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WIREs Dev Biol
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Altered development and function of the placental regions in preeclampsia and its association with long‐chain polyunsaturated fatty acids

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The placenta is an essential organ formed during pregnancy that mainly transfers nutrients from the mother to the fetus. Nutrients taken up by the placenta are required for its own growth and development and to optimize fetal growth. Hence, placental function is an important determinant of pregnancy outcome. Among various nutrients, fatty acids, especially long‐chain polyunsaturated fatty acids (LCPUFAs), including omega 3 and omega 6 fatty acids, are essential for placental development from the time of implantation. Studies have associated these LCPUFAs with placental development through their roles in regulating oxidative stress, angiogenesis, and inflammation, which may in turn influence their transfer to the fetus. The placenta has a heterogeneous morphology with variable regional vasculature, oxidative stress, and LCPUFA levels in healthy pregnancies depending upon the location within the placenta. However, these regional structural and functional parameters are found to be disturbed in pathological conditions, such as preeclampsia (PE), thereby affecting pregnancy outcome. Hence, the alterations in LCPUFA metabolism and transport in different regions of the PE placenta as compared with normal placenta could potentially be contributing to the pathological features of PE. The regional variations in development and function of the placenta and its possible association with placental LCPUFA metabolism and transport in normal and PE pregnancies are discussed in this review. WIREs Dev Biol 2016, 5:582–597. doi: 10.1002/wdev.238 This article is categorized under: Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Early Embryonic Development > Fertilization to Gastrulation Vertebrate Organogenesis > Musculoskeletal and Vascular
Basic structure of the placenta showing maternal and fetal sides and central, mid‐disc and peripheral regions based on the cord insertion site.
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Overview of proposed altered regional fatty acid metabolism and transfer in preeclampsia placenta. In preeclampsia, the disturbed maternal LCPUFA supply to the placenta alters its regional development. This affects LCPUFA transfer to the fetus which hampers intrauterine fetal growth and increases the risk of noncommunicable diseases in the adult life.
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Development of the placenta across gestation. (a) Rapidly proliferating young placental trophoblast cells at the site of implantation in the endometrium of the uterus; (b) matured syncytiotrophoblast cells propagate toward the periphery increasing the surface area of the placenta; (c) formation of intervillous space and extension of maternal blood vessels toward the developing placenta; (d) remodeling of terminal spiral arteries and plugging the inlet with cytotrophoblast cells to restrict the entry of maternal blood inside the developing placenta; (e) unplugging of spiral arteries inlet and onset of maternal blood flow in the placenta starting from periphery and progressing toward the center; (f) complete establishment of blood flow in the placenta leading to the formation of villous tree lobules; (g) fully developed placenta to accelerate the process of nutrient transfer from maternal to the fetal circulation.
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Metabolic pathways of fatty acids in syncytiotrophoblast layer of the placenta. (1, 2, & 3) NEFA are up taken by FATP, FAT/CD36) and p‐FABPpm from maternal circulation in the IVS or (4) get directly diffused through plasma membrane. (5) Up taken fatty acids get activated by ACSL to form fatty acid acyl‐CoA or (6) bind to FABP which is (7) interconvertable. Fatty acids take various pathways based on the requirement which includes (8, 9, & 10) transport to the fetal circulation, (11) mitochondrial β‐oxidation, (12) storage in the form of lipid droplets, (13) incorporation in PL of plasma membrane, (14) synthesis of LCPUFA with the help of FADS, (15) formation of active metabolites. (16) Fatty acids and its metabolites are ligands of transcription factors like PPAR which then forms heterodimer with RXR to initiate transcription of genes. NEFA, nonesterified fatty acid; IVS, intervillous space; MVM, microvillus membrane; BM, basal membrane; PL, phospholipids; PGs, prostaglandins; LCPUFA, long‐chain polyunsaturated fatty acid; ER, endoplasmic reticulum; PPAR, peroxisome proliferators‐activated receptor; RXR, retinoid X receptor; FABP, fatty acid binding protein; p‐FABPpm, placenta‐specific plasma membrane; FABP, FAT/CD36, fatty acid translocase; FATP, fatty acid transport protein; ACSL, acyl co‐A synthetase; FADS, fatty acid desaturase.
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Vertebrate Organogenesis > Musculoskeletal and Vascular
Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing
Early Embryonic Development > Fertilization to Gastrulation