Fertility researchers have shown that nicotine and cotinine, a substance produced by nicotine’s breakdown, cause sperm to change in ways that could reduce fertility potential. In results presented at the 2002 annual meeting of the American Society for Reproductive Medicine, lead researcher Lani Burkman, Ph.D., reported that in laboratory experiments these chemicals, singly and in combination, decreased the capacity of sperm to perform functions necessary to fertilize a human egg.From the University at Buffalo :Nicotine Affects Sperm Adversely; Creates Changes that Reduce Fertility Potential, UB Research Finds
Sperm’s fertilizing potential in male smokers now the focus of study
BUFFALO, N.Y. — Fertility researchers at the University at Buffalo have shown that nicotine and cotinine, a substance produced by nicotine’s breakdown, cause sperm to change in ways that could reduce fertility potential.
In results presented at the 2002 annual meeting of the American Society for Reproductive Medicine, lead researcher Lani Burkman, Ph.D., reported that in laboratory experiments these chemicals, singly and in combination, decreased the capacity of sperm to perform functions necessary to fertilize a human egg.
Burkman is assistant professor and head of the Section on Andrology in the Department of Gynecology and Obstetrics in the UB School of Medicine and Biomedical Sciences, and assistant professor of urology.
Based on these results, Burkman’s research group is preparing to conduct the first study of nicotine’s effect on specific sperm functions in semen samples taken from a group of male smokers who agree to stop smoking. Sperm samples will be collected before and after the men quit. The study is expected to get underway in June.
“Smoking is huge in many countries of the world, and it is clear that nicotine does affect sperm,” Burkman said. “I believe that our laboratory findings and the upcoming clinical study will provide dramatic new information on smoking’s effect on human reproduction and the time required for sperm to regain normal capacity.”
Nicotine also binds to receptors for acetylcholine, an important neurotransmitter. Burkman’s research also will help to determine how this action affects normal body functioning.
Burkman conducted the research in her andrology laboratory in Children’s Hospital of Buffalo. Sperm from healthy men were subjected to several diagnostic tests that assess their ability to accomplish three functions necessary for egg fertilization: vigorous hyperactivated swimming, proper acrosomal changes and effective binding to the egg cover, or zona.
The researchers assessed the ability of sperm to pass these diagnostic tests while subjected to increasing amounts of nicotine, cotinine or both drugs. Sperm function was tested hourly for at 1-6 hours and after 24 hours. Control sperm, not exposed to drugs, were observed over the same time period.
Highest concentrations of the drugs separately or in combination simulated a smoker’s system, while lowest levels simulated acetylcholine effects.
Hyperactivated swimming refers to very vigorous swimming patterns that enable sperm to reach the egg and penetrate the zona. Significant changes in hyperactivation, either a decline or an extreme increase, will destroy the critical timing for the sperm to meet the egg, a discovery made by Burkman.
The acrosome is an enzyme-filled cap covering half the sperm head that must be activated at the proper time to soften the egg’s zona and permit sperm binding to the zona. These actions allow the sperm head, with its genetic material, to fertilize the egg. If the acrosome actions are blocked or the enzymes are released too soon, sperm are rendered useless. Malformations of the acrosome caused by toxic conditions, such as smoking, also may prevent zona binding.
Results showed that the presence of the two drugs separately or in combination (smokers will have both nicotine and cotinine in their system) affected sperm function in several dramatic ways.
Sperm exposed to nicotine had decreased tight binding to the zona, which lowers fertilizing potential. At higher concentrations, nicotine increased the percent of sperm with changed acrosomes after two hours, indicating that acrosomes were being modified too quickly.
The percentage of mobile sperm was not altered during the first six hours of drug exposure, but motility fell significantly — about 25 percent — after 24 hours among sperm treated with cotinine and the drug combination.
The mix of the two drugs had different effects on vigorous hyperactivated swimming depending on drug concentration, results showed. In the smokers’ range, hyperactivation was far above normal — 171 percent of the control — after 6 hours. But at very low doses, hyperactivation decreased to 43 percent of control sperm.
“These results show that chronic smoking may suppress hyperactivated motility and tight binding of sperm to the egg, leading to some reduction in fertility potential,” said Burkman. “In men who smoke, these drugs are continually in contact with the testes, where the sperm are formed.
“Many studies have shown that smoking women also tend to have lower fertility,” Burkman said. “This is no surprise, since nicotine and cotinine will be present in the fluid of their oviduct, where fertilization occurs, and the sperm will be affected there. The drugs also will pervade the uterus, where the growing egg will implant, and the placenta, which nourishes the embryo.”
Burkman noted that a large study conducted in China, where smoking is rampant, showed that some heavy smokers produced sperm with damaged DNA, which were passed on to the children. These children eventually had an abnormally high occurrence of cancers.
“I received email questions on fertility from a smoker just recently,” Burkman said. “My reply was, ‘If you want to have children, stop smoking.'”
MaryLou Bodziak and Roxanne Mroz, UB research associates, along with Rachana Gurunatha and Dawn Palaszewski, students in Burkman’s lab, contributed to this research.
The current work and upcoming clinical study are funded by Philip Morris, which retains no proprietary interest in the research. Neither Burkman nor anyone involved in the work has any connection to the company.