Environmental causes of infertility


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Environmental causes of infertility

  1. 1. Environmental Causes of Infertility Afolabi, Michael O.S. Chemical Pathology Department, University College Hospital, Ibadan, Oyo State. cur i ousm kl @yahoo.com ai
  2. 2. Introduction & Background Infertility is an increasingly common reproductive dysfunction that affects over 10% of couples worldwide (Kumar, 2007) which translates into roughly 80 million couples (Inhorn et al, 2008). 2
  3. 3. Increased industrialization as well asthe rise in the incidence of infertilityhas stimulated the scientificcommunity to begin exploringpossible nexus between infertilityand environmental factors. 3
  4. 4. Background to Vaccination in Nigeria Such a view may be justified on the ground that contemporary life involves unavoidable interface with the biologically active products of industrial and agricultural processes that continuously alter the physical, chemical and thermal environment. 4
  5. 5. B A C K GROU ND TO VACCINATION IN NIG ERIA On the other hand, biological man lives in and interacts with a socio-cultural environment which prescribes and proscribes conventions and practices that may have attendant health sequelae. 5
  6. 6. Against this conceptual template, this paperexplores the cause and effect relationshipsbetween some “non-self” environmentalfactors on the aetiology of infertility.Specifically, it examines the effects of heavymetals such as lead (Pb), arsenic(As), cadmium (Cd); chemicals such asbisphenol A and socio-cultural practicessuch as female circumcision andcontraception vis-a-vis infertility.
  7. 7. Methodsh This paper adopts an analytic and conceptual approach to its subject matter. It employs the archival method of academic research. Relevant extant literature in the fields of endocrinology, clinical and reproductive toxicology were consulted. 7
  8. 8. Conceptual ClarificationsCausalityIn the natural sciences, the notion ofcausality implies being the triggering factorfor the occurrence of a phenomenon.Importantly, the phenomenon and its causeexist in a one to one relationship such thatthe presence of the cause guarantees thehappening of the phenomenon. 8
  9. 9. Aim However, causal claims are not always explicit in the biological and medical sciences due to the influence of the mantra ‘correlation does not imply causation’ (Russo and Williamson, 2011); 9
  10. 10. a The Environment The environment connotes the surrounding(s) of an organism and constitutes what is external as opposed to the internal milieu. To borrow the phraseology of Burnet (1969), the environment may be seen as the non- self, external agents and forces to which all forms of life including man are exposed. 10
  11. 11. sToday, mankind unavoidably comes incontact with several non-self environmentalfactors such as heavy metals and severalchemicals many of which can modulatebiological systems to influence physiologyand promote disease states(Skinner, Manikkam and Guerrero-Bosagna, 2011). 11
  12. 12. a Infertility Literarily, this means absence of reproductive capacity. In more scientific terms, however, infertility is commonly defined as the failure of conception after at least 12 months of unprotected coital intercourse between a couple (Irvine, 1998). Infertility may also entail the inability to carry a pregnancy term(Sule, Erigbali and Eruom, 2008). 12
  13. 13. Non-self Environmental Realities & InfertilityAli-Saleh et al (2008) argued that exposure toenvironmental factors exert varying effects onfertility. As noted earlier, mankind faces anumber of unavoidable non-self environmentalfactors which include:Heavy MetalsChemicalsHeatSocio-cultural factors 13
  14. 14. A Heavy Metals Several heavy metals are present in the environment in amounts alarmingly unsafe for human health (Ali and Ali, 2010). These metals such as cadmium, lead, arsenic, and mercury are primarily nonessential xenobiotics (Meeker et al, 2010) that have accumulatory potential (Hanf et al, 1996) . 14
