156 Cycloastragenol activation of telomerase reverse transcriptase improves β-Klotho expression and attenuates age-related malfunctioning in ovarian tissues
M. Idrees A B , A. M. Khan A B , S.-H. Lee A B , S.-M. Kang A B , J. Kang A B , Z. Haider A B , M.-D. Joo A B and I.-K. Kong A CA Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, Gyeongnam-do, South Korea
B Department of Animal Science, Division of Applied Life Science, Gyeongsang National University, Jinju, Gyeongnam-do, South Korea
C The King Kong Corp. Ltd., Gyeongsang National University, Jinju, Gyeongnam-do, South Korea
Reproduction, Fertility and Development 35(2) 206-206 https://doi.org/10.1071/RDv35n2Ab156
Published: 5 December 2022
© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of the IETS
Age-related deterioration in women’s reproductive capacity is directly related to the poor developmental potential of ovarian follicles. Although telomerase plays a crucial role in female fertility, telomerase reverse transcriptase (TERT)-targeting therapeutic strategies for age-related female infertility have yet to be investigated. This study elucidated the effect of TERT activation on mice ovary and Klb (β-Klotho) expression, which is linked to ageing, female hormonal regulation, and cyclicity. Homology modelling was performed to generate a three-dimensional structure of human TERT, then the validated model was used for molecular docking and molecular dynamics simulation with cycloastragenol (CAG). CAG treatment of granulosa cells (COV434) and activation of TERT were examined via telomere chromosome-oriented FISH (telomeric CO-FISH) and ELISA assay. Aged granulosa cells showed reduced expression of β-Klotho, which is associated with hormonal regulation and female cyclicity. We found that CAG-mediated TERT activation significantly enhanced the expression of Klb and its downstream signalling proteins in the D-galactose-induced ovarian ageing mouse model. Telomerase inhibition reduced the expression of β-Klotho in the ovaries of mice, demonstrating that Klb expression is TERT dependent. In conclusion, TERT-dependent β-Klotho regulation is one of the mechanisms that can overcome age-related female infertility.
This work was partly supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (grant no. NRF-2020R1A2C2006614), and a scholarship from the BK21 Four program.
