Reproductive Systemic Toxicity and Mechanism of Glucosides of Tripterygium wilfordii Hook. F. (GTW).

BACKGROUND: To study the mechanism of reproductive systemic toxicity of Tripterygium wilfordii on SD rats.

METHODS: The SD rats were randomly divided into groups and allocated three different treatments: control, 37.8 mg/kg Tripterygium glycosides, and 94.5 mg/kg Tripterygium glycosides, with each treatment applied for different lengths of time to 20 animals. Each group received treatment by intragastric administration once per day for 90 days. The estrus cycle was continuously observed throughout treatment. Animals were killed at each time point and analyses of sex hormones, sexual organ weights and coefficients, semen, pathology, and immunohistochemistry were conducted.

RESULTS: The metestrus phase of the rats administered the low-dose and high-dose treatments was significantly decreased. The uterus organ-body coefficients of female rats were significantly increased, whereas the testis and epididymis organ-body and organ-brain coefficients in male rats were significantly decreased by the high-dose and low-dose treatments at different time points. An increase in immature sperm and sperm abnormality rate was observed at different times in the low-dose and high-dose groups. Pathological changes were clear in the testis, epididymis, ovary, and uterus. The levels of multiple hormones were significantly decreased. The hypothalamus estrogen receptor alpha (ER-α) receptor expression in female rats was also significantly decreased. The androgen receptor (AR) expression in the hypothalamus and the testis and epididymis was significantly decreased at different times by the high-dose treatment.

CONCLUSION: Tripterygium glycosides affected the estrus cycle in female rats and caused damage to the uterus; in male rats, the testicles and sperm were damaged. The mechanism of reproductive toxicity occurred through the secretion of multiple hormones.