Histopathology of the Uterus and Ovary in Experimentally- Induced Lead Poisoning in Rabbit-Does
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Abstract
Many previous studies have established the adverse effect of lead poisoning on many body systems including reproduction. The objective of the present study was to determine the reproductive implication of experimental lead poisoning in rabbit-doe with emphasis on histo-pathology of the ovary and uterus. Nine New Zealand adult rabbit does weighing between 1.5 ± 0.2 to 2.2 ± 0.2Kg were randomly selected into three groups of three animals each. The first group (control) received 2 ml of sterile water per os throughout the period of the study. The second lead group received 5 mg/Kg body weight of lead dissolved in water per as for a period of fourteen days. The third lead group received 10 mg/Kg lead for the same period. The blood samples were taken prior to commencement of lead administration and every 72 hours to the end of the treatment to determine haematological parameters that include packed cell volume (PCV) and haemoglobin concentration while clinical parameters were also measured. Ovaries and uteri were harvested for histo-morphological examination at the end of the study. No significant changes were observed in clinical parameters and haemoglobin concentration between treatment groups compared to the control whereas, anaemia was observed with the 10 mg/Kg lead group. Follicles in the control was healthy morphologically as against atretic follicles observe with lead treated group. Endometrium of the control group showed normal morphology while thinning of the endometrial epithelium was observed with lead treated groups especially the 10 mg/Kg lead group. The reproductive implication of lead treatment in rabbit-doe is possible sub-fertility due to reduced ova at ovulation and thinning of the endometrial epithelium sequel to which is loss of implantation competence of the endometrium. Further studies with more sample size are suggested to validate the results obtained in this study and several mechanisms proposed.
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References
Acosta, M. R., K. H. Roux, S. S. Teuber, and S. K. Sathe. (1999) "Production and Characterization of Rabbit Polyclonal Antibodies to Almond (Prunus Dulcis L.) Major Storage Protein." J Agric Food Chem 47, no. 10: 4053-9.
Aplin, John D, Asgerally T Fazleabas, Stanley R Glasser, and Linda C Giudice. (2008) "(Eds) the Endometrium." Reproductive Medicine & Assisted Reproductive Techniques Series, no. 2nd Edition Informa healthcare UK Ltd.: pp 922.
Assi, M. A., M. N. Hezmee, Y. Abba, M. S. Yusof, A. W. Haron, M. A. Rajion, and M. A. Al-Zuhairy. (2016) "Prophylactic Effect of Nigella Sativa against Lead Acetate Induced Changes in Spermiogram, Reproductive Hormones and Gonadal Histology of Rats." Vet World 9, no. 11: 1305-11.
Baby, T. E., and P. M. Bartlewski. (2011) "Circulating Concentrations of Ovarian Steroids and Follicle-Stimulating Hormone (Fsh) in Ewes with 3 or 4 Waves of Antral Follicle Emergence Per Estrous Cycle." Reprod Biol 11, no. 1: 19-36.
Burger, J., and M. Gochfeld. (2000) "Effects of Lead on Birds (Laridae): A Review of Laboratory and Field Studies." J Toxicol Environ Health B Crit Rev 3, no. 2: 59-78.
el Feki, A., F. Ghorbel, M. Smaoui, F. Makni-Ayadi, and A. Kammoun. (2000) "[Effects of Automobile Lead on the General Growth and Sexual Activity of the Rat]." Gynecol Obstet Fertil 28, no. 1: 51-9.
Etim, NseAbasi N., Glory E. Enyenihi, Uduak Akpabio, Edem, A. Offiong. (2012) "Effects of Nutrition on Haematology of Rabbits: A Review." European Scientific Journal 10, no. 3: 413-24.
Feksa, L.R. , E. Oliveira, T. Trombini, M. Luchese, S. Bisi, R. Linden, DB. Berlese, DB. Rojas, RB. Andrade, PF. Schuck, LM. Lacerda, M. Wajner, CM. Wannmacher, and T. Emanuelli. (2012) "Pyruvate Kinase Activity and Aminolevulinic Aciddehydratase Activity as Biomarkers of Toxicity in Workersexposed to Lead." Arch. Environ. Contam. Toxicol. 63: 453-60.
Flora, G., D. Gupta, and A. Tiwari. (2012) "Toxicity of Lead: A Review with Recent Updates." Interdiscip Toxicol 5, no. 2: 47-58.
