Metformin reverses infertility in a mouse model of endometriosis: unveiling disease pathways and implications for future clinical approaches

• Type: Article in International Scientific Journal
• Date: 2025

Authors

Neto, AC (Author) Other; Botelho, M (Author) Other; Rodrigues, AR (Author) Other; Lamas, S (Author) Other; Araújo, B (Author) Other; Guimara, JT (Author) Other; Gouveia, Alexandra (Author) FMUP; Almeida, H (Author) Other; D Neves (Author) FMUP

Journal

Title: Reproductive BioMedicine Online

Vol. 50

ISSN: 1472-6483

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 0 Citations

Other information

Authenticus ID: P-017-66W

DOI: 10.1016/j.rbmo.2024.104474

Abstract (EN): Research question Does metformin reverse endometriosis-associated infertility? Design Endometriosis was induced by transplanting uterus fragments from B6CBAF1 mice into recipients of the same strain. The mice were divided into groups: endometriosis (End, n = 24), sham-operated (Sham, n = 12), endometriosis with metformin (0.5mg/ml) orally administered for 3 months (EndMet, n = 21) and sham-operated metformin-treated (ShamMet, n = 16). Implant growth was monitored using ultrasonography. Fibrosis was computer-assisted quantified in Masson's trichrome-stained sections of eutopic (EuEnd) and ectopic (EcEnd) endometrium. PCNA, CYP17a1, F4/80 and galectin-3 were analysed by immunofluorescence and western blotting, and NFkB, GPX-1 and HO-1 only by western blotting. Statistical significance was set at P <0.05. Results The endometriosis model was successfully established. The End groups showed lower fertility rates than sham-operated mice (P = 0.0034), whereas metformin treatment increased the number of fetuses per pregnant mouse (P = 0.0295), restoring fertility to control levels; it also slowed implant growth and vascularization. Metformin also restored PCNA expression and fibrosis levels to those of non-treated EuSham mice. PCNA expression decreased in pregnant mice (P <0.0178). Metformin diminished CYP17a1 expression in EcEnd versus EuEnd non-treated tissues and conversely up-regulated F4/80 in EuEnd tissue (P <0.0170), and galectin-3, NFkB and the antioxidant enzymes HO-1 and GPX-1 in EcEnd tissue (P <0.0293), in non-mated mice. Conclusions These results indicate that application of metformin can alleviate oxidative stress and mitigate fibrosis in endometriosis lesions in a murine model of endometriosis, which highlights metformin's potential as a pharmacological intervention for improving infertility in endometriosis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15