  15. 15. CadmiumCd is used in industry principally in galvanizing andelectroplating, batteries and electrical conductors.Its toxicity lies in the fact that it modulates geneexpression and signal transduction. Akinloye et al(2006) opine that Cd interferes with testicularsteroidogenesis whereas Siu et al (2009) haveaverred that the deleterious action involves thedisruption of the blood–testis barrier . 15
  16. 16. ArsenicAs exposure occurs via food and water. It isalarming to note that in Asia rice and productssuch as rice bran and rice crackers have elevatedlevels of As (Stone, 2008). Arsenic exertsdeleterious effect on the Y chromosome (Ali andAli, 2010). However, chromosomal abnormalitiessuch as this are associated with infertility as well ashabitual abortion (Massolini, Menaton andCastagna, 2000; Musacchio, 2010). As also hasoestrogenic effects 16
  17. 17. LeadEpidemiologic studies have found reducedfertility rates among the families of exposed men(Markku, Marja-Lissa and Markku, 2000). Pbcauses oligospermia, poor sperm motility(Hammond and Gronowski, 2006) as well asdecrease in testicular function via thehypothalamic-pituitary axis (Sokol, Maddingand Swerdloff, 1985). 17
  18. 18. ChemicalsAnetor, Adeniyi and Anetor (2009) notethat there has been a three-fold increase inthe use of chemicals in the last fifty years.Many of these chemicals are present in dailylife and household products and exert theireffects even at very low concentrations(Giudice, 2006). Being on top of the foodchain means that humans accumulateseveral of these toxicants. 18
  19. 19. Bisphenol ABPA is an ingredient used in manufacturingpolycarbonate plastic and epoxy resins(Kuehn, 2007). It is contained in consumerproducts including baby bottles, plasticcontainers and dental sealants (Kaiser, 2007;Li et al, 2010). It is a genotoxic chemical withclastogenic properties (Tiwari et al, 2012).Studies have shown that BPA affectsandrogen receptors, male reproductiveorgans including, seminal vesicles, testesand epididymis, (Richter et al, 2007;Bouskine et al, 2009). 19
  20. 20. DichlorodiphenyltrichloroethaneDDT is an organochlorine compoundwhich is used as a pesticide inagriculture and public health programsin developing countries. Jaga (2000)notes that it has estrogenic activity.Because ERs are normally found in suchsites as Leydig cells, ovary, uterus andcervix, exposure to DDT constitutes achemical agent of infertility in male andfemale humans. 20
  21. 21. DrugsDrugs are compounds of chemical elementsthat interacts with the body’s chemistrycausing a chain reaction of events (Kamienskiand Keogh, 2006) and are one of man’sgreatest arsenals against diseases. Some drugshave however been linked with infertility 21
  22. 22. Csoka and Szyf (2009) note that antidepressantsexert epigenetic effects that may give rise toinfertility. Anti-cancer drugs such as 5-aza-20-deoxycystidine decrease global DNA methylationwhich leads to altered spermmorphology, decreased sperm motility, decreasedfertilization capacity, and decreased embryosurvival (Rajender, Avery and Agarwal, 2011). Inthe same vein, Hammond and Gronowski (2006)observe that use of chlorambucil may give rise toazoospermia while cyclophosphamide depressesspermatogenesis. 22
  23. 23. HeatGlobal warming and certain industrialization-associated occupations expose humans to highertemperatures. However, heat stress exerts deleteriouseffects on testicular functioning and impairsspermatogenesis (Ahmad et al, 2012) and maylikewise give rise to oligozoospermia,asthenozoospermia, and teratozoospermia. Theheat/infertility connection is further exacerbated bythe fact that increased atmospheric temperaturesenhance the release of heavy metals from the soilinto the environment (Egli et al, 2010). 23
