In Utero and Lactational Exposure of F1 Adult Pups to Ethanol and Nicotine: Alteration of The Reproductive System and Epigenetic Modifying Enzymes of Sperm Cells?

Co-use of alcohol and nicotine is a common habit which could affect reproductive system. The present study was designed to investigate the effect of in-utero and lactational exposure of offspring to alcohol, nicotine, and combinations on the reproductive system and epigenetic alterations of male gamete. Pregnant mice and lactating NMRI pups randomly received nicotine, ethanol, and combinations during gestational days 1 until weaning. Sperm and testes were collected on postnatal day 90 for further experiments. Exposure to these substances, particularly, nicotine, highly affected testicular Johnsen’s score, sperm parameters including; number, motility, viability, DNA integrity and also serum MDA level. Interestingly, concurrent exposure to nicotine and alcohol somehow reversed the effects. Quantitative real-time PCR data showed an increase in the mRNA level of histone deacetylation 1 and 2 and a decrease in the level of DNA methyltransferase (DNMT) 3A, while no marked differences in the expression level of DNMT1 and 3B were observed between the exposed and non-exposed pups. Alleviating effects were observed in the epigenetic modifying enzymes transcripts of co-exposed pups compared with the exposure to nicotine or alcohol. Taken together, our findings determined that exposure of offspring in-utero and during lactational period to these substances could result in lasting epigenetic changes in sperm cells. However, unexpectedly co-exposure of pups to nicotine and alcohol lessened these negative effects.

[1]  S. H. Eftekhar-Vaghefi,et al.  The prophylactic effect of date palm (Phoenix dactylifera L.) fruit extract on testicular toxicity induced by formaldehyde: An experimental study , 2020, International journal of reproductive biomedicine.

[2]  B. Nixon,et al.  Molecular Changes Induced by Oxidative Stress that Impair Human Sperm Motility , 2020, Antioxidants.

[3]  Subhrajit Bhattacharya,et al.  Concurrent nicotine exposure to prenatal alcohol consumption alters the hippocampal and cortical neurotoxicity , 2020, Heliyon.

[4]  V. Sheibani,et al.  Alcohol and nicotine co-Administration during pregnancy and lactation periods alters sensory discrimination of adult NMRI mice offspring , 2020, Physiology & Behavior.

[5]  F. Sharififar,et al.  Protective effects of hydro-alcoholic extract of foeniculum vulgare and linum usitatissimum on ovarian follicle reserve in the first-generation mouse pups , 2019, Heliyon.

[6]  L. Pignataro.  Alcohol protects the CNS by activating HSF1 and inducing the heat shock proteins , 2019, Neuroscience Letters.

[7]  K. Godfrey,et al.  Maternal Smoking During Pregnancy Induces Persistent Epigenetic Changes Into Adolescence, Independent of Postnatal Smoke Exposure and Is Associated With Cardiometabolic Risk , 2019, Front. Genet..

[8]  T. Haghpanah,et al.  Preventative Effects of Vitamin E on Testicular Damage and Sperm Parameters in the First-Generation Mice Pups due to Pre- and Postnatal Mancozeb Exposure , 2019, Journal of toxicology.

[9]  M. Järvelin,et al.  DNA methylation links prenatal smoking exposure to later life health outcomes in offspring , 2018, Clinical Epigenetics.

[10]  Hui Wang,et al.  Corticosterone rather than ethanol epigenetic programmed testicular dysplasia caused by prenatal ethanol exposure in male offspring rats , 2019, Epigenetics.

[11]  M. Salehi,et al.  Impact of sperm DNA fragmentation on ICSI outcome and incidence of apoptosis of human pre-implantation embryos obtained from in vitro matured MII oocytes. , 2019, Biochemical and biophysical research communications.

[12]  I. Adcock,et al.  Epigenetic impacts of maternal tobacco and e-vapour exposure on the offspring lung , 2019, Clinical Epigenetics.

[13]  S. H. Eftekhar-Vaghefi,et al.  The Effects of Olive Leaf Extract on The Testis, Sperm Quality and Testicular Germ Cell Apoptosis in Male Rats Exposed to Busulfan , 2019, International journal of fertility & sterility.

