Gil-Sánchez Alfonso, Demmelmair Hans, Parrilla J J, Koletzko Berthold, Larqué Elvira
Service of Gynecology and Obstetrics, Virgen de la Arrixaca Hospital Murcia, Spain.
Front Genet. 2011 Sep 6;2:57. doi: 10.3389/fgene.2011.00057. eCollection 2011.
The concentration of long chain polyunsaturated fatty acid (LCPUFA) in the fetal brain increases dramatically from the third trimester until 18 months of life. Several studies have shown an association between the percentage of maternal plasma docosahexaenoic acid (DHA) during gestation and development of cognitive functions in the neonate. Since only very low levels of LCPUFA are synthesized in the fetus and placenta, their primary source for the fetus is the maternal circulation. Both in vitro and human in vivo studies using labeled fatty acids have shown preferential transfer of LCPUFA from the placenta to the fetus compared with other fatty acids, although the mechanisms involved are still uncertain. The placenta takes up circulating maternal non-esterified fatty acids (NEFA) and fatty acids released mainly by maternal lipoprotein lipase and endothelial lipase. These NEFA may enter the cell by passive diffusion or by means of membrane carrier proteins. Once in the cytosol, NEFA bind to cytosolic fatty acid-binding proteins for transfer to the fetal circulation or can be oxidized within the trophoblasts, and even re-esterified and stored in lipid droplets. Although trophoblast cells are not specialized for lipid storage, LCPUFA may up-regulate peroxisome proliferator activated receptor-γ (PPARγ) and hence the gene expression of fatty acid transport carriers, fatty acid acyl-CoA-synthetases and adipophilin or other enzymes involved in lipolysis, modifying the rate of placental transfer, and metabolism. The placental transfer of LCPUFA during pregnancy seems to be a key factor in the neurological development of the fetus. Increased knowledge of the factors that modify placental transfer of fatty acids would contribute to our understanding of this complex process.
从妊娠晚期到出生后18个月，胎儿大脑中长链多不饱和脂肪酸（LCPUFA）的浓度会急剧增加。多项研究表明，孕期母体血浆中二十二碳六烯酸（DHA）的百分比与新生儿认知功能的发育之间存在关联。由于胎儿和胎盘自身只能合成极低水平的LCPUFA，胎儿的主要来源是母体循环。使用标记脂肪酸进行的体外和人体体内研究均表明，与其他脂肪酸相比，LCPUFA能更优先地从胎盘转运至胎儿体内，不过其中涉及的机制仍不明确。胎盘摄取循环中的母体非酯化脂肪酸（NEFA）以及主要由母体脂蛋白脂肪酶和内皮脂肪酶释放的脂肪酸。这些NEFA可能通过被动扩散或借助膜载体蛋白进入细胞。一旦进入胞质溶胶，NEFA会与胞质脂肪酸结合蛋白结合，以便转运至胎儿循环，或者可在滋养层细胞内被氧化，甚至重新酯化并储存于脂滴中。尽管滋养层细胞并非专门用于脂质储存，但LCPUFA可能会上调过氧化物酶体增殖物激活受体γ（PPARγ），从而上调脂肪酸转运载体、脂肪酸酰基辅酶A合成酶和脂肪亲和素或其他参与脂解的酶的基因表达，进而改变胎盘转运和代谢的速率。孕期LCPUFA的胎盘转运似乎是胎儿神经发育的关键因素。深入了解影响脂肪酸胎盘转运的因素，将有助于我们理解这一复杂过程。
