All Title Author
Keywords Abstract

PLOS ONE  2014 

The Effects of Cigarette Smoke Extract on Ovulation, Oocyte Morphology and Ovarian Gene Expression in Mice

DOI: 10.1371/journal.pone.0095945

Full-Text   Cite this paper   Add to My Lib


Cigarette smoking can harm fertility, but the existing research has targeted primarily on ovarian follicles, embryos or sex hormone. In this study, we tested cigarette smoke extract on ovulation, oocyte morphology and ovarian gene expression associated with inhibition of oxidative stress using C57BL/6 mice. Mice in the experimental group were administered a cigarette smoke extract (CSE) solution (2 mg/ml) orally daily, while the blank control group was given dimethylsulfoxide (DMSO). A positive control group (menadione) was used that received an intraperitoneal injection of 15 mg/kg menadione in oil solution daily. We found that the CSE group manifested a reduced diameter of zona pellucida-free oocyte (ZP-free OD) and a morphologically misshapen first polar body (PB). Our results suggest that CSE exposure is associated with a shrink size and poor quality of oocytes. Quitting smoking is a wise choice to ensure good fertility.


[1]  Europe WHOROf (2007) The European tobacco control report: 2007. WHO Regional Office Europe.
[2]  Organization WH (2008) WHO report on the global tobacco epidemic, 2008: the MPOWER package.
[3]  Sims TH (2009) From the American Academy of Pediatrics: Technical report—Tobacco as a substance of abuse. Pediatrics 124: e1045–1053.
[4]  Paixao LL, Gaspar-Reis RP, Gonzalez GP, Santos AS, Santana AC, et al. (2012) Cigarette smoke impairs granulosa cell proliferation and oocyte growth after exposure cessation in young Swiss mice: an experimental study. J Ovarian Res 5: 25.
[5]  Augood C, Duckitt K, Templeton AA (1998) Smoking and female infertility: a systematic review and meta-analysis. Hum Reprod 13: 1532–1539.
[6]  Cooper AR, Moley KH (2008) Maternal tobacco use and its preimplantation effects on fertility: more reasons to stop smoking. Semin Reprod Med 26: 204–212.
[7]  Giovannucci E, Martinez ME (1996) Tobacco, colorectal cancer, and adenomas: a review of the evidence. J Natl Cancer Inst 88: 1717–1730.
[8]  Potter JD, Bigler J, Fosdick L, Bostick RM, Kampman E, et al. (1999) Colorectal adenomatous and hyperplastic polyps: smoking and N-acetyltransferase 2 polymorphisms. Cancer Epidemiol Biomarkers Prev 8: 69–75.
[9]  McLachlan JA, Dames NM, Sieber SM, Fabro S (1976) Accumulation of nicotine in the uterine fluid of the six-day pregnant rabbit. Fertil Steril 27: 1204–1213.
[10]  Paszkowski T (1998) [Concentration gradient of cotinine between blood serum and preovulatory follicular fluid]. Ginekol Pol 69: 1131–1136.
[11]  Huang J, Okuka M, McLean M, Keefe DL, Liu L (2009) Effects of cigarette smoke on fertilization and embryo development in vivo. Fertil Steril 92: 1456–1465.
[12]  Soldin OP, Makambi KH, Soldin SJ, O'Mara DM (2011) Steroid hormone levels associated with passive and active smoking. Steroids 76: 653–659.
[13]  Neal MS, Zhu J, Holloway AC, Foster WG (2007) Follicle growth is inhibited by benzo-[a]-pyrene, at concentrations representative of human exposure, in an isolated rat follicle culture assay. Hum Reprod 22: 961–967.
[14]  Roth LK, Taylor HS (2001) Risks of smoking to reproductive health: assessment of women's knowledge. Am J Obstet Gynecol 184: 934–939.
[15]  de Mouzon J, Belaisch-Allart J (2005) [Consequences on women's fecundity and on assisted reproductive technology]. J Gynecol Obstet Biol Reprod (Paris) 34 Spec No 1: 3S112–118.
[16]  Bolumar F, Olsen J, Boldsen J (1996) Smoking reduces fecundity: a European multicenter study on infertility and subfecundity. The European Study Group on Infertility and Subfecundity. Am J Epidemiol 143: 578–587.
[17]  Hull MG, North K, Taylor H, Farrow A, Ford WC (2000) Delayed conception and active and passive smoking. The Avon Longitudinal Study of Pregnancy and Childhood Study Team. Fertil Steril 74: 725–733.
[18]  Neal MS, Hughes EG, Holloway AC, Foster WG (2005) Sidestream smoking is equally as damaging as mainstream smoking on IVF outcomes. Hum Reprod 20: 2531–2535.
