| . Depletion of 22:6n-3 from the retina and brain results in reduced visual function and learning deficits: these may involve critical roles of 22:6n-3 in membrane-dependent signaling pathways and neurotransmitter metabolism. Transfer of 22:6n-3 across the placenta involves specific binding and transfer proteins that facilitate higher concentrations of 22:6n-3 and 20:4n-6, but lower linoleic acid (18:2n-6) in fetal compared with maternal plasma, or in the breast-fed or formula-fed infant. However, human and animal studies both demonstrate that maternal diet impacts fetal 22:6n-3 and 20:4n-6 accretion. After birth, parenteral lipid, human milk and infant formula feeding all result in a marked decrease in plasma 22:6n-3 and 20:4n-6 and an increase in 18:2n-6. Estimation of fetal tissue fatty acid accretion suggests that current preterm infant feeds are unlikely to meet in utero rates of 22:6n-3 accretion. Consideration needs to be given to whether fetal plasma 22:6n-3 and 20:4n-6 enrichment and the low 18:2n-6 facilitates accretion of 22:6n-3 and 20:4n-6 in developing tissues. Show
IntroductionThe n-6 and n-3 polyunsaturated fatty acids are essential nutrients that are required for growth and normal cell function. These fatty acids are present in cells as the acyl moieties of phospholipids which make up the structural matrix of cell and subcellular membranes, and function directly, or as precursors to other molecules that modulate cell growth, metabolism, inter- and intracellular communication, protein function and gene expression [1], [2]. The n-3 fatty acid docosahexaenoic acid (22:6n-3) is of particular interest because it is selectively accumulated in the membrane amino phospholipids (phosphatidylethanolamine (PE) and phosphatidylserine (PS)) of the retina and brain grey matter [1], [2], [3], [4]. Docosahexaenoic acid is accumulated in the brain during brain growth and development; however, 22:6n-3 is also continually turned over, recycled and replenished by uptake from plasma during membrane signal transduction. Many studies have shown that depletion of 22:6n-3 from retinal and neural membranes results in reduced visual function, behavioural abnormalities, alterations in the metabolism of several neurotransmitters, and decreased membrane protein, receptor and ion channel activities [1], [2]. Recent studies have also shown G-protein coupled receptor signaling, including the activity of phosphodiesterase, is decreased by depletion of 22:6n-3 from retinal rod outer segment membranes [5]. The n-6 and n-3 fatty acids cannot be formed de novo by mammalian cells; thus all of the n-6 and n-3 fatty acids accumulated by the fetus must ultimately be derived from the mother by placental transfer, and after birth all must be provided by the infant diet. The n-6 and n-3 fatty acids recognized as essential dietary nutrients are linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3), respectively, and these fatty acids are formed in plant, but not animal cells [1], [2]. Once obtained from the diet, 18:2n-6 and 18:3n-3 can be further desaturated and elongated by Δ6 desaturase, elongation and Δ5 desaturase to arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3) from 18:2n-6 and 18:3n-3, respectively. Synthesis of 22:6n-3 proceeds by successive elongation of 20:5n-3 to 24:5n-3, followed by desaturation at position 6 to 24:6n-3, and chain shortening to 22:6n-3 [1], [2]. Synthesis of 22:5n-6 from 20:4n-6 occurs in an analogous pathway. Unlike 18:2n-6, 18:3n-3 is not known to have any essential biological functions in humans; rather the biological role of n-3 fatty acids appears to be fulfilled by 20:5n-3 and 22:6n-3. Placental transfer of 20:4n-6 and 22:6n-3 is believed to involve a multi-step process of uptake and intracellular translocation that is facilitated by several membrane-associated and cytosolic fatty acid binding proteins; these proteins favour n-6 and n-3 fatty acids over non-essential fatty acids, and 20:4n-6 and 22:6n-3 over 18:2n-6 or 18:3n-3 [6], [7], [8], [9], [10]. However, although the relative proportions of 20:4n-6 and 22:6n-3 in plasma lipids are higher in the fetus than in the mother, the maternal dietary intake of n-6 and n-3 fatty acids does influence the transfer of these fatty acids to the fetus [11], [12]. This paper focuses on the importance of maternal dietary fatty acids to the transfer of n-6 and n-3 fatty acids to the fetus, n-6 and n-3 fatty acid transport in fetal plasma, and the implications for the feeding of prematurely born infants. As introduced above, all of the n-6 and n-3 fatty acids accumulated by the fetus are derived by transfer across the placenta and ultimately originate from the maternal diet. The n-6 and n-3 fatty acids may be provided as 20:4n-6 and 22:6n-3, or as their 18:2n-6 and 18:3n-3 precursors, respectively. Experimental studies have shown that placental fatty acid transfer involves diffusion as well as membrane and cytosolic fatty acid binding proteins; membrane binding proteins that favour n-6 and n-3 fatty acids over non-essential fatty acids and 20:4n-6 and 22:6n-3 over 18:2n-6 and 18:3n-3 may be important in facilitating placental transfer of the latter longer chain n-6 and n-3 fatty acids to the fetus [6], [7], [8], [9], [10]. Recent reviews of placental