Wang Q, Fujii H, Knipp G T
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854-8022, USA.
Placenta. 2002 Sep-Oct;23(8-9):661-71. doi: 10.1053/plac.2002.0855.
Placental fatty acid transfer is critical to meet the foetal requirements necessary for the biosynthesis of biological membranes, myelin, and various signaling molecules. The primary objective of this research was to elucidate the placental expression patterns of genes that may potentially regulate placental fatty acid transfer and homeostasis. In this study, we have elucidated the temporal and spatial patterns of expression of peroxisome proliferator-activated receptor (PPAR) and 9-cis retinoic acid receptor (RXR) isoforms in the junctional and labyrinth zones of the developing rat chorioallantoic placenta and in human term placenta. PPAR (alpha, beta, and gamma) and RXR (alpha, beta, and gamma) isoforms are nuclear hormone receptors that are known to regulate gene transcription and protein expression levels of fatty acid transport and metabolism mediating proteins through the formation of a DNA binding heterodimer complex. In the present study, the expression patterns of PPAR and RXR isoforms were determined in developing rat placenta and human term placenta using RT-PCR and immunohistochemical analyses. PPARalpha, beta, gamma, RXRalpha, beta and gamma were expressed in both junctional (invasive/endocrine function) and labyrinth (transport barrier) zones of the rat placenta, from day 13 to day 21 of gestation. In the human term placenta, PPARalpha, beta, gamma, RXRalpha and gamma were observed, while RXRbeta was not detected. Immunocytochemistry staining results determined the presence of PPARalpha, beta, gamma, RXRalpha and gamma to be specific to the syncytial trophoblast layer of the human chorionic villi. The presence of PPAR and RXR isoforms in both the rat and human placentas suggest that PPAR and RXR isoforms are potential regulators of placental lipid transfer and homeostasis. Our work provides a framework for the further investigation of PPAR and RXR isoform specific regulation of placental fatty acid uptake, transport and metabolism.
胎盘脂肪酸转运对于满足胎儿生物合成生物膜、髓磷脂及各种信号分子所需的营养至关重要。本研究的主要目的是阐明可能潜在调节胎盘脂肪酸转运和稳态的基因在胎盘中的表达模式。在本研究中,我们已经阐明了过氧化物酶体增殖物激活受体(PPAR)和9-顺式视黄酸受体(RXR)亚型在发育中的大鼠绒毛膜尿囊胎盘的结合区和迷路区以及足月人胎盘中的时空表达模式。PPAR(α、β和γ)和RXR(α、β和γ)亚型都是核激素受体,已知它们通过形成DNA结合异二聚体复合物来调节脂肪酸转运和代谢介导蛋白的基因转录和蛋白表达水平。在本研究中,使用逆转录聚合酶链反应(RT-PCR)和免疫组织化学分析确定了PPAR和RXR亚型在发育中的大鼠胎盘和足月人胎盘中的表达模式。从妊娠第13天到第21天,PPARα、β、γ、RXRα、β和γ在大鼠胎盘的结合区(侵袭/内分泌功能)和迷路区(转运屏障)均有表达。在足月人胎盘中,观察到了PPARα、β、γ、RXRα和γ,而未检测到RXRβ。免疫细胞化学染色结果确定PPARα、β、γ、RXRα和γ定位于人绒毛膜绒毛的合体滋养层。大鼠和人胎盘中均存在PPAR和RXR亚型,这表明PPAR和RXR亚型可能是胎盘脂质转运和稳态的调节因子。我们的工作为进一步研究PPAR和RXR亚型对胎盘脂肪酸摄取、转运和代谢的特异性调节提供了框架。