Smoking may provide an explanation for reduced fertility, results of two studies suggested.
The first, by Claus Yding Andersen, MD, of the University of Copenhagen, and colleagues, found significant reductions in germ and somatic cells in the testes of male embryos from mothers who smoked during pregnancy, possibly related to the polycyclic aromatic hydrocarbons found in cigarette smoke.
"This effect may have long-term consequences on the future fertility of exposed offspring," the authors wrote online in Human Reproduction.
The second study, by Mohamed Hammadeh, DVM, of Saarland University in Saarbrücken, Germany, and colleagues, found that adult males who smoked had reduced levels of one of the proteins important in sperm formation. The findings were also published in Human Reproduction.
"Smoking male partners of couples facing infertility should be counseled to stop smoking," Hammadeh and his colleagues wrote.
Andersen's group assessed the numbers of germ and somatic cells in the testes of 24 male embryos obtained following abortion during the first trimester (mean ages 37 to 68 days post-conception).
According to self-report and confirmed by cotinine testing, fifteen of the mothers smoked during pregnancy. Median intake was 11 to 15 cigarettes a day.
The smoking and nonsmoking mothers were similar in age, height, and body mass index.
Compared with embryos from nonsmoking mothers, those from smoking mothers had significant reductions in germ cells (by 55%) and somatic cells (by 37%; P<0.05 for both). The relationship was dose-dependent, with greater reductions associated with heavier smoking.
The researchers combined the data from the current study with data on 28 female embryos from a previous study.
Regardless of gender, there were still reductions in germ cells (by 41%) and somatic cells (by 29%) in embryonic gonads exposed to smoking in utero (P<0.05 for both).
The findings remained consistent after controlling for alcohol use and coffee consumption.
The authors noted that the study could not determine whether the declines were permanent or a reflection of a growth delay that would be compensated for later in life.
The study by Hammadeh and his colleagues evaluated the relationship between smoking and the formation of sperm -- specifically the protamination process -- among 53 heavy smokers (more than 20 cigarettes a day) and 63 nonsmokers. All were partners of a couple seeking treatment for infertility.
Although smoking was not associated with semen volume or sperm concentration, smokers had significantly lower sperm vitality, motility, membrane integrity, and morphology (P<0.05 for all).
The researchers also looked at levels of protamines 1 and 2, which are integral in sperm formation.
Concentrations of protamine 2 -- but not protamine 1 -- were significantly lower in smokers (P<0.05). Consequently, the P1/P2 ratio was greater in smokers (P<0.01).
Cotinine levels and three oxidative stress biomarkers -- reactive oxygen species, malondialdehyde, 8-hydroxyguanosine -- were higher in smokers and correlated with P1/P2 ratios (P<0.01 for all).
The findings suggest that oxidative stress -- which has been shown to be a major cause of male infertility -- is greater in smokers, according to the researchers.
The study provided support for the link between oxidative stress and infertility by showing that the oxidative stress biomarkers were significantly related to the percentages of sperm that had noncondensed chromatin and DNA fragmentation.
"Taken together, the results of the present study suggest a negative biological effect of smoking on spermatozoa DNA integrity and protamine distribution," the authors wrote.
The study by Andersen and colleagues was funded by the Danish Medical Research Council. The authors reported no conflicts of interest.
Hammadeh and his colleagues did not report any funding sources or conflicts of interest.
Zalman S. Agus, MD Emeritus Professor
University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Human ReproductionSource Reference: Mamsen L, et al "Cigarette smoking during early pregnancy reduces the number of embryonic germ and somatic cells" Hum Reprod 2010; DOI: 10.1093/humrep/deq215.
Human ReproductionSource Reference: Hammadeh M, et al "Protamine contents and P1/P2 ratio in human spermatozoa from smokers and non-smokers" Hum Reprod 2010; DOI: 10.1093/humrep/deq226.