Skip to main content

Advertisement

SpringerLink
Log in

Mechanism of Human Tubal Ectopic Pregnancy Caused by Cigarette Smoking

  • Review
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

In the past few decades, the smoking rate of women of childbearing age has increased. Epidemiological data has repeatedly shown that smoking women have an increased risk of various reproductive diseases, including ectopic pregnancy (EP), decreased fertility, adverse pregnancy outcomes, and failure of assisted reproduction. The oviduct was the target of cigarette smoke in many in vivo and in vitro studies. The fallopian tube is a well-designed organ. Its function is to collect and transport the ova to the fertilized site and provide a suitable environment for fertilization and early embryonic development. Lastly, the fallopian tube transports the pre-implantation embryo to the uterus. Various biological processes can be studied in the fallopian tubes, making it an excellent model for toxicology. This paper reviews the roles of the fallopian tube in gametes and embryo transportation, and the possible mechanism tobacco smoke contributes to tubal EP. A possible signal pathway might be a model to develop intervention of EP for pregnant women exposed to smoking.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. No Tobacco Team. WHO report on the global tobacco epidemic, 2021: addressing new and emerging products: executive summary. World Health Organization. 2021. https://www.who.int/publications/i/item/9789240032842. Accessed 30 Dec 2021.

  2. Data and Analytic Team. State of inequality: HIV, tuberculosis and malaria. World Health Organization. 2021. https://www.who.int/publications/i/item/9789240039445. Accessed 30 Dec 2021.

  3. Lyon & France. IARC monographs on the evaluation of carcinogenic risks to humans. Tobacco Smoking. International Agency for Research on Cancer, World Health Organization. 1986;38:83.

  4. Bekki K, Inaba Y, Uchiyama S, Kunugita N. Comparison of chemicals in mainstream smoke in heat-not-burn tobacco and combustion cigarettes. J UOEH. 2017;39(3):201–7. https://doi.org/10.7888/juoeh.39.201.

    Article  CAS  PubMed  Google Scholar 

  5. Grimmer G, Naujack KW, Dettbarn G. Gaschromatographic determination of polycyclic aromatic hydrocarbons, aza-arenes, aromatic amines in the particle and vapor phase of mainstream and sidestream smoke of cigarettes. Toxicol Lett. 1987 Jan;35(1):117–24. https://doi.org/10.1016/0378-4274(87)90095-6.

    Article  CAS  PubMed  Google Scholar 

  6. Geng ZL, Zhang J, Ge YH, Xiang ZM, Cai K, Zhu XL, et al. Correlation between endogenous harmful components in mainstream cigarette smoke and chemical constituents in tobacco leaves. Ying Yong Sheng Tai Xue Bao. 2015;26:1447–53.

    CAS  PubMed  Google Scholar 

  7. Laking GR. Human exposure to radioactivity from tobacco smoke: systematic review. Nicotine Tob Res. 2019;21:1172–80.

    Article  CAS  PubMed  Google Scholar 

  8. Torkashvand J, Farzadkia M, Sobhi HR, Esrafili A. Littered cigarette butt as a well-known hazardous waste: a comprehensive systematic review. J Hazard Mater. 2020;383:121242.

    Article  CAS  PubMed  Google Scholar 

  9. Macacu A, Autier P, Boniol M, Boyle P. Active and passive smoking and risk of breast cancer: a meta-analysis. Breast Cancer Res Treat. 2015 Nov;154(2):213–24. https://doi.org/10.1007/s10549-015-3628-4.

    Article  PubMed  Google Scholar 

  10. Mukharjee S, Bank S, Maiti S. Chronic tobacco exposure by smoking develops insulin resistance. Endocr Metab Immune Disord Drug Targets. 2020;20(6):869–77. https://doi.org/10.2174/1871530320666200217123901.