[14]  L. Kolesnikova,et al.  The effect of low alcohol consumption during pregnancy on the lipid peroxidation-antioxidant defense system of women, their alcohol-exposed infants, and growth, health, and developmental outcomes. , 2019, Birth defects research.

[15]  B. Bonevski,et al.  Nicotine replacement therapy for smoking cessation during pregnancy , 2018, The Medical journal of Australia.

[16]  Y. Chong,et al.  Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring , 2017, Genes.

[17]  M. Faiq,et al.  Oxidative stress and male infertility , 2017, Nature Reviews Urology.

[18]  A. Allam,et al.  Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns , 2017, Oxidative medicine and cellular longevity.

[19]  D. Sarkar,et al.  Alcohol effects on the epigenome in the germline: Role in the inheritance of alcohol-related pathology. , 2017, Alcohol.

[20]  M. Milekic,et al.  In utero exposure to maternal smoking is associated with DNA methylation alterations and reduced neuronal content in the developing fetal brain , 2017, Epigenetics & Chromatin.

[21]  M. Salehi,et al.  DECREASED FERTILIZATION: HUMAN SPERM DNA FRAGMENTATION AND IN VITRO MATURATION OF OOCYTE IN STIMULATED ICSI CYCLES. , 2017, Acta endocrinologica.

[22]  O. Erel,et al.  Exposure to Environmental Tobacco Smoke during Pregnancy Restrain the Antioxidant Response of their Neonates , 2016 .

[23]  S. M. Miraglia,et al.  Late reproductive analysis in rat male offspring exposed to nicotine during pregnancy and lactation , 2016, Andrology.

[24]  Antoine H. F. M. Peters,et al.  Disruption of histone methylation in developing sperm impairs offspring health transgenerationally , 2015, Science.

[25]  D. Sarkar,et al.  Fetal Alcohol Exposure Reduces Dopamine Receptor D2 and Increases Pituitary Weight and Prolactin Production via Epigenetic Mechanisms , 2015, PloS one.

[26]  M. Golding,et al.  Dose-dependent alcohol-induced alterations in chromatin structure persist beyond the window of exposure and correlate with fetal alcohol syndrome birth defects , 2015, Epigenetics & Chromatin.

[27]  Heidi M. Schambra,et al.  Low and moderate prenatal ethanol exposures of mice during gastrulation or neurulation delays neurobehavioral development. , 2015, Neurotoxicology and teratology.

[28]  E. McLaughlin,et al.  Damaging legacy: maternal cigarette smoking has long-term consequences for male offspring fertility. , 2014, Human reproduction.

[29]  S. Milne,et al.  Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility. , 2014, Reproductive biomedicine online.

[30]  I. Kruman,et al.  Impaired one carbon metabolism and DNA methylation in alcohol toxicity , 2014, Journal of neurochemistry.

[31]  Marjan Omidi,et al.  Effects of different doses of ethanol on sperm parameters, chromatin structure and apoptosis in adult mice. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[32]  J. Weinberg,et al.  Prenatal ethanol exposure delays the onset of spermatogenesis in the rat. , 2013, Alcoholism, clinical and experimental research.

[33]  S. McKee,et al.  How can we use our knowledge of alcohol-tobacco interactions to reduce alcohol use? , 2013, Annual review of clinical psychology.

[34]  A. Aydın,et al.  Effects of Smoking during Pregnancy on DNA Damage and ROS Level Consequences in Maternal and Newborns’ Blood , 2013, Arhiv za higijenu rada i toksikologiju.

[35]  F. Leslie.  Multigenerational epigenetic effects of nicotine on lung function , 2013, BMC Medicine.

[36]  M. Ramsay,et al.  In Utero Alcohol Exposure, Epigenetic Changes, and Their Consequences , 2013, Alcohol research : current reviews.

[37]  J. Torday,et al.  Perinatal nicotine exposure induces asthma in second generation offspring , 2012, BMC Medicine.

[38]  Scott M Langevin,et al.  In Utero Exposures, Infant Growth, and DNA Methylation of Repetitive Elements and Developmentally Related Genes in Human Placenta , 2011, Environmental health perspectives.

