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Environmental Causes of Infertility


       Afolabi, Michael O.S.
       Chemical Pathology Department, University
         College Hospital, Ibadan, Oyo State.
          cur i ousm kl @yahoo.com
                    ai
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.

                                           3
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
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
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.
Methods
h




    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
Conceptual Clarifications
Causality
In 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.

                                                8
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
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
s




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).


                                               11
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
Non-self Environmental Realities & Infertility
Ali-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 Metals
Chemicals
Heat
Socio-cultural factors

                                                 13
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
Cadmium
Cd 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 .

                                                  15
Arsenic
As 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

                                                   16
Lead
Epidemiologic 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).


                                               17
Chemicals
Anetor, 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.
                                                18
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).                           19
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.
                                            20
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



                                  21
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.                               22
Heat
Global 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).


                                                    23
Socio-cultural Factors
Female Circumcision
FC 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.
                                                    24
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).
                                                      25
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
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
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
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
         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

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Environmental causes of infertility

  • 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. 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. 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. 3
  • 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. 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. 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.
  • 7. Methods h 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. Conceptual Clarifications Causality In 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. 8
  • 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. 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. s 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). 11
  • 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. Non-self Environmental Realities & Infertility Ali-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 Metals Chemicals Heat Socio-cultural factors 13
  • 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. Cadmium Cd 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 . 15
  • 16. Arsenic As 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 16
  • 17. Lead Epidemiologic 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). 17
  • 18. Chemicals Anetor, 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. 18
  • 19. 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). 19
  • 20. 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. 20
  • 21. 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 21
  • 22. 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. 22
  • 23. Heat Global 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). 23
  • 24. Socio-cultural Factors Female Circumcision FC 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. 24
  • 25. 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). 25
  • 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. 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
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  • 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
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