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Roscovitine treatment caused impairment of fertilizing ability in mice
Xiang Yin1, Yan Qi1, Ming Ren2
1Department of Neurology, The First Clinical College of Harbin Medical University, Harbin 150001, Heilongjiang, PR China.
Objective:
To explore the adverse effect of roscovitine on reproductive system of male mice.
Materials And Methods:
Male hSOD1(G93A) 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.
Results:
In male hSOD1(G93A) transgenetic mice treated with 72 nmol/d roscovitine for 4 w and C57BL/6 male mice treated with 72 nmol/d roscovitine for 8w 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.
Conclusion:
These 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.
Insights
Roscovitine negatively impacts male mouse fertility by reducing sperm quality and damaging testicular tubules. Male mice with Amyotrophic Lateral Sclerosis (ALS) showed greater susceptibility to these reproductive effects.
Area of Science:
- Reproductive toxicology
- Pharmacology
- Mouse models in research
Background:
- Roscovitine is a cyclin-dependent kinase inhibitor.
- Investigating drug effects on male reproductive health is crucial.
Purpose of the Study:
- To evaluate the adverse effects of roscovitine on the male reproductive system.
- To assess the impact on fertility and sperm parameters in mice.
Main Methods:
- Male mice (hSOD1(G93A) transgenic and C57BL/6) were treated with varying doses and durations of roscovitine.
- Fertility, sperm quality, and testicular histology were analyzed.
- CDK5 activity and BrdU-positive cells were measured.
Main Results:
- Roscovitine treatment led to decreased sperm count and motility, and increased sperm abnormality.
- Histological examination revealed damage to seminiferous tubules.
- Inhibition of CDK5 activity and reduced BrdU-positive cells were observed.
Conclusions:
- Roscovitine impairs male reproductive function and fertilizing ability.
- Male mice with ALS exhibited heightened sensitivity to roscovitine's reproductive toxicity.
