FoxM1 Directs STAT3 Expression Essential for Human Endometrial Stromal Decidualization

Area of Science:

• Reproductive biology
• Molecular endocrinology
• Cellular and molecular physiology

Background:

• Human endometrial decidualization is vital for embryo implantation and successful pregnancy.
• Forkhead Box M1 (FoxM1) is a key transcription factor regulating cell proliferation and cell cycle progression.
• The role of FoxM1 in human endometrial decidualization is currently unknown.

Purpose of the Study:

• To investigate the molecular mechanism of FoxM1 during human endometrial decidualization.
• To determine FoxM1's role in human endometrial stromal cell (HESC) proliferation and differentiation.

Main Methods:

• Analysis of FoxM1 expression during the human menstrual cycle.
• Inhibition of FoxM1 in HESCs to assess effects on cell cycle and differentiation.
• Chromatin immunoprecipitation (ChIP) and luciferase assays to identify FoxM1 targets.

Main Results:

• FoxM1 expression is dynamic during the menstrual cycle.
• FoxM1 inhibition delays G2/M phase transition by downregulating cyclin B1 in HESCs.
• Loss of FoxM1 blocks HESC differentiation and impairs estrogen, progesterone, and dbcAMP response.
• FoxM1 transcriptionally activates STAT3, essential for HESC differentiation.

Conclusions:

• FoxM1 is a critical regulator of human endometrial decidualization.
• FoxM1 controls HESC proliferation and differentiation through cyclin B1 and STAT3 pathways.
• Dysregulation of FoxM1 may contribute to human endometrial disorders and infertility.