Low Dose Antifibrotic Drugs Slow Ovarian Aging in Mice
As organisms age, fibrosis often occurs in various organs, including the ovaries. Fibrosis, characterized by the excessive deposition of collagen, can disrupt normal tissue function. Recent research has shown that administering low doses of antifibrotic drugs to mice can effectively slow down ovarian aging, leading to improved function and extended reproductive lifespan.
The female reproductive system is particularly prone to aging effects, resulting in infertility and endocrine imbalances. Aging ovaries develop a fibro-inflammatory environment that negatively impacts egg quantity and quality, as well as ovulation. In a study, researchers tested the effects of anti-inflammatory (Etanercept) and anti-fibrotic (Pirfenidone) drugs on ovarian aging in mice. While Etanercept had minimal effect on fibro-inflammatory gene expression, Pirfenidone notably reduced collagen expression.
Further experiments involved systemic delivery of Pirfenidone through mini-osmotic pumps for 6 weeks in mice. The drug successfully lowered age-related ovarian fibrosis without adverse effects on overall health. Ovarian function showed improvement in Pirfenidone-treated mice, with increased follicles, corpora lutea numbers, AMH levels, and enhanced estrous cyclicity. Transcriptomic analysis revealed upregulation of reproductive genes and downregulation of inflammatory genes, indicating improved ovarian function and longevity with Pirfenidone treatment.
Link: https://doi.org/10.1101/2024.06.21.600035
