FIGURE 2.

Schematic of our hypothesis. (A) Sex biases have different origins depending on the developmental stage of the organism. Before gonadogenesis, sex chromosomes are the primary determinants of sex differences. Sex hormones influence the transcriptome and epigenome independently of and in combination with sex chromosome effects. (B) Soon after fertilization, male and female cells have sex-specific transcriptomes, epigenomes, and phenotypes (for example, male embryos grow faster than female embryos). At implantation, lineage determination begins and gene expression differences are reduced. Epigenetic marks, however, are less constrained and some are maintained, affecting gene expression, and phenotype later in development. Once specific lineages are established, differences in gene expression increase again due to environmental, hormonal and genetic factors, some of which act on sex-specific epigenetic features established prior to differentiation.