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EDITORIAL: High Prevalence of Male infertility in Africa: Are Mycotoxins to Blame?

Ukpai Agwu Eze, Friday E Okonofua


There is an increase in reports indicating a continuous decline in human fertility in both developed and developing countries1. The infertility prevalence varies between developing and developed countries. For instance, in the United States of America it is estimated to be 6%2 whereas it is 10-15% in United Kingdom3. In Africa, infertility prevalence rates are higher and range from 20-35%4-7. The “infertility belt”, geographical regions with high infertility prevalence, is well-known to Africa, stretching from West Africa, through Central to East Africa7.
Several reports have shown deterioration of male sperm quality worldwide. Carlsen et al.8 carried out a meta-analysis of 61 studies published between 1938 and 1991 involving semen quality of 14,947 men with no history of infertility and showed that the sperm concentration of fertile males have dropped from a mean concentration of 133 million/mL in 1940 to 66 million/mL in 1990, indicating an average yearly decrease of 1%,. Sperm morphology/motility abnormalities were also significantly increased. In addition, this report showed that sperm count declined to a mean of 71.2 million/ml in Ibadan, Nigeria, 54.6 million/ml in Lagos, Nigeria, 65.0 million/ml in Salem, Libya, 66.9 million/ml in Dar Es salaam, Tanzania and 57.4 million/ml in Copenhagen, Denmark. Swan and colleagues re-evaluated Carson’s publication and confirmed that sperm concentrations in fertile males have gradually declined overtime globally9. Also, in 2000, Swan and colleagues10 conducted another analysis based on 101 papers published between 1934-1996, involving only English-language studies and concluded that the decline in sperm quality of fertile men were as previously reported. This continuous decline in human fertility worldwide has been attributed to many factors including activities of endocrine-disrupting chemicals (EDCs) such as mycotoxins and pesticides11-14. Recent reports indicate that EDCs may affect the development and functioning of the reproductive system in both sexes, particularly in fetuses, causing developmental and reproductive disorders, including infertility.
Mycotoxins are pharmacologically active secondary metabolites produced by fungal species, particularly Aspergillus, Fusarium and Penicillium species, which elicit some complicated toxicological effects in man and animals. More than 400 of these secondary metabolites have been identified. However, the mycotoxins of major public health concern are aflatoxins (e.g. AFB1), ochratoxin A (OTA), deoxynivalenol (DON), zearalenone (ZEN) and fumonisins (e.g. FB1) because of their prevalence in agricultural produce and their adverse health effects in animals and humans15. Mycotoxin contamination of food is a global health problem as it is estimated that more than 25% of world agricultural produce are contaminated by mycotoxins16. Due to the more conducive climatic and environmental conditions for fungal growth in developing countries, mycotoxins contamination and exposure is more common than in developed countries17. In addition, the occurrence of mycotoxins is regulated by legal limits in developed countries; however, there is little or no regulation/legislation in place for monitoring mycotoxin contamination of agricultural products and foodstuffs in most developing countries which results to higher exposure in these regions.
Studies show that mycotoxins are common contaminants of staple foods in Nigeria, including garri, beans, yam flour, cassava flour, melon, rice, plantain, red pepper, onion, maize, groundnuts, guinea corn, sorghum, and millets18. Human exposure can be either through the consumption of contaminated agricultural products, or the consumption of contaminated animal products containing residual amounts of the mycotoxin ingested by the food producing animals19. Chronic exposure of a large proportion of African population to mycotoxins is a serious problem and in utero exposure is a common phenomenon20. Apart from contaminating agricultural products, human exposures to mycotoxins have also been reported using exposure biomarkers. High levels of single or multiple mycotoxin biomarkers have been reported in several population studies which show that humans are often simultaneously exposed to mixtures of mycotoxins21. Multi-mycotoxins exposures have also been reported in South Africa22, Cameroun23 and Nigeria24. Multiple exposures to mycotoxins pose a significant threat to human health since combinationsof mycotoxins could be agonistic, additive or antagonistic in nature.
The well-known adverse health effects of mycotoxins in humans include liver cancer25, Balkan Endemic Nephropathy25, child growth impairment26, modification of immune function27, esophageal cancer28, neural tube defects29 and death in acute exposure30. In particular, there is growing evidence suggesting that mycotoxins may negatively influence human fertility.
Studies using animal and cellular models indicate that zearalenone (ZEN) and metabolites [α-zearalenol (α-ZOL), β- zearalenol (β-ZOL)], deoxynivalenol (DON), ochratoxin A (OTA) and aflatoxin B1 (AFB1) can adversely affect fertility, through damage to sex organs, gametes and disruption of steroidogenesis. For instance, studies using animal and cellular models have described that exposure to the aforementioned mycotoxins can promote adverse effects on spermatozoa, Sertoli and Leydig cell function, oocyte maturation, and uterine and ovarian development and function, both in vivo, ex-vivo and in vitro31-35. They may also induce oxidative stress resulting in sperm DNA damage36 and sperm DNA damage reduces fertilization rates and lowers embryo quality37. Furthermore, mycotoxins may act as endocrine disrupters, altering the steroid hormone homeostasis and interfering with receptor signaling38-44. It is well known that proper steroid hormones homeostasis and oocyte/sperm quality are the major determinants of reproductive function in both humans and animals and therefore, their impairment leads to subfertility/ infertility.
Interestingly, the impact of mycotoxins on reproductive function have also been reported in humans. In Benin City-Nigeria, Ibe and colleagues11 reported higher concentrations of aflatoxin B1 (AFB1) in the semen of infertile men compared to the semen of fertile controls and proposed that exposure to AFB1 could be a potential contributory factor to male infertility in Nigeria. In this study, 50% of infertile men with AFB1 in their semen had a greater percentage of abnormalities in sperm count, motility and morphology compared to the fertile men (10-15%). In male rats fed with AFB1 contaminated feeds (8.5 μg AFB1/g of feed) for 14 days, the observed effects on the sperm parameters were similar to those found in the sperm of infertile men exposed to AFB1. In another study, Uriah et al.12 conducted a case-control study involving 30 infertile and 25 fertile males. Detectable levels of AFB1 were found in the semen and blood of 37% of the infertile males with abnormal sperm profile and AFB1 levels in infertile males were significantly higher than the fertile males. The levels of AFB1 ranged from 700 to 1392 ng/ml, exceeding the World Health Organisation recommended level. Although these data indicate a possible link between AFB1 and male infertility, the use of valid aflatoxin exposure biomarkers (blood aflatoxin-albumin adduct; AF-alb or urinary aflatoxin M1) and properly designed epidemiological study would certainly provide stronger evidence for establishing a causal association. Mycotoxins as endocrine disrupters may also be involved in female reproductive disorders since other EDCs have been implicated in endometriosis, premature ovarian failure (POF) and polycystic ovary syndrome (PCOS)45. In a study in Puerto-Rico, zearalenone (ZEN) was associated with precocious puberty in girls13 correlating with significantly high estrogen levels (25 pg/mL).
From the above data, it is plausible that mycotoxins might produce some adverse reproductive health effects in exposed individuals, and might be implicated in the declining fertility rate, especially in Africa. This constitutes a serious public health threat that should not be overlooked. Therefore, this growing body of evidence should increase public awareness of the serious implications of mycotoxin exposures in human fertility and should warrant a greater study of reproductive impacts of these mycotoxins through in vitro and in vivo bioassays and human epidemiological studies.

