Granulocyte Colony Stimulating Factor Enhances Decidualization Process of Endometrial Stromal Cells Through STAT3/HOXA10 Axis

Abstract

Background: Recurrent implantation failure (RIF) is characterized by the repeated failure of implantation, often linked to impaired endometrial receptivity. This study investigates how granulocyte colony‐stimulating factor (G‐CSF) promotes endometrial stromal cell decidualization. Methods: THESCs (human telomerase reverse transcriptase‐immortalized endometrial stromal cells) were used as an in vitro cell model to induce decidualization. The effects of G‐CSF on the expression of decidualization genes and apoptosis during decidualization were examined. Additionally, a chemical inhibitor of signal transducer and activator of transcription 3 (STAT3) and the small interfering RNA (siRNA) targeting Homeobox A10 (Hoxa10) were employed to explore the involvement of the STAT3/HOXA10 axis in the action of G‐CSF. Results: G‐CSF promoted decidualization markers expression and suppressed apoptosis in THESCs Treatment with G‐CSF enhanced STAT3 activation during decidualization induction. STAT3 inhibition diminished the effects of G‐CSF on decidualization marker expression and apoptosis suppression. Furthermore, it was demonstrated that G‐CSF increased Hoxa10 expression in a STAT3‐dependent manner. Silencing Hoxa10 abrogated the effects of G‐CSF on promoting decidualization. Conclusion: G‐CSF enhances decidualization of endometrial stromal cells via STAT3/HOXA10 axis activation. These findings suggest that optimal G‐CSF delivery strategies could improve endometrial receptivity in RIF patients.