Talk:Abnormal Development - Smoking

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Cite this page: Hill, M.A. (2019, August 23) Embryology Abnormal Development - Smoking. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Abnormal_Development_-_Smoking

2018

Toxic Effect of Cigarette Smoke on Brainstem Nicotinic Receptor Expression: Primary Cause of Sudden Unexplained Perinatal Death

Toxics. 2018 Oct 18;6(4). pii: E63. doi: 10.3390/toxics6040063.

Lavezzi AM1.

Abstract

Among the neurotoxicants contained in tobacco smoke, if absorbed during pregnancy, nicotine significantly affects α7-nicotinic acetylcholine receptors, which play essential roles in the development of the brainstem regions receiving cholinergic projections in perinatal life. Immunohistochemical procedures for analysing formalin-fixed and paraffin-embedded brainstem samples from 68 fetuses and early newborns, with smoking and non-smoking mothers, who died of known and unknown causes, were carried out in order to determine if nicotine had activated the α7-nicotinic acetylcholine receptors. High α7-nicotinic acetylcholine receptor expression levels were only observed in the victims with smoking mothers. Frequently, these findings were associated with the hypoplasia of the brainstem structures controlling vital functions. The results of this study indicate that the exposition to nicotine in pregnancy exerts a strong direct effect on α7-nicotinic acetylcholine receptor activity especially in perinatal life and may be one of the primary risk factors leading to the sudden unexplained death of fetuses and newborns. KEYWORDS: Kölliker-Fuse nucleus; brainstem; immunohistochemistry; nicotine; nicotinic acetylcholine receptors; sudden fetal death; sudden neonatal death PMID: 30340403 DOI: 10.3390/toxics6040063


Nicotine exposure of male mice produces behavioral impairment in multiple generations of descendants

PLoS Biol. 2018 Oct 16;16(10):e2006497. doi: 10.1371/journal.pbio.2006497. eCollection 2018 Oct.

McCarthy DM1, Morgan TJ Jr1, Lowe SE1, Williamson MJ1, Spencer TJ2, Biederman J2, Bhide PG1.

Abstract

Use of tobacco products is injurious to health in men and women. However, tobacco use by pregnant women receives greater scrutiny because it can also compromise the health of future generations. More men smoke cigarettes than women. Yet the impact of nicotine use by men upon their descendants has not been as widely scrutinized. We exposed male C57BL/6 mice to nicotine (200 μg/mL in drinking water) for 12 wk and bred the mice with drug-naïve females to produce the F1 generation. Male and female F1 mice were bred with drug-naïve partners to produce the F2 generation. We analyzed spontaneous locomotor activity, working memory, attention, and reversal learning in male and female F1 and F2 mice. Both male and female F1 mice derived from the nicotine-exposed males showed significant increases in spontaneous locomotor activity and significant deficits in reversal learning. The male F1 mice also showed significant deficits in attention, brain monoamine content, and dopamine receptor mRNA expression. Examination of the F2 generation showed that male F2 mice derived from paternally nicotine-exposed female F1 mice had significant deficits in reversal learning. Analysis of epigenetic changes in the spermatozoa of the nicotine-exposed male founders (F0) showed significant changes in global DNA methylation and DNA methylation at promoter regions of the dopamine D2 receptor gene. Our findings show that nicotine exposure of male mice produces behavioral changes in multiple generations of descendants. Nicotine-induced changes in spermatozoal DNA methylation are a plausible mechanism for the transgenerational transmission of the phenotypes. These findings underscore the need to enlarge the current focus of research and public policy targeting nicotine exposure of pregnant mothers by a more equitable focus on nicotine exposure of the mother and the father. PMID: 30325916 DOI: 10.1371/journal.pbio.2006497

Developmental effects of maternal smoking during pregnancy on the human frontal cortex transcriptome

Semick SA, Collado-Torres L, Markunas CA, Shin JH, Deep-Soboslay A, Tao R, Huestis MA, Bierut LJ, Maher BS, Johnson EO, Hyde TM, Weinberger DR, Hancock DB, Kleinman JE & Jaffe AE. (2018). Developmental effects of maternal smoking during pregnancy on the human frontal cortex transcriptome. Mol. Psychiatry , , . PMID: 30131587 DOI.

