Aps. Hikim et al., Posttesticular antifertility action of triptolide in the male rat: Evidence for severe impairment of cauda epididymal sperm ultrastructure, J ANDROLOGY, 21(3), 2000, pp. 431-437
A variety of active diterpene epoxides, including the triptolide (isolated
from Tripterygium wilfordii) have been reported to cause infertility in mal
e rats. Previously, we showed that oral administration of triptolide at a d
osage of 100 mu g/kg per body weight for 70 days completely inhibited ferti
lity in male rats, with little or no demonstrable detrimental effect on spe
rmatogenesis and Leydig cell function as determined by testicular light mic
roscopic appearance and serum and intratesticular testosterone levels. Desp
ite the apparent absence of effects on the testes, cauda epididymal sperm w
ere abnormal, with complete cessation of sperm motility and some reduction
in sperm numbers. This study was undertaken to provide additional insight i
nto the subcellular sites and possible mechanisms of action of this compoun
d using ultrastructural analysis of the testes and epididymidis. The most s
triking effect of triptolide treatment was observed in sperm in the epididy
mis. In rats rendered infertile with 100 mu g/kg per body weight of triptol
ide daily for 70 days, virtually all cauda epididymal sperm exhibited compl
ete absence of plasma membrane over the entire middle and principal piece,
premature decondensation of the nuclei, and disorganization of the mitochon
drial sheath with many vacuolated mitochondria. No ultrastructural differen
ces in the epididymal epithelium were observed between control and triptoli
de-treated rats. The testes appeared to be mildly affected after triptolide
treatment but exhibited only subtle ultrastructural defects in the germ ce
lls. The findings of severe impairment of cauda epididymal sperm ultrastruc
ture, along with minimal discernible abnormalities in the fine structural c
ytology of the testes, further suggest that the site of action of this comp
ound is posttesticular and may be confined to the cauda epididymal sperm. H
owever, we cannot rule out an effect of triptolide that occurs during germ
cell maturation but is delayed in its manifestation or triggered at the ret
e testis and epididymal level.