Establishment and comparison of positive models of fertility and early embryonic developmental toxicity in female rats

  The purpose is to compare the changes in reproduction and development indexes of female rats given different doses and times of cyclophosphamide before mating, and establish a standardized positive control model for fertility and early embryonic developmental toxicity test (paragraph I). Methods 150 SD rats, half male and half male, were randomly divided into vehicle control group, CTX20mg/kg and CTX100mg/kg groups according to their body weight. Each group had 50 rats, half of which were male and female. Female rats were divided into 5 times and 14 days before mating. One intraperitoneal injection (intraperitoneal, ip) was given 20mg/kg and 100mg/kg of CTX once a day. The vehicle control group was given the same amount of normal saline by the same route. The male rats in each group used for mating were not administered every day. Observe the general condition of SD rats, measure the body weight and food intake twice a week. Female rats are sacrificed on the 14th day of pregnancy (GD14, the day when sperm or vaginal thrombus is found is GD0) for final examination and calculation of pregnancy rate. Indexes such as pre-implantation loss rate, implantation rate, average corpus luteum, average implantation number, post-implantation loss rate, average live birth rate, live birth rate, continuous uterine fetal weight and absorbed fetal rate. Results Compared with the vehicle control group, the body weight and food intake of SD rats in each CTX group were significantly reduced (P<0.05 or P<0.01), pregnancy rate, preimplantation loss rate, implantation rate, and average corpus luteum There was no statistical difference between the number and the average number of implants. The uterine fetal weight in the CTX20mg/kg group was significantly reduced (P<0.01), and the loss rate after implantation of CTX100mg/kg was significantly increased (P<0.01). Fetal count, live birth rate, and uterine continuous fetal weight were significantly lower, and the absorption rate was significantly higher (P<0.05 or P<0.01). Conclusion Female SD rats were given CTX at 20 mg/kg and 100 mg/kg for 5 and 1 intraperitoneal injections 14 days before mating. Both of them can successfully establish a positive model of SD female rat fertility and early embryonic developmental toxicity, and CTX The best choice is a dosing regimen of 100 mg/kg once.