Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL), TRAIL Receptors, and the Soluble Receptor Osteoprotegerin in Human Gestational Membranes and Amniotic Fluid during Pregnancy and Labor at Term and Preterm

Abstract

We have studied TNF-related apoptosis-inducing ligand (TRAIL) and its membrane-bound (R1-R4) and soluble receptors [osteoprotegerin (OPG)] in gestational membranes to assess their significance in preterm parturition and premature rupture of membranes (PROM). TRAIL was detected by ELISA in extracts of term choriodecidual (but not amnion) tissues and explant-conditioned media. Concentrations of OPG (determined using ELISA) in gestational membranes were 20- to 50-fold greater than those of TRAIL. Median OPG concentrations in amniotic fluid (AF) at 15-17 wk gestation were similar to those at term before and during labor, whereas levels in pregnancies sampled preterm were significantly elevated. OPG levels in AF from women with preterm PROM were similar to those from women in preterm labor. In contrast, in pooled AF samples (n = 23-33), TRAIL concentrations at term with and without labor were elevated compared with samples from preterm deliveries. TRAIL-R3 and -R4 decoy receptors were detected in term amnion and choriodecidual extracts by immunoblotting and were localized by immunohistochemistry to amnion epithelial cells and chorionic trophoblasts. TRAIL (100 ng/ml) had little or no effect on amnion or choriodecidual cell viability or apoptosis, although these tissues responded to TNF-alpha with increased prostaglandin E(2) production. Our findings suggest that OPG is abundant in gestational membranes and, in concert with TRAIL decoy receptors, may protect resident cells of the fetal membranes against the proapoptotic effects of TRAIL and other related ligands during pregnancy.

ENDOCRINOLOGY IN PREGNANCY: Bone metabolic changes during pregnancy: a period of vulnerability to osteoporosis and fracture

“…OPG has received particular attention; its levels are stable during pregnancy and only rise at term, when they double in parallel with an apparently paradoxical increase in bone resorption (38,39). The rapid post partum fall in OPG suggests a placental origin, which has been corroborated by the finding of a high concentration of OPG in placental membranes (40). The circulating levels of RANKL have been investigated in studies that have reported parallel changes to those of OPG (41,42).…”

Immunoregulatory molecules in human placentas: potential for diverse roles in pregnancy

“…The same lines could not be killed by recombinant TRAIL, indicating that, at least in trophoblast tumor cell lines, DcR1 (TRAIL-R3) may protect against apoptosis. More recently, Lonergan et al (2003) have reported that osteoprotegerin, a soluble receptor for TRAIL, as well as the two TRAIL decoy receptors, TRAIL-R3 and -R4, are high in gestational membranes and may protect against the proapoptotic effects of locally produced TRAIL. Thus, all three receptors may be important.…”

Csf2 Null Mutation Alters Placental Gene Expression and Trophoblast Glycogen Cell and Giant Cell Abundance in Mice1

“…The Csf 2 null mutation increased expression of Cd24a, which encodes a mucin-like cell adhesion molecule, CD24, that shows reduced placental expression in preeclampsia [63]. Tnfrsf11b, which was downregulated in Csf 2 null mutant placentae, encodes osteoprotegerin, a cytokine that may protect gestational tissues from apoptosis [64]. Another gene strongly downregulated by the Csf 2 null mutation was Lilrb4, which encodes a leukocyte immunoglobulin-like receptor, CD85K, that is implicated in the signaling pathway through which placental HLA-G exerts immunosuppressive effects in T lymphocytes [65].…”