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Mascarenhas MN, Flaxman SR, Boerma T, Vanderpoel S, Stevens GA. (2012). National, Regional, and Global Trends in Infertility Prevalence since 1990: A Systematic Analysis of 277 Health Surveys. PLoS Medicine. 9(12): e1001356.

Chandra A, Copen CE, Stephen EH. (2013). Infertility and Impaired Fecundity in the United States, 1982–2010: Data from the National Survey of Family Growth. National Health Statistics Reports no 67. National Center for Health Statistics: Hyattsville, MD.

Oakley L, Doyle P, Maconochie N. (2008). Lifetime prevalence of infertility and infertility treatment in the UK: results from a population-based survey of reproduction. Human Reproduction.23(2): 447–450.

Adetoro OO, Ebomoyi EW. The prevalence of infertility in a rural Nigerian community. African Journal of Medicine and Medical Sciences. 1991; 20:23-27.

Okonofua FE, Harris D, Odebiyi A, Thomas K, Snow RC. (1997). The social meaning of infertility in Southwest Nigeria. Health Transition Review.7:205–220.

Larsen U. (2000). Primary and secondary infertility in sub-Saharan Africa. International Journal of Epidemiology. 29: 285-291.

Etuk SJ. (2009). Reproductive health: Global infertility trend. Nigerian Journal of Physiological Sciences.24(2):85-90.

Carlsen E., Giwercman, A., Keiging, N. And Skakkebaek, N. (1992) Evidence for decreasing quality of decreasing quality of semen during past 50 years. British Medical Journal. 305: 609 613.

