A novel long-acting, follicle stimulating hormone-Fc fusion protein displays Gonal-f-like function in vitro and in vivo

Autor: Yang Cuima, Wan Deyou, Gao Xin, Fang Chen, Yang Yi, Li Hongjie, Guili Xu, Lihou Dong, Liu Yunhui
Rok vydání: 2021
Předmět:
DOI: 10.21203/rs.3.rs-694716/v1
Popis: Purpose To explore whether X002 can enhance bioactivity and has a long half-time in vitro and in vivo. Methods For the in vitro study, GVBD rate and COC expansion were applied. In the GVBD test, 21–24-day-old female KM mice were stimulated with PMSG for 46 h, and the naked oocytes of ovaries were then collected. Four hours after X002 treatment at 37℃, the GVBD rates of naked oocytes were counted. In COC expansion, COCs were collected from mice stimulated with PMSG. After coculture of COCs and X002 for 14 h, COC diameter was measured, and the expression of genes involved in COC expansion was also determined by RT-qPCR. For the in vivo study, 6–8-week-old female SD rats were administered a subcutaneous injection of X002 for pharmacokinetics. Serum was assayed by ELISA at different time points. For pharmacodynamics, 26-day-old female SD rats were used in ovarian weight and superovulation assay. To assay ovarian weight, rats were stimulated with hCG 84 h after X002 treatment. At 12 h after hCG injection, ovaries were weighted and E2 or P4 in serum was quantified. To assay superovulation, rats were treated with the above methods. At 108 h after X002 treatment, oocytes were counted from fallopian tubes. Results X002 promoted GVBD and COC expansion in vitro and effectively promoted significant ovarian weight gain and superovulation, similar to Gonal-f; Meanwhile, it had a longer T1/2. Conclusions X002 is a long-acting FSH-liked agent which has good bioactivity, similar to Gonal-f.
Databáze: OpenAIRE