inhibition, with inhibitory deficits in children of smokers found to be almost four times higher than in the control group (p = 0.006). Inhibitory deficits were reported both by parents and by preschool teachers. Discussion: The increased percentage of executive function deficits described here, particularly the increased inhibitory deficits, confirms the current state of research on smoking during pregnancy. Poor inhibition or impulse control is a key symptom of ADHD.

Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny.

Postnatal nicotine exposure leads to obesity and hypothyroidism in adulthood. We studied the effects of maternal nicotine exposure during lactation on thyroid hormone (TH) metabolism and function in adult offspring. Lactating rats received implants of osmotic minipumps releasing nicotine (NIC, 6 mg/kg per day s.c.) or saline (control) from postnatal days 2 to 16. Offspring were killed at 180 days. We measured types 1 and 2 deiodinase activity and mRNA, mitochondrial α-glycerol-3-phosphate dehydrogenase (mGPD) activity, TH receptor (TR), uncoupling protein 1 (UCP1), hypothalamic TRH, pituitary TSH, and in vitro TRH-stimulated TSH secretion. Expression of deiodinase mRNAs followed the same profile as that of the enzymatic activity. NIC exposure caused lower 5'-D1 and mGPD activities; lower TRβ1 content in liver as well as lower 5'-D1 activity in muscle; and higher 5'-D2 activity in brown adipose tissue (BAT), heart, and testis, which are in accordance with hypothyroidism. Although deiodinase activities were not changed in the hypothalamus, pituitary, and thyroid of NIC offspring, UCP1 expression was lower in BAT. Levels of both TRH and TSH were lower in offspring exposed to NIC, which presented higher basal in vitro TSH secretion, which was not increased in response to TRH. Thus, the hypothyroidism in NIC offspring at adulthood was caused, in part, by in vivo TRH-TSH suppression and lower sensitivity to TRH. Despite the hypothyroid status of peripheral tissues, these animals seem to develop an adaptive mechanism to preserve thyroxine to triiodothyronine conversion in central tissues.

Maternal nicotine exposure leads to higher liver oxidative stress and steatosis in adult rat offspring

Early nicotine exposure causes future obesity and insulin resistance. We evaluated the long-term effect of the maternal nicotine exposure during lactation in liver oxidative status, insulin sensitivity and morphology in adult offspring. Two days after birth, osmotic minipumps were implanted in the dams: nicotine (N), 6 mg/kg/day for 14 days or saline (C). Offspring were killed at 180 days. Protein content of superoxide dismutase, glutathione peroxidase, catalase, nitrotyrosine, 4HNE, IRS1, Akt1 and PPARs were measured. MDA, bound protein carbonyl content, SOD, GPx and catalase activities were determined in liver and plasma. Hepatic morphology and triglycerides content were evaluated. Albumin and bilirubin were determined. In plasma, N offspring had higher catalase activity, and SOD/GPx ratio, albumin and bilirubin levels but lower MDA content. In liver, they presented higher MDA and 4HNE levels, bound protein carbonyl content, SOD activity but lower GPx activity. N offspring presented an increase of lipid droplet, higher triglyceride content and a trend to lower PPARα in liver despite unchanged insulin signaling pathway. Early nicotine exposure causes oxidative stress in liver at adulthood, while protect against oxidative stress at plasma level. In addition, N offspring develop liver microsteatosis, which is related to oxidative stress but not to insulin resistance.

White matter integrity and cognitive performance in children with prenatal methamphetamine exposure

There is emerging evidence on the harmful effects of prenatal methamphetamine (MA) exposure on the structure and function of the developing brain. However, few studies have assessed white matter structural integrity in the presence of prenatal MA exposure, and results are inconsistent. This investigation thus used diffusion tensor imaging (DTI) to investigate white matter microstructure and cognitive performance in a group of prenatal MA exposed (or MA) children and controls of similar age. Seventeen MA children and 15 healthy controls (aged 6–7 years) underwent DTI and assessment of motor function and general cognitive ability. Whole brain analyses of white matter structure were performed using FSL's tract-based spatial statistics comparing fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Mean diffusion values were extracted from white matter regions shown to differ across groups to determine whether variations in FA predicted cognitive performance. Analyses were controlled for maternal nicotine use. MA children showed significantly lower FA as well as higher MD, RD and AD in tracts that traverse striatal, limbic and frontal regions. Abnormal FA levels in MA children were significantly associated with poorer motor coordination and general cognitive ability sub-items that relate to aspects of executive function. Our findings suggest that, consistent with previous studies in older children, there are disruptions of white matter microstructural integrity in striatal, limbic and frontal regions of young MA exposed children, with prominent cognitive implications. Future longitudinal studies may clarify how prenatal MA exposure affects white matter structural connectivity at different stages of brain maturation.

