2. Academic Validation
  3. Ribosome dysregulation and intervention in age-related infertility

Ribosome dysregulation and intervention in age-related infertility

  • Cell Rep Med. 2025 Oct 27:102424. doi: 10.1016/j.xcrm.2025.102424.
Jie Li 1,  Honghong Wang 2,  Pengfei Zhu 2,  Haixia Chen 3,  Haiyang Zuo 4,  Chang Liu 1,  Linlin Liu 1,  Xiaoying Ye 1,  Guofeng Feng 1,  Yiwei Wu 1,  Qinli Liu 5,  Tao Yang 6,  David L Keefe 7,  Xiaohong Bai 8,  Wei Shang 9,  Xueqing Wu 10,  Lin Liu 11
Affiliations

Affiliations

  • 1 State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China; Department of Cell Biology and Genetics, Nankai University, 94 Weijin Road, Tianjin 300071, China.
  • 2 Center for Reproductive Medicine, Children's Hospital of Shanxi and Women Health Center of Shanxi, Taiyuan 030013, China; Shanxi Center of Technology Innovation for Fertility Optimization, Taiyuan 030001, Shanxi, China.
  • 3 Center for Reproductive Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
  • 4 Department of Obstetrics and Gynecology, The Sixth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing 100142, China.
  • 5 Reproductive Medical Center, Amcare Women's & Children's Hospital, Tianjin 300381, China.
  • 6 Higher Education Key Laboratory of Tumor Immunology & Targeted Drug Development in Shanxi Province, Shanxi Medical University, Taiyuan 030001, Shanxi, China; Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
  • 7 Department of Obstetrics and Gynecology, NYU Langone Health, 550 First Avenue, New York, NY 10012, USA.
  • 8 Center for Reproductive Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: bxhjj@163.com.
  • 9 Department of Obstetrics and Gynecology, The Sixth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing 100142, China. Electronic address: shang.wei@163.com.
  • 10 Center for Reproductive Medicine, Children's Hospital of Shanxi and Women Health Center of Shanxi, Taiyuan 030013, China; Shanxi Center of Technology Innovation for Fertility Optimization, Taiyuan 030001, Shanxi, China. Electronic address: wuxueqq@hotmail.com.
  • 11 State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300350, China; Department of Cell Biology and Genetics, Nankai University, 94 Weijin Road, Tianjin 300071, China; Institute of Translational Medicine, Tianjin Union Medical Center, Nankai University, Tianjin 300000, China. Electronic address: liulin@nankai.edu.cn.
PMID: 41151579 DOI: 10.1016/j.xcrm.2025.102424
Abstract

Fertility in women decreases with age, but the molecular basis for age-related, unexplained infertility remains elusive. Here, we reveal distinct transcriptome changes in oocytes and surrounding cumulus cells from women in their mid-thirties, as evidenced by notably increased transcription of ribosome genes. Additionally, meiosis genes and actin and cohesin components are downregulated in oocytes with age. Lysosomes and proteostasis are also disrupted in cumulus cells. Moreover, DNA hypomethylation and altered heterochromatin deposition at specific genomic loci are linked to increased transcription of ribosome genes. Rapamycin effectively reduces translation and promotes protein homeostasis in cumulus cells. Remarkably, short-term rapamycin allows patients who fail repeated in vitro fertilization cycles with embryo developmental arrest to achieve high-quality blastocysts that yield successful pregnancy and live birth. These data suggest a causal role for elevated transcription of ribosome genes in aging oocytes and cumulus cells and identify rapamycin as a promising treatment for age-related infertility. This study is registered at Chinese Clinical Trial Registry (ChiCTR2300069828).

Keywords

aging; cumulus cells; infertility; oocyte; rapamycin; ribosome.

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