Table of Contents  
Year : 2014  |  Volume : 16  |  Issue : 1  |  Page : 3-4

Environmental xenobiotics and male reproductive health

1 Department of Occupational and Environmental Medicine, Frederiksberg and Bispebjerg Hospital, University of Copenhagen, Denmark
2 Reproductive Medicine Centre, Skåne University Hospital, Malmö, Sweden

Date of Web Publication16-Dec-2013

Correspondence Address:
Jens Peter Bonde
Department of Occupational and Environmental Medicine, Frederiksberg and Bispebjerg Hospital, University of Copenhagen
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1008-682X.122191

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How to cite this article:
Bonde JP, Giwercman A. Environmental xenobiotics and male reproductive health. Asian J Androl 2014;16:3-4

How to cite this URL:
Bonde JP, Giwercman A. Environmental xenobiotics and male reproductive health. Asian J Androl [serial online] 2014 [cited 2022 Aug 16];16:3-4. Available from:

Guest editors for this special issue: Prof. Jens Peter Bonde and Prof. Aleksander Giwercman

Lessons from the occupational arena demonstrate the potential of industrial chemicals to damage human testicular function. An important but still unresolved question is whether low-level xenobiotic exposure of the general population poses a hazard. In this volume of the Asian Journal of Andrology, this issue is addressed by a series of reviews on xenobiotic exposure profiles, possible biological mechanisms, research methods and knowledge on impact of specific exposures. Interdisciplinary research fields as gene-environment interaction and male-mediated developmental toxicity is also addressed. Papers are cross-linked by answers to questions mutually put forward by the authors.

Several undisputed lessons from the past demonstrate how xenobiotics in the environment may have profound impact on male reproductive health. The most known cases are from the occupational arena and following environmental disasters. More than 30 years ago it was almost concomitantly reported from the United States and from Israel that the nematocide dibromochloropropane (DBCP) causes severely reduced sperm counts and even sterility in workers manufacturing or applying this pesticide. [1],[2] Since this discovery numerous occupational semen studies have provided considerable although less compelling evidence that some heavy metals, some halogenated organic solvents, some fungicides and other compounds are male reproductive toxicants. [3] Following the Seveso disaster in northern Italy in 1976, a remarkable increase in the proportion of girls was reported among offspring of heavily dioxin exposed men. [4] Thus, the overarching question is not whether environmental chemicals may represent a hazard to male reproductive health, but how important this hazard at exposure levels found in the general population is in comparison with other risk factors and causes.

Alarming reports from the 1880's and 1990's including the Danish 1992 report on a global major decline in sperm count [5] have fuelled speculations that the environmental impact may be substantial because only changing environmental factors can explain dramatic changes in health outcomes across short time period. With one notable exception, testicular cancer, there is, however, no scientific consensus that sperm counts and various testicular disorders have changed markedly over past 50 -0 100 years, [6],[7] and some researchers doubt that there ever will be provided valid data to corroborate or refute alleged changes in male reproductive health. [8] The only long-term prospective study of semen quality with repeated yearly examinations in Denmark do not indicate that changes of sperm count has taken place during past 15 years. [9] There is more reliable, but yet limited evidence indicating regional differences in sperm counts, [10],[11] but other comparative studies of semen quality have shown remarkable similar sperm count distributions in different regions including remote populations. [12],[13]

In this special issue of the Asian Journal of Andrology, the environmental xenobiotic impact on male reproductive health is highlighted through a series of invited papers by authors who have advanced knowledge in this field during past 20 -0 30 years. First thing to notice is the current strong evidence that not only workers in specific occupations, but the general population worldwide is exposed above natural background levels to hundreds of chemicals that have been released into the environment, in particular during the last half of the twentieth century. [14] Some of these chemicals are biopersistent and are eliminated at an extremely slow rate in spite of a total worldwide ban of production and use several years ago. There has been a great development in epidemiological and laboratory methods to perform observational studies in humans; in particular with respect to functional measures of fertility and laboratory refinements of studies of semen quality. [15],[16] We have also seen developments in understanding of the mechanisms by which environmental xenobiotics may impact on male reproductive function. Processes related to oxidative stress at the cellular level may be an important mechanism explaining loss of fertilizing capacity of spermatozoa. [17] But although it is well-established that some chemicals may produce oxidative stress in the male reproductive tract and in spermatozoa, it is still unknown whether exposures to occupational and environmental man-made chemicals are doing harm through such mechanisms. Tobacco smoking is a very strong inducer of oxidative stress in the organism and effects on sperm structure and function may be mediated thorough this mechanism in the adult as well as the fetal male gonad. [18],[19]

Endocrine disruption is another mechanistic pathway that has received considerable attention. It is beyond any doubt that sexual hormones are playing a profound role for proper development and functioning of male reproductive capability. During past 20 years, it has become evident that numerous chemicals in our environment may interfere with endogenous hormone signaling or by themselves act as hormones by interference with steroid hormone receptors. Therefore, it seems reasonable to speculate that disruption of endocrine pathways is an important mechanism by which xenobiotics can interfere with male reproductive function, in vitro and animal studies being of great importance for clarifying the mechanistic aspects of such effects. [20],[21] There is evidence that high occupational exposure and extreme environmental exposure to the antiandrogenic dichlorodiphenyltrichloroethane metabolite dichlorodiphenyldichloroethylene reduces sperm counts in adult males. However, the evidence on adverse effects of low-level exposure to biopersistent compounds as organochlorines and rapidly metabolized compounds as phthalates is conflicting. So far no clear picture of the magnitude of impact of these compounds in the general population (if any) has emerged. [22] Similarly, there is strong experimental evidence of developmental toxicity mediated through exposure of male gametes, [23] but still the importance of environmental xenobiotic exposure is very scarce, perhaps except the convincing data indicating increased risk of congenital malformations in offspring of male smokers. [23]