[19]  Wright K, Trimarchi J, Allsworth J, Keefe D (2006) The effect of female tobacco smoking on IVF outcomes. Hum Reprod 21: 2930–2934.
[20]  Waylen AL, Metwally M, Jones GL, Wilkinson AJ, Ledger WL (2009) Effects of cigarette smoking upon clinical outcomes of assisted reproduction: a meta-analysis. Hum Reprod Update 15: 31–44.
[21]  Harrison KL, Breen TM, Hennessey JF (1990) The effect of patient smoking habit on the outcome of IVF and GIFT treatment. Aust N Z J Obstet Gynaecol 30: 340–342.
[22]  Zenzes MT (2000) Smoking and reproduction: gene damage to human gametes and embryos. Hum Reprod Update 6: 122–131.
[23]  Winter E, Wang J, Davies MJ, Norman R (2002) Early pregnancy loss following assisted reproductive technology treatment. Hum Reprod 17: 3220–3223.
[24]  Ness RB, Grisso JA, Hirschinger N, Markovic N, Shaw LM, et al. (1999) Cocaine and tobacco use and the risk of spontaneous abortion. N Engl J Med 340: 333–339.
[25]  Kristensen P, Eilertsen E, Einarsdottir E, Haugen A, Skaug V, et al. (1995) Fertility in mice after prenatal exposure to benzo[a]pyrene and inorganic lead. Environ Health Perspect 103: 588–590.
[26]  Mattison DR PB, Meadows MJ, Miller MM, Malek A, London S (1989) The effect of smoking on oogenesis, fertilization, and implantation. Seminars in reproductive endocrinology 7: 291–304.
[27]  Madden JA, Hoyer PB, Devine PJ, Keating AF (2014) Acute 7,12-dimethylbenz[a]anthracene exposure causes differential concentration-dependent follicle depletion and gene expression in neonatal rat ovaries. Toxicol Appl Pharmacol.
[28]  Sobinoff AP, Beckett EL, Jarnicki AG, Sutherland JM, McCluskey A, et al. (2013) Scrambled and fried: cigarette smoke exposure causes antral follicle destruction and oocyte dysfunction through oxidative stress. Toxicol Appl Pharmacol 271: 156–167.
[29]  Gannon AM, Stampfli MR, Foster WG (2012) Cigarette smoke exposure leads to follicle loss via an alternative ovarian cell death pathway in a mouse model. Toxicol Sci 125: 274–284.
[30]  Jennings PC, Merriman JA, Beckett EL, Hansbro PM, Jones KT (2011) Increased zona pellucida thickness and meiotic spindle disruption in oocytes from cigarette smoking mice. Hum Reprod 26: 878–884.
[31]  Shiloh H, Lahav-Baratz S, Koifman M, Ishai D, Bidder D, et al. (2004) The impact of cigarette smoking on zona pellucida thickness of oocytes and embryos prior to transfer into the uterine cavity. Hum Reprod 19: 157–159.
[32]  Van Voorhis BJ, Dawson JD, Stovall DW, Sparks AE, Syrop CH (1996) The effects of smoking on ovarian function and fertility during assisted reproduction cycles. Obstet Gynecol 88: 785–791.
[33]  Hannoun A, Nassar AH, Usta IM, Abu Musa A (2010) Effect of female nargile smoking on in vitro fertilization outcome. Eur J Obstet Gynecol Reprod Biol 150: 171–174.
[34]  Khalil WA, Marei WF, Khalid M (2013) Protective effects of antioxidants on linoleic acid-treated bovine oocytes during maturation and subsequent embryo development. Theriogenology 80: 161–168.
[35]  Nordberg J, Arner ES (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31: 1287–1312.
[36]  Guerin P, El Mouatassim S, Menezo Y (2001) Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update 7: 175–189.
[37]  Feugang JM, de Roover R, Moens A, Leonard S, Dessy F, et al. (2004) Addition of beta-mercaptoethanol or Trolox at the morula/blastocyst stage improves the quality of bovine blastocysts and prevents induction of apoptosis and degeneration by prooxidant agents. Theriogenology 61: 71–90.
[38]  Lopes S, Jurisicova A, Sun JG, Casper RF (1998) Reactive oxygen species: potential cause for DNA fragmentation in human spermatozoa. Hum Reprod 13: 896–900.
[39]  Kowaltowski AJ, Vercesi AE (1999) Mitochondrial damage induced by conditions of oxidative stress. Free Radic Biol Med 26: 463–471.
[40]  Lim J, Luderer U (2011) Oxidative damage increases and antioxidant gene expression decreases with aging in the mouse ovary. Biol Reprod 84: 775–782.
[41]  Bermejo-Alvarez P, Rosenfeld CS, Roberts RM (2012) Effect of maternal obesity on estrous cyclicity, embryo development and blastocyst gene expression in a mouse model. Hum Reprod 27: 3513–3522.
