Sex-Dependent Effects of Anterior Cruciate Ligament Reconstruction on Muscle Atrophy in Rats

Previous studies reported greater knee extensor muscle weakness in female patients compared with males after anterior cruciate ligament (ACL) reconstruction. However, the mechanisms underlying this sex difference remain unclear. We investigated whether there are sex differences in muscle atrophy after ACL reconstruction. Rats were divided into four groups: Male control, male ACL reconstruction, female control, and female ACL reconstruction. To quantify the amount of weight-bearing, gait analysis was performed during the experimental period. Muscle atrophy was assessed by measuring muscle fiber cross-sectional area (CSA) at 7, 28, and 84 days after starting the experiment. In the rectus femoris, a similar extent of atrophy was observed at 7 days after ACL reconstruction, but atrophy recovered by 28 days in both males and females. However, at 84 days, rectus femoris atrophy occurred again in females only. In the semitendinosus and gastrocnemius, significant atrophy was detected at 7 days after ACL reconstruction in males, but not in females. Both males and females showed a reduction in weight-bearing early after ACL reconstruction, with a more pronounced reduction in males. Early semitendinosus and gastrocnemius atrophy was more severe in males, and this may be explained by differences in weight-bearing. Delayed rectus femoris atrophy, observed exclusively in females, may explain the weakened knee extensor strength observed in female patients.