Fig. 5. Conceptual model for how sex-specific epigenetic development in the ARH could underlie sex differences in susceptibility to developmental programming.

Illustrations depict early postnatal methylation dynamics at a female-precocious neuronal mDMR (i.e., one at which methylation increases earlier in female than in male ARH neurons). Under normal postnatal nutrition (top), the same developmental outcome is achieved in both male and female ARH neurons (potential conversion of some nascent 5mC to 5hmC is illustrated by dotted arrows projecting out of the page). In this hypothetical example, overnutrition from P2 to P10 (bottom) impairs de novo methylation only in females, because this epoch overlaps the critical window for ARH neuronal epigenetic maturation at this female-precocious locus.