Swan SH, Elkin EP, Fenster L. (1997). Have sperm densities declined? A re-analysis of global trend data. Environmental Health Perspectives. 105:1228-1232.

Swan SH, Elkin EP, Fenster L. (2000). The question of declining sperm density revisited: An analysis of 101 studies published. Environmental Health Perspectives. 108: 961-966.

Ibeh IN, Uriah N, Ogonor JI. (1994). Dietary exposure to aflatoxin in human male fertility in Benin City, Nigeria. International Journal of Fertility. 39(4): 208-214.

Uriah N, Ibeh NI, Oluwafemi F. (2001). A study on the impact of aflatoxins on human reproduction. African Journal of Reproductive Health. 5(1), 106-110.

Massart F, Meucci V, Saggese G, Soldani G. (2008). High growth rate of girls with precocious puberty exposed to oestrogenic mycotoxins. Journal of Paediatrics. 152: 690-695.

Martenies SE, Perry MJ. (2013). Environmental and occupational pesticide exposure and human sperm parameters: A systematic review. Toxicology. 307: 66-73.

Richard JL. (2007). Some major mycotoxins and their mycotoxicoses- an overview. International Journal of Food Microbiology.119: 3-10.

CAST; Council for Agricultural Science and Technology. (2003). Mycotoxins, risks in plants, animal and human systems. Ames. IA.

Shephard, G. S. 2008. Impact of Mycotoxins on Human Health in Developing Countries. Food Additives and Contaminants, 25(2): 146-151.

Adejumo TO, Adejoro DO. (2014) Incidence of aflatoxins, fumonisins, trichothecenes and ochratoxins in Nigerian foods and possible intervention strategies. Food Science and Quality Management. 31: 127-146.

Bryden WL. (2007). Mycotoxins in the food chain: human health implications. Asia Pacific Journal of Clinical Nutrition. 16(1): 95-101.

Gong YY, Cardwell KF, Hounsa A, Egal S, Turner PC, Hall AJ, Wild CP. (2002). Dietary aflatoxin exposure and impaired growth in young children from Benin and Togo: cross sectional study. British Medical Journal. 325: 20-21.

Warth, B., Sulyok, M. and Krska, R. (2013). LC-MS based multibiomarker approaches for the assessment of human exposure to mycotoxins. Analytical and Bioanalytical Chemistry. 405: 5687-5695.

Shephard GS, Burger H-S, Gambacorta L, Gong YY, Krska R, Rheeder JP, Solfrizzo M, Srey C, Sulyok M, Visconti A, Warth B, van der Westhuizen L. (2013). Multiple mycotoxin exposure determined by urinary biomarkers in rural subsistence farmers in the former Transkei, South Africa. Food and Chemical Toxicology. 62: 217-225.

Ediage EM, Mavungu JDD, Song S, Sioen I, Saeger SD. (2013). Multimycotoxin analysis in urines to assess infant exposure: A case study in Cameroon. Environment International. 57-58: 50-59.

Ezekiel CN, Warth B, Ogara I., Abia WA, Ezekiel VC, Atehnkeng J, Sulyok M, Turner PC, Tayo GO, Krska R, Bandyopadyay R. (2014). Mycotoxin exposure in rural residents in Northern Nigeria: A pilot study using multi-urinary biomarkers. Environment International. 66: 138-145.

International Agency for Research on Cancer. (2002). IARC monographs on the evaluation of carcinogenic risks to humans, vol. 82. Lyon, International Agency for Research on Cancer.

Gong YY, Hounsa A, Egal S, Turner PC, Sutcliffe AE, Hall AJ, Cardwell K, Wild CP. (2004). Postweaning Exposure to Aflatoxin Results in Impaired Child Growth: A Longitudinal Study in Benin, West Africa. Environmental Health Perspectives. 112: 1334–1338.

Jiang YI, Jolly PE, Ellis WO, Wang JS, Phillips TD, Williams JH. (2005). Aflatoxin B1 albumin adduct levels and cellular immune status in Ghanaians. International Immunology. 17(6): 807-814.

Rheeder JP, Marasas WFO, Theil PG, Sydenham EW, Shephard GS, Van Schalkwyk DJ. (1992). Fusarium moniliforme and fumonisins in corn in relation to human oesophageal cancer in Transkei. Phytopathology. 82(3): 353-357.