  24. 24. Socio-cultural FactorsFemale CircumcisionFC is practiced in more than 30 Africancountries, mainly in a belt reaching from east to westAfrica north of the equator (Almroth et al, 2005), andabout 2 million procedures are done every year(WHO, 1998). Almroth et al (2005) reported a positiveassociation between the anatomical extent of FC andprimary infertility. Infections arising from Fc andsubsequent development of tubal-factor infertility.Des has also been reported. Dessel (2006) reported ahigher prevalence of genital mutilation involving thelabia majora in women with primary infertility. 24
  25. 25. Contraception Today, contraception is seen as a fundamental humanright of persons wishing to prevent unwantedpregnancies (Hatcher et al, 1997). Some contraceptiveapproaches however appear to play a role in infertility.Huhtamemi (1994) reported the adverse effects ofhormone-based contraceptives on sperm counts andfertility. Ethinyl oestradiol has also been linked withfemale infertility (Joffe, 2003) and diethylstilbestrolhas been linked with testicular dysgenesis, (Yiee andBaskin, 2010). There have also been reports of delayedconception of up to 42 months following use of pills(Speroff, Glass and Kase, 2000). 25
  26. 26. Concluding Remarks A commonsensical approach to avoiding the effect of these environmental non- self factors involves limiting contact which will however not work in all contexts. Nutrigenomics has been suggested as a more promising panacea as it offers a strong defence against the adverse effects of these toxicants on the genome (Anetor, 2010). 26
  27. 27. References  Ahmad, G., Moinard, N. and Esquerr-Lamare, C. et al (2012) Mild induced Testicular and Epididymal Hyperthermia alters Sperm Chromatin Integrity in Men Fertility and Sterility, Article in Press.  Akinloye, O., Arowojolu, A.O., Shittu, O.B. and Anetor, J.I. (2006) Cadmium Toxicity: a possible Cause of Male Infertility in Nigeria Reproductive Biology 6,1 17-30.  Ali, Safdar and Ali, Sher (2010) Genetic Integrity of the Human Y Chromosome exposed to Groundwater Arsenic BMC Medical Genomics 3, 35.; 1-12.  Almroth, L., Elmusharaf, S. and Hadi, F.E. et al (2005) Primary Infertility after Genital Mutilation in Girlhood in Sudan: a Case-control Study The Lancet 366, 385-391.  Al-Saleh, I., Coshkun, S. and Mashour, A. et al (2008) Exposure to Heavy Metals and its Effect on the Outcome of In-vitro Fertilization Treatment International Journal of Hygiene and Environmental Health 211, 560-579.  Anetor, J. and Anetor .I. (2010) Industrialisation and the increasing Risk of Genome Instability in Developing Countries: Nutrigenomics as a promising Antidote African Journal of Medicine and Medical Sciences- Suppl, 7-20.  Anetor, J.I., Adeniyi, F.A.A and Anetor, G.O. (2009) Global Explosion in the Incidence of Diabetes Mellitus: is it Due to Changes in Dietary Habits & Life Styles alone or is there the Role of a Persistent Exposure to Toxic Chemicals in the Environment, Paper delivered at the 1st African Conference of Clinical Chemistry, Univ ersity of Ibadan, Nigeria.  Bouskine, A., Nebout, M. and Brucker-Davis F. et al (2009) Low Doses of Bisphenol A promote Human Seminoma Cell Proliferation by activating PKA and PKG via a Membrane Gprotein- coupled Estrogen Receptor Environmental Health Perspective 117:1053–1058. 27