Franks, P. A., N. K. Laughlin, D. J. Dierschke, R. E. Bowman, and P. A. Meller. (1989) "Effects of Lead on Luteal Function in Rhesus Monkeys." Biol Reprod 41, no. 6: 1055-62.
Gandhi, J., R. J. Hernandez, A. Chen, N. L. Smith, Y. R. Sheynkin, G. Joshi, and S. A. Khan. (2017) "Impaired Hypothalamic-Pituitary-Testicular Axis Activity, Spermatogenesis, and Sperm Function Promote Infertility in Males with Lead Poisoning." Zygote 25, no. 2: 103-10.
Gorbel, F., M. Boujelbene, F. Makni-Ayadi, F. Guermazi, F. Croute, J. P. Soleilhavoup, and A. el Feki. (2002) "[Cytotoxic Effects of Lead on the Endocrine and Exocrine Sexual Function of Pubescent Male and Female Rats. Demonstration of Apoptotic Activity]." C R Biol 325, no. 9: 927-40.
Gwiazda, R., C. Campbell, and D. Smith. (2005) "A Noninvasive Isotopic Approach to Estimate the Bone Lead Contribution to Blood in Children: Implications for Assessing the Efficacy of Lead Abatement." Environ Health Perspect 113, no. 1: 104-10.
Heuser, A., L. Mecklenburg, D. Ockert, M. Kohler, and J. Kemkowski. (2013) "Selective Inhibition of Pde4 in Wistar Rats Can Lead to Dilatation in Testis, Efferent Ducts, and Epididymis and Subsequent Formation of Sperm Granulomas." Toxicol Pathol 41, no. 4: 615-27.
Kempe, D. S., P. A. Lang, K. Eisele, B. A. Klarl, T. Wieder, S. M. Huber, C. Duranton, and F. Lang. (2005) "Stimulation of Erythrocyte Phosphatidylserine Exposure by Lead Ions." Am J Physiol Cell Physiol 288, no. 2: C396-402.
Kimmel, C.A., L.D. Grant, Sloan C.S., and Gladen B.C. ( 1980) "Chronic Low-Level Lead Toxicity in the Rat. I. Maternal Toxicity and Perinatal Effects." Toxicol. Appl. Pharmacol. 56: 28-41.
Lo, Y. C., C. A. Dooyema, A. Neri, J. Durant, T. Jefferies, A. Medina-Marino, L. de Ravello, D. Thoroughman, L. Davis, R. S. Dankoli, M. Y. Samson, L. M. Ibrahim, O. Okechukwu, N. T. Umar-Tsafe, A. H. Dama, and M. J. Brown. (2012) "Childhood Lead Poisoning Associated with Gold Ore Processing: A Village-Level Investigation-Zamfara State, Nigeria, October-November 2010." Environ Health Perspect 120, no. 10: 1450-5.
Mapara, M., B. S. Thomas, and K. M. Bhat. (2012) "Rabbit as an Animal Model for Experimental Research." Dent Res J (Isfahan) 9, no. 1: 111-8.
Nakade, U. P., S. K. Garg, A. Sharma, S. Choudhury, R. S. Yadav, K. Gupta, and N. Sood. (2015) "Lead-Induced Adverse Effects on the Reproductive System of Rats with Particular Reference to Histopathological Changes in Uterus." Indian J Pharmacol 47, no. 1: 22-6.
Noakes, D. E., T. J. Parkinson, and G. C. England. Veterinary Reproduction and Obstetrics. 9th ed. China: Elsevier, 2009.
NRC, National Research Council. Lead in Perspective. . Washington, D.C.: National Academy Press, , 1972.
Odenbro, A., Kihlström, J.E. . (1977) "Frequency of Pregnancy and Ova Implantation in Triethyl Lead-Treated Mice." Toxicol Appl Pharmacol. 39: 359-63.
Omobowale, T. O., A. A. Oyagbemi, A. S. Akinrinde, A. B. Saba, O. T. Daramola, B. S. Ogunpolu, and J. O. Olopade. (2014) "Failure of Recovery from Lead Induced Hepatoxicity and Disruption of Erythrocyte Antioxidant Defence System in Wistar Rats." Environ Toxicol Pharmacol 37, no. 3: 1202-11.
