Table 2 Comparative effects of lifestyle factors on epigenetic markers in the sperm epigenome. The table summarises how obesity, high-fat diet, smoking, stress, and exposure to endocrine-disrupting chemicals (EDCs) influence three key epigenetic mechanisms: DNA methylation, histone modifications, and small non-coding RNAs (sncRNAs). Observed effects include disruptions in metabolism, sperm quality, and developmental processes in offspring, highlighting the significance of these factors in reproductive health and transgenerational inheritance

Obesity

Hypomethylation of IGF2, MEST, PEG3, and NNAT associated with altered metabolism and cancer risks in offspring

Retention of H3K27me3 in certain genes affects gene regulation during embryonic development

Altered expression of miRNAs and tsRNAs, linked to metabolic disorders in offspring

High-fat diet

Altered methylation of imprinted genes affects insulin secretion and glucose metabolism

Increased H3K27me3 in metabolic and growth-related genes in sperm

Dysregulation of tsRNAs and miRNAs linked to metabolic changes and testicular function

Smoking

Hyper- and hypomethylation of specific genes (e.g. TYRO3, PGAM5) linked to infertility and metabolic diseases

Increased retention of histone H2B, affecting chromatin remodelling during fertilisation

Altered miRNA expression (e.g. miR-204-5p), linked to reduced sperm quality

Stress

DNA methylation changes in stress-response genes (e.g. MeCP2, CB1) associated with behavioral changes

Not well documented for stress but may involve loss of key histone marks during sperm formation

Alterations in miRNA and piRNA levels, linked to behavioral traits and HPA axis function

Endocrine-disrupting chemicals (EDCs)

Hypomethylation of DNA regions regulating developmental and metabolic genes in offspring

Altered histone modifications affecting gene regulation and embryonic development

Dysregulation of miRNAs involved in spermatogenesis and embryogenesis