Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis

Area of Science:

• Reproductive biology
• Molecular endocrinology
• Cellular signaling

Background:

• Endometriosis is associated with infertility and pregnancy complications, often linked to defective endometrial decidualization.
• Identifying the molecular mechanisms underlying these reproductive issues is crucial for developing effective treatments.

Approach:

• Transcriptomic analysis of endometrial tissue from individuals with and without endometriosis.
• Investigation of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) signaling pathways.
• Utilized 3D endometrial assembloid models to assess the impact of BMP2 on decidualization.

Key Points:

• Transforming growth factor beta (TGFβ) pathways, including SMAD4, are impaired in the endometrium of individuals with endometriosis.
• Bone morphogenetic protein (BMP) signaling, critical for endometrial receptivity, shows compromised activity.
• Exogenous BMP2 administration enhanced decidual marker expression in endometriosis assembloids.

Conclusions:

• A previously unrecognized dysfunction in BMP/SMAD signaling contributes to defective decidualization in endometriosis.
• This signaling defect explains the increased risk of infertility and pregnancy complications in individuals with endometriosis.
• Targeting BMP/SMAD signaling may offer a therapeutic strategy for improving reproductive outcomes in endometriosis.