Semick SA1, Collado-Torres L1,2, Markunas CA3, Shin JH1, Deep-Soboslay A1, Tao R1, Huestis MA4, Bierut LJ5, Maher BS6, Johnson EO7, Hyde TM1,8,9, Weinberger DR1,8,9,10,11, Hancock DB3, Kleinman JE12,13, Jaffe AE14,15,16,17,18. Author information Abstract Cigarette smoking during pregnancy is a major public health concern. While there are well-described consequences in early child development, there is very little known about the effects of maternal smoking on human cortical biology during prenatal life. We therefore performed a genome-wide differential gene expression analysis using RNA sequencing (RNA-seq) on prenatal (N = 33; 16 smoking-exposed) as well as adult (N = 207; 57 active smokers) human postmortem prefrontal cortices. Smoking exposure during the prenatal period was directly associated with differential expression of 14 genes; in contrast, during adulthood, despite a much larger sample size, only two genes showed significant differential expression (FDR < 10%). Moreover, 1,315 genes showed significantly different exposure effects between maternal smoking during pregnancy and direct exposure in adulthood (FDR < 10%)-these differences were largely driven by prenatal differences that were enriched for pathways previously implicated in addiction and synaptic function. Furthermore, prenatal and age-dependent differentially expressed genes were enriched for genes implicated in non-syndromic autism spectrum disorder (ASD) and were differentially expressed as a set between patients with ASD and controls in postmortem cortical regions. These results underscore the enhanced sensitivity to the biological effect of smoking exposure in the developing brain and offer insight into how maternal smoking during pregnancy affects gene expression in the prenatal human cortex. They also begin to address the relationship between in utero exposure to smoking and the heightened risks for the subsequent development of neuropsychiatric disorders. PMID: 30131587 DOI: 10.1038/s41380-018-0223-1

Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation

BMC Genomics. 2018 Apr 25;19(1):290. doi: 10.1186/s12864-018-4652-7.

Witt SH1, Frank J2, Gilles M3, Lang M2, Treutlein J2, Streit F2, Wolf IAC3, Peus V3, Scharnholz B3, Send TS3, Heilmann-Heimbach S4,5, Sivalingam S4,5, Dukal H2, Strohmaier J2, Sütterlin M6, Arloth J7, Laucht M8,9, Nöthen MM4,5, Deuschle M3, Rietschel M2.

Abstract BACKGROUND: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels. METHODS: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females. RESULTS: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns. CONCLUSION: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight. KEYWORDS: Birth weight; DNA methylation; Mediation analysis; Smoking PMID: 29695247 DOI: 10.1186/s12864-018-4652-7


2015

The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice

PLoS One. 2015 Feb 23;10(2):e0118344. doi: 10.1371/journal.pone.0118344. eCollection 2015.

McGrath-Morrow SA1, Hayashi M2, Aherrera A2, Lopez A3, Malinina A4, Collaco JM1, Neptune E4, Klein JD5, Winickoff JP6, Breysse P7, Lazarus P8, Chen G8.

Abstract

BACKGROUND/OBJECTIVE: Electronic cigarette (E-cigarettes) emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth. METHODS/MAIN RESULTS: Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG) or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI) method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml). After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (p<.054 trial 1; p<.006 trial 2). These studies indicate that exposure to E-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

PMID 25706869

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118344

2014

Fetal Exposure to Parental Smoking and the Risk of Type 2 Diabetes in Adult Women

Diabetes Care. 2014 Aug 4. pii: DC_131679.

Jaddoe VW1, de Jonge LL2, van Dam RM3, Willett WC4, Harris H5, Stampfer MJ4, Hu FB4, Michels KB6.

Abstract

OBJECTIVE: We evaluated the associations of both maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters and explored whether any association was explained by weight at birth or BMI throughout life. RESEARCH DESIGN AND METHODS: We used data from 34,453 participants of the Nurses' Health Study II. We used Cox proportional hazards models to examine the associations of maternal and paternal smoking during pregnancy with incidence of type 2 diabetes in daughters between 1989 and 2009. RESULTS: Maternal smoking during first trimester only was associated with the risk of type 2 diabetes in the offspring, independent of confounders, birth weight, and later-life BMI (fully adjusted hazard ratio 1.34 [95% CI 1.01, 1.76]). In the age-adjusted models, both continued maternal smoking during pregnancy and paternal smoking tended to be associated with an increased risk of type 2 diabetes in daughters. Perinatal and adult life variables did not explain these associations, but additional adjustment for current BMI fully attenuated the effect estimates. CONCLUSIONS: The associations of maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters were largely explained by BMI throughout the life course. Further studies are needed to explore the role of first-trimester-only maternal smoking on insulin resistance in the offspring. Also, similar effect estimates for maternal and paternal smoking suggest that the associations reflect shared family-based or lifestyle-related factors. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

PMID 25092685


Helping pregnant smokers to quit

Brose LS. BMJ. 2014 Mar 11;348:g1808. doi: 10.1136/bmj.g1808.

