Myonuclear addition is associated with sex-specific fiber hypertrophy and occurs in relation to fiber perimeter not cross-sectional area.

It is unclear whether resistance training-induced myofiber hypertrophy is affected by sex, and whether myonuclear addition occurs in relation to the myonuclear domain and can contribute to explaining a potential sex-specific hypertrophic response. This study investigated the effect of 8 wk of resistance training on myofiber hypertrophy and myonuclear addition in 12 males (28 ± 7 yr; mean ± SD) and 12 females (27 ± 7 yr). Muscle biopsies were collected from m. vastus lateralis before and after the training intervention and were analyzed by immunohistochemistry for fiber type and size, satellite cells, and myonuclei. Hypertrophy of type I fibers was greater in males than females ( < 0.05), whereas hypertrophy of type II fibers was similar between sexes ( = 0.158-0.419). Expansion of the satellite cell pool ( = 0.132-0.667) and myonuclear addition ( = 0.064-0.228) did not differ significantly between sexes, irrespective of myofiber type. However, when individual responses to resistance training were assessed, myonuclear addition was strongly correlated with fiber hypertrophy ( = 0.68-0.85, < 0.001). Although myofiber hypertrophy was accompanied by an increase in myonuclear domain ( < 0.05), fiber perimeter per myonucleus remained constant throughout the study ( = 0.096-0.666). These findings indicate that myonuclear addition occurs in relation to the fiber perimeter per myonucleus, not the myonuclear domain, and has a substantial role in resistance training-induced muscle hypertrophy but does not fully explain greater hypertrophy of type I fibers in males than females. Here, we show that resistance training-induced hypertrophy of type I fibers is greater in males than females. Myonuclear addition was strongly associated with fiber hypertrophy but did not differ between sexes in type I fibers. Furthermore, whereas muscle hypertrophy was accompanied by an increase in myonuclear domain, fiber perimeter per myonucleus remained constant. Thus, myonuclear addition occurs in relation to fiber perimeter during muscle hypertrophy but does not explain sex-specific hypertrophy of type I fibers.