Decidual Cells Block Inflammation-Mediated Inhibition of 15-Hydroxyprostaglandin Dehydrogenase in Trophoblasts

Chorioamnionitis generates prostaglandin (PG) E₂ and F_2α, promoting fetal membrane rupture, cervical ripening, and uterine contractions. 15-Hydroxyprostaglandin dehydrogenase (HPGD) contributes to pregnancy maintenance by inactivating PGs. Herein, the role of decidual cells in the regulation of HPGD expression at the maternal-fetal interface was investigated. HPGD immunostaining was primarily detected in anchoring villi and choriodecidual extravillous trophoblasts (EVTs) during pregnancy. Chorionic EVTs adjacent to the decidua parietalis exhibited significantly higher HPGD levels than those adjacent to the amnion. HPGD histologic score levels were significantly lower in choriodecidua from chorioamnionitis versus gestational age-matched controls (means ± SEM, 132.6 ± 3.8 versus 31.2 ± 7.9; P < 0.05). Conditioned media supernatant (CMS) from in vitro decidualized term decidual cells (TDCs) up-regulated HPGD levels in differentiated EVTs, primary trophoblasts, and HTR8/SV^neo cells. However, CMS from 5 μg/mL lipopolysaccharide or 10 ng/mL IL-1β pretreated TDC cultures down-regulated HPGD levels in HTR8/SV^neo cultures. Similarly, direct treatment of HTR8/SV^neo with lipopolysaccharide or IL-1β significantly reduced HPGD levels versus control (P < 0.05) but not in TDC-CMS pretreated HTR8/SV^neo cultures. Collectively, these results uncover a novel decidual cell–mediated paracrine mechanism that stimulates levels of trophoblastic HPGD, whose function is to inactivate labor-inducing PGs, thereby promoting uterine quiescence during pregnancy. However, infectious/inflammatory stimuli in decidual cells cause a paracrine inhibition of trophoblastic HPGD expression, increasing PGE₂/PGF_2α levels, thereby contributing to preterm birth.