Maternal nicotine exposure during gestation and lactation induces kidney injury and fibrosis in rat offspring

Maternal tobacco smoke exposure adversely affected fetal kidney development. Nicotine stimulates epithelial-mesenchymal transition and connective tissue growth factor (CTGF) expression in the renal epithelium. We hypothesized that maternal nicotine exposure would induce kidney fibrosis and involve CTGF in newborn rats. Nicotine was administered to pregnant Sprague-Dawley rats at a dose of 6 mg/kg/d from gestational days 7-21 and gestational day 7 to postnatal day 14. A control group was injected with normal saline. Neonatal kidney tissues underwent histological analysis, collagen measurement, and western blot analysis. Tubular injury scores and total collagen contents were significantly higher in rats born to nicotine-treated dams than in rats born to normal saline-treated dams on postnatal days 7 and 21. Masson's trichrome staining further verified the presence of kidney fibrosis. Prenatal and/or postnatal nicotine exposure increased CTGF expression on postnatal days 7 and 21. Maternal nicotine exposure during gestation and lactation induces neonatal kidney fibrosis, and CTGF may be involved in the pathogenesis of kidney fibrosis. These results may be relevant to premature low-birth-weight infants who are conveyed a high risk of developing chronic kidney disease and exposed to breast milk of smoking mothers during the neonatal period.

Maternal nicotine exposure during gestation and lactation induces cardiac remodeling in rat offspring.

The aim of this study was to evaluate the effects of maternal nicotine exposure on heart morphology and fibrosis in rat offspring. Nicotine was administered to pregnant Sprague-Dawley rats by using a subcutaneous osmotic mini-pump at a dose of 6 mg/kg/day from Gestational Days 7-21 or Gestational Day 7 to Postnatal Day 14. A control group received an equal volume of saline by the same route as nicotine. Rats born to prenatal nicotine-treated dams exhibited significantly greater cell width of cardiomyocytes, fewer cardiomyocyte nuclei number, higher β-myosin heavy chain and transforming growth factor (TGF-β1) expression, and higher collagen deposition in heart compared with rats born to normal saline-treated dams on Postnatal Days 7 and 21. Postnatal nicotine exposure further enhances these effects. We conclude that TGF-β1 may be involved in the pathogenesis of cardiac remodeling induced by maternal nicotine exposure during gestation and lactation in rat offspring.

Parental smoking during pregnancy and ADHD in children: the Danish national birth cohort.

Prenatal maternal smoking has been associated with attention-deficit/hyperactivity disorder (ADHD) in children, but the causal nature of this association is still under scrutiny. We examined the association with maternal smoking and nicotine replacement use during pregnancy, using association with paternal smoking as a marker of potential genetic or social confounding. We included 84 803 singletons who participated in the Danish National Birth Cohort. Information on parental smoking was reported by the mothers during pregnancy. Children with ADHD were identified from the Danish Psychiatric Central Register, the Danish National Patient Register, and the Register of Medicinal Product Statistics by the International Classification of Diseases, 10th Revision diagnosis or medication. We also used hyperactivity/inattention score of the parent-reported Strengths and Difficulties Questionnaire, included in the 7-year follow-up of the National Birth Cohort. Maternal and paternal smoking during pregnancy were associated with an elevated risk of ADHD defined by hospital diagnosis, medication, and hyperactivity/inattention score, but the association was stronger for maternal smoking than for paternal smoking. Compared with children born to nonsmoking mothers and smoking fathers, children born of smoking mothers and nonsmoking fathers had a higher risk of ADHD (adjusted hazard ratio = 1.26; 95% confidence interval, 1.03 to 1.53). We also saw a higher risk of ADHD in children of mothers who used nicotine replacement during pregnancy. Our findings indicate that the association between prenatal maternal smoking and ADHD may overestimate a causal link, but nicotine exposure or related factors may still play a causal role.

