Role of the Glycogen Synthase Kinase 3-Cyclic AMP/Protein Kinase A in the Immobilization of Human Sperm by Tideglusib.

Autor: Wang W; NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China., Guo L; NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China., Jiang B; College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China., Yan B; Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Li Y; NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China., Ye X; College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China., Yang Y; NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China., Liu S; Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China., Shao Z; College of Chemistry and Chemical Engineering, Donghua University, Shanghai, 201620, China. zyshao@dhu.edu.cn., Diao H; NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China. diaohua@sibpt.com.
Jazyk: angličtina
Zdroj: Reproductive sciences (Thousand Oaks, Calif.) [Reprod Sci] 2023 Apr; Vol. 30 (4), pp. 1281-1290. Date of Electronic Publication: 2022 Oct 07.
DOI: 10.1007/s43032-022-01086-8
Abstrakt: Tideglusib is considered to be a promising alternative to nonyl alcohol-9 contraceptives. Previous studies have demonstrated that the rapid spermicidal effect of tideglusib at a high concentration (≥ 10 μM) may occur through detergent-like activity; however, the effect of low concentrations of tideglusib (< 5 μM) on sperm is unknown. We explored the intracellular mechanism of tideglusib (< 5 μM) on the immobilization of human sperm by exploring related signaling pathways in human sperm. After treatment with tideglusib (1.25 μM) for 2 h, sperm motility rate decreased to 0, while sperm membrane integrity rate was 70%. Protein tyrosine phosphorylation level and intracellular cyclic adenosine 3,5-monophosphate (cAMP) concentration decreased significantly compared to those in the control group. Isobutylmethylxanthine and 8-Bromo-cAMP relieved the inhibition of spermatozoa tyrosine phosphorylation, while tyrosine phosphorylation of sperm protein in the H89 and CALP1 treatment groups was significantly inhibited, and there was no difference in the tideglusib treatment group. H-89 and CALP1 reduced the level of serine phosphorylation of GSK-3α/β (Ser21/9), while its level was enhanced by IBMX and 8-Bromo-cAMP. Our results show the existence of the GSK3-cAMP/PKA regulatory loop in human sperm, which may mediate the immobilization effect of tideglusib at low of concentrations (e.g., 1.25 μM) on sperm motility.
(© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)
Databáze: MEDLINE
Externí odkaz: