Smoking has been linked to male infertility by affecting the sperm epigenome and genome.
In this study, we aimed to determine possible changes in the transcript levels of PGAM5 (the phosphoglycerate mutase family member 5), PTPRN2 (protein tyrosine phosphatase, N2-type receptor),
and TYRO3 (tyrosine protein kinase receptor) in heavy smokers compared to non-smokers, and to
investigate their association with the fundamental sperm parameters. In total, 118 sperm samples
(63 heavy-smokers (G1) and 55 non-smokers (G2)) were included in this study. A semen analysis
was performed according to the WHO guidelines. After a total RNA extraction, RT-PCR was used
to quantify the transcript levels of the studied genes. In G1, a significant decrease in the standard
semen parameters in comparison to the non-smokers was shown (p < 0.05). Moreover, PGAM5 and
PTPRN2 were differentially expressed (p ≤ 0.03 and p ≤ 0.01, respectively) and downregulated in the
spermatozoa of G1 compared to G2. In contrast, no difference was observed for TYRO3 (p ≤ 0.3). In
G1, the mRNA expression level of the studied genes was correlated negatively with motility, sperm
count, normal form, vitality, and sperm membrane integrity (p < 0.05). Therefore, smoking may affect
gene expression and male fertility by altering the DNA methylation patterns in the genes associated
with fertility and sperm quality, including PGAM5, PTPRN2, and TYRO3