[Male contraception of triptonide and its function mechanism].
OBJECTIVE
The male contraceptive mechanism in rats of triptonide, isolated from Multiglycosides of Tripterygium wilfordii (GTW), was investigated.


METHODS
The dosage of triptonide was 200 micrograms/(kg.d), fed for 8 weeks via gastric intubation. Sperm counts, sperm motility, and sperm silver staining were used to test the antispermatogenic effect of triptonide; the study of morphology was learned from paraffin sections of testis and visceras of triptonide-treated rats; protamine was abstracted from testis by electrophoresis; using antisense mRNA of cyclin D1 and Cdk4 as prodes, we examined the expression of cyclin D1 and Cdk4 through hybridization in situ.


RESULTS
Sperm counts (26.43 +/- 3.90) x 10(6)/g and sperm motility(66.0 +/- 6.8)% of triptonide-treated rats were substantially different from those of control, (41.15 +/- 5.51) x 10(6)/g (P < 0.01) and (88.0 +/- 2.0)% (P < 0.001). Paraffin sections of testis of triptonide-treated rats stained by PAS showed that the number of spermatids per 100 sertoli cells (9.15 +/- 0.33) was remarkably decreased compared with control's (10.73 +/- 0.38) (P < 0.001). At the same time, delaying sperm-released process was observed, which affects the nature course of sperm. And the extended vacuoles of vary sizes, the segregation of cells in lumens were also found in the cross-section of testis of rats treated with triptonide. In addition, the contents of protamine (4.6 +/- 2.2)% was extremely decreased, compared with the control's (40.6 +/- 7.2)% (P < 0.001). By using antisense mRNA of cyclin D1 and Cdk4 as prodes, we detected that the expression of the genes was notably increased in spermatids.


CONCLUSIONS
The results suggest the antispermatogenic effect of triptonide is very well and it mainly plays its role on spermatids by increasing the expression of cyclin D1 and Cdk4, meanwhile, decreasing the biosynthesis of protamine. The appropriate target region of triptonide makes itself most potency to be a suitable male antifertility drug.
Wang
L
L
Department of Histology and Embryology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing 100005, China.
Ye
W
W
Hui
L
L
Liu
X
X
Guo
Y
Y
D000818:Animals; D003272:Contraceptive Agents, Male / Q000494:pharmacology*; D019938:Cyclin D1 / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D015870:Gene Expression; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013087:Spermatids / Q000187:drug effects* / Q000502:physiology; D014315:Triterpenes / Q000494:pharmacology*
D003272:Contraceptive Agents, Male; D009687:Nuclear Proteins; D014315:Triterpenes; D019938:Cyclin D1; C084079:triptonide; D018844:Cyclin-Dependent Kinases