Clarifying the Effect of Smoking on Male Fertility

By Brittain Whiteside-Galloway
Monday, January 30, 2017

Recent research demonstrates the chief mechanism by which smoking damages sperm.

In a cross-sectional study, Brazilian scientists confirmed earlier findings that men who regularly smoke have damaged sperm more often than do nonsmokers, which can render them less able to fertilize an egg. The study also helps establish the primary means by which the damage occurs: altered seminal plasma proteins.

Research stretching back decades has indicated smokers have fewer, less motile and abnormally shaped sperm, in addition to atypically structured acrosomes, structures on the head of sperm that allow the sperm to penetrate and fertilize the egg.

A potential cause of sperm damage has been thought to be seminal oxidative stress (OS). OS can occur when smokers inhale toxins, such as nicotine, carbon monoxide and cadmium, and it appears to have an adverse effect on sperm function, as found in a 2002 study by researchers at the Cleveland Clinic Foundation.

“Compared to nonsmokers, we found substantially higher levels of seminal oxidative stress (OS) in men who smoke, as evidenced by a significant reduction in reactive oxygen species and total antioxidant capacity (ROS-TAC) scores,” they wrote. “The link between cigarette smoking and increased levels of seminal ROS may be, at least in part, related to the significant increase in leukocyte concentrations in the semen of infertile smokers ... . Though the exact mechanisms by which increased seminal leukocytes infiltrate semen are unclear, a potential explanation is that smoking metabolites may induce an inflammatory reaction in the male genital tract with a subsequent release of chemical mediators of inflammation.”

Zeroing in

For the more recent study, researchers at Sao Paulo Federal University in Brazil led by Ricardo Pimenta Bertolla, DVM, PhD, Head of Research and Vice Coordinator of the Graduate Program in Urology, and Mariani Antoniassi, PhD candidate, analyzed the sperm of 20 nonsmokers and 20 men who smoked at least 10 cigarettes a day. All were 20 to 50 years old. Participants’ sperm were tested for mitochondrial activity, acrosome integrity and DNA fragmentation. Smokers had a substantially higher percentage of sperm DNA damage, partially and fully inactive mitochondria, and nonintact acrosomes, all of which contribute to impaired fertilization.

“We knew from some of our earlier studies, as well as those of other authors, that smoking alters cellular mechanisms of semen — that smoking is associated with increased fragmentation of sperm DNA ... and that alterations in mitochondria, for example, are a first sign of in loco OS, as mitochondrial membranes are very sensitive to oxidative damage,” Dr. Bertolla says. “However, we did not know what were the mechanisms that caused this alteration.”

In their analysis, the team discovered altered seminal proteins’ interactions with sperm can impair fertilization.

“We found ... that smokers’ [sperm] presents some differences in seminal plasma proteins, which are required to protect and nourish spermatozoa,” Antoniassi says. “These [altered] proteins are responsible for an increase in seminal inflammation and seem to be the main mechanism behind sperm alteration.”

Reporting their findings in BJU International, the researchers concluded that the inflammation “causes an alteration in sperm functional quality, which is characterized by decreased acrosome integrity and mitochondrial activity, as well as by increased nuclear DNA fragmentation.”