Smoking cigarettes is associated with increased sperm disomy in teenage men Jir ˇı ´ Rubes, Ph.D., †‡ Xiu Lowe, M.D., † Dan Moore II, Ph.D., † Sally Perreault, Ph.D., § Valerie Slott, Ph.D.,  Donald Evenson, Ph.D., ¶ Sherry G. Selevan, Ph.D.,** and Andrew J. Wyrobek, Ph.D. † Lawrence Livermore National Laboratory, Livermore, California; Veterinary Research Institute, Brno, Czech Republic; U.S. Environmental Protection Agency, Research Triangle Park; and University of North Carolina, Chapel Hill, North Carolina; South Dakota State University, Brookings, South Dakota; and U.S. Environmental Protection Agency, Washington, DC Objective: To determine whether moderate cigarette smoking and alcohol consumption in teenage men is associated with increases in disomic sperm and detectable changes in semen quality. Design: Cohort study. Setting: Military recruiting station, Teplice, Czech Republic. Patient(s): Ten current smokers (20 cigarettes per day for at least 2 years, exposure confirmed by urine cotinine) who also consumed alcohol and 15 nonsmokers. All patients were exactly 18 years old, healthy, and of unproven fertility. Main Outcome Measure(s): Sperm aneuploidy by multicolor fluorescence in situ hybridization for chromosomes 8, X, and Y; conventional semen analyses; computer-aided sperm analysis for motility; and sperm chromatin structure analysis. Results: Smokers showed elevated frequencies of sperm aneuploidy (Y disomy, P 0.001; aggregate of X, Y, and 8 disomies, P 0.01); reduced linearity of sperm motion (P 0.05); and more “round-headed” sperm (P 0.01). Smokers’ semen contained fewer sperm (P 0.001) and fewer motile sperm (P 0.02), which was attributable, in part, to shorter abstinence intervals among smokers (P 0.02). Conclusion(s): Cigarette smoking among teenagers was associated with increases in disomic sperm and a diminution in specific aspects of semen quality. Such defects may affect male fertility and may increase future chances of fathering offspring with aneuploidy syndromes. (Fertil Steril 1998;70:715–23. ©1998 by American Society for Reproductive Medicine.) Key Words: Cigarette-smoking lifestyle, sperm disomy, multicolor sperm FISH, CASA, SCSA, semen quality, urine cotinine Cigarette smoking is a pervasive personal habit that is highly addictive, with strong ap- peal among teenagers and young adults. Since the number of young smokers is increasing steadily in the United States and worldwide, it is important to understand fully the reproduc- tive and potential heritable genetic risks asso- ciated with smoking. For women, there is evi- dence that cigarette smoking imparts an elevated risk for a wide variety of abnormal reproductive outcomes, including infertility, spontaneous abortion, stillbirth and neonatal death, low birth weight, congenital malforma- tions, and other abnormal reproductive out- comes (1, 2). The evidence linking paternal smoking to abnormal reproductive outcomes is still con- flicting, with some evidence of detrimental ef- fects on fertility (3–5), neonatal mortality (6), perinatal mortality (7), miscarriage (8), and Received December 12, 1997; revised and accepted May 6, 1998. Presented at the 2nd International Conference on Environmental Mutagens in Human Populations, Prague, Czech Republic, August 20 –25, 1995, and the Meeting of the American Society of Human Genetics, Minneapolis, Minnesota, October 24 –28, 1995. Reprint requests: Andrew J. Wyrobek, Ph.D., Molecular and Structural Biology Division, Biology and Biotechnology Research Program, L-452, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, California 94550 (FAX: 925-422-2282; E-mail: wyrobek1@llnl.gov). This study was performed in part under the auspices of the U.S. DOE by the Lawrence Livermore National Laboratory under contract W-7405-ENG-48 with support from U.S. Environmental Protection Agency IA DW8 9936308 and Tobacco-Related Disease Research Program 3RT-0223. Recruitment, field work, and conventional semen analyses were supported by the Czech Ministry of the Environment (Teplice Program), the U.S. Environmental Protection Agency/U.S. AID and CEC (PHARE II, EC/HEA/18/CZ), and U.S. Environmental Protection Agency R820968 (DPE) and CR820076. This manuscript has been reviewed in accordance with the policy of the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for their use. † Lawrence Livermore National Laboratory. ‡ Veterinary Research Institute. § U.S. Environmental Protection Agency, Research Triangle Park, North Carolina.  University of North Carolina. ¶ South Dakota State University. ** U.S. Environmental Protection Agency, Washington, D.C. MALE FACTOR FERTILITY AND STERILITY VOL. 70, NO. 4, OCTOBER 1998 Copyright ©1998 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A. 0015-0282/98/$19.00 PII S0015-0282(98)00261-1 715