Stress-induced fetal programming contributes to the manifestation of Duchenne muscular dystrophy in mdx mice

Prenatal stress predisposes offspring to neurocognitive, metabolic, and cardiovascular complications in adulthood, but the programming effects on the presentation of hereditary diseases are unknown. We investigate this in a mouse model of Duchenne muscular dystrophy (DMD), an X-linked neuromuscular disease that widely affects the central nervous system and peripheral tissues. Simulating the inheritance patterns of DMD by mating <i>mdx</i>-heterozygous females with wildtype males, we compare the central, autonomic, and peripheral phenotypes of healthy and DMD-affected (<i>mdx</i>) male offspring born from mothers that were either stressed or non-stressed during gestation. Prenatal stress predisposed <i>mdx</i> offspring to anxiety-like behavior and reduced bone mass but did not exacerbate stress hypersensitivity or skeletal muscle mass and function. In fact, prenatal stress increases blood pressure and may be protective against hypotension-induced mortality to stress. This demonstrates that offspring genetics influence the outcomes of fetal programming, and fetal programming influences the presentation of a hereditary disease.