- Full (HTML) - Full (PDF) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

Paolo Mocarelli,^1,2 Pier Mario Gerthoux,¹ Donald G. Patterson Jr.,³ Silvano Milani,⁴ Giuseppe Limonta,¹ Maria Bertona,¹ Stefano Signorini,¹ Pierluigi Tramacere,¹ Laura Colombo,¹ Carla Crespi,¹ Paolo Brambilla,¹ Cecilia Sarto,¹ Vittorio Carreri,⁵ Eric J. Sampson,³ Wayman E. Turner,³ and Larry L. Needham³

¹University Department of Laboratory Medicine, Hospital of Desio, Milano, Italy; ²School of Medicine, University Milano-Bicocca, Milano, Italy; ³National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ⁴Institute of Medical Statistics and Biometrics, University of Milano, Milano, Italy; ⁵Department for Preventive Medicine, Ministry of Health of Regione Lombardia, Milano, Italy

Abstract
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 10⁶ ; 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 10⁶ ; p = 0.042) , total motile sperm count (105 vs. 64.9 x 10⁶ ; 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.10399 available via http://dx.doi.org/ [Online 29 October 2007]

Address correspondence to P. Mocarelli, University Department of Laboratory Medicine, Hospital of Desio, Via Mazzini 1, 20033 Desio, Milano, Italy. Telephone: 39 0362 383296. Fax: 39 0362 383464. E-mail: mocarelli@uds.unimib.it

We are indebted to all the people of the Seveso area for their civic example of courage and responsibility in a dramatic situation and for their great cooperation in permitting this sensitive study. We thank E. Acmet, L. Basso, and M. Solaro (University Department of Laboratory Medicine, Hospital of Desio) for special assistance, and all the staff of our laboratories. We also thank J. Auger (Hospital Cochin, Paris, France) for his training on classification of sperm morphology.

This study was supported by grant 2896 from Regione Lombardia, Milano, Italy, and by the Centers for Disease Control and Prevention.

The authors declare they have no competing financial interests.

Received 24 April 2007 ; accepted 29 October 2007.