Modulating IL-11-dependent matrix stiffness to delay ovarian aging

Wu M, Zhu Q, Xiong J, Tang W, Wang W, Li Y, Dai J, Wang S, Zhang J

1. 01

   Atomic force microscopy confirmed increased human ovarian matrix stiffness with age and in chemotherapy-induced premature ovarian insufficiency, PCOS and endometriosis

2. 02

   IL-11 is elevated in aging mouse, rat and human ovary and activates fibroblasts to secrete extracellular matrix

3. 03

   Genetic deletion of Il11ra1 in mice mitigated age-, POI- and PCOS-associated stiffening and functional decline

4. 04

   Single-nuclei RNA-seq showed Il11ra1 blockade reduces the proportion of activated fibroblasts

5. 05

   siIl11 nanoparticles in aged mice and rats reduced ovarian matrix stiffness and enhanced fertility

Study Design

Preclinical Study

Sample Size

Not reported

Study Duration

Preclinical (rodent) with human tissue characterization

Methodology

Atomic force microscopy of human ovarian tissue; proteomics of human ovary integrated with transcriptomics of human ovarian fibroblasts; Il11ra1 knockout mice; single-nuclei RNA sequencing; siIl11 nanoparticle administration in aged mice and rats.

Limitations

Human data are descriptive (tissue stiffness and IL-11 expression); every intervention result is rodent. No human anti-IL-11 trial in ovarian aging exists. Anti-IL-11 antibodies in clinical development for fibrotic disease have their own safety profile that has not been characterized in a reproductive-aging population.