Thrombin Alters Human Endometrial Stromal Cell Differentiation During Decidualization

Area of Science:

• Reproductive biology
• Cellular and molecular biology
• Obstetrics and gynecology

Background:

• Vaginal bleeding and subchorionic hematomas increase risks of early and late pregnancy loss.
• Thrombin generation is implicated in the pathogenesis of these pregnancy complications.

Purpose of the Study:

• To investigate the effects of thrombin on human endometrial stromal cells (hESCs).
• To elucidate the role of thrombin in decidualization and early pregnancy support.

Main Methods:

• hESCs were treated with thrombin at baseline and during decidualization induced by cyclic adenosine monophosphate (cAMP) and medroxyprogesterone acetate (MPA).
• Next-generation RNA sequencing was employed to analyze gene expression changes.
• Key markers of decidualization and inflammation were assessed.

Main Results:

• Thrombin suppressed the expression of decidualization markers (IGF-1, IGFBP-1, PRL) both at baseline and during decidualization.
• Thrombin reduced PRL secretion, altered hESC morphology, and activated genes for matrix degradation and inflammation (IL-8, IL-6).
• Genes crucial for matrix stability (COL1A1, LOX) were suppressed.

Conclusions:

• Intrauterine bleeding and thrombin generation exacerbate endometrial inflammation and impair decidualization.
• Thrombin negatively impacts the endometrial support necessary for early pregnancy.
• These findings suggest a mechanism linking bleeding complications to pregnancy loss.