fatty acid transfer have been published [9], [13], [14]. The Δ6 and Δ5 desaturases are present in fetal liver from early in gestation, but the activity of these enzymes appears to be low before birth [1], [15], [16], [17], [18]. Further, experimental studies have clearly shown that preformed 22:6n-3 provided in the maternal diet is much more efficacious than 18:3n-3 as a source of n-3 fatty acids for fetal tissue 22:6n-3 accretion [19], [20], [21], [22], [23]. Similarly, although desaturation of 18:3n-3 to 22:6n-3 occurs in infants and adults, including preterm infants, the activity of the pathway appears to be low with <1–9% 18:3n-3 converted to 22:6n-3 [24], [25], [26], [27]. There is no evidence that the ability to form 20:4n-6 from 18:2n-6 is low in humans, although providing a source of preformed 20:4n-6 in the diet increases plasma and red blood cell phospholipid 20:4n-6 in adults and infants [28], [29], [30], and increases tissue 20:4n-6 in animals [31], [32]. Analyses of the n-6 and n-3 fatty acids in maternal and fetal plasma (cord blood collected immediately following term birth) has shown that the relative proportions of 20:4n-6 and 22:6n-3 are higher, while 18:2n-6 is lower in triglycerides, phospholipids and cholesterol esters in the fetal than maternal plasma (Table 1). Similarly, 20:4n-6 and 22:6n-3 represent a higher proportion while 18:2n-6 is lower in the unsaturated fatty acids of fetal plasma esterified lipids than in the plasma of one-month-old breast-fed infants or infants fed formula (Table 2). However, despite higher proportions of 20:4n-6, 18:2n-6 is clearly transported across the placenta. The contribution of preferential acylation of 20:4n-6 and 22:6n-3 into esterified lipids released by the placenta to the fetal circulation and of specificity of acyltransferases involved in triglyceride and phospholipid synthesis in fetal liver to the high proportions of 20:4n-6 and 22:6n-3 in fetal plasma is not yet known. In this regard, recent studies have shown that the placenta secretes apo B containing particles in the low density lipoprotein (LDL) density range [33], suggesting that the placenta could contribute to the molecular species of phospholipids, triglycerides and cholesterol esters characteristic of fetal plasma lipids. In addition, both Δ6 and Δ5-desaturase have been identified in the placenta [34], [35]; thus it is possible that placental synthesis of 20:4n-6 from 18:2n-6 could contribute to 20:4n-6 in the fetal circulation. The unusual distribution of fatty acids in fetal plasma esterified lipids includes about 40% 20:4n-6 in cholesterol ester fatty acids whereas about 80% of cholesterol esters in maternal plasma are esterified with 18:2n-6 (Figure 1). After birth, plasma cholesteryl esters are derived from the action of lecithin:cholesterol acyltransferase (LCAT), which esterifies unesterified cholesterol with the fatty acid from the sn-2 position of high density lipoprotein (HDL) phospholipid [36]. The phospholipid fatty acid substrate available in utero for LCAT is predominately 20:4n-6 rather than 18:2n-6 (Table 2), however, LCAT activity appears to be low in fetal plasma [37]. In addition, the major of lipoprotein in fetal plasma is HDL, rather than low density lipoprotein (LDL) as in the adult [38], [39]. The high apo E content of fetal HDL has led to the suggestion that HDL could be important in delivering cholesterol to tissues prior to birth [38]. Although the fetal rat brain appears to synthesize cholesterol de novo, rather than acquiring cholesterol for new membrane synthesis by uptake from plasma [40], it is not clear if the developing human brain is similarly autologous with respect to cholesterol synthesis. Several studies have shown that unesterified 20:4n-6 and 22:6n-3 are readily incorporated into the brain [41], [42]. Although the proportions of 20:4n-6 and 22:6n-3 in plasma unesterified fatty acids are relatively low, the high turnover of this pool of fatty acids could support an important role in providing 20:4n-6 and 22:6n-3 for the developing brain [43]. Despite experimental and clinical evidence consistent with preferential transfer across the placenta, information from both human and animal studies has shown that the maternal dietary intake of n-6 and n-3 fatty acids influences maternal to fetal 20:4n-6 and 22:6n-3 transfer. The relative proportions of 20:4n-6 and 22:6n-3 in maternal plasma are significantly and positively correlated with the proportion of the same fatty acid in fetal plasma [12]. Studies to show that supplementation of pregnant women with 22:6n-3 from fish or fish oils increases 22:6n-3 in plasma and red blood cell lipids of the infant at birth [44], [45], [46] show that placental transfer of 22:6n-3 is dependent on maternal plasma 22:6n-3. However, supplementation of pregnant women with 18:3n-3 does not result in higher umbilical cord blood levels of 22:6n-3 [47]. Information to show that infants born with higher blood levels of 22:6n-3 and 20:4n-6 maintain this advantage for several weeks after birth [48], [49] suggests that these fatty acids must be accumulated in fetal tissue lipids and do contribute to the circulating lipid pool after birth. In animals, low intakes of n-3 fatty acids in gestation result in decreased 22:6n-3 in neural growth