Cigarette smoking is associated with abnormal histone to protamine transition in human sperm

Cigarette smoking is associated with abnormalities in histone-to-protamine transition independent of semen quality, and interferes with the mRNA expression of protamines in human sperm and TM3 cell lines.

Bolan Yu, Ph.D., Yanbin Qi, B.S., Dan Liu, B.S., Xingcheng Gao, Ph.D., Hui Chen, B.S., Chuan Bai, Ph.D., Zhaofeng Huang, Ph.D.

Volume 101, Issue 1, Pages 51-57.e1, January 2014


To investigate the association between smoking, semen quality, and the histone-to-protamine transition ratio in mature sperm.

Biochemical and molecular analysis in human samples and a cell line.

Andrology laboratory in a university-affiliated hospital.

Semen samples from 147 heavy smokers and 175 nonsmokers receiving infertility treatment.


Main Outcome Measure(s):
Basic semen parameters, histone-to-protamine ratios, and number of sperm cells with abnormal histone transition were calculated. The relative messenger RNA (mRNA) expression levels of protamine 1 and protamine 2 were assayed in human sperm and in TM3 cells exposed to cigarette smoke condensate. T tests, Spearman tests, and nonparametric Mann-Whitney U tests were used to detect significant differences.

Normozoospermic smokers had significantly higher abnormalities than their nonsmoking counterparts. Sperm histone replacement abnormalities were found to be closely correlated with sperm motility, viability, concentration, counts, and cotinine levels. The ratios of protamine 1 to protamine 2 mRNA expression significantly increased in heavy smokers and in TM3 cells treated with cigarette smoke condensate.

Smoking is strongly associated with abnormalities in histone-to-protamine transition and with alteration of protamine mRNA expression in human sperm.

  • Jason Kovac

    This is an interesting idea – especially given the paucity of information regarding the effects of smoking on spermatogenesis. The addition of data from a cell-line gives the authors additional ammunition for their claims; however, studies like this are very difficult to conduct in a human cohort.
    With regards to this subset, cigarette smoking often goes hand-in-hand with alcohol consumption. Unless I missed it, the authors did not consider this at all in this study. Given that alcohol modifies protamine-protamine or protamine-DNA interactions (Zygote. 1998 Aug;6(3):233-8), further work clarifying the contributions of these factors would be beneficial.

  • Good paper presenting the negative effects of smoking on sperm quality and genetic integrity. What is interesting is the effect of tobacco on histone replacement abnormalities actually has a direct effect on sperm function, viability, and overall counts. This provides additional evidence for smoking cessation in our fertility patients.

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