GM-CSF improves the receptivity of thin endometrium by promoting glandular and stromal cell proliferation in mice and humans

Abstract

Thin endometrium (TE, ≤7 mm) is widely recognized as a critical cause of infertility, recurrent pregnancy losses, and placental abnormalities. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a crucial role in tissue repair, but its effect on endometrial regeneration has been less investigated. We employed a thin endometrium mouse model established through unilateral 95% ethanol injury in an animal study and thin endometrium patients in a parallel clinical study. Both mice and patients were randomly apportioned into two groups: the Saline group and the GM-CSF group. We demonstrate that GM-CSF significantly increases endometrium thickness and gland number, promotes the proliferation of stromal cells, and improves the number of embryo implantation sites in the mouse model (P < 0.05). GM-CSF significantly (P < 0.05) promotes the proliferation of glandular cells, but not stromal cells in humans due to species-specific differential effects. GM-CSF treatment in humans induces upregulation of tissue repair/regeneration genes and enrichment of angiogenesis, cell adhesion, and epithelial proliferation pathways at the transcriptional level. The pregnancy outcomes, implantation rate (24.10% vs. 17.39%), and clinical pregnancy rate (34.78% vs. 26.32%), were both enhanced by GM-CSF compared to the Saline group. The delivery rate shows no statistically significant discrepancy between the two groups. GM-CSF has a positive role in endometrial regeneration and pregnancy outcomes in a thin endometrium. In conclusion, our study provides a novel therapeutic approach for thin endometrium and related infertility.