Pearce, A. I., R. G. Richards, S. Milz, E. Schneider, and S. G. Pearce. (2007) "Animal Models for Implant Biomaterial Research in Bone: A Review." Eur Cell Mater 13: 1-10.
Qureshi, N. , and R. Sharma. (2012 ) "Lead Toxicity and Infertility in Female Swiss Mice: A Review." J Chem Biol Physi Sci. 2: 1849-61.
Raheem, A. K. (2013)"Steroids Regulation of Hyaluronan During Oestrous Cycle and Implantation in Sheep Endometrium." The Royal Veterinary College, University of London.
Raheem, K. A., W. F. A. Marei, B. K. Campbell, and A. A. Fouladi-Nashta. (2016) "In Vivo and in Vitro Studies of Muc1 Regulation in Sheep Endometrium." Theriogenology 85, no. 9: 1635-43.
Ronis, M. J., T. M. Badger, S. J. Shema, P. K. Roberson, and F. Shaikh. (1998) "Effects on Pubertal Growth and Reproduction in Rats Exposed to Lead Perinatally or Continuously Throughout Development." J Toxicol Environ Health A 53, no. 4: 327-41.
Scaramuzzi, R. J., D. T. Baird, B. K. Campbell, M. A. Driancourt, J. Dupont, J. E. Fortune, R. B. Gilchrist, G. B. Martin, K. P. McNatty, A. S. McNeilly, P. Monget, D. Monniaux, C. Vinoles, and R. Webb. (2011) "Regulation of Folliculogenesis and the Determination of Ovulation Rate in Ruminants." Reprod Fertil Dev 23, no. 3: 444-67.
Sharma, R., Garu, U., Panwar, K. . (2012 ) "Developing Gonads and Lead Exposure. ." World J Environ Biosci. 1: 30-7.
Sharpe, R. T., and C. T. Livesey. (2006) "Lead Poisoning in Cattle and Its Implications for Food Safety." Vet Rec 159, no. 3: 71-4.
Siddiqui, M.F.M, and Gayatri R Rajurkar. (2008) "Lead - an Emerging Threat to Livestock." Veterinary World 1, no. 17: 213-16.
Simons, T. J. (1993) "Lead Transport and Binding by Human Erythrocytes in Vitro." Pflugers Arch 423, no. 3-4: 307-13.
Spencer, Thomas E., Allison G. Stagg, Margaret M. Joyce, Guido Jenster, Christopher G. Wood, Fuller W. Bazer, Anne A. Wiley, and Frank F. Bartol. (1999) "Discovery and Characterization of Endometrial Epithelial Messenger Ribonucleic Acids Using the Ovine Uterine Gland Knockout Model." Endocrinology 140, no. 9: 4070-80.
Sudjarwo, S. A., K. Eraiko, G. W. Sudjarwo, and Koerniasari. (2017) "Protective Effects of Piperine on Lead Acetate Induced-Nephrotoxicity in Rats." Iran J Basic Med Sci 20, no. 11: 1227-31.
Taupeau, C., J. Poupon, F. Nome, and B. Lefevre. (2001) "Lead Accumulation in the Mouse Ovary after Treatment-Induced Follicular Atresia." Reprod Toxicol 15, no. 4: 385-91.
Tchernitchin, A. N., L. Gaete, R. Bustamante, and A. Baez. (2011) "Effect of Prenatal Exposure to Lead on Estrogen Action in the Prepubertal Rat Uterus." ISRN Obstet Gynecol 2011: 329692.
Tchernitchin, N. N., A. Clavero, M. A. Mena, C. Unda, R. Villagra, M. Cumsille, and A. N. Tchernitchin. (2003) "Effect of Chronic Exposure to Lead on Estrogen Action in the Prepubertal Rat Uterus." Environ Toxicol 18, no. 4: 268-77.
Ukaejiofo, E. O., N. Thomas, and S. O. Ike. (2009) "Haematological Assessment of Occupational Exposure to Lead Handlers in Enugu Urban, Enugu State, Nigeria." Niger J Clin Pract 12, no. 1: 58-64.
Vermande-Van Eck, G. J., and J. W. Meigs. (1960) "Changes in the Ovary of the Rhesus Monkey after Chronic Lead Intoxication." Fertil Steril 11: 223-34.
