Placental regulation of fetal nutrient supply

Purpose of review Placental nutrient uptake and transfer may have a unique role, as changes in trophoblast nutrient-sensing signaling pathways regulate cell metabolism and may affect the fetal growth and health programming in the offspring. Recent findings The functionality of the placenta could affect the neonatal adiposity and the fetal levels of key nutrients such as long-chain polyunsaturated fatty acids. Insulin, oxygen and amino acid concentrations may regulate the mammalian target of rapamycin (mTOR) nutrient sensor in the human placenta affecting trophoblast metabolism and nutrient delivery. Summary The mechanisms involved in both placental uptake and transfer of macronutrients are reviewed. Fatty acid, cholesterol and amino acid transport across the placenta involves a complex system to ensure nutrient delivery to the growing fetus. The placental glucose transfer is important for fetal macrosomia, but lipid disturbances in both maternal and placental compartments may contribute to neonatal fat accretion. Maternal insulin has little effect on the avidity of glucose transport by the placenta, but may interfere in placental metabolism via mTOR nutrient sensor. mTOR is a positive regulator of the amino acid carriers and constitutes a critical link between maternal nutrient availability and fetal growth, thereby influencing the long-term health of the fetus

Omega 3 fatty acids, gestation and pregnancy outcomes

Pregnancy is associated with a reduction in maternal serum docosahexaenoic acid (DHA, 22:6 n-3) percentage and its possible depletion in the maternal store. Since the synthesis of long chain polyunsaturated fatty acids (LCPUFA) in the fetus and placenta is low, both the maternal LCPUFA status and placental function are critical for their supply to the fetus. Maternal supplementation with DHA up to 1 g/d or 2·7 g n-3 LCPUFA did not have any harmful effect. DHA supplementation in large studies slightly the enhanced length of gestation (by about 2 days), which may increase the birth weight by about 50 g at delivery. However no advice can be given on their general using to avoid preterm deliveries in low or high risk pregnancies. Several studies, but not all, reported improvements of the offspring in some neurodevelopmental tests as a result of DHA supplementation during gestation, or, at least, positive relationships between maternal or cord serum DHA percentages and cognitive skills in young children. The effect seems more evident in children with low DHA proportions, which raises the question of how to identify those mothers who might have a poor DHA status and who could benefit from such supplementation. Most studies on the effects of n-3 LCPUFA supplementation during pregnancy on maternal depression were judged to be of low-to-moderate quality, mainly due to small sample sizes and failure to adhere to Consolidated Standards of Reporting Trials guidelines. In contrast, the effects of n-3 LCPUFA supplementation on reducing allergic diseases in offspring are promising.</jats:p

Placental regulation of fetal nutrient supply

Purpose of review Placental nutrient uptake and transfer may have a unique role, as changes in trophoblast nutrient-sensing signaling pathways regulate cell metabolism and may affect the fetal growth and health programming in the offspring. Recent findings The functionality of the placenta could affect the neonatal adiposity and the fetal levels of key nutrients such as long-chain polyunsaturated fatty acids. Insulin, oxygen and amino acid concentrations may regulate the mammalian target of rapamycin (mTOR) nutrient sensor in the human placenta affecting trophoblast metabolism and nutrient delivery. Summary The mechanisms involved in both placental uptake and transfer of macronutrients are reviewed. Fatty acid, cholesterol and amino acid transport across the placenta involves a complex system to ensure nutrient delivery to the growing fetus. The placental glucose transfer is important for fetal macrosomia, but lipid disturbances in both maternal and placental compartments may contribute to neonatal fat accretion. Maternal insulin has little effect on the avidity of glucose transport by the placenta, but may interfere in placental metabolism via mTOR nutrient sensor. mTOR is a positive regulator of the amino acid carriers and constitutes a critical link between maternal nutrient availability and fetal growth, thereby influencing the long-term health of the fetus

Placental fatty acid transfer: a key factor in fetal growth

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 &lt;sup&gt;13&lt;/sup&gt;C-palmitic, &lt;sup&gt;13&lt;/sup&gt;C-oleic, and &lt;sup&gt;13&lt;/sup&gt;C-linoleic acids and &lt;sup&gt;13&lt;/sup&gt;C-docosahexaenoic acid (&lt;sup&gt;13&lt;/sup&gt;C-DHA) 12 h before an elective caesarean section. FA were quantified by gas chromatography and &lt;sup&gt;13&lt;/sup&gt;C enrichments by gas chromatography-isotope ratio mass spectrometry. The &lt;sup&gt;13&lt;/sup&gt;C-FA concentration was higher in total lipids of maternal plasma in GDM patients versus controls, except for &lt;sup&gt;13&lt;/sup&gt;C-DHA. Moreover, &lt;sup&gt;13&lt;/sup&gt;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 &lt;sup&gt;13&lt;/sup&gt;C-DHA placental uptake occurred in GDM patients treated with diet or insulin, while the latter also had lower &lt;sup&gt;13&lt;/sup&gt;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 &lt;sup&gt;13&lt;/sup&gt;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 &lt;sup&gt;13&lt;/sup&gt;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.</jats:p

Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy

Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephaly and intellectual impairments. Herein, we intended to identify early blood biomarkers that may be of use during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDM groups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects

Perinatal long chain polyunsaturated fatty acid supply Are there long term consequences?

Long-chain polyunsaturated fatty acids (LC-PUFA), especially docosahexaenoic acid (DHA), are essential components of biological membranes or act as precursors for eicosanoid formation, in case of the 20 carbon atom fatty acids, arachidonic acid (AA), dihomo-c-linolenic acid and eicosapentaenoic acid. During pregnancy LC-PUFA are enriched in the fetal circulation relative to maternal plasma. The corresponding placental processes have not been fully elucidated so far, but there are good indications that the LC-PUFA enrichment during the materno-fetal transfer is mediated by differences in the incorporation into lipid classes within the placenta between fatty acids and that specific fatty acid binding and transfer proteins are of major importance. In vitro a plasma membrane fatty acid binding protein could be identified, which preferentially binds DHA and AA compared to linoleic and oleic acids; in addition the m-RNA expression of fatty acid transfer protein 4 (FATP-4) in placental tissue was found to correlate significantly with the DHA percentage in cord blood phospholipids. After birth the percentage of LC-PUFA in infantile blood rapidly declines to levels depending on the dietary LC-PUFA supply, although preterm and full-term babies can convert linoleic and _-linolenic acids into AA and DHA, respectively. Breast milk provides preformed LC-PUFA, and breastfed infants have higher LC-PUFA levels in plasma and tissue than infants fed formulas without LC-PUFA. The high percentage of DHA in brain and other nervous tissue and the fact that the perinatal period is a period of fast brain growth suggests the importance of placental DHA transfer and dietary DHA content for optimal infantile development. Most but not all randomized, double blind, controlled clinical trials in preterm and in healthy full term infants demonstrated benefits of formulas supplemented with DHA and AA for the neurological development compared to formulas without LC-PUFA. Furthermore, according to the concept of “metabolic programming” during the perinatal period a dietary factor, such as the availability of LC-PUFA, might have long term consequences. From the available data it has to be assumed that LC-PUFA are conditionally essential substrates during early life and a further investigation of the biological mechanisms related to their availability for the infant and of potential life long effects on cognitive function and potentially also risk factors for cardiovascular diseases and allergy are certainly warranted