The review stresses the importance of large, longitudinal human studies and standardized epigenome assays to better understand causality and develop effective clinical interventions.

It advocates for conducting trials on preconception lifestyle interventions to establish causal links and enhance reproductive outcomes and offspring health.

Exposure to endocrine-disrupting chemicals like BPA and phthalates can cause transgenerational DNA methylation changes, impacting fertility and increasing disease susceptibility across generations.

Incorporating epigenetic screening and lifestyle modifications into fertility care could optimize assisted reproductive technology (ART) success rates and help mitigate intergenerational health risks, emphasizing male preconception health as a modifiable factor.

Preconception stress in fathers is associated with modifications in sperm microRNAs, piRNAs, and methylation patterns, with animal studies showing these changes can lead to behavioral and metabolic effects in descendants.

In ART, paternal factors such as BMI, diet, and alcohol intake influence embryo quality and ICSI success, with sperm epigenetic profiles showing potential as biomarkers to improve outcomes.

Paternal lifestyle factors such as diet, obesity, smoking, exposure to endocrine-disrupting chemicals (EDCs), and stress can leave lasting epigenetic marks on sperm, including DNA methylation, histone modifications, and small non-coding RNAs, which persist at fertilization.

Clinical recommendations now emphasize lifestyle modifications—like maintaining a healthy weight, quitting smoking, eating a balanced diet rich in folate, reducing toxin exposure, managing stress, and consulting fertility specialists—to improve sperm epigenetic health.

A comprehensive review in Clinical Epigenetics highlights that paternal environmental and lifestyle exposures influence sperm epigenetics, subsequently affecting fertility, embryo development, and the health of offspring.

Smoking is linked to methylation changes in genes related to antioxidant defenses, insulin signaling, and spermatogenesis, and it also reduces sperm motility and morphology.