Placenta (2000), 21, 367–375 doi:10.1053/plac.1999.0484, available online at http://www.idealibrary.com on Fatty Acid Transport Regulatory Proteins in the Developing Rat Placenta and in Trophoblast Cell Culture Models G. T. Knipp a,b,c , B. Liu a , K. L. Audus d , H. Fujii e , T. Ono e and M. J. Soares e a Department of Molecular and Integrative Physiology, The University of Kansas Medical Center, 39 011 Rainbow Boulevard, Kansas City, Kansas 66160; d Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Ave, Lawrence, Kansas 66045, USA e Department of Biochemistry, Niigata University School of Medicine, Niigata 951, Japan Paper accepted 9 November 1999 The placenta forms a selective barrier that is able to transport nutrients that are of critical use to the fetus. Delivery of essential fatty acids to the fetus is dependent upon transplacental transport and provides the backbone for the biosynthesis of biological membranes, myelin and various signalling molecules. The primary objective of this research was to elucidate the expression patterns of genes that regulate fatty acid transport across the placenta. Several fatty acid transport regulatory genes have been identified in the rat including; cytoplasmic heart fatty acid binding protein (hFABP), plasma membrane fatty acid binding protein (FABPpm), fatty acid translocase (FAT) and fatty acid transport protein (FATP). In this study, we have elucidated temporal and spatial expression patterns for these genes in the rat placenta and in cell culture models of the rat placenta by Northern blot, RT-PCR, Western blot and/or by in situ hybridization analyses. Expression of hFABP was specific to the labyrinth zone, the main barrier and site of transplacental transport in the rat placenta. In addition, the levels of hFABP expression increased with gestational age, suggesting a growing requirement for fatty acid transport with advancing stages of pregnancy. FABPpm, FAT and FATP are expressed in both the junctional and labyrinth zones of the rat placenta. FAT was predominantly localized to the labyrinth zone by in situ hybridization analysis. The placental cell expression patterns of the genes involved in fatty acid transport were supported by our observations of HRP-1 (labyrinth zone) and Rcho-1 (junctional zone) trophoblast cell culture models. Given their cell surface location, we predict that FABPpm, FAT and FATP potentially participate in placental fatty acid uptake. The predominant expression of hFABP and FAT in the labyrinth zone of the chorioallantoic placenta implicates hFABP and FAT in the transplacental movement of fatty acids from maternal to fetal compartments.  2000 Harcourt Publishers Ltd Placenta (2000), 21, 367–375 INTRODUCTION The placenta is comprised of highly specialized trophoblast cells that form a barrier between the maternal uterus and fetus. Trophoblast cells directionally regulate the transport of nutri- ents from the maternal blood supply to the fetal blood supply (Knipp, Audus and Soares, 1999). The active transport of nutrients, including fatty acids, across the placenta is critical for the development of a healthy fetus. For example, unsatu- rated fatty acids of the n-3 and n-6 classification are considered to be essential because mammals are unable to synthesize them and must acquire them through their diet (Nettleton, 1993; Jumpsen and Clandinin, 1995). The fetus must rely on maternal circulation and transfer across the placenta as its source of these essential fatty acids (Nettleton, 1993; Jumpsen and Clandinin, 1995). Essential fatty acids of both the n-3 and n-6 series (e.g., linoleic and linolenic acid) are involved in the synthesis of several compounds involved in cell–cell signalling including: prostaglandins, prostacyclins, leukotrienes, throm- boxanes and lipoxins. Essential fatty acids are also involved in the synthesis of phospholipids, a primary component of bio- logical membranes and myelin, a principle constituent of the nervous system (Jumpsen and Clandinin, 1995; Nettleton, 1993). The importance of fatty acid transport to the fetus is further demonstrated by the fact that transfer is highly directional from the mother to the fetus (Crawford et al., 1993; Nettleton, 1993; Jumpsen and Clandinin, 1995; Viscardi, 1995; Robillard and Christon, 1997). The ability of fatty acids to cross the placenta is critical for proper fetal growth (Hornstra et al., 1995), including the development of the fetal lungs (Viscardi, b Recipient of a postdoctoral fellowship from the NIH and American Heart Association, present address: College of Pharmacy, Rutgers University, 160 Frelinghuysen Road, Piscataway, New Jersey 08854- 8022, USA. c To whom correspondence should be addressed at: College of Pharmacy, Rutgers University, 160 Frelinghuysen Road, Piscataway, New Jersey 08854-8022, USA. Fax: +1 732 445-3134; E-mail: gknipp@cop.rutgers.edu 0143–4004/00/040367+09 $35.00/0  2000 Harcourt Publishers Ltd