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Updated: Jul 14, 2026
Mouse Model of Surgically-induced Endometriosis by Auto-transplantation of Uterine Tissue
Published on: January 6, 2012
Metformin reverses infertility in a mouse model of endometriosis: unveiling disease pathways and implications for
A Catarina Neto1, Maria Botelho1, Adriana R Rodrigues2
1Department of Biomedicine Experimental Biology Unit, Faculty of Medicine of the University of Porto, Porto, Portugal.; Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal.
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.
Insights
Metformin treatment improved fertility in a mouse model of endometriosis by reducing lesion growth and fibrosis. This suggests metformin may be a potential therapy for endometriosis-associated infertility.
Area of Science:
- Reproductive biology and endocrinology
- Pharmacology and drug discovery
- Gynecological pathology
Background:
- Endometriosis is a condition characterized by endometrial tissue outside the uterus, often leading to chronic pelvic pain and infertility.
- The exact mechanisms underlying endometriosis-associated infertility are complex and multifactorial, involving inflammation, oxidative stress, and altered endometrial receptivity.
- Current treatments for endometriosis-associated infertility are limited and often focus on surgical intervention or hormonal suppression, which may not address underlying reproductive dysfunction.
Purpose of the Study:
- To investigate the potential of metformin, a widely used antidiabetic drug, in reversing endometriosis-associated infertility.
- To evaluate the effects of metformin on endometriosis lesion growth, fibrosis, and key molecular markers in a murine model.
Main Methods:
- A murine model of endometriosis was established by transplanting uterine fragments.
- Mice with induced endometriosis were treated with metformin (0.5mg/ml) orally for 3 months.
- Endometriosis implant growth, fibrosis, and expression of markers like PCNA, CYP17a1, F4/80, galectin-3, NFkB, GPX-1, and HO-1 were assessed.
Main Results:
- Metformin treatment significantly increased fertility rates in mice with endometriosis, restoring them to control levels.
- Metformin administration slowed endometriosis implant growth and vascularization.
- The treatment reduced fibrosis and modulated the expression of key molecular markers, including PCNA, CYP17a1, F4/80, galectin-3, NFkB, GPX-1, and HO-1.
Conclusions:
- Metformin effectively alleviates oxidative stress and mitigates fibrosis in endometriosis lesions within a murine model.
- These findings suggest that metformin holds promise as a pharmacological intervention to improve infertility associated with endometriosis.
- Further research is warranted to explore the clinical application of metformin for managing endometriosis-related infertility in humans.
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