Effects of metformin and ganirelix on subcutaneous endometriosis in a mouse model of autophagy-related cell death.

Objective: This study aimed to investigate the efficacy of metformin and ganirelix on subcutaneous endometriotic tissues created in an experimental mouse model.

Materials and methods: Five groups were formed with eight animals in each group. One of the groups was set as the control group. Endometriotic lesions were created by transplanting 40 mouse autologous endomyometrial tissues into the mouse subcutaneous tissue to a highly vascular surface. Gene expression analyzes of tissues were performed as HIF-1α, ATG5, ATG12, Beclin2, Beclin1, LC3BII, CateninB, GSK3b, TCF, WNT2, WNT7α, and WNT10α gene analyzes. Drug effects were examined by histological examination. HIF1a and WNT2 protein expressions were examined immunohistochemically. Gene expression coefficients of control, metformin day 1 (Met1g), metformin day 7 (Met7g), ganirelix day 1 (Gnx1g), and ganirelix day 7 (Gnx7g) groups are shown in tables. Data are presented as mean and standard error.

Results: Beclin2 gene expression coefficients of metformin 1^st day, metformin 7^th day, ganirelix 1^st day, and general 7^th day groups were found to have significantly decreased compared with the control group coefficient. Beclin1 gene expression coefficients of metformin 1^st day, metformin 7^th day, ganirelix 1^st day, and genirelix 7^th day groups were found to have significantly decreased compared with the control group coefficient. LC3BII gene expression coefficients of metformin 1^st day and metformin 7^th day groups were found to have significantly decreased compared with LC3BII gene expression coefficients of control, genirelix 1^st day, and genirelix 7^th day groups. These findings were supported by histological and immunohistochemical staining.

Conclusion: These genes are actively involved in the autophagy pathway, and we think that the use of metformin in endometriosis might create an autophagy-based suppression mechanism.