[39]  C. Valenzuela,et al.  Alcohol Exposure Decreases CREB Binding Protein Expression and Histone Acetylation in the Developing Cerebellum , 2011, PloS one.

[40]  A. Paoloni-Giacobino,et al.  Prenatal exposure to ethanol: a specific effect on the H19 gene in sperm. , 2011, Reproductive toxicology.

[41]  M. Buhr,et al.  Effect of in utero and lactational nicotine exposure on the male reproductive tract in peripubertal and adult rats. , 2011, Reproductive toxicology.

[42]  J. Toppari,et al.  Prenatal and adult exposures to smoking are associated with adverse effects on reproductive hormones, semen quality, final height and body mass index. , 2011, Human reproduction.

[43]  J. Gajewska,et al.  The effect of tobacco smoking during pregnancy on plasma oxidant and antioxidant status in mother and newborn. , 2011, European journal of obstetrics, gynecology, and reproductive biology.

[44]  K. Soderstrom,et al.  Role of mouse cerebellar nicotinic acetylcholine receptor (nAChR) α4β2- and α7 subtypes in the behavioral cross-tolerance between nicotine and ethanol-induced ataxia , 2011, Behavioural Brain Research.

[45]  L. Hurley,et al.  Positive and Negative Effects of Alcohol and Nicotine and Their Interactions: A Mechanistic Review , 2011, Neurotoxicity Research.

[46]  E. Neafsey,et al.  Neuroprotective preconditioning of rat brain cultures with ethanol: potential transduction by PKC isoforms and focal adhesion kinase upstream of increases in effector heat shock proteins , 2010, The European journal of neuroscience.

[47]  S. Skouby,et al.  Cigarette smoking during early pregnancy reduces the number of embryonic germ and somatic cells. , 2010, Human reproduction.

[48]  Guozhen Chen,et al.  Ethanol and Its Metabolites Induce Histone Lysine 9 Acetylation and an Alteration of the Expression of Heart Development-Related Genes in Cardiac Progenitor Cells , 2010, Cardiovascular Toxicology.

[49]  K. Strandberg-Larsen,et al.  Maternal alcohol consumption during pregnancy and semen quality in the male offspring: two decades of follow-up. , 2010, Human reproduction.

[50]  A. Lajtha,et al.  Nicotine: Alcohol Reward Interactions , 2010, Neurochemical Research.

[51]  D. Wolgemuth,et al.  Acute Alcohol Exposure Induces Apoptosis and Increases Histone H3K9/18 Acetylation in the Mid-Gestation Mouse Lung , 2010, Reproductive Sciences.

[52]  D. Carrell,et al.  The human sperm epigenome and its potential role in embryonic development. , 2010, Molecular human reproduction.

[53]  K. Tremellen,et al.  Oxidative DNA damage impairs global sperm DNA methylation in infertile men , 2009, Journal of Assisted Reproduction and Genetics.

[54]  M. Ramsay,et al.  Exposure of Mouse Embryos to Ethanol During Preimplantation Development: Effect on DNA Methylation in the H19 Imprinting Control Region1 , 2009, Biology of reproduction.

[55]  R. Tyndale,et al.  Differential induction of ethanol-metabolizing CYP2E1 and nicotine-metabolizing CYP2B1/2 in rat liver by chronic nicotine treatment and voluntary ethanol intake. , 2009, European journal of pharmacology.

[56]  Andrea Baccarelli,et al.  Epigenetics and environmental chemicals , 2009, Current opinion in pediatrics.

[57]  James L. Sanders.  Were our forebears aware of prenatal alcohol exposure and its effects? A review of the history of fetal alcohol spectrum disorder. , 2009, The Canadian journal of clinical pharmacology = Journal canadien de pharmacologie clinique.

[58]  Z. Herceg,et al.  Epigenetic interplay between histone modifications and DNA methylation in gene silencing. , 2008, Mutation research.

[59]  P. Baker,et al.  Maternal smoking during pregnancy specifically reduces human fetal desert hedgehog gene expression during testis development. , 2008, The Journal of clinical endocrinology and metabolism.

