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  3. Revitalising Aging Oocytes: Echinacoside Restores Mitochondrial Function and Cellular Homeostasis Through Targeting GJA1/SIRT1 Pathway

Revitalising Aging Oocytes: Echinacoside Restores Mitochondrial Function and Cellular Homeostasis Through Targeting GJA1/SIRT1 Pathway

  • Cell Prolif. 2025 Apr 18:e70044. doi: 10.1111/cpr.70044.
Liuqing Yang 1 2 3 4,  Xinle Lai 1 2 3,  Fangxuan Lin 5,  Nan Shi 5,  Xinya Xu 1 2 3,  Heng Wang 1,  Xiaotian Li 5,  Dan Shen 1 2 3,  Haimo Qian 1 2 3,  Xin Jin 5,  Jiayi Chen 5,  Zhongwei Huang 4 6 7,  Xing Duan 8,  Qin Zhang 1 2 3
Affiliations

Affiliations

  • 1 Department of TCM Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
  • 2 Research Institute of Women's Reproductive Health, Zhejiang Chinese Medical University, Hangzhou, China.
  • 3 Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou, China.
  • 4 NUS Bia-Echo Asia Centre of Reproductive Longevity and Equality, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 5 Zhejiang Chinese Medical University, Hangzhou, China.
  • 6 Institute of Molecular and Cell Biology, Agency of Science Research and Technology, Singapore, Singapore.
  • 7 Department of Obstetrics and Gynaecology, National University Health Systems, Singapore, Singapore.
  • 8 Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
PMID: 40251808 DOI: 10.1111/cpr.70044
Abstract

As maternal age increases, the decline in oocyte quality emerges as a critical factor contributing to reduced reproductive capacity, highlighting the urgent need for effective strategies to combat oocyte aging. This study investigated the protective effects and underlying mechanisms of Echinacoside (ECH) on aging oocytes. ECH significantly improved cytoskeletal stability and chromosomal integrity, as demonstrated by restored spindle morphology and reinforced F-actin structures, essential for meiotic progression. It also preserved mitochondrial function by restoring membrane potential and dynamics, reducing ROS levels, and downregulating the DNA damage marker γ-H2AX, thereby alleviating oxidative stress and enhancing genomic stability. Furthermore, ECH promoted cellular homeostasis through modulation of lipid metabolism, Autophagy and lysosomal function. Transcriptomic analyses identified GJA1 as a pivotal mediator of ECH's effects, validated through molecular docking and bio-layer interferometry. Functional studies showed that inhibiting GJA1 significantly reduced ECH's ability to enhance first polar body extrusion rates, mitochondrial function and antioxidant capacity, validating the critical role of the GJA1/SIRT1 pathway in combating oocyte aging. This study provides novel insights into the mechanisms of oocyte rejuvenation and highlights ECH as a promising therapeutic candidate for addressing age-related reproductive challenges.

Keywords

GJA1/SIRT1 pathway; cellular homeostasis; echinacoside; mitochondrial function; oocyte aging; oxidative stress.

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