Placental Fatty Acid Transfer: A Key Factor in Fetal Growth

Abstract

The functionality of the placenta may affect neonatal adiposity and fetal levels of key nutrients such as long-chain polyunsaturated fatty acids. Fetal macrosomia and its complications may occur even in adequately controlled gestational diabetic (GDM) mothers, suggesting that maternal glycemia is not the only determinant of fetal glycemic status and wellbeing. We studied in vivo the placental transfer of fatty acids (FA) labeled with stable isotopes administered to 11 control and 9 GDM pregnant women (6 treated with insulin). Subjects received orally <sup>13</sup>C-palmitic, <sup>13</sup>C-oleic, and <sup>13</sup>C-linoleic acids and <sup>13</sup>C-docosahexaenoic acid (<sup>13</sup>C-DHA) 12 h before an elective caesarean section. FA were quantified by gas chromatography and <sup>13</sup>C enrichments by gas chromatography-isotope ratio mass spectrometry. The <sup>13</sup>C-FA concentration was higher in total lipids of maternal plasma in GDM patients versus controls, except for <sup>13</sup>C-DHA. Moreover, <sup>13</sup>C-DHA showed a lower placenta/maternal plasma ratio in GDM patients versus controls and a significantly lower cord/maternal plasma ratio. Other FA ratios studied were not different between GDM and controls. A disturbed <sup>13</sup>C-DHA placental uptake occurred in GDM patients treated with diet or insulin, while the latter also had lower <sup>13</sup>C-DHA levels in the venous cord. The tracer study pointed towards an impaired placental DHA uptake as a critical step, while the transfer of other <sup>13</sup>C-FA was less affected. Patients with GDM treated with insulin could also have a greater fetal fat storage, which may have contributed to the reduced <sup>13</sup>C-DHA in the venous cord observed. The DHA transfer to the fetus was reduced in GDM pregnancies compared to controls. This might have an influence on fetal neurodevelopment and long-term consequences for the child.

Early Programming of Obesity Throughout the Life Course: A Metabolomics Perspective

“…Following observations in mice [26], the major facilitator super family domain containing 2a was identified as a preferred transporter of DHA in the human placenta [27] . This observation reinforced the hypothesis that a disturbed lipid metabolism, and not the glucose tolerance, is crucial in the fetal fat mass and subsequent adiposity onset [22][23][24] .…”

“…Over the last years, the placental fatty acid transport was identified as a key factor in fetal growth, as unexpected NEFA profiles were observed in mothers with different glucose tolerance levels or pBMI and in their children [22] . Schaefer-Graf et al [23] detected no significant difference in the NEFA levels between healthy and GDM mothers, yet higher NEFA levels were measured in the cord blood of GDM children.…”

Ontogeny of Sex-Related Differences in Foetal Developmental Features, Lipid Availability and Fatty Acid Composition

“…Our data indicate significant sex-related differences in content of essential fatty acids, which are so-called because they must be obtained from maternal transfer in the case of foetuses [22,63] or from diet in the case of adults [64]. The major essential fatty acids are linolenic PUFA (an omega-3 fatty acid) and linoleic PUFA (an omega-6 fatty acid); the long-chain omega-3 PUFA eicosapentaenoic and docosahexaenoic acids and the long-chain omega-6 PUFA gamma-linolenic and arachidonic acids are also essential.…”

Estimating the contribution of surfactant replacement therapy to the alveolar pool: An in vivo study based on 13C natural abundance in rabbits

“…Studies describing the metabolic fate of nutrients based on the variation of 13 C content have been performed in the past by our group and by several other investigators . In the present study, we explored the feasibility of using the isotopes natural abundance approach applied to drug delivery, in particular the delivery of poractant alfa (Curosurf®, Chiesi pharmaceuticals, Parma, Italy).…”