[60]  J. Olsen,et al.  Is prenatal exposure to tobacco smoking a cause of poor semen quality? A follow-up study. , 2007, American journal of epidemiology.

[61]  Natalie Ceballos.  Tobacco Use, Alcohol Dependence, and Cognitive Performance , 2006, The Journal of general psychology.

[62]  J. West,et al.  Nicotine decreases blood alcohol concentrations in adult rats: a phenomenon potentially related to gastric function. , 2006, Alcoholism, clinical and experimental research.

[63]  S. Al-Rejaie,et al.  Antagonism of ethanol ataxia by intracerebellar nicotine: Possible modulation by mouse cerebellar nitric oxide and cGMP , 2006, Brain Research Bulletin.

[64]  A. R.,et al.  Review of literature , 1951, American Potato Journal.

[65]  B. Ermiş,et al.  Influence of smoking on maternal and neonatal serum malondialdehyde, superoxide dismutase, and glutathione peroxidase levels. , 2004, Annals of clinical and laboratory science.

[66]  H. Beere.  `The stress of dying': the role of heat shock proteins in the regulation of apoptosis , 2004, Journal of Cell Science.

[67]  L. Bizarro,et al.  Comprehensive deficits in performance of an attentional task produced by co-administering alcohol and nicotine to rats. , 2003, Drug and alcohol dependence.

[68]  .. J.E.Onu,et al.  Histological Evidence of Retardation of Spermatogenesis in Mice in Experimentally Induced Fetal Alcohol Syndrome , 2003 .

[69]  Hui Li,et al.  Effects of ethanol on embryonic and neonatal rat testes in organ cultures. , 2003, Journal of andrology.

[70]  H. Rumpf,et al.  Probabilities of alcohol high-risk drinking, abuse or dependence estimated on grounds of tobacco smoking and nicotine dependence. , 2003, Addiction.

[71]  R. Sharpe,et al.  Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. , 2003, Reproduction.

[72]  S. Heales,et al.  Nitric oxide-induced mitochondrial dysfunction: implications for neurodegeneration. , 2003, Free radical biology & medicine.

[73]  N. Martin,et al.  Smoking and the Genetic Contribution to Alcohol-Dependence Risk , 2000, Alcohol research & health : the journal of the National Institute on Alcohol Abuse and Alcoholism.

[74]  N. Mcclure,et al.  Direct effect of alcohol on the motility and morphology of human spermatozoa , 1999, Andrologia.

[75]  T. Slotkin.  Fetal nicotine or cocaine exposure: which one is worse? , 1998, The Journal of pharmacology and experimental therapeutics.

[76]  S. Tiffany,et al.  The effect of alcohol consumption on craving to smoke. , 1997, Addiction.

[77]  S. J. Briggs,et al.  Prenatal nicotine effects on memory in rats: pharmacological and behavioral challenges. , 1996, Brain research. Developmental brain research.

[78]  B. Gladen,et al.  Does early exposure to maternal smoking affect future fertility in adult males? , 1992, Reproductive toxicology.

[79]  C. Lieber,et al.  Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. , 1991, Alcoholism, clinical and experimental research.

[80]  T. Bien,et al.  Smoking and drinking: a review of the literature. , 1990, The International journal of the addictions.

[81]  J. Difranza,et al.  Alcoholism and smoking. , 1990, Journal of studies on alcohol.

[82]  N. Woo,et al.  Rat embryogenesis following exposure to alcohol and nicotine. , 1988, Acta anatomica.

[83]  M. Lawton,et al.  Alcohol in Breast Milk , 1985, The Australian & New Zealand journal of obstetrics & gynaecology.

[84]  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.

[85]  J. M. Argiles,et al.  Ethanol and acetaldehyde concentrations in the rat foeto-maternal system after an acute ethanol administration given to the mother. , 1984, Archives internationales de physiologie et de biochimie.

[86]  D. Wilson,et al.  Determination of nicotine concentrations in human milk. , 1976, American journal of diseases of children.

[87]  S. Johnsen.  Testicular biopsy score count--a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. , 1970, Hormones.

[88]  H. Laborit,et al.  [Experimental study]. , 1958, Bulletin mensuel - Societe de medecine militaire francaise.