Although most smokers manage to quit during pregnancy, a proportion does not. In England, 26% of women smoke in the year before their pregnancy and 12% smoke through to delivery.1 The rate is similar in other high income countries, whereas in low and middle income countries, smoking rates are more variable and seem to be increasing among young women.2 In addition to the countless negative consequences for the smoker’s own mental and physical health, smoking in pregnancy is linked to a wide range of poor health outcomes for the child.3 Thus there is an urgent need to help pregnant smokers who find it difficult to quit.

PMID 24620362

2013

Smoking overrules many other risk factors for small for gestational age birth in less educated mothers

Early Hum Dev. 2013 Jul;89(7):497-501. doi: 10.1016/j.earlhumdev.2013.03.007. Epub 2013 Apr 8.

van den Berg G1, van Eijsden M, Galindo-Garre F, Vrijkotte TG, Gemke RJ. Author information

Abstract

BACKGROUND: Although there is convincing evidence for the association between small for gestational age (SGA) and socioeconomic status (SES), it is not known to what extent explanatory factors contribute to this association. AIM: To examine to what extent risk factors could explain educational inequalities in SGA. STUDY DESIGN: In this study fully completed data were available for 3793 pregnant women of Dutch origin from a population-based cohort (ABCD study). Path-analysis was conducted to examine the role of explanatory factors in the relation of maternal education to SGA. RESULTS: Low-educated pregnant women had a higher risk of SGA offspring compared to the high-educated women (OR 1.98, 95% CI 1.35-2.89). In path-analysis, maternal cigarette smoking and maternal height explained this association. Maternal age, hypertension, chronic disease, late entry into antenatal care, neighborhood income, underweight, environmental cigarette smoking, drug abuse, alcohol use, caffeine intake, fish intake, folic acid intake, anxiety, and depressive symptoms did not play a role in the association between maternal education and SGA birth. CONCLUSION: Among a large array of potential factors, the elevated risk of SGA birth among low-educated women appeared largely attributable to maternal smoking and to a lesser extent to maternal height. To reduce educational inequalities more effort is required to include low-educated women especially in prenatal intervention programs such as smoking cessation programs instead of effort into reducing other SGA-risk factors, though these factors might still be relevant at the individual level. Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID 23578734

Influence of Smoking and Alcohol during Pregnancy on Outcome of VLBW Infants

Z Geburtshilfe Neonatol. 2013 Dec;217(6):215-219. Epub 2013 Dec 20.

Spiegler J1, Jensen R2, Segerer H3, Ehlers S4, Kühn T5, Jenke A6, Gebauer C7, Möller J8, Orlikowsky T9, Heitmann F10, Boeckenholt K11, Herting E1, Göpel W1. Author information

Abstract

Nicotine and alcohol consumption have been associated with premature delivery and adverse neonatal outcome. We wanted to analyze the influence of self-reported nicotine and alcohol consumption on outcome of VLBW infants.In an ongoing multicenter study 2 475 parents of former very low birth weight (VLBW) infants born between January 2009 and December 2011 answered questionnaires about maternal smoking habits and alcohol consumption during pregnancy. 2 463 (99.5%) completed questions on alcohol consumption and 2 462 (99.5%) on smoking habits. These infants were stratified to reported maternal smoking and alcohol consumption during pregnancy. We compared the reasons for premature delivery, neonatal outcome and parental reports on bronchitis during the first year of life, as well as growth and development at age 2 years to pregnancy exposure.In nicotine exposed infants intrauterine growth restriction (31 vs. 21%, p<0.01), a birth weight below the 10th percentile (26 vs. 17%, p<0.01) and placenta abruption (9.2 vs. 5.8%, p<0.05) was seen more often. Premature rupture of membranes (24 vs. 30%, p<0.05) or HELLP syndrome (6 vs. 11%, p<0.01) was less frequent. A birth weight below the 3rd percentile was seen more frequently in mothers with reported alcohol consumption (13 vs. 6%, p<0.05). We noted an increased rate of BPD and ROP if mothers reported smoking during pregnancy (p<0.05). Growth parameters and scores on Bayley Sscales of infant development at age 2 years did not differ.Smoking during pregnancy results in a high rate of growth restricted VLBW infants. Prenatal exposition to nicotine seems to increase postnatal complications such as BPD und ROP. © Georg Thieme Verlag KG Stuttgart · New York. PMID 24363249

2011

Maternal smoking during pregnancy and kidney volume in the offspring: the Generation R Study

Pediatr Nephrol. 2011 Aug;26(8):1275-83. Epub 2011 May 27.

