Context: Pre-term delivery is commonly caused by intraamniotic infection with expression of pro-inflammatory cytokines (IL-1) or by abruption resulting in generation of decidual thrombin. While human parturition is not preceded by overt progesterone withdrawal, progesterone resistance likely leads to labor. The uteri of Hoxa10(-) mice demonstrate progesterone resistance; several genes, including prostaglandin receptors, are inappropriately regulated in response to progesterone.

Objective: We hypothesized that IL-1 or thrombin would decrease HOXA10 expression, contributing to the progestin resistant environment. We analyzed expression of HOX genes and their regulation by IL-1 or thrombin in decidual cells.

Design: In vitro experiment.

Setting: Academic Medical Center

Intervention: Term decidual cells were treated with estradiol (E₂) or E₂+ medroxyprogesterone acetate (MPA) followed by addition of thrombin or IL-1.

Main Outcome Measure: HOX mRNA was evaluated by microarray and confirmed by quantitative RT-PCR. Protein expression was detected using immunohistochemistry and western analysis.

Results: HOXA9, HOXA10, and HOXA11 were expressed in decidual cells and regulated by IL-1 and thrombin. HOXA10 was further analyzed due to its association with progesterone responsiveness. After E₂ treatment, IL-1 or thrombin decreased HOXA10 mRNA by 94% and 81%, respectively. After E₂+MPA treatment IL-1 or thrombin resulted in an 86% and 72% decrease in HOXA10 mRNA, respectively. A similar decrease was noted in HOXA10 protein expression.

Conclusion: The expression of HOXA10 protein at term indicates that it may have a role in maintaining decidual cell phenotype and pregnancy. The dramatic decrease of HOXA10 in response to IL-1 or thrombin may contribute to progestin resistance in pre-term labor, mimicking progesterone resistance seen in Hoxa10(-) mice.