    Article  CAS  PubMed  Google Scholar 

  11. Wong J, Magun BE, Wood LJ. Lung inflammation caused by inhaled toxicants: a review. Int J Chron Obstruct Pulmon Dis. 2016;11:1391–401. https://doi.org/10.2147/COPD.S106009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Inoue-Choi M, Hartge P, Liao LM, Caporaso N, Freedman ND. Association between long-term low-intensity cigarette smoking and incidence of smoking-related cancer in the national institutes of health-AARP cohort. Int J Cancer. 2018;142(2):271–80. https://doi.org/10.1002/ijc.31059.

    Article  CAS  PubMed  Google Scholar 

  13. Astuti Y, Wardhana A, Watkins J, Wulaningsih W. PILAR Research Network. Cigarette smoking and telomere length: a systematic review of 84 studies and meta-analysis. Environ Res. 2017;158:480–9. https://doi.org/10.1016/j.envres.2017.06.038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, et al. Effects of cigarette smoking on reproduction. Hum Reprod Update. 2011;17:76–95.

    Article  CAS  PubMed  Google Scholar 

  15. Practice Committee of the American Society for Reproductive Medicine. Smoking and infertility: a committee opinion. Fertil Steril. 2018;110(4):611–8.

  16. Fronczak A, Polanska K, Makowiec-Dabrowska T. Kaleta D [Smoking among women–strategies for fighting the tobacco epidemic]. Przegl Lek. 2012;69:1103–7.

    PubMed  Google Scholar 

  17. Gaskins AJ, Missmer SA, Rich-Edwards JW, Williams PL, Souter I, Chavarro JE. Demographic, lifestyle, and reproductive risk factors for ectopic pregnancy. Fertil Steril. 2018;110:1328–37.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Santos-Ribeiro S, Tournaye H, Polyzos NP. Trends in ectopic pregnancy rates following assisted reproductive technologies in the UK: a 12-year nationwide analysis including 160 000 pregnancies. Hum Reprod. 2016;31(2):393–402.

    PubMed  Google Scholar 

  19. Malak M, Tawfeeq T, Holzer H, Tulandi T. Risk factors for ectopic pregnancy after in vitro fertilization treatment. J Obstet Gynaecol Can. 2011;33(6):617–9.

    Article  PubMed  Google Scholar 

  20. Rosman ER, Keegan DA, Krey L, Liu M, Licciardi F, Grifo JA. Ectopic pregnancy rates after in vitro fertilization: a look at the donor egg population. Fertil Steril. 2009;92:1791–3.

    Article  PubMed  Google Scholar 

  21. Trindade VD, Burmann L, Viégas D, Hentschke MR, Azambuja R, Okada L, et al. Ectopic pregnancy in left ovary and contralateral uterine tube diagnosed one week apart in In Vitro Fertilization with donor eggs. JBRA Assisted Reproduction. 2019;23(4):439–41.

    PubMed  PubMed Central  Google Scholar 

  22. Acet F, Goker ENT, Hortu I, Sahin G, Tavmergen E. A rare case of bilateral tubal ectopic pregnancy following intracytoplasmic sperm injection-embryo transfer (ICSI-ET). Rev Bras Ginecol Obstet. 2020;42(3):165–8.

    Article  PubMed  Google Scholar 

  23. Altinkaya SO, Ozat M, Pektas MK, Gungor T, Mollamahmutoglu L. Simultaneous bilateral tubal pregnancy after in vitro fertilization and embryo transfer. Taiwan J Obstet Gynecol. 2008;47(3):338–40.

    Article  PubMed  Google Scholar 

  24. Hendriks E, Rosenberg R, Prine L. Ectopic pregnancy: diagnosis and management. Am Fam Physician. 2020;101(10):599–606.

    PubMed  Google Scholar 

  25. Ranji GG, Usha Rani G, Varshini S. Ectopic pregnancy: risk factors, clinical presentation and management. J Obstet Gynaecol India. 2018;68:487–92.

    Article  PubMed  Google Scholar 

  26. Zhang RP, Zhao WZ, Chai BB, Wang QY, Yu CH, Wang HY, et al. The effects of maternal cigarette smoking on pregnancy outcomes using assisted reproduction technologies: an updated meta-analysis. J Gynecol Obstet Hum Reprod. 2018;47:461–8.

