The epigenetic alterations of human sperm cells caused by heroin use disorder.

Abstract

The molecular mechanisms of drug use on sexual health are largely unknown. We investigated, the relationship between heroin use disorder and epigenetic factors influencing histone acetylation in sperm cells. The volunteers included twenty-four 20- to 50-year-old men with a normal spermogram who did not consume any drugs and twenty-four age- to BMI-matched men who consume only the drug heroin for more than last four months. HDAC1 and HDAC11 mRNA expression levels in spermatozoa and miR-34c-5p and miR-125b-5p expression levels in seminal plasma were measured. The heroin-user group showed significantly increased white blood cell counts and decreased sperm motility and survival rates (8.61±1.73, 21.50±3.11, 69.90±4.69 respectively) as compared to the control group (1.49±0.32, 38.82±3.05, 87.50±0.99 respectively) (p≤.001). An increase in DNA fragmentation index (DFI) (heroin-user group: 41.93±6.59% and control group: 10.14±1.43%, p=.003), a change in frequency of HDAC1 (heroin-user group: 1.69±0.55 and control group: 0.45±0.14, p=.045) and HDAC11 (heroin-user group: 0.29±0.13 and control group: 2.36±0.76, p=.019) in spermatozoa and a significant decrease in seminal miR-125b-5p abundance (heroin-user group: 0.37±0.11 and control group: 1.59±0.47, p=.028) were reported in heroin consumers. Heroin use can lead to male infertility by causing leukocytospermia, asthenozoospermia, DFI elevation in sperm cells and alterations in seminal RNA profile.