Plasma progesterone levels remain elevated throughout human pregnancy, suggesting that reduced reproductive-tract progesterone receptor (PR) initiates labor. Placental abruption and excess thrombin generation elicit preterm delivery (PTD). PR, glucocorticoid receptor (GR), and total and p-ERK1/2 in decidual cells (DCs) and interstitial trophoblasts (IT) were assessed via immunohistochemical staining in abruption-associated PTD versus gestational-age matched control placentas, and in cultured DCs incubated with estradiol (E2) ± medroxyprogesterone acetate (MPA) ± thrombin. Immunostaining for PR was lower in DC nuclei in abruption versus control decidua and was absent from ITs; GR was higher in IT than DCs, with no abruption-related changes in either cell type; p-ERK1/2 was higher in DCs in abruption than control decidua, with total ERK 1/2 unchanged. Immunoblotting of cultured DCs demonstrated strong E2, weak MPA, and intermediate E2+MPA mediated elevation of PR-A and PR-B levels, with constitutive GR expression. In cultured DCs, thrombin inhibited PR but not GR mRNA levels, reduced PR binding to DNA and [(3)H]progesterone binding to PR, and enhanced phosphorylated but not total ERK1/2 levels. Coincubation with a specific p-ERK1/2 inhibitor reversed thrombin-enhanced p-ERK1/2 and lowered PR levels. Thus, abruption-associated PTD is initiated by functional progesterone withdrawal, as indicated by significantly reduced DC nuclear expression of PR-A and PR-B. Functional withdrawal of progesterone results in increased p-ERK1/2, and is thus one pathway initiating abruption-associated PTD.

Problem Toll receptor-4 (TLR-4) protects against gram-negative bacteria expressed lipopolysaccharide and “danger signals” from injured or dying cells. Although decidual cells (DCs) and interstitial trophoblasts (ITs) are in close contact, TLR-4 has been studied extensively only in ITs. Method of Study Formalin-fixed, paraffin-embedded serial sections of endometrium in follicular and luteal phases and deciduas from first and second trimester elective terminations and third trimester normal deliveries were immunostained for TLR-4, trophoblast-specific cytokeratin and DC-specific vimentin. HSCORE assessed TLR-4 immunostaining in DCs vs. ITs. Results TLR-4 HSCORES were significantly higher in: 1) first trimester DCs than luteal phase pre-decidual stromal cells; 2) first and third vs. second trimester DCs, but similar between third trimester deciduas parietalis and basalis; 3) first vs. second trimester ITs; 4) DCs vs. ITs across gestation. Conclusion Higher TLR-4 in DCs than ITs suggests DCs as primary targets for gram negative bacteria and/or inflammation-related danger signals.