    Article  PubMed  Google Scholar 

  27. Hunter RH. Components of oviduct physiology in eutherian mammals. Biol Rev Camb Philos Soc. 2012;87:244–55.

    Article  CAS  PubMed  Google Scholar 

  28. Halbert SA, Tam PY, Blandau RJ. Egg transport in the rabbit oviduct: the roles of cilia and muscle. Science. 1976;191:1052–3.

    Article  CAS  PubMed  Google Scholar 

  29. Jansen RP. Endocrine response in the fallopian tube. Endocr Rev. 1984;5:525–51.

    Article  CAS  PubMed  Google Scholar 

  30. Aviles M, Gutierrez-Adan A, Coy P. Oviductal secretions: will they be key factors for the future ARTs? Mol Hum Reprod. 2010;16:896–906.

    Article  PubMed  Google Scholar 

  31. Shaw JL, Horne AW. The paracrinology of tubal ectopic pregnancy. Mol Cell Endocrinol. 2012;358:216–22.

    Article  CAS  PubMed  Google Scholar 

  32. Shaw JL, Oliver E, Lee KF, Entrican G, Jabbour HN, Critchley HO, et al. Cotinine exposure increases Fallopian tube PROKR1 expression via nicotinic AChRalpha-7: a potential mechanism explaining the link between smoking and tubal ectopic pregnancy. Am J Pathol. 2010;177:2509–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. AssouniMindjah YA, Essiben F, Foumane P, Dohbit JS, Mboudou ET. Risk factors for ectopic pregnancy in a population of Cameroonian women: a case-control study. PLoS One. 2018;13:e0207699.

    Article  Google Scholar 

  34. Jiang H, Li JX. Interaction networks between the fallopian tubes and the embryo in human tubal pregnancy: current knowledge and perspectives. J Obstet Gynaecol Res. 2021;47(12):4139–47. https://doi.org/10.1111/jog.15033.

    Article  PubMed  Google Scholar 

  35. Wang X, Lee CL, Li RHW, Vijayan M, Duan YG, Yeung WSB, et al. Alteration of the immune cell profiles in the pathophysiology of tubal ectopic pregnancy. Am J Reprod Immunol. 2019;81(4):e13093. https://doi.org/10.1111/aji.13093.

    Article  PubMed  Google Scholar 

  36. Quintar AA, Mukdsi JH, del Valle BM, Aoki A, Maldonado CA, Perez AJ. Increased expression of uteroglobin associated with tubal inflammation and ectopic pregnancy. Fertil Steril. 2008;89:1613–7.

    Article  CAS  PubMed  Google Scholar 

  37. Kontomanolis EN, Kalagasidou S, Fasoulakis Z. MicroRNAs as potential serum biomarkers for early detection of ectopic pregnancy. Cureus. 2018;10(3):e2344. https://doi.org/10.7759/cureus.2344.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Riveles K, Tran V, Roza R, Kwan D, Talbot P. Smoke from traditional commercial, harm reduction and research brand cigarettes impairs oviductal functioning in hamsters (Mesocricetus auratus) in vitro. Hum Reprod. 2007;22:346–55.

    Article  CAS  PubMed  Google Scholar 

  39. Gieseke C, Talbot P. Cigarette smoke inhibits hamster oocyte pickup by increasing adhesion between the oocyte cumulus complex and oviductal cilia. Biol Reprod. 2005;73:443–51.

    Article  CAS  PubMed  Google Scholar 

  40. Chung MI, Kwon T, Tu F, Brooks ER, Gupta R, Meyer M, et al. Coordinated genomic control of ciliogenesis and cell movement by RFX2. Elife. 2014;3:e01439. https://doi.org/10.7554/eLife.01439.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Vladar EK, Stratton MB, Saal ML, Salazar-De Simone G, Wang X, Wolgemuth D, et al. Cyclin-dependent kinase control of motile ciliogenesis. Elife. 2018;7:e36375. https://doi.org/10.7554/eLife.36375.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Pier B, Kazanjian A, Gillette L, Strenge K, Burney RO. Effect of cigarette smoking on human oviductal ciliation and ciliogenesis. Fertil Steril. 2013;99(1):199–205. https://doi.org/10.1016/j.fertnstert.2012.08.041.