Waldner, C., S. Checkley, B. Blakley, C. Pollock, and B. Mitchell. (2002) "Managing Lead Exposure and Toxicity in Cow-Calf Herds to Minimize the Potential for Food Residues." J Vet Diagn Invest 14, no. 6: 481-6.
WHO. "Exposure to Lead: A Major Public Health Concern." 1-6. World Health Organisation, Geneva, Switzerland. https://www.who.int/ipcs/features/lead..pdf?ua=1: World Health Organisation, Geneva, Switzerland, 2010.
WHO. " Global Health Risks: Mortality and Burden of Disease Attributable to Selected Major Risks. (Http://Www.Who.Int/Healthinfo/Global_Burden_Disease/Globalhealthrisks_Report_Full.Pdf).". Geneva: World Health Organization 2009.
Wong, E.P., and C.Y. Cheng. (2011) "Impacts of Environmental Toxicants on Male Reproductive Dysfunction. ." Trends Pharmacol Sci 32 no. 32: 290-9.
Aplin, John D, Asgerally T Fazleabas, Stanley R Glasser, and Linda C Giudice. (2008) "(Eds) the Endometrium." Reproductive Medicine & Assisted Reproductive Techniques Series, no. 2nd Edition Informa healthcare UK Ltd.: pp 922.
Assi, M. A., M. N. Hezmee, Y. Abba, M. S. Yusof, A. W. Haron, M. A. Rajion, and M. A. Al-Zuhairy. (2016) "Prophylactic Effect of Nigella Sativa against Lead Acetate Induced Changes in Spermiogram, Reproductive Hormones and Gonadal Histology of Rats." Vet World 9, no. 11: 1305-11.
Baby, T. E., and P. M. Bartlewski. (2011) "Circulating Concentrations of Ovarian Steroids and Follicle-Stimulating Hormone (Fsh) in Ewes with 3 or 4 Waves of Antral Follicle Emergence Per Estrous Cycle." Reprod Biol 11, no. 1: 19-36.
Burger, J., and M. Gochfeld. (2000) "Effects of Lead on Birds (Laridae): A Review of Laboratory and Field Studies." J Toxicol Environ Health B Crit Rev 3, no. 2: 59-78.
el Feki, A., F. Ghorbel, M. Smaoui, F. Makni-Ayadi, and A. Kammoun. (2000) "[Effects of Automobile Lead on the General Growth and Sexual Activity of the Rat]." Gynecol Obstet Fertil 28, no. 1: 51-9.
Etim, NseAbasi N., Glory E. Enyenihi, Uduak Akpabio, Edem, A. Offiong. (2012) "Effects of Nutrition on Haematology of Rabbits: A Review." European Scientific Journal 10, no. 3: 413-24.
Feksa, L.R. , E. Oliveira, T. Trombini, M. Luchese, S. Bisi, R. Linden, DB. Berlese, DB. Rojas, RB. Andrade, PF. Schuck, LM. Lacerda, M. Wajner, CM. Wannmacher, and T. Emanuelli. (2012) "Pyruvate Kinase Activity and Aminolevulinic Aciddehydratase Activity as Biomarkers of Toxicity in Workersexposed to Lead." Arch. Environ. Contam. Toxicol. 63: 453-60.
Flora, G., D. Gupta, and A. Tiwari. (2012) "Toxicity of Lead: A Review with Recent Updates." Interdiscip Toxicol 5, no. 2: 47-58.
Franks, P. A., N. K. Laughlin, D. J. Dierschke, R. E. Bowman, and P. A. Meller. (1989) "Effects of Lead on Luteal Function in Rhesus Monkeys." Biol Reprod 41, no. 6: 1055-62.
Gandhi, J., R. J. Hernandez, A. Chen, N. L. Smith, Y. R. Sheynkin, G. Joshi, and S. A. Khan. (2017) "Impaired Hypothalamic-Pituitary-Testicular Axis Activity, Spermatogenesis, and Sperm Function Promote Infertility in Males with Lead Poisoning." Zygote 25, no. 2: 103-10.
Gorbel, F., M. Boujelbene, F. Makni-Ayadi, F. Guermazi, F. Croute, J. P. Soleilhavoup, and A. el Feki. (2002) "[Cytotoxic Effects of Lead on the Endocrine and Exocrine Sexual Function of Pubescent Male and Female Rats. Demonstration of Apoptotic Activity]." C R Biol 325, no. 9: 927-40.
