Alcohol and male infertility: is there a safe dose? Evidence of accessory gland dysfunction, oxidative stress, and sperm DNA damage.

Abstract

Introduction: Alcohol consumption is a recognized modifiable lifestyle factor affecting male reproductive health. Yet, its dose-dependent effects on accessory gland function and sperm genomic integrity remains poorly elucidated. This cross-sectional study examined the relationship between alcohol consumption and the accessory gland-sperm function axis, focusing on the mediating role of oxidative stress in cellular and molecular damage.

Methods: A total of 126 men undergoing fertility evaluation were stratified into a control cohort (non-drinkers with normozoospermia, n = 25) and three alcohol-consuming infertile cohorts: mild (n = 37), moderate (n = 31), and heavy (n = 33). A standard semen analysis was performed following world Health Organization (2021) guidelines, while seminal plasma was quantified for accessory gland markers (fructose and total protein concentration) and an oxidative stress marker (malondialdehyde levels). Nuclear maturity and DNA integrity were evaluated using aniline blue and acridine orange fluorescence staining.

Results: The findings demonstrated that alcohol consumption was associated with a dose-dependent deterioration across all standard semen parameters, particularly correlating with teratozoospermia (<4% normal morphology). Seminal fructose and total protein concentrations were decreased significantly with alcohol intake levels (p < 0.0001), whereas MDA levels exhibited a drastic elevation (p < 0.0001). A correlation analysis revealed a strong positive association between seminal fructose and total motility (r = 0.867, p < 0.0001). Furthermore, MDA levels were strongly correlated with chromatin condensation defects (r = 0.841) and the sperm DNA fragmentation index (r = 0.880, p < 0.0001).

Discussion: These findings suggest that chronic alcohol consumption is associated with impaired male fertility potential by supressing accessory gland secretory function and with elevated systemic oxidative stress. Even long-term mild alcohol consumption was associated with considerable levels of oxidative stress that affect chromatin packaging and DNA integrity. Men undergoing fertility evaluation, particularly prior to assisted reproductive techniques, may benefit from counseling on alcohol reduction or abstinence to safeguard embryo genomic integrity.