Nicotine exposure increases the complexity of dopamine neurons in the parainterfascicular nucleus (PIF) sub-region of VTA.

BackgroundRecent publications highlight differences within the sub-regions of the ventral tegmental area (VTA) including the parabrachial pigmented nucleus (PBP), parainterfascicular nucleus (PIF) and paranigral nucleus (PN) in the projections to the prefrontal cortex (PFC) and the glutamatergic pathway.MethodsIn order to characterize the effects of prenatal nicotine exposure on the mesocorticolimbic system of the rat offspring, local field potentials were recorded from 27 sites across the VTA of 9 rats aged 40–55 days. The extracellular VTA neural activities were analyzed using Approximate Entropy (ApEn) method. Approximate entropy values were then grouped according to each anatomic location including the PBP, PIF and PN.ResultsOur results have shown that the local field potentials corresponding to the neurons located in the PIF region of the VTA have ApEn values significantly higher (p = 2x10-4) in the maternal nicotine cases when compared to the saline.ConclusionTherefore, we speculate that the dopamine neurons located in the PIF sub-region of the VTA are very likely involved with the nicotine addiction.

Maternal Nicotine Exposure Exacerbates Neonatal Hyperoxia-Induced Lung Fibrosis in Rats

Background: Maternal nicotine exposure increases lung collagen in fetal and newborn animals. Connective tissue growth factor (CTGF) plays a role in hyperoxia-induced pulmonary fibrosis. Objective: To determine whether pre- and postnatal nicotine exposure can augment CTGF expression and postnatal hyperoxia-induced lung fibrosis. Methods: Nicotine was administered to pregnant Sprague-Dawley rats at a dose of 6 mg/kg/day from gestational days 7-21 (prenatal nicotine-treated group) and gestational day 7 to postnatal day 14 (pre- and postnatal nicotine-treated group). A control group of pregnant dams was injected with an equal volume of saline. Within 12 h of birth, rats were exposed to room air or 1 week of >95% O₂ and an additional 2 weeks of 60% O₂ (3 weeks of hyperoxia). Lungs were taken for total collagen, CTGF expression and histological analyses. Results: In each maternal treatment group, the rats reared in hyperoxia had a higher total collagen compared with rats reared in room air on postnatal days 7 and 21. Collagen content was significantly higher in rats born to pre- and postnatal nicotine-treated dams than rats born to saline-treated and prenatal nicotine-treated dams on postnatal days 7 and 21. Pre- and postnatal nicotine exposure and neonatal hyperoxia exposure increased CTGF expression on postnatal days 7 and 21. Conclusions: CTGF may be involved in the pathogenesis of lung fibrosis induced by maternal nicotine and neonatal hyperoxia, and maternal nicotine exposure exacerbates neonatal hyperoxia-induced lung fibrosis. These results are relevant to neonates who require supplemental oxygen and are exposed to the breast milk of smoking mothers during infancy.

Prenatal testosterone increases sensitivity to prenatal stressors in males with disruptive behavior disorders

Disruptive Behavior Disorders (DBD) exhibit a sex-biased prevalence rate favoring boys, and prenatal testosterone exposure appears to be part of the complex etiology of these disorders. The current study examines whether high prenatal testosterone exposure may heighten the risk for DBD symptoms in males by increasing susceptibility to negative environmental conditions such as maternal nicotine and alcohol use during pregnancy. Participants were 109 three- to six-year-olds (64% male; 72% with DBD) and their 109 primary caregivers and 55 daycare providers/teachers who completed a multi-informant diagnostic procedure. A proxy of prenatal testosterone exposure, finger-length ratios, interacted with maternal report of prenatal nicotine use to predict teacher-rated hyperactivity–impulsivity during preschool, for boys, but not girls, although the three-way interaction was not significant. Prenatal testosterone interacted with prenatal alcohol exposure to predict teacher-rated hyperactivity–impulsivity and ODD symptoms differentially based on child sex (significant three-way interaction). Boys with higher levels of prenatal testosterone who were also exposed to higher levels of nicotine and alcohol during pregnancy exhibited increased hyperactivity–impulsivity during early childhood, but girls did not exhibit this same pattern. Thus, high prenatal testosterone exposure seems to increase risk for DBD symptoms particularly in males by increasing susceptibility to prenatal environmental stressors.

