Sex Differences in Biological Responses: Mechanisms, Evolution, and Environmental Interactions

Sex-specific phenotypes arise from complex interactions among genetic, epigenetic, hormonal, and environmental factors throughout development and across the lifespan. Although sex-determination mechanisms establish gonadal identity, they also initiate differences in sex-specific responses beyond reproductive tissues. Here, we review the diverse genetic and environmental sex-determination systems, highlighting how these mechanisms regulate sex-specific gene expression. We further examine the roles of hormones, epigenetic modifications, and environmental factors in shaping physiological, behavioral, and life-history differences between the sexes. Early-life conditions, social environments, and reproductive strategies further modify these trajectories, producing substantial within- and among-species variations in sex-specific phenotypes during development and aging. By integrating evidence across vertebrates and invertebrates, we propose a unified framework in which sex-specific phenotypes emerge from dynamic interactions between genomes, epigenomes, and environments. This comparative perspective discusses conserved and lineage-specific principles underlying the evolution, phenotypic plasticity, and adaptive significance of sex differences across diverse taxa.