Table II.

Critical issues of age-associated sperm epigenetic changes (AASEC) that still poorly addressed in human and animals. 

Critical issues	Description
Genomic elements	Which sperm genomic elements are affected by age?
Lifetime dynamics	Are AASEC linear? Or are changes that occur during peripubertal period more significant? What is the direction of DNA methylation change?
Species specificity	Are AASEC the same in humans and animals?
Cofactors and vulnerable periods	What factors affect AASEC in different sensitive windows?
Inheritance	Do AASEC survive epigenome remodeling in early embryo?
Interventions	What critical knowledge gaps need to be addressed to develop therapeutic interventions?