Roscovitine treatment caused impairment of fertilizing ability in mice

Abstract

ObjectiveTo explore the adverse effect of roscovitine on reproductive system of male mice. Materials and methodsMale hSOD1G93A transgenetic mice received roscovitine 72nmol/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 72nmol/d or 144nmol/d for 4w or 8w, 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 72nmol/d roscovitine for 4w and C57BL/6 male mice treated with 72nmol/d roscovitine for 8w and 144nmol/d roscovitine for 4w and 8w, 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.