Metformin-mediated amelioration of the ovarian microenvironment in autoimmune premature ovarian insufficiency
Abstract
Premature ovarian insufficiency (POI), characterized by diminished ovarian function in women under 40, has immune factors as one of the significant etiological factors. Metformin, a frontline medication for type 2 diabetes and it may also modulate immune responses, suggesting potential immunomodulatory and anti-inflammatory properties. This study investigates the therapeutic potential of metformin in autoimmune POI. We established an autoimmune POI mouse model by immunizing with the peptide zona pellucida 3 (pZP3) and administered metformin via drinking water to assess its impact on ovarian and immune functions. Flow cytometry revealed an increase in the number of Treg cells in the POI group (pZP3), while the metformin-treated group showed a decrease close to the control group (CON) levels. Under transmission electron micros-copy, the pZP3 exhibited collapse and thinning of the zona pellucida, vacuolization of granulosa cells, and mitochondrial damage, with improvements observed in the metformin-treated group. In paraffin sections of mouse ovaries stained with Sirius Red, the pZP3 displayed a greater number of strong orange signals indicative of fibrosis, and in immunofluorescence, the macrophages in the pZP3 showed a clear polarization ab-normality in M1/M2, which was significantly reduced in the metformin-treated group. Our findings indicate that metformin significantly enhances ovarian function in pZP3-induced autoimmune POI mice and mitigates inflammation and fibrosis…
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