    Article  CAS  PubMed  Google Scholar 

  43. Magers T, Talbot P, DiCarlantonio G, Knoll M, Demers D, Tsai I, et al. Cigarette smoke inhalation affects the reproductive system of female hamsters. Reprod Toxicol. 1995;9:513–25.

    Article  CAS  PubMed  Google Scholar 

  44. Duran M, Ustunyurt E, Kosus A, Kosus N, Turhan N, Hızlı D, et al. Does vitamin E prevent tubal damage caused by smoking? A light microscopy and animal study. Eur J Obstet Gynecol Reprod Biol. 2014;175:149–51. https://doi.org/10.1016/j.ejogrb.2014.01.020.

    Article  CAS  PubMed  Google Scholar 

  45. Knoll M, Shaoulian R, Magers T, Talbot P. Ciliary beat frequency of hamster oviducts is decreased in vitro by exposure to solutions of mainstream and sidestream cigarette smoke. Biol Reprod. 1995;53(1):29–37. https://doi.org/10.1095/biolreprod53.1.29.

    Article  CAS  PubMed  Google Scholar 

  46. Knoll M, Talbot P. Cigarette smoke inhibits oocyte cumulus complex pick-up by the oviduct in vitro independent of ciliary beat frequency. Reprod Toxicol. 1998;12(1):57–68. https://doi.org/10.1016/s0890-6238(97)00100-7.

    Article  CAS  PubMed  Google Scholar 

  47. Horne AW, Brown JK, Nio-Kobayashi J, Abidin HB, Adin ZE, Boswell L, et al. The association between smoking and ectopic pregnancy: why nicotine is BAD for your fallopian tube. PLoS One. 2014;9:e89400.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Hang B, Wang P, Zhao Y, Sarker A, Chenna A, Xia Y, et al. Adverse health effects of thirdhand smoke: from cell to animal models. Int J Mol Sci. 2017;18(5):932–9.

  49. Wyatt TA, Schmidt SC, Rennard SI, Tuma DJ, Sisson JH. Acetaldehyde-stimulated PKC activity in airway epithelial cells treated with smoke extract from normal and smokeless cigarettes. Proc Soc Exp Biol Med. 2000;225:91–7.

    Article  CAS  PubMed  Google Scholar 

  50. Shao R, Weijdegard B, Fernandez-Rodriguez J, Egecioglu E, Zhu C, Andersson N, et al. Ciliated epithelial-specific and regional-specific expression and regulation of the estrogen receptor-beta2 in the fallopian tubes of immature rats: a possible mechanism for estrogen-mediated transport process in vivo. Am J Physiol Endocrinol Metab. 2007;293:E147–58.

    Article  CAS  PubMed  Google Scholar 

  51. Vrsanska S, Nagyova E, Mlynarcikova A, Fickova M, Kolena J. Components of cigarette smoke inhibit expansion of oocyte-cumulus complexes from porcine follicles. Physiol Res. 2003;52:383–7.

    CAS  PubMed  Google Scholar 

  52. Cooper AR, Moley KH. Maternal tobacco use and its preimplantation effects on fertility: more reasons to stop smoking. Seminars Reprod Med. 2008;26:204–12.

    Article  CAS  Google Scholar 

  53. Gieseke C, Talbot P. Cigarette smoke inhibits hamster oocyte pickup by increasing adhesion between the oocyte cumulus complex and oviductal cilia. Biol Reprod. 2005;73(3):443–51. https://doi.org/10.1095/biolreprod.105.041152.

    Article  CAS  PubMed  Google Scholar 

  54. Nio-Kobayashi J, Abidin HB, Brown JK, Iwanaga T, Horne AW, Duncan WC. Cigarette smoking alters sialylation in the Fallopian tube of women, with implications for the pathogenesis of ectopic pregnancy. Mol Reprod Dev. 2016;83:1083–91.