Taal HR, Geelhoed JJ, Steegers EA, Hofman A, Moll HA, Lequin M, van der Heijden AJ, Jaddoe VW. Source The Generation R Study Group (Ae-006), Erasmus Medical Center, PO Box 2040, 3000, CA, Rotterdam, The Netherlands.

Abstract

An adverse fetal environment leads to smaller kidneys, with fewer nephrons, which might predispose an individual to the development of kidney disease and hypertension in adult life. In a prospective cohort study among 1,072 children followed from early fetal life onward, we examined whether maternal smoking during pregnancy, as a significant adverse fetal exposure, is associated with fetal (third trimester of pregnancy, n = 1,031) and infant kidney volume (2 years of age, n = 538) measured by ultrasound. Analyses were adjusted for various potential confounders. Among mothers who continued smoking, we observed dose-dependent associations between the number of cigarettes smoked during pregnancy and kidney volume in fetal life. Smoking less than five cigarettes per day was associated with larger fetal combined kidney volume, while smoking more than ten cigarettes per day tended to be associated with smaller fetal combined kidney volume (p for trend: 0.002). This pattern was not significant for kidney volume at the age of 2 years. Our results suggest that smoking during pregnancy might affect kidney development in fetal life with a dose-dependent relationship. Further studies are needed to assess the underlying mechanisms and whether these differences in fetal kidney volume have postnatal consequences for kidney function and blood pressure.

PMID 21617916

Effects of chronic carbon monoxide exposure on fetal growth and development in mice

BMC Pregnancy Childbirth. 2011 Dec 14;11:101.

Venditti CC, Casselman R, Smith GN. Source Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada. Abstract BACKGROUND: Carbon monoxide (CO) is produced endogenously, and can also be acquired from many exogenous sources: ie. cigarette smoking, automobile exhaust. Although toxic at high levels, low level production or exposure lends to normal physiologic functions: smooth muscle cell relaxation, control of vascular tone, platelet aggregation, anti- inflammatory and anti-apoptotic events. In pregnancy, it is unclear at what level maternal CO exposure becomes toxic to the fetus. In this study, we hypothesized that CO would be embryotoxic, and we sought to determine at what level of chronic CO exposure in pregnancy embryo/fetotoxic effects are observed. METHODS: Pregnant CD1 mice were exposed to continuous levels of CO (0 to 400 ppm) from conception to gestation day 17. The effect on fetal/placental growth and development, and fetal/maternal CO concentrations were determined. RESULTS: Maternal and fetal CO blood concentrations ranged from 1.12- 15.6 percent carboxyhemoglobin (%COHb) and 1.0- 28.6%COHb, respectively. No significant difference was observed in placental histological morphology or in placental mass with any CO exposure. At 400 ppm CO vs. control, decreased litter size and fetal mass (p < 0.05), increased fetal early/late gestational deaths (p < 0.05), and increased CO content in the placenta and the maternal spleen, heart, liver, kidney and lung (p < 0.05) were observed. CONCLUSIONS: Exposure to levels at or below 300 ppm CO throughout pregnancy has little demonstrable effect on fetal growth and development in the mouse.

PMID 22168775

Parental smoking during pregnancy, early growth, and risk of obesity in preschool children: the Generation R Study

Am J Clin Nutr. 2011 May 18. [Epub ahead of print]

Durmus B, Kruithof CJ, Gillman MH, Willemsen SP, Hofman A, Raat H, Eilers PH, Steegers EA, Jaddoe VW. Source Generation R Study Group and the Departments of Pediatrics, Erasmus Medical Center, Rotterdam, Netherlands, and the Harvard Medical School/Harvard Pilgrim Health Care Institute, Boston, MA.

Abstract

OBJECTIVE: We assessed the associations of active maternal and paternal smoking during pregnancy with early growth characteristics and risks of overweight and obesity in preschool children.

DESIGN: This study was a population-based, prospective cohort study from early fetal life until the age of 4 y in 5342 mothers and fathers and their children. Growth characteristics [head circumference, length, weight, and body mass index (BMI; in kg/m(2))] and overweight and obesity were repeatedly measured at the ages of 1, 2, 3, and 4 y.

