Reversing Ovarian Fibrosis in Mice
Researchers here provide evidence for ovarian fibrosis to be an important mechanism in limiting the age at which female mammals can remain fertile. Interestingly, existing antifibrotic drugs can produce some reversal of this fibrosis, enough to restore ovulation in mice. Fibrosis is a malfunction of tissue maintenance; cells produce too much collagen, creating scar-like deposits that disrupt tissue structure and function. The range of present drug treatments can produce only a little benefit for most fibrotic conditions, and thus the positive results here are quite intriguing.
The female ovary contains a finite number of oocytes, and their release at ovulation becomes sporadic and disordered with aging and with obesity, leading to loss of fertility. Understanding the molecular defects underpinning this pathology is essential as age of childbearing and obesity rates increase globally. We identify that fibrosis within the ovarian stromal compartment is an underlying mechanism responsible for impaired oocyte release, which is initiated by mitochondrial dysfunction leading to diminished bioenergetics, oxidative damage, inflammation, and collagen deposition.
Furthermore, antifibrosis drugs (pirfenidone and BGP-15) eliminate fibrotic collagen and restore ovulation in reproductively old and obese mice, in association with dampened M2 macrophage polarization and up-regulated MMP13 protease. This is the first evidence that ovarian fibrosis is reversible and indicates that drugs targeting mitochondrial metabolism may be a viable therapeutic strategy for women with metabolic disorders or advancing age to maintain ovarian function and extend fertility.