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Shanna H. Swan,¹ Robin L. Kruse,¹ Fan Liu,¹ Dana B. Barr,² Erma Z. Drobnis,³ J. Bruce Redmon,⁴ Christina Wang,⁵ Charlene Brazil,⁶ James W. Overstreet,⁶ and the Study for Future Families Research Group

¹Department of Family and Community Medicine, University of Missouri-Columbia School of Medicine, Columbia, Missouri, USA; ²Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ³Department of Obstetrics and Gynecology, University of Missouri-Columbia, Columbia, Missouri, USA; ⁴Departments of Medicine and Urologic Surgery, University of Minnesota, Minneapolis, Minnesota, USA; ⁵Harbor-UCLA Medical Center, Torrance, California, USA; ⁶University of California, Davis, California, USA

Abstract
We previously reported reduced sperm concentration and motility in fertile men in a U.S. agrarian area (Columbia, MO) relative to men from U.S. urban centers (Minneapolis, MN ; Los Angeles, CA ; New York, NY) . In the present study we address the hypothesis that pesticides currently used in agriculture in the Midwest contributed to these differences in semen quality. We selected men in whom all semen parameters (concentration, percentage sperm with normal morphology, and percentage motile sperm) were low (cases) and men in whom all semen parameters were within normal limits (controls) within Missouri and Minnesota (sample sizes of 50 and 36, respectively) and measured metabolites of eight current-use pesticides in urine samples provided at the time of semen collection. All pesticide analyses were conducted blind with respect to center and case-control status. Pesticide metabolite levels were elevated in Missouri cases, compared with controls, for the herbicides alachlor and atrazine and for the insecticide diazinon [2-isopropoxy-4-methyl-pyrimidinol (IMPY) ] ; for Wilcoxon rank test, p = 0.0007, 0.012, and 0.0004 for alachlor, atrazine, and IMPY, respectively. Men from Missouri with high levels of alachlor or IMPY were significantly more likely to be cases than were men with low levels [odds ratios (ORs) = 30.0 and 16.7 for alachlor and IMPY, respectively], as were men with atrazine levels higher than the limit of detection (OR = 11.3) . The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and metolachlor were also associated with poor semen quality in some analyses, whereas acetochlor levels were lower in cases than in controls (p = 0.04) . No significant associations were seen for any pesticides within Minnesota, where levels of agricultural pesticides were low, or for the insect repellant DEET (N,N-diethyl-m-toluamide) or the malathion metabolite malathion dicarboxylic acid. These associations between current-use pesticides and reduced semen quality suggest that agricultural chemicals may have contributed to the reduction in semen quality in fertile men from mid-Missouri we reported previously. Key words: agriculture, pesticides, semen quality, sperm concentration, sperm morphology, sperm motility. Environ Health Perspect 111:1478-1484 (2003) . doi:10.1289/ehp.6417 available via http://dx.doi.org/ [Online 18 June 2003]