Missmer SA, Suarez L, Felkner M, Wang E, Merrill Jr AH, Rothman K.J, Hendricks KA. (2006). Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border. Environmental Health Perspectives. 114(2): 237-241.

Probst C, Njapau H, Cotty PJ. (2007). Outbreak of an acute aflatoxicosis in Kenya in 2004: identification of the causal agent. Applied and Environmental Microbiology. 73(8): 2762-2764.

Sprando R, Collins T, Black T, Olejnik N, Rorie J, Eppley R, Ruggles D. (2005). Characterization of the effect of deoxynivalenol on selected male reproductive endpoints. Food and Chemical Toxicology.43:623–635.

Malekinejad H, Schoevers EJ, Daemen IJJM, Zijstra C, Colenbrander BM, Fine-Gremmels J, Roelen BAJ. (2007). Exposure to Fusarium toxins zearalenone and deoxynivalenol causes aneuploidy and abnormal embryo development in pigs. Biology of Reproduction. 77: 840-847.

Schoevers EJ, Fink-Gremmels J, Colenbrandera B, Roelen BAJ. (2010). Porcine oocytes are most vulnerable to the mycotoxin deoxynivalenol during formation of the meiotic spindle. Theriogenology. 74: 968–978.

Hou Y-J, Xiong B, Zheng W-J, Duan X., Cui X-S, Kim N-H, Wang Q, Xu Y-X, Seun S-C. (2014). Oocyte quality in mice is affected by a mycotoxin-contaminated diet. Environmental and Molecular Mutagenesis. 55: 354-362. DOI 10.1002/em.21833

Supriya C, Girish BP, Reddy PS. (2014) Aflatoxin# B1-induced reproductive toxicity in male rats: possible mechanism of action. International Journal of Toxicology. 33(3): 155-161.

Tsakmakidis IA, Lymberopoulos AG, Khalifa TAA, Boscos CM, Saratsi A, Alexopoulos C. (2008). Evaluation of zearalenone and α-zearalenol toxicity on boar sperm DNA integrity. Journal of Appied Toxicology. 28: 681–688.

Lewis SE, Aitken RJ. (2005). DNA damage to sperm has impacts on fertilisation and pregnancy. Cell and Tissue

Research. 322: 33-41.

Frizzell C, Ndossi D, Verhaegen S, Dahl E, Eriksen G, Sørlie, Ropstad E, Muller M, Elliott CT, Connolly L. (2011). Endocrine disrupting effects of zearalenone, alpha- and beta-zearalenol at the level of nuclear receptor binding and steroidogenesis. Toxicology Letters. 206: 210-217.

Storvik M, Huuskonen P, Kyllonen J, Lohtenen S, El Nezami H,Auriola S, Pasanen M. (2011). Aflatoxin B1-a potential endocrine disruptor-upregulate CYP19A1 in JEG-3 cells. Toxicology Letters. 202: 161-167.

Ndossi DG, Frizzell C, Tremoena NH, Fæsted CK, Verhaegena S, Dahla E, Eriksend GS, Sørlie M, Connolly L, Ropstada. E. (2012). An in vitro investigation of endocrine disrupting effects of trichothecenes deoxynivalenol (DON), T-2 and HT-2 toxins. Toxicology Letters. 214: 268– 278.

Huuskonen P, Myllynenm P, Storvik M, Pasanen M. (2013). The effects of aflatoxin B1 on transporters and steroid metabolizing enzymes in JEG-3 cells. Toxicology Letters. 218: 200-206.

Frizzell C, Verhaegen S, Ropstad E, Elliott CT, Connolly L. (2013). Endocrine disrupting effects of Ochratoxin A at the level of nuclear receptor binding and

steroidogenesis. Toxicology Letters. 217: 243-250.

Woo CSJ, Wan MLY, Ahokas J, El-Nezamia H. (2013). Potential Endocrine Disrupting Effect of Ochratoxin A on Human Placental 3β-Hydroxysteroid Dehydrogenase/Isomerase in JEG-3 Cells at Levels Relevant to Human Exposure. Reproductive Toxicology. 38: 47- 52.

Adedara IA, Nanjappa MK, Faromi EO, Akingbemi BT. (2014) Aflatoxin B1 disrupts the androgen biopathway in rat Leydig cells. Food and Chemical Toxicology. 65 :252-259.

Caserta D, Mantovani A, Marci R, Fazi A, Ciardo F, La Rocca C, Maranghi F, Moscarini M. (2011). Environment and women’s reproductive health. Human Reproduction Update. 17: 418–433.


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