Academic journal article Environmental Health Perspectives

Dioxin Exposure, from Infancy through Puberty, Produces Endocrine Disruption and Affects Human Semen Quality

Academic journal article Environmental Health Perspectives

Dioxin Exposure, from Infancy through Puberty, Produces Endocrine Disruption and Affects Human Semen Quality

Article excerpt

BACKGROUND: Environmental toxicants are allegedly involved in decreasing semen quality in recent decades; however, definitive proof is not yet available. In 1976 an accident exposed residents in Seveso, Italy, to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

OBJECTIVE: The purpose of this study was to investigate reproductive hormones and sperm quality in exposed males.

METHODS: We studied 135 males exposed to TCDD at three age groups, infancy/prepuberty (1-9 years), puberty (10-17 years), and adulthood (18-26 years), and 184 healthy male comparisons using 1976 serum TCDD levels and semen quality and reproductive hormones from samples collected 22 years later.

RESULTS: Relative to comparisons, 71 men (mean age at exposure, 6.2 years; median serum TCDD, 210 ppt) at 22-31 years of age showed reductions in sperm concentration (53.6 vs. 72.5 million/mL; p = 0.025); percent progressive motility (33.2% vs. 40.8%; p < 0.001); total motile sperm count (44.2 vs. 77.5 x [10 sup.6]; p = 0.018); estradiol (76.2 vs. 95.9 pmol/L; p = 0.001); and an increase in follicle-stimulating hormone (FSH; 3.58 vs. 2.98 IU/L; p = 0.055). Forty-four men (mean age at exposure, 13.2 years; median serum TCDD, 164 ppt) at 32-39 years of age showed increased total sperm count (272 vs. 191.9 x [10.sup.6]; p = 0.042), total motile sperm count (105 vs. 64.9 x [10.sup.6]; p = 0.036), FSH (4.1 vs. 3.2 UI/L; p = 0.038), and reduced estradiol (74.4 vs. 92.9 pmol/L; p < 0.001). No effects were observed in 20 men, 40-47 years of age, who were exposed to TCDD (median, 123 ppt) as adults (mean age at exposure, 21.5 years).

CONCLUSIONS: Exposure to TCDD in infancy reduces sperm concentration and motility, and an opposite effect is seen with exposure during puberty. Exposure in either period leads to permanent reduction of estradiol and increased FSH. These effects are permanent and occur at TCDD concentrations < 68 ppt, which is within one order of magnitude of those in the industrialized world in the 1970s and 1980s and may be responsible at least in part for the reported decrease in sperm quality, especially in younger men.

KEY WORDS: dioxin, endocrine disruption, environmental contaminants, human sperm quality, reproductive hormones, TCDD. Environ Health Perspect 116:70-77 (2008). doi:10.1289/ehp.l0399 available via [Online 29 October 2007]


In the last 50 years a significant global decline in human sperm concentrations of about 1% per year (Auger et al. 1995; Carlsen et al. 1992; Menchini-Fabris et al. 1996; Sharpe and Skakkebaek 1993; Swan et al. 2000) has been reported in Western countries, although with regional differences (Jorgensen et al. 2001; Swan et al. 2003). Furthermore, the youngest generations within a single country have been found to have lower sperm counts (Andersen et al. 2000; Auger et al. 1995; Van Waeleghem et al. 1996).

These phenomena may be related to increasing exposures to estrogenic, or antiandrogenic chemicals during critical phases of testicular development (Damstra et al. 2002; Sharpe 2001; Sharpe and Skakkebaek 1993). Exposures to polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated biphenyls (PCBs), and polychlorinated dibenzofurans (PCDFs), which are products and by-products of industrial or combustion processes, have the potential to disrupt multiple endocrine pathways and induce toxic responses. For example, experimental animal data have shown adverse effects in testicular function, including reduced sperm counts and motility, after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Faqi et al. 1998; Mably et al. 1992; Roman and Peterson 1998).

The prenatal and perinatal periods are particularly sensitive, and indeed, higher exposure doses are required to produce similar effects in adult animals (Damstra et al. 2002; Roman and Peterson 1998; Theobald et al. 2003). No definitive data are available for men, but Guo et al. …

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