Sex-dependent effects of anterior cruciate ligament reconstruction on muscle atrophy in rats

Background: Previous studies reported greater knee extensor muscle weakness in female patients compared to males after anterior cruciate ligament reconstruction. However, the mechanisms underlying this sex difference remain unclear. We investigated whether there are sex differences in muscle atrophy after anterior cruciate ligament reconstruction. Methods: Rats were divided into four groups: male control, male anterior cruciate ligament reconstruction, female control, and female anterior cruciate ligament 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 at 7, 28, and 84 days after starting the experiment. Findings: In the rectus femoris, a similar extent of atrophy was observed at 7 days after anterior cruciate ligament 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 anterior cruciate ligament reconstruction in males, but not in females. Both males and females showed a reduction in weight-bearing early after anterior cruciate ligament reconstruction, with a more pronounced reduction in males. Interpretation: 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.