RESULTS: In comparison with children from nonsmoking mothers, children from mothers who continued smoking during pregnancy had persistently smaller head circumferences and heights until the age of 4 y, whereas their weights were only lower until the age of 3 mo. This smaller length and normal to higher weight led to an increased BMI [SD score difference: 0.11; 95% CI: 0.02, 0.20; P < 0.05)] and an increased risk of obesity (odds ratio: 1.61; 95% CI: 1.03, 2.53; P < 0.05) at the age of 4 y. In nonsmoking mothers, paternal smoking was not associated with postnatal growth characteristics or risk of obesity of offspring. Maternal smoking during pregnancy was associated with a higher BMI at the age of 4 y in children with a normal birth weight and in those who were small for gestational age at birth.

CONCLUSION: Our findings suggest that direct intrauterine exposure to smoke until late pregnancy leads to different height and weight growth adaptations and increased risks of overweight and obesity in preschool children.

PMID: 21593510 http://www.ncbi.nlm.nih.gov/pubmed/21593510

2005

The adverse effects of maternal smoking on the human placenta: a review

Placenta. 2005 Apr;26 Suppl A:S81-6.

Zdravkovic T, Genbacev O, McMaster MT, Fisher SJ. Source Department of Cell and Tissue Biology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0512, USA.

Abstract

Studies of placental pathologies associated with maternal cigarette smoking have led to many interesting observations. For example, maternal smoking impairs human placental development by changing the balance between cytotrophoblast (CTB) proliferation and differentiation. It is likely that chronic exposure to tobacco constituents in early pregnancy can affect placental development directly or indirectly by reducing blood flow, which creates a pathologically hypoxic environment. To understand this process at a molecular level, tissue samples from non-smoking and smoking mothers were studied to determine whether active and/or passive cigarette smoke exposure affects CTB expression of molecules that govern cellular responses to oxygen tension: the von Hippel-Lindau tumor suppressor protein (pVHL), hypoxia-inducible transcription factors (HIFs) and vascular endothelial growth factor-A (VEGF). The results show that maternal smoking dysregulates CTB expression of all three types of molecules. In addition, cell columns and proliferating cells were reduced while there was a corresponding increase in cell islands. All three phenomena were most obvious in the placentas of heavy smokers. Interestingly, a subset of the aforementioned effects can be detected in samples obtained from women who were passively exposed to cigarette smoke during pregnancy. These observations suggest that tobacco constituents exert direct effects on CTB proliferation and differentiation and help to explain the mechanisms by which smoking negatively effects human pregnancy outcome.

PMID: 15837073

1999

Cigarette smoking and pregnancy I: ovarian, uterine and placental effects

Placenta. 1999 May;20(4):265-72.

Shiverick KT, Salafia C. Source Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville 32610-0267, USA. kshiveri@pharmacology.ufl.edu

Abstract

This review examines the major observations and principal controversies relating to the effects of smoking and the constituents of tobacco on ovarian, uterine and placental tissues. Maternal exposure is assessed relative to specific tobacco-related chemicals and the feto-placental impact of mutagenic products, in addition to nicotine replacement as a pharmacological intervention for smoking cessation. Important new information is being learned from clinical in vitro fertilization and assisted reproduction technologies regarding the effects of smoking on fertility. Present evidence supports an adverse effect of smoking on ovarian function which is prolonged and dose-dependent, whereas there appear to be more reversible effects on implantation and ongoing pregnancy. The anti-oestrogenic effect of smoking is reviewed in terms of direct effects of nicotine, cadmium and polyaromatic hydrocarbons on oestrogen synthesis and metabolism, oocytes and granulosa-luteal function. Innovative new models provide evidence that smoking may alter fertility through effects on uterine-fallopian tube functions which mediate gamete and conceptus transport. It is of interest that smoking is associated with a decreased incidence of uterine fibroids, endometriosis and uterine cancer, which may reflect inhibitory effects of smoke constituents on uterine cell proliferation and extracellular matrix interactions. The increased miscarriage rate among mothers who smoke may be related to direct adverse effects of nicotine, cadmium and polyaromatic hydrocarbons on trophoblast invasion and proliferation. In this respect, alterations in trophoblast differentiation along invasive or proliferative pathways may explain the changes in endocrine function and vascular morphology that are observed in smokers. In summary, significant advances are being made in the understanding of cellular and molecular mechanisms which underlie the differential effects of cigarette smoking on reproductive tissues.

PMID: 10329346