Expression and role of peroxisome proliferator-activated receptors in the porcine early placenta trophoblast

Peroxisome proliferator-activated receptors (PPARs) are members of a nuclear receptor family of ligand-dependent transcription factors. Three isoforms of PPAR named PPAR alpha, PPAR beta/delta, and PPAR gamma have been described, each encoded by a separate gene: PPARA, PPARD, and PPARG, respectively. In the present study, we examined the profiles of PPAR and retinoid X receptor (RXR; PPAR heterodimer partner) mRNA expression and PPAR DNA binding activity in porcine trophoblast tissue collected on days 15, 20, 25, and 30 of pregnancy and in day-20 embryos. Placenta trophoblast cells isolated on day 25 of pregnancy were used to determine effects of (1) cytokines on PPAR and RXR mRNA expression and (2) PPAR agonists on prostaglandin (PG) E2 synthesis and the expression of genes involved in steroidogenesis, fatty acid binding, and PG transport, as well as on cell proliferation. The mRNA expression of PPARA and RXRB was greater in trophoblast tissue collected on days 25 and 30 of pregnancy compared with day 15 (P < 0.05), while DNA binding activity of PPAR alpha decreased between day 15 and 25 (P < 0.05). Increased concentrations of PPARD and RXRA transcripts were observed in trophoblasts collected on day 20 compared to trophoblasts from days 15 and 30 (P < 0.05). Moreover, concentrations of DNA-bound PPAR beta/delta, and PPAR gamma proteins increased in day-30 trophoblasts compared to day 15 (P < 0.01) and day 20 (P < 0.05), respectively. On day 20 of gestation, the mRNA expression of PPARD, PPARG, and RXRA and protein levels of PPAR alpha and PPAR gamma isoforms were greater in trophoblast than embryonic tissue (P < 0.01). Interleukin 1 beta and/or interferon gamma, but not IL6 and leukemia inhibitory factor, upregulated PPAR and RXR mRNA expression in placenta trophoblast cells in vitro (P < 0.05). Rosiglita-zone (a PPAR gamma agonist) stimulated prostaglandin E synthase mRNA expression in trophoblast cells and PGE2 accumulation in incubation medium (P < 0.05). Moreover, activation of PPAR isoforms differentially affected the expression of genes involved in steroidogenesis, fatty acid binding, and PG transport in studied cells. Finally, PPAR alpha and PPAR gamma agonists stimulated trophoblast cell proliferation (P < 0.05), and this effect was abolished by the addition of a respective PPAR antagonist (P < 0.05). Overall, these results point to a role of PPAR isoforms in porcine placenta development and function. (C) 2018 Elsevier Inc. All rights reserved.