[42]  Mazurek B, Amarjargal N, Haupt H, Fuchs J, Olze H, et al. (2011) Expression of genes implicated in oxidative stress in the cochlea of newborn rats. Hear Res 277: 54–60.
[43]  Yu B, Lin H, Yang L, Chen K, Luo H, et al. (2012) Genetic variation in the Nrf2 promoter associates with defective spermatogenesis in humans. J Mol Med (Berl) 90: 1333–1342.
[44]  Hayes JD, Strange RC (2000) Glutathione S-transferase polymorphisms and their biological consequences. Pharmacology 61: 154–166.
[45]  Eaton DL, Bammler TK (1999) Concise review of the glutathione S-transferases and their significance to toxicology. Toxicol Sci 49: 156–164.
[46]  Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta 1830: 3143–3153.
[47]  Sobinoff AP, Pye V, Nixon B, Roman SD, McLaughlin EA (2010) Adding insult to injury: effects of xenobiotic-induced preantral ovotoxicity on ovarian development and oocyte fusibility. Toxicol Sci 118: 653–666.
[48]  Radjendirane V, Joseph P, Lee YH, Kimura S, Klein-Szanto AJ, et al. (1998) Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity. J Biol Chem 273: 7382–7389.
[49]  Frei B, Forte TM, Ames BN, Cross CE (1991) Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in lipoprotein properties in human blood plasma. Protective effects of ascorbic acid. Biochem J 277 (Pt 1): 133–138.
[50]  Church DF, Pryor WA (1985) Free-radical chemistry of cigarette smoke and its toxicological implications. Environ Health Perspect 64: 111–126.
[51]  Stone KK, Bermúdez E, Pryor WA (1994) Aqueous extracts of cigarette tar containing the tar free radical cause DNA nicks in mammalian cells. Environ Health Perspect 102: 173.
[52]  Zhou J, Yan X, Guo F, Sun N, Qian Z, et al. (2000) Effects of cigarette smoking and smoking cessation on plasma constituents and enzyme activities related to oxidative stress. Biomed Environ Sci 13: 44–55.
[53]  Hulea S, Olinescu R, Nita S, Crocnan D, Kummerow F (1994) Cigarette smoking causes biochemical changes in blood that are suggestive of oxidative stress: a case-control study. J Environ Pathol Oncol 14: 173–180.
[54]  Fraga CG, Motchnik PA, Wyrobek AJ, Rempel DM, Ames BN (1996) Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat Res 351: 199–203.
[55]  Paszkowski T, Clarke RN, Hornstein MD (2002) Smoking induces oxidative stress inside the Graafian follicle. Hum Reprod 17: 921–925.
[56]  Siddique S, Sadeu JC, Foster WG, Feng Yl, Zhu J (2014) In vitro exposure to cigarette smoke induces oxidative stress in follicular cells of F1 hybrid mice. J Appl Toxicol 34: 224–226.
[57]  Strange RC, Spiteri MA, Ramachandran S, Fryer AA (2001) Glutathione-S-transferase family of enzymes. Mutat Res 482: 21–26.
[58]  Stella L, Pallottini V, Moreno S, Leoni S, De Maria F, et al. (2007) Electrostatic association of glutathione transferase to the nuclear membrane. Evidence of an enzyme defense barrier at the nuclear envelope. J Biol Chem 282: 6372–6379.
[59]  Lee CK, Brown BG, Rice WY Jr, Doolittle DJ (1989) Role of oxygen free radicals in the induction of sister chromatid exchanges by cigarette smoke. Environ Mol Mutagen 13: 54–59.
[60]  van der Vaart H, Postma DS, Timens W, ten Hacken NH (2004) Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax 59: 713–721.
[61]  Kim SJ, Jeong HJ, Myung NY, Kim MC, Lee JH, et al. (2008) The protective mechanism of antioxidants in cadmium-induced ototoxicity in vitro and in vivo. Environ Health Perspect 116: 854–862.
[62]  Nampoothiri LP, Agarwal A, Gupta S (2007) Effect of co-exposure to lead and cadmium on antioxidant status in rat ovarian granulose cells. Arch Toxicol 81: 145–150.
[63]  Paksy K, Rajczy K, Forgács Z, Lázár P, Bernard A, et al. (1997) Effect of cadmium on morphology and steroidogenesis of cultured human ovarian granulosa cells. J Appl Toxicol 17: 321–327.
[64]  Sharovskaya J, Kobliakova I, Solomatina N, Kobliakov V (2006) Effect of some carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons on gap junction intercellular communication in hepatoma cell cultures. Eur J Cell Biol 85: 387–397.
