Environmental Causes of Infertility

Afolabi, Michael O.S.

Chemical Pathology Department, University College Hospital, Ibadan, Oyo State. curiousmaikl@yahoo.com

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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

Increased industrialization as well as the rise in the incidence of infertility has stimulated the scientific community to begin exploring possible nexus between infertility and environmental factors.

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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.

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BACKGROUND TO VACCINATION IN NIGERIA

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.

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Against this conceptual template, this paper explores the cause and effect relationships between some “non-self” environmental factors on the aetiology of infertility. Specifically, it examines the effects of heavy metals such as lead (Pb), arsenic (As), cadmium (Cd); chemicals such as bisphenol A and socio-cultural practices such as female circumcision and contraception vis-a-vis infertility.

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MethodsThis 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.

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Conceptual ClarificationsCausalityIn the natural sciences, the notion of causality implies being the triggering factor for the occurrence of a phenomenon. Importantly, the phenomenon and its cause exist in a one to one relationship such that the presence of the cause guarantees the happening of the phenomenon.

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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);

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The EnvironmentThe 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.

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Today, mankind unavoidably comes in contact with several non-self environmental factors such as heavy metals and several chemicals many of which can modulate biological systems to influence physiology and promote disease states (Skinner, Manikkam and Guerrero- Bosagna, 2011).

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InfertilityLiterarily, 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).

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Non-self Environmental Realities & InfertilityAli-Saleh et al (2008) argued that exposure to environmental factors exert varying effects on fertility. As noted earlier, mankind faces a number of unavoidable non-self environmental factors which include:Heavy MetalsChemicals Heat Socio-cultural factors

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A Heavy MetalsSeveral 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) .

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CadmiumCd is used in industry principally in galvanizing and electroplating, batteries and electrical conductors. Its toxicity lies in the fact that it modulates gene expression and signal transduction. Akinloye et al (2006) opine that Cd interferes with testicular steroidogenesis whereas Siu et al (2009) have averred that the deleterious action involves the disruption of the blood–testis barrier .

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ArsenicAs exposure occurs via food and water. It is alarming to note that in Asia rice and products such as rice bran and rice crackers have elevated levels of As (Stone, 2008). Arsenic exerts deleterious effect on the Y chromosome (Ali and Ali, 2010). However, chromosomal abnormalities such as this are associated with infertility as well as habitual abortion (Massolini, Menaton and Castagna, 2000; Musacchio, 2010). As also has oestrogenic effects

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LeadEpidemiologic studies have found reduced fertility rates among the families of exposed men (Markku, Marja-Lissa and Markku, 2000). Pb causes oligospermia, poor sperm motility (Hammond and Gronowski, 2006) as well as decrease in testicular function via the hypothalamic-pituitary axis (Sokol, Madding and Swerdloff, 1985).

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ChemicalsAnetor, Adeniyi and Anetor (2009) note that there has been a three-fold increase in the use of chemicals in the last fifty years. Many of these chemicals are present in daily life and household products and exert their effects even at very low concentrations (Giudice, 2006). Being on top of the food chain means that humans accumulate several of these toxicants.

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Bisphenol A BPA is an ingredient used in manufacturing polycarbonate plastic and epoxy resins (Kuehn, 2007). It is contained in consumer products including baby bottles, plastic containers and dental sealants (Kaiser, 2007; Li et al, 2010). It is a genotoxic chemical with clastogenic properties (Tiwari et al, 2012). Studies have shown that BPA affects androgen receptors, male reproductive organs including, seminal vesicles, testes and epididymis, (Richter et al, 2007; Bouskine et al, 2009).

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Dichlorodiphenyltrichloroethane

DDT is an organochlorine compound which is used as a pesticide in agriculture and public health programs in developing countries. Jaga (2000) notes that it has estrogenic activity. Because ERs are normally found in such sites as Leydig cells, ovary, uterus and cervix, exposure to DDT constitutes a chemical agent of infertility in male and female humans.

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Drugs Drugs are compounds of chemical elements that interacts with the body’s chemistry causing a chain reaction of events (Kamienski and Keogh, 2006) and are one of man’s greatest arsenals against diseases. Some drugs have however been linked with infertility

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Csoka and Szyf (2009) note that antidepressants exert epigenetic effects that may give rise to infertility. Anti-cancer drugs such as 5-aza-20-deoxycystidine decrease global DNA methylation which leads to altered sperm morphology, decreased sperm motility, decreased fertilization capacity, and decreased embryo survival (Rajender, Avery and Agarwal, 2011). In the same vein, Hammond and Gronowski (2006) observe that use of chlorambucil may give rise to azoospermia while cyclophosphamide depresses spermatogenesis.

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HeatGlobal warming and certain industrialization-associated occupations expose humans to higher temperatures. However, heat stress exerts deleterious effects on testicular functioning and impairs spermatogenesis (Ahmad et al, 2012) and may likewise give rise to oligozoospermia, asthenozoospermia, and teratozoospermia. The heat/infertility connection is further exacerbated by the fact that increased atmospheric temperatures enhance the release of heavy metals from the soil into the environment (Egli et al, 2010).

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Socio-cultural FactorsFemale CircumcisionFC is practiced in more than 30 African countries, mainly in a belt reaching from east to west Africa north of the equator (Almroth et al, 2005), and about 2 million procedures are done every year (WHO, 1998). Almroth et al (2005) reported a positive association between the anatomical extent of FC and primary infertility. Infections arising from Fc and subsequent development of tubal-factor infertility. Des has also been reported. Dessel (2006) reported a higher prevalence of genital mutilation involving the labia majora in women with primary infertility.

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Contraception Today, contraception is seen as a fundamental human right of persons wishing to prevent unwanted pregnancies (Hatcher et al, 1997). Some contraceptive approaches however appear to play a role in infertility. Huhtamemi (1994) reported the adverse effects of hormone-based contraceptives on sperm counts and fertility. Ethinyl oestradiol has also been linked with female infertility (Joffe, 2003) and diethylstilbestrol has been linked with testicular dysgenesis, (Yiee and Baskin, 2010). There have also been reports of delayed conception of up to 42 months following use of pills (Speroff, Glass and Kase, 2000).

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Concluding RemarksA 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).

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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.

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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.

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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 Testosterone is Inversely associated with Blood Molybdenum Fertility and Sterility 93, 1:130–40.

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References Musacchio, Andrea (2010) Surfing Chromosomes (and Survivin) Science 330, 183-184.

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.

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