Roscovitine treatment caused impairment of fertilizing ability in mice

• We firstly investigated the reproductive toxicity of roscovitine both in hSOD1G93A-positive male mice and C57BL6 male mice.
• Roscovitine affects fertility of those male mice. Decreased sperm counts and damaged seminiferous tubules were found after roscovitine treatment.
• Reproductive system of ALS male mice was more susceptible to the adverse effect of roscovitine.

ObjectiveTo explore the adverse effect of roscovitine on reproductive system of male mice.Materials and methodsMale hSOD1G93A transgenetic mice received roscovitine 72 nmol/day (d) for 4 weeks (w), with normal control and dimethyl sulfoxide (DMSO)-treated animals served as controls (n = 4). Male C57BL/6 mice were treated with roscovitine at either 72 nmol/d or 144 nmol/d for 4 w or 8 w, and normal control and DMSO treated mice served as controls. Fertility of male mice, sperm quality parameters, histological and related pathological changes of seminiferous tubules associated with roscovitine treatment were evaluated.ResultsIn male hSOD1G93A transgenetic mice treated with 72 nmol/d roscovitine for 4 w and C57BL/6 male mice treated with 72 nmol/d roscovitine for 8 w and 144 nmol/d roscovitine for 4 w and 8 w, sperm counts and sperm motility rates decreased and sperm abnormality rates increased, and damage of seminiferous tubules were detected. Roscovitine treatment induced inhibition of CDK5 activities and decrease of BrdU-positive tubuler cells.ConclusionThese results demonstrated that roscovitine treatment induced interference of male reproductive system and caused impairment of fertilizing ability. Reproductive system of ALS male mice was more susceptible to roscovitine induced impaired fertilizing ability.