Gwiazda, R., C. Campbell, and D. Smith. (2005) "A Noninvasive Isotopic Approach to Estimate the Bone Lead Contribution to Blood in Children: Implications for Assessing the Efficacy of Lead Abatement." Environ Health Perspect 113, no. 1: 104-10.
Heuser, A., L. Mecklenburg, D. Ockert, M. Kohler, and J. Kemkowski. (2013) "Selective Inhibition of Pde4 in Wistar Rats Can Lead to Dilatation in Testis, Efferent Ducts, and Epididymis and Subsequent Formation of Sperm Granulomas." Toxicol Pathol 41, no. 4: 615-27.
Kempe, D. S., P. A. Lang, K. Eisele, B. A. Klarl, T. Wieder, S. M. Huber, C. Duranton, and F. Lang. (2005) "Stimulation of Erythrocyte Phosphatidylserine Exposure by Lead Ions." Am J Physiol Cell Physiol 288, no. 2: C396-402.
Kimmel, C.A., L.D. Grant, Sloan C.S., and Gladen B.C. ( 1980) "Chronic Low-Level Lead Toxicity in the Rat. I. Maternal Toxicity and Perinatal Effects." Toxicol. Appl. Pharmacol. 56: 28-41.
Lo, Y. C., C. A. Dooyema, A. Neri, J. Durant, T. Jefferies, A. Medina-Marino, L. de Ravello, D. Thoroughman, L. Davis, R. S. Dankoli, M. Y. Samson, L. M. Ibrahim, O. Okechukwu, N. T. Umar-Tsafe, A. H. Dama, and M. J. Brown. (2012) "Childhood Lead Poisoning Associated with Gold Ore Processing: A Village-Level Investigation-Zamfara State, Nigeria, October-November 2010." Environ Health Perspect 120, no. 10: 1450-5.
Mapara, M., B. S. Thomas, and K. M. Bhat. (2012) "Rabbit as an Animal Model for Experimental Research." Dent Res J (Isfahan) 9, no. 1: 111-8.
Nakade, U. P., S. K. Garg, A. Sharma, S. Choudhury, R. S. Yadav, K. Gupta, and N. Sood. (2015) "Lead-Induced Adverse Effects on the Reproductive System of Rats with Particular Reference to Histopathological Changes in Uterus." Indian J Pharmacol 47, no. 1: 22-6.
Noakes, D. E., T. J. Parkinson, and G. C. England. Veterinary Reproduction and Obstetrics. 9th ed. China: Elsevier, 2009.
NRC, National Research Council. Lead in Perspective. . Washington, D.C.: National Academy Press, , 1972.
Odenbro, A., Kihlström, J.E. . (1977) "Frequency of Pregnancy and Ova Implantation in Triethyl Lead-Treated Mice." Toxicol Appl Pharmacol. 39: 359-63.
Omobowale, T. O., A. A. Oyagbemi, A. S. Akinrinde, A. B. Saba, O. T. Daramola, B. S. Ogunpolu, and J. O. Olopade. (2014) "Failure of Recovery from Lead Induced Hepatoxicity and Disruption of Erythrocyte Antioxidant Defence System in Wistar Rats." Environ Toxicol Pharmacol 37, no. 3: 1202-11.
Pearce, A. I., R. G. Richards, S. Milz, E. Schneider, and S. G. Pearce. (2007) "Animal Models for Implant Biomaterial Research in Bone: A Review." Eur Cell Mater 13: 1-10.
Qureshi, N. , and R. Sharma. (2012 ) "Lead Toxicity and Infertility in Female Swiss Mice: A Review." J Chem Biol Physi Sci. 2: 1849-61.
Raheem, A. K. (2013)"Steroids Regulation of Hyaluronan During Oestrous Cycle and Implantation in Sheep Endometrium." The Royal Veterinary College, University of London.
Raheem, K. A., W. F. A. Marei, B. K. Campbell, and A. A. Fouladi-Nashta. (2016) "In Vivo and in Vitro Studies of Muc1 Regulation in Sheep Endometrium." Theriogenology 85, no. 9: 1635-43.
