Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labor

Abstract

Background: Human labor is a complex series of cellular and molecular events that occur at the materno-fetal and uterine levels. Many hypotheses have been proposed for the initiation of human labor, one hypothesis suggests that maturation of the fetus releases a signal in the amniotic fluid that will be transmitted to myometrium via the fetal membranes and initiate uterine contractions. There is strong evidence that prostaglandins (PGs) play a central role in initiation and progression of human labor.

Objectives: In this study we intended to investigate the expression of prostaglandin F synthase and the prostaglandin transporter in the human fetal membranes and to explore the relationship between cytokines and PGs in the mechanism of human labor.

Methods: We used fetal membranes obtained before labor at term and after spontaneous labor at term or preterm to identify the changes in prostaglandin F synthase (AKR1B1) and human prostaglandin transporter (SLCO2A1) proteins in relation to parturition. Using fetal membranes explants we tested the effect of cytokines (interleukin-1 and tumor necrosis factor alpha) on PG production and the concomitant changes in cyclooxygenase-2 (PTGS2), AKR1B1 and SLCO2A1 expression.

Results: Expression of PTGS2 and AKR1B1 was upregulated in the fetal membranes in association with term labor while SLCO2A1 was downregulated with advancing gestation and during term labor. Before labor, IL-1 increased the expression of PTGS2, however during labor TNF upregulated PTGS2 and AKR1B1 proteins.

Conclusions: The prostaglandin F synthase AKR1B1 is upregulated while prostaglandin transporter is downregulated during term labor. The amnion is more responsive than choriodecidua to stimulation with pro-inflammatory cytokines. The mechanisms of term and preterm labor are different.

Keywords: cytokines; parturition; placenta; preterm birth; prostaglandins; uterus.

Figure 1

Immunohistochemistry staining of term decidua basalis (A), chorionic villi (B) and fetal membranes (C) with AKR1B1 antibody (D–F), SLCO2A1 antibody (G–I), and PTGS2 antibody (J–L). Primary antibodies were omitted in (A–C) which served as controls. DC, decidual cells; Syn, syncytiotrophoblast; Cyt, cytotrophoblast; IVS, intervillous space; De, decidua parietalis; Ch, chorion; and A, amnion. Bar = 100 μm.

Figure 2

Expression of AKR1B1 and SLCO2A1 protein in the fetal membranes in association with term and preterm labor compared to not in labor. TNIL, term not in labor; PNIL, preterm not in labor; SPL, spontaneous preterm labor; STL, spontaneous term labor; IOL, induction of labor. Westerns are representative of immunoblots prepared from fetal membranes collected immediately after delivery, ^**p < 0.005.

Figure 3

Effect of IL-1β on PGE₂ and PGF_2α production from the fetal side of membranes. C, control; M, maternal side exposure; F, fetal side exposure; and M&F, exposure to maternal and fetal sides; TNIL, term not in labor; STL, spontaneous term labor; SPL, spontaneous preterm labor. The bars represent the mean ± SD; n = 4, ^*p < 0.05 and ^**p < 0.005.

Figure 4

Effect of TNF-α on expression of AKR1B1 protein in the fetal membranes and the associated changes in PGF_2α production from fetal side of membranes. C, control; M, maternal side exposure; F, fetal side exposure; and M&F, maternal and fetal sides exposure. TNIL, term not in labor; STL, spontaneous term labor; SPL, spontaneous preterm labor. The bars represent the mean ± SD; n = 4, ^*p < 0.05.