In any case, it is too early to conclude that concerns about major impact of male reproductive health from environmental chemicals has been exaggerated, because studies addressing risk related to early exposures in fetal life and childhood are still almost missing. This major research gap needs to be remedied and the development of large mother child cohort with biobanked blood specimens provides hope that this gap in knowledge will be filled in within a foreseeable future. Moreover, interdisciplinary research collaboration which enables large studies of gene-environment interactions may prove an important tool to distinguish random from genuine biological associations and for identifying subpopulations with increased sensitivity to the adverse effect of environmental chemicals. [24]

  References Top

1.Whorton MD, Krauss RM, Marshall S, Milby TH. Infertility in male pesticide workers. Lancet 1977; 2: 1259-61.  Back to cited text no. 1
2.Potashnik G, Ben-Aderet N, Israeli R, Yanai-Inbar I, Sober I. Suppressive effect of 1,2-dibromo-3-chloropropane on human spermatogenesis. Fertil Steril 1978; 30: 444-7.  Back to cited text no. 2
3.Bonde JP, Giwercman A. Occupational hazards to male fecundity. Reprod Med Rev 1995; 4: 59-73.  Back to cited text no. 3
4.Mocarelli P, Gerthoux PM, Ferrari E, Patterson DG Jr, Kieszak SM, et al. Paternal concentrations of dioxin and sex ratio of offspring. Lancet 2000; 355: 1858-63.  Back to cited text no. 4
5.Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ 1992; 305: 609-13.  Back to cited text no. 5
6.Wilcox AJ, Bonde JP. On environmental threats to male infertility. Asian J Androl 2013; 15: 199-200.  Back to cited text no. 6
7.Bonde JP, Ramlau-Hansen CH, Olsen J. Trends in sperm counts: the saga continues. Epidemiology 2011; 22: 617-9.  Back to cited text no. 7
8.Sallmen M, Weinberg CR, Baird DD, Lindbohm ML, Wilcox AJ. Has human fertility declined over time? Why we may never know. Epidemiology 2005; 16: 494-9.  Back to cited text no. 8
9.Jørgensen N, Joensen UN, Jensen TK, Jensen MB, Almstrup K, et al. Human semen quality in the new millennium: a prospective cross-sectional population-based study of 4867 men. BMJ Open 2012; 2.  Back to cited text no. 9
10.Jørgensen N, Andersen AG, Eustache F, Irvine DS, Suominen J, et al. Regional differences in semen quality in Europe. Hum Reprod 2001; 16: 1012-9.  Back to cited text no. 10
11.Jørgensen N, Carlsen E, Nermoen I, Punab M, Suominen J, et al. East-West gradient in semen quality in the Nordic-Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland. Hum Reprod 2002; 17: 2199-208.  Back to cited text no. 11
12.Bonde JP, Joffe M, Danscher G, Apostoli P, Bisanti L, et al. Objectives, designs and populations of the European Asclepios study on occupational hazards to male reproductive capability. Scand J Work Environ Health 1999; 25 Suppl 1: 49-61; discussion 76-8.   Back to cited text no. 12
13.Toft G, Axmon A, Giwercman A, Thulstrup AM, Rignell-Hydbom A, et al. INUENDO. Fertility in four regions spanning large contrasts in serum levels of widespread persistent organochlorines: a cross-sectional study. Environ Health 2005; 4: 26.  Back to cited text no. 13
14.Faniband M, Lindh CH, Jönsson BA. Human biological monitoring of suspected endocrine-disrupting compounds. Asian J Androl 2013; 16: 5-16.  Back to cited text no. 14
15.Olsen J, Ramlau-Hansen CH. Epidemiologic methods for investigating male fecundity. Asian J Androl 2013; 16: 17-22.  Back to cited text no. 15
16.Schrader SM, Marlow KL. Assessing the reproductive health of men with occupational exposures. Asian J Androl 2013; 16: 23-30.  Back to cited text no. 16
17.Aitken RJ, Smith TB, Jobling MS, Baker MA, De Iuliis GN. Oxidative stress and male reproductive health. Asian J Androl 2013; 16: 31-8.  Back to cited text no. 17
18.Vine MF. Smoking and male reproduction: a review. Int J Androl 1996; 19: 323-37.  Back to cited text no. 18
19.Håkonsen LB, Ernst A, Ramlau-Hansen CH. Maternal cigarette smoking during pregnancy and reproductive health in children: a review of epidemiological studies. Asian J Androl 2013; 16: 39-49.  Back to cited text no. 19
20.Svechnikov K, Stukenborg JB, SavchuckI, Söder O. Similar causes of various reproductive disorders in early life. Asian J Androl 2013: 50-9.  Back to cited text no. 20
21.Auger J, Eustache F, Rouiller-Fabre V, Canivenc MC, Gabriel L. Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances. Asian J Androl 2013: 60-70.  Back to cited text no. 21
22.Vested A, Giwercman A, Bonde JP, Toft G. Persistent organic pollutants and male reproductive health. Asian J Androl 2013: 71-80.  Back to cited text no. 22
23.Anderson D, Schmid TE, Baumgartner A. Male-mediated developmental toxicity. Asian J Androl 2013; 16: 81-8.  Back to cited text no. 23
24.Brokken LJ, Giwercman YL. Gene-environment interactions in male reproductive health: special reference to the aryl hydrocarbon receptor signalling pathway. Asian J Androl 2013; 16: 89-96.  Back to cited text no. 24

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