Ronis, M. J., T. M. Badger, S. J. Shema, P. K. Roberson, and F. Shaikh. (1998) "Effects on Pubertal Growth and Reproduction in Rats Exposed to Lead Perinatally or Continuously Throughout Development." J Toxicol Environ Health A 53, no. 4: 327-41.
Scaramuzzi, R. J., D. T. Baird, B. K. Campbell, M. A. Driancourt, J. Dupont, J. E. Fortune, R. B. Gilchrist, G. B. Martin, K. P. McNatty, A. S. McNeilly, P. Monget, D. Monniaux, C. Vinoles, and R. Webb. (2011) "Regulation of Folliculogenesis and the Determination of Ovulation Rate in Ruminants." Reprod Fertil Dev 23, no. 3: 444-67.
Sharma, R., Garu, U., Panwar, K. . (2012 ) "Developing Gonads and Lead Exposure. ." World J Environ Biosci. 1: 30-7.
Sharpe, R. T., and C. T. Livesey. (2006) "Lead Poisoning in Cattle and Its Implications for Food Safety." Vet Rec 159, no. 3: 71-4.
Siddiqui, M.F.M, and Gayatri R Rajurkar. (2008) "Lead - an Emerging Threat to Livestock." Veterinary World 1, no. 17: 213-16.
Simons, T. J. (1993) "Lead Transport and Binding by Human Erythrocytes in Vitro." Pflugers Arch 423, no. 3-4: 307-13.
Spencer, Thomas E., Allison G. Stagg, Margaret M. Joyce, Guido Jenster, Christopher G. Wood, Fuller W. Bazer, Anne A. Wiley, and Frank F. Bartol. (1999) "Discovery and Characterization of Endometrial Epithelial Messenger Ribonucleic Acids Using the Ovine Uterine Gland Knockout Model." Endocrinology 140, no. 9: 4070-80.
Sudjarwo, S. A., K. Eraiko, G. W. Sudjarwo, and Koerniasari. (2017) "Protective Effects of Piperine on Lead Acetate Induced-Nephrotoxicity in Rats." Iran J Basic Med Sci 20, no. 11: 1227-31.
Taupeau, C., J. Poupon, F. Nome, and B. Lefevre. (2001) "Lead Accumulation in the Mouse Ovary after Treatment-Induced Follicular Atresia." Reprod Toxicol 15, no. 4: 385-91.
Tchernitchin, A. N., L. Gaete, R. Bustamante, and A. Baez. (2011) "Effect of Prenatal Exposure to Lead on Estrogen Action in the Prepubertal Rat Uterus." ISRN Obstet Gynecol 2011: 329692.
Tchernitchin, N. N., A. Clavero, M. A. Mena, C. Unda, R. Villagra, M. Cumsille, and A. N. Tchernitchin. (2003) "Effect of Chronic Exposure to Lead on Estrogen Action in the Prepubertal Rat Uterus." Environ Toxicol 18, no. 4: 268-77.
Ukaejiofo, E. O., N. Thomas, and S. O. Ike. (2009) "Haematological Assessment of Occupational Exposure to Lead Handlers in Enugu Urban, Enugu State, Nigeria." Niger J Clin Pract 12, no. 1: 58-64.
Vermande-Van Eck, G. J., and J. W. Meigs. (1960) "Changes in the Ovary of the Rhesus Monkey after Chronic Lead Intoxication." Fertil Steril 11: 223-34.
Waldner, C., S. Checkley, B. Blakley, C. Pollock, and B. Mitchell. (2002) "Managing Lead Exposure and Toxicity in Cow-Calf Herds to Minimize the Potential for Food Residues." J Vet Diagn Invest 14, no. 6: 481-6.
WHO. "Exposure to Lead: A Major Public Health Concern." 1-6. World Health Organisation, Geneva, Switzerland. https://www.who.int/ipcs/features/lead..pdf?ua=1: World Health Organisation, Geneva, Switzerland, 2010.
WHO. " Global Health Risks: Mortality and Burden of Disease Attributable to Selected Major Risks. (Http://Www.Who.Int/Healthinfo/Global_Burden_Disease/Globalhealthrisks_Report_Full.Pdf).". Geneva: World Health Organization 2009.
Wong, E.P., and C.Y. Cheng. (2011) "Impacts of Environmental Toxicants on Male Reproductive Dysfunction. ." Trends Pharmacol Sci 32 no. 32: 290-9.