[65]  Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, et al. (2011) Effects of cigarette smoking on reproduction. Hum Reprod Update 17: 76–95.
[66]  Van Voorhis BJ, Syrop CH, Hammitt DG, Dunn MS, Snyder GD (1992) Effects of smoking on ovulation induction for assisted reproductive techniques. Fertil Steril 58: 981–985.
[67]  Van Voorhis BJ, Dawson JD, Stovall DW, Sparks AE, Syrop CH (1996) The effects of smoking on ovarian function and fertility during assisted reproduction cycles. Obstet Gynecol 88: 785–791.
[68]  Vidal JD, VandeVoort CA, Marcus CB, Lazarewicz NR, Conley AJ (2006) In vitro exposure to environmental tobacco smoke induces CYP1B1 expression in human luteinized granulosa cells. Reprod Toxicol 22: 731–737.
[69]  Sobinoff AP, Pye V, Nixon B, Roman SD, McLaughlin EA (2012) Jumping the gun: smoking constituent BaP causes premature primordial follicle activation and impairs oocyte fusibility through oxidative stress. Toxicol Appl Pharmacol 260: 70–80.
[70]  Gruber I, Just A, Birner M, Losch A (2008) Effect of a woman's smoking status on oocyte, zygote, and day 3 pre-embryo quality in in vitro fertilization and embryo transfer program. Fertil Steril 90: 1249–1252.
[71]  Otoi T, Yamamoto K, Koyama N, Tachikawa S, Suzuki T (1997) Bovine oocyte diameter in relation to developmental competence. Theriogenology 48: 769–774.
[72]  Jin X, Xiao LJ, Zhang XS, Liu YX (2011) Apotosis in ovary. Front Biosci (Schol Ed) 3: 680–697.
[73]  Perez G, Knudson C, Brown G, Korsmeyer S, Tilly J (1997) Resistance of BAX-deficient mouse oocytes to apoptosis induced by 7, 12-dimethylbenz [a] anthracene (DMBA) in vitro. Toxicologist 36: 250.
[74]  Tilly JL, Tilly KI, Perez GI (1997) The genes of cell death and cellular susceptibility to apoptosis in the ovary: a hypothesis. Cell Death Differ 4: 180–187.
[75]  Balaban B, Urman B (2006) Effect of oocyte morphology on embryo development and implantation. Reprod Biomed Online 12: 608–615.
[76]  Ebner T, Yaman C, Moser M, Sommergruber M, Feichtinger O, et al. (2000) Prognostic value of first polar body morphology on fertilization rate and embryo quality in intracytoplasmic sperm injection. Hum Reprod 15: 427–430.
[77]  Ebner T, Moser M, Yaman C, Feichtinger O, Hartl J, et al. (1999) Elective transfer of embryos selected on the basis of first polar body morphology is associated with increased rates of implantation and pregnancy. Fertil Steril 72: 599–603.
[78]  Ebner T, Moser M, Sommergruber M, Yaman C, Pfleger U, et al. (2002) First polar body morphology and blastocyst formation rate in ICSI patients. Hum Reprod 17: 2415–2418.
[79]  Whitcomb BW, Bodach SD, Mumford SL, Perkins NJ, Trevisan M, et al. (2010) Ovarian function and cigarette smoking. Paediatr Perinat Epidemiol 24: 433–440.
[80]  Cooper GS, Baird DD, Hulka BS, Weinberg CR, Savitz DA, et al. (1995) Follicle-stimulating hormone concentrations in relation to active and passive smoking. Obstet Gynecol 85: 407–411.
[81]  Freour T, Masson D, Mirallie S, Jean M, Bach K, et al. (2008) Active smoking compromises IVF outcome and affects ovarian reserve. Reprod Biomed Online 16: 96–102.
[82]  Elenbogen A, Lipitz S, Mashiach S, Dor J, Levran D, et al. (1991) The effect of smoking on the outcome of in-vitro fertilization-embryo transfer. Hum Reprod 6: 242–244.
[83]  Hughes E, Yeo J, Claman P, YoungLai E, Sagle M, et al. (1994) Cigarette smoking and the outcomes of in vitro fertilization: measurement of effect size and levels of action. Fertil Steril 62: 807–814.
[84]  El-Nemr A, Al-Shawaf T, Sabatini L, Wilson C, Lower A, et al. (1998) Effect of smoking on ovarian reserve and ovarian stimulation in in-vitro fertilization and embryo transfer. Hum Reprod 13: 2192–2198.
[85]  Klonoff-Cohen H, Natarajan L, Marrs R, Yee B (2001) Effects of female and male smoking on success rates of IVF and gamete intra-Fallopian transfer. Hum Reprod 16: 1382–1390.
[86]  Fuentes A, Mu?oz A, Barnhart K, Argüello B, Díaz M, et al. (2010) Recent cigarette smoking and assisted reproductive technologies outcome. Fertil Steril 93: 89–95.


comments powered by Disqus

Contact Us


微信:OALib Journal