  28. 28. References  Burnet, Macfarlane F (1969) Self, Not Self London: Heinemann p. 3.  Csoka and Szyf (2009) Epigenetic Side-effects of Common Pharmaceuticals: a Potential New Field in Medicine and Pharmacology Medical Hypothesis 73, 770–780.  Dessel, Thierry (2006) A Positive Association existed between the Extent of Female Genital Mutilation and Primary Infertility Evidence-based Obstetrics and Gynecology 8, 38-39.  Egli, M., Sartori, G. and Mirabella, A. et al (2010) The Influence of Weathering and Organic Matter on Heavy Metals Lability in Silicatic, Alpine Soils Science of the Total Environment 408-931-946.  Guidice, Linda (2006) Infertility and the Environment: the Medical Context Seminars in Reproductive Medicine 24, 3; 129-133.  Hanf, V., Forstmann, A. and Costea, J.E. et al (1996) Mercury in Urine and Ejaculate in Husbands of Barren Couples Toxicology Letters 87, 227-231.  Hatcher (1997) The Essentials of Contraceptive Technology Baltimore: Population Information Program, pp. viii, 2.  Haymond, S. and Gronowski, A.M. (2006) Reproductive Related Disorders In: Tietz Teztbook of Clinical Chemistry and Molecular Diagnostics 4th Ed. (Eds.) Burtis, C.A., Ashwood, E.R. and Burns, D.E. Elsevier Inc. pp. 2120, 2122.  Irvine, D.S. (1998) Epidemiology and Aetiology of Male Infertility Human Reproduction 13, 1; 33-44. 28
  29. 29. References  Jaga, K. (2000) What are the Implications of the Interaction between DDT and Estrogen Receptors in the Body? Medical Hypothesis 54, 1; 18-25.  Kaiser, Jocelyn (2007) Controversy Continues After Panel Rules on Bisphenol A Science 317, 884-885.  Kamienski, M. Keogh, J. (2006) Pharmacology Demystified New York: McGraw Hill, p. 1.  Kuehn, B.M. (2007) Expert Panels weigh Bisphenol-A Risks Journal of American Medical Association 298:1499–1503.  Kumar, D. (2007) Prevalence of Female Infertility and its Socioeconomic Factors in Tribal Communities of Central India Rural and Remote Health 7, 456; 1-5.  Li, D., Zhou, Z., and Miao, M. et al (2010a) Relationship between Urine Bisphenol-A Level and Declining Male Sexual Function Journal of Andrology 31, 5; 500-506.  Markku, S., Majar-Liisa, L. and Markku, N. (2000) Paternal Exposure to Lead and Infertility Epidemiology 7, 148-152.  Massolini, M., Menaton, G., and Castagna, P. (2000) Subset Distribution and Proliferative Assessment of Peripheral Blood T-cells of Patients with Recurrent Spontaneous Abortion In: Advances in Gynaecologic Endocrionology (Eds.) Genazzani, F.P. and Astini, P.G., Boca Paton: the Parthenon Publishing Company, p. 52.  Meeker, J.D., Rossano, M.G. and Protas, B. et al. (2010) Environmental Exposure to Metals and Male Reproductive Hormones: Circulating 29 Testosterone is Inversely associated with Blood Molybdenum Fertility and
  30. 30.  Musacchio, Andrea (2010) Surfing Chromosomes (and Survivin) Science 330, 183-184. References Richter, C.A., Birnbaum, L.S. and Farabollini, F. et al (2007) In vivo effects of bisphenol A in laboratory rodent studies Reproductive Toxicology 24:199–224. Russo, F. and Williamson, J. (2011) Epistemic Causality and Evidence-based Medicine European Journal of the Philosophy of Science 8, 1-14. Siu, E.R., Mruk, D.D., Porto, C.S. and Cheng, C.Y. (2009) Cadmium-induced Testicular Injury Toxicology and Applied Pharmacology 238, 240–249. Skinner, M.K., Manikkam, M. and Guerrero-Bosagna, C. (2011) Epigenetic Transgenerational actions of Endocrine Disruptors Reproductive Toxicology 31, 337–343. Sokol, R.Z., Madding, C.E. and Swerdoff, R.S. (1985) Lead Toxicity and the Hypothalamic- Pituitary-Testicular Axis Biology of Reproduction 33, 722-728. Speroff, L., Glass, R.H. and Kase, N. (1999) Clinical Gynecologic Endocrinology and Infertility 6th Ed., Baltimore: Lippincott Williams and Wilkins, p. 1014. Steel, Daniel (2011) Causal Interference and Medical Experiments In: Handbook of the Philosophy of Science. Volume 16: Philosophy of Medicine (Ed.) Gilford, F. Elsevier, p. 161. Stone, Richard (2008) Arsenic and Paddy Rice: a Neglected Cancer Risk? Science 321 184-185. Sule, J.O., Erigbali, P. and Eruom, L. (2008)Prevalence of Infertility in Women in a Southwestern Nigerian Community African Journal of Biomedical Research 11, 225 – 227. Tiwari. D., Kamble, J. and Chilgunde, S. et al (2012) Clastogenic and mutagenic effects of bisphenol A: An endocrine disruptor Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Article in Press. WHO (1998) Female Genital Mutilation: an Overview Geneva: World Health Organization. 30