    Article  CAS  PubMed  Google Scholar 

  55. Saint-Dizier M, Schoen J, Chen S, Banliat C, Mermillod P. Composing the early embryonic microenvironment: physiology and regulation of oviductal secretions. Int J Mol Sci. 2019;21(1):223–43.

  56. Yoshinaga K, Rice C, Krenn J, Pilot RL. Effects of nicotine on early pregnancy in the rat. Biol Reprod. 1979;20:294–303.

    Article  CAS  PubMed  Google Scholar 

  57. Akpak YK, Cekmez Y, Erdogan Cakir A, Karaca N, Batmaz G, Gulsen S, et al. An animal model of effects of nicotine exposure on endometrial receptivity and embryo implantation in pregnancy. J Matern Fetal Neonatal Med. 2017;30:2818–23.

    Article  CAS  PubMed  Google Scholar 

  58. Fukui Y, Hirota Y, Matsuo M, Gebril M, Akaeda S, Hiraoka T, et al. Uterine receptivity, embryo attachment, and embryo invasion: multistep processes in embryo implantation. Reprod Med Biol. 2019;18:234–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Horne AW, King AE, Shaw E, McDonald SE, Williams AR, Saunders PT, et al. Attenuated sex steroid receptor expression in fallopian tube of women with ectopic pregnancy. J Clin Endocrinol Metab. 2009;94:5146–54.

    Article  CAS  PubMed  Google Scholar 

  60. Yildiz D. Nicotine, its metabolism and an overview of its biological effects. Toxicon. 2004;43:619–32.

    Article  CAS  PubMed  Google Scholar 

  61. Ezzati M, Djahanbakhch O, Arian S, Carr BR. Tubal transport of gametes and embryos: a review of physiology and pathophysiology. J Assist Reprod Genet. 2014;31:1337–47.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Evans J, Catalano RD, Morgan K, Critchley HO, Millar RP, Jabbour HN. Prokineticin 1 signaling and gene regulation in early human pregnancy. Endocrinology. 2008;149:2877–87.

    Article  CAS  PubMed  Google Scholar 

  63. Riveles K, Roza R, Arey J, Talbot P. Pyrazine derivatives in cigarette smoke inhibit hamster oviductal functioning. Reprod Biol Endocrinol. 2004;2:23.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Talbot P, DiCarlantonio G, Knoll M, Gomez C. Identification of cigarette smoke components that alter functioning of hamster (Mesocricetus auratus) oviducts in vitro. Biol Reprod. 1998;58:1047–53.

    Article  CAS  PubMed  Google Scholar 

  65. Akar Y, Ahmad N, Khalid M. The effect of cadmium on the bovine in vitro oocyte maturation and early embryo development. Int J Vet Sci Med. 2018;6:S73–7.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by a grant from the National Natural Science Foundation of China (No. 81872125) and The Science and Technology Planning Projects of Guangzhou City (No. 2016201604030009).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Heping District Shenyang, 36 Sanhao Street, 110004, Shenyang, China

    Quan Guo

  2. Reproductive Medicine Center, Seventh Affiliated Hospital, Sun Yat-Sen University, 628 Zhenyuan Road, Xinhu Street, Guangming District, Shenzhen, Guangdong, 510000, China

    Zaiyi Li & Lin Ma

  3. RD Center, Pacificbio Inc. Irvine, Irvine, CA, 92602, USA

    Steve Jia

  4. Murray Edwards College, University of Cambridge, Cambridge, CB3 0DF, UK

    Fangze Tong

Authors
  1. Quan Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zaiyi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Steve Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fangze Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lin Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Quan Guo or Lin Ma.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

This study does not include images or other personal or clinical details of participants.

Conflict of Interest

The authors declare no competing interests.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Guo, Q., Li, Z., Jia, S. et al. Mechanism of Human Tubal Ectopic Pregnancy Caused by Cigarette Smoking. Reprod. Sci. 30, 1074–1081 (2023). https://doi.org/10.1007/s43032-022-00947-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-022-00947-6

Keywords

Search

Navigation