Invited commentary: Parental smoking as a risk factor for adult tobacco use: can maternal smoking during pregnancy be distinguished from the social environmental influence during childhood?

Parental smoking is known to have prenatal health effects on developing fetuses, and postnatal exposure to secondhand smoke causes adverse health effects during childhood and beyond. Further, there is solid evidence that parental smoking during childhood is a potent risk factor for smoking in offspring. In this issue of the Journal, Rydell et al. (Am J Epidemiol. 2014;179(12):1409-1417) add to a growing body of evidence showing that maternal smoking during pregnancy is statistically associated with the long-term risk of tobacco use in offspring. The data revealed a strong signal between maternal smoking during pregnancy and tobacco use in young adulthood, an association that was largely concentrated in snus use but not cigarette smoking. This new study adds to a growing body of epidemiologic evidence that consistently points toward maternal smoking during pregnancy being associated with an increased risk of offspring tobacco use in later life. There is also evidence from animal models indicating that fetal exposure to maternal nicotine use in utero can have a durable impact on the neural pathways that affect lifetime sensitivity to nicotine. This is an important research topic that continues to yield a consistent signal despite an array of inferential challenges.

Associations Between Prenatal Nicotine Exposure, Oxidative Stress, and Postpartum Visceral Fat

This study aimed to examine the associations among prenatal nicotine exposure, oxidative stress, and postpartum visceral fat among women exposed to secondhand smoke (SHS). The study was conducted in Kelantan, Malaysia, from April 2010 to December 2012. Blood samples were collected in the second and third trimesters from 135 healthy pregnant women who were followed-up at delivery, 2 months, 6 months and 12 months postpartum. Maternal hair nicotine and oxidative stress markers during pregnancy were measured. Visceral fat was assessed by bioelectrical impedance. Multiple linear regression analysis revealed that maternal hair nicotine concentration was associated with increased DNA damage (tail moment:β = 0.580, p = 0.001) and decreased glutathione peroxidase (β = –12.100; p = 0.009) in the second trimester of pregnancy. Increased DNA damage, protein oxidation and total antioxidant capacity in the second trimester were associated with 2, 6, and 12 months postpartum visceral fat. No direct association was found between prenatal hair nicotine level and postpartum visceral fat; however, these results suggest that any relation of SHS to visceral adiposity may be indirect, mediated via enhanced oxidative stress.

Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway.

Impact of Maternal Nicotine Exposure on Expression of Myelin-Related Genes in Zebrafish Larvae

Although maternal smoking during pregnancy disrupts offspring development, it is not clear whether smoking before pregnancy has any effect on the next generation. Given that nicotine, the major psychoactive component in cigarettes, is toxic to many organs, we hypothesized that maternal smoking even before a pregnancy affects offspring development. Myelin is an important structure in the nervous system, and deficits in myelin are related to many psychiatric disorders and drug addiction. We therefore examined the effect of maternal exposure to nicotine on the expression of myelin genes in the offspring using zebrafish as a model. Female adult zebrafish were exposed to nicotine through water at a concentration of 1, 5, 10, 15, 20, 25, or 30 μM (nicotine base) for either 1 h or a continuous 24 h each day for 4 months. The nicotine-treated females were then bred with drug-naive males, and the embryos and larvae were grown in a nicotine-free environment. Maternal survival rates were calculated. Larvae of those exposed to nicotine at a dose of 1, 5, 10, 15, or 20 μM for 24 h each day were collected at 4, 7, or 14 days postfertilization (dpf). The mRNA expression of myelin-related genes was examined using quantitative RT-PCR. The mRNA expression of most genes encoding myelin major proteins increased with age. These genes were generally downregulated by maternal nicotine exposure in 4 dpf larvae, whereas they were upregulated in 14 dpf larvae. The expression of myelin-related transcription regulators correlated well with that of myelin major proteins. Prepregnancy nicotine exposure altered myelin gene expression in the offspring, implying that maternal smoking before pregnancy affects the next generation.

P.6.a.007 Low dose maternal nicotine and alcohol exposure disrupt hippocampal long-term potentiation and Morris water maze performance in the offsprings

P.6.a.007 Low dose maternal nicotine and alcohol exposure disrupt hippocampal long-term potentiation and Morris water maze performance in the offsprings

Effects of maternal nicotine on breastfeeding infants

OBJECTIVE To assess scientific evidence about the effects of maternal nicotine on infant by an integrative review. DATA SOURCES Studies published in Portuguese, English and Spanish, from 1990 to 2009, with abstracts available in the Latin American Health Sciences Literature (Lilacs) and Medical Literature Analysis and Retrieval System On-Line (Medline) databases. The descriptors were: "breastfeeding", "lactation" and "smoking". DATA SYNTHESIS The main identified effects of nicotine on infants were: changes in sleep and wakefulness patterns; reduction of iodine supply; hystopathological damage on liver and lung; intracellular oxidative damage; reduction of pancreatic ß cells; and decreased glucose tolerance. CONCLUSIONS It is recommended to inform mothers about harmful chemicals contained in cigarettes that can be secreted into breast milk. They should be strongly encouraged to stop smoking during lactation.

Maternal nicotine exposure during lactation alters hypothalamic neuropeptides expression in the adult rat progeny

Maternal exposure to nicotine during lactation causes hyperleptinemia in the pups and, at adulthood, these animals are overweight and hyperleptinemic, while, in their hypothalamus, the leptin signaling pathway is reduced, evidencing a central leptin resistance. Then, we evaluated the expression of pro-opiomelanocortin (POMC), alpha-melanocyte stimulating hormone (α-MSH), cocaine and amphetamine-regulated transcript (CART), neuropeptide Y (NPY), agouti-related peptide (AgRP) and others in different hypothalamic nuclei in order to better understand the mechanisms underlying the obese phenotype observed in these animals at adulthood. On the 2nd postnatal day (P2), dams were subcutaneously implanted with osmotic minipumps releasing nicotine (NIC-6 mg/kg/day) or saline for 14 days. Offspring were killed in P180 and immunohistochemistry and Western blot analysis were carried out. Significance data had p<0.05. Adult NIC offspring showed more intense NPY staining in the paraventricular nucleus (PVN) (+21%) and increased number of POMC-positive cells in the: arcuate nucleus (+33%), as an increase in fiber density of α-MSH in PVN (+85%). However, the number of CART-positive cells was reduced in the PVN (-25%). CRH staining was more intense in NIC offspring (+136%). Orexins and AgRP were not altered. Thus, maternal nicotine exposure changes hypothalamic neuropeptides in the adult progeny that is partially compatible with leptin resistance.

The effect of grand maternal nicotine exposure during gestation and lactation on lung integrity of the F2 generation

Maternal nicotine exposure during gestation and lactation adversely affects lung development in the offspring. It has been suggested that the "program" that control long-term maintenance of the structural integrity of the lung may be compromised. The aim of the study was to establish whether the effect of grand-maternal nicotine exposure during gestation and lactation can be transferred to the F2 generation. After mating, rats were randomly divided into two groups (F0). One group received nicotine (1 mg/kg body weight/day). The controls receive saline. Body weight (BW), lung volume (Lv), linear intercept (Lm), alveolar wall thickness (Tsept), senescent and proliferating cell numbers were used to evaluate changes in the lung structure of the offspring (F1). The F1 generation was divided into four groups, namely, (1) control (F1 males mated with F1 females, (2) NmCf (F1 nicotine exposed male mated with F1 control female), (3) NfCm (F1 nicotine exposed female mated with F1 control male), and (4) NmNf (F1 male exposed to nicotine mated with F1 female also exposed to nicotine). The F1 nicotine exposed males and females were exposed to nicotine via the placenta and mother's milk (F0 generation) only. The F2 progeny was never exposed to nicotine. Grand-maternal nicotine (F0) resulted in parenchymal deterioration and emphysema in the F2 progeny due to increased numbers of premature senescent cells together with a slower cell proliferation. The transfer of premature aging characteristics from the F1 progeny to the F2 progeny is via the male and female germ cell line. Grand-maternal nicotine exposure induces structural changes in the lungs of the F2 generation that resembled premature aging.