cones, the amoeboid leading edge of the growing neurite in fetal brain and liver, as well as in the placenta [23], [50]. Reduced accretion of 22:6n-3 in the retina and brain during development results in decreased electroretinogram responses, decreased performance in behaviour tests of learning, exploratory activity and auditory brain stem evoked potential responses, and changes in dopamine and serotonin metabolism [23], [29], [51], [52]. High maternal intakes of 20:5n-3 and 22:6n-3, however, also decrease 20:4n-6 in the placenta, as well as in the fetal liver and brain [23], [50]. In humans, several studies have reported a positive association between cord plasma 20:4n-6 and infant birthweight [12], [53] and in preterm infants, plasma 20:4n-6 is positively related to growth [54]. Clinical trials have also noted higher growth in preterm infant fed with formula containing 20:4n-6 and 22:6n-3 [53], [55]. Although a dietary intake of about 0.2% energy as 20:4n-6 fulfills the essential role of n-6 fatty acids for growth [1], [2], an explanation for a positive effect of 20:4n-6 on growth in the presence of a maternal or postnatal dietary supply of 18:2n-6 is not available. Only limited information is as yet available on the possible physiological significance of differences in maternal dietary 22:6n-3 intake to fetal development in humans. Studies using electroencephalography (EEG) at 2 days after birth as a measure of CNS maturity have reported that infants with a more mature EEG pattern had significantly higher 22:6n-3 in cord plasma phospholipids than infants with a less mature EEG pattern [45]. In the latter study, however, supplementation of pregnant women from 16 weeks of gestation with 22:6n-3 in the form of cod liver oil had no effect on the EEG measures in the infants [45]. Other epidemiologic studies have reported an inverse relationship between maternal plasma 22:6n-3 and active sleep and sleep–wake transitions, and a positive association between 22:6n-3 and wakefulness in 2-day-old infants [56]. Measures of cognitive performance in older children in relation to their cord blood levels of 22:6n-3 have yielded inconsistent data [57], [58], [59]. These types of epidemiological studies will require large cohorts to control for socio-demographic, family and other maternal and early childhood dietary variables that influence early child development, including potential confounding effects of developmental neurotoxins, such as methyl mercury and PCBs in fish. Information of the importance of 22:6n-3 for the developing human fetal brain and retina is also available from clinical studies on n-3 fatty acid nutrition in preterm infants. Meta-analyses have shown that providing preterm infants with a dietary source of 22:6n-3 results in higher visual acuity during the first months after birth [60]. In addition to higher visual acuity, preterm infants <1250 g birthweight fed formula containing about 1.2% energy as 18.3n-3 supplemented with 22:6n-3 showed an advantage in test scores on the Bayley mental developmental inventories and in the MacArthur Communicative Inventories at 12 months corrected term age [61]. These latter controlled, randomized clinical studies show that the n-3 fatty acid requirements of preterm infants are not met by 1.2% dietary energy as 18:3n-3, and that a small amount of 22:6n-3 facilitates early advantages in visual and neural development. The long-term significance of these early benefits to the developing central nervous system, however, has yet to be demonstrated. In animals, n-3 fatty acid deficiency results in decreased 22:6n-3 and a marked increase in docosapentaenoic acid (22:5n-6), formed from 18:2n-6 in a parallel pathway to that involved in synthesis of 22:6n-3 from 18:3n-3 [1], [2]. This leads to a decrease in the ratio of 22:6n-3/22:5n-6 in membrane PE in n-3 fatty acid deficient animals, and suggests that the ratio of 22:6n-3/22:5n-3 in phospholipids could be a useful biochemcial marker of inadequate n-3 fatty acid nutrition. However, 22:6n-3 and 22:5n-6 are positively, not inversely related in young children; similarly in infants fed formula with no 22:6n-3, neither plasma nor red blood cell PE show an increase in 22:5n-6 when compared to breast-fed infants or infants fed formula containing 22:6n-3 [62]. A similar situation occurs in the fetus; despite a wide range of 22:6n-3 in red blood cell membrane PE of 2.2–12.8% total fatty acids, 22:6n-3 and 22:5n-6 are significantly and positively, not inversely correlated, r = 0.3, P < 0.001, n = 148, (unpublished data). These findings suggest that the desaturation of both n-6 and n-3 fatty acids in humans may be slow beyond the Δ5 desaturase step [62], which may result in important differences in the functional effects of n-3 fatty acid deficiency in humans from those effects demonstrated in n-3 fatty acid deficient rodents. Premature infants are particularly vulnerable to nutritional deficiency because of their limited adipose tissue mass and immaturity in many metabolic and physiologic pathways at birth. In addition, the growth of dendritic arbors and peak formation of synapses, which are enriched in 22:6n-3, extends from about 34 weeks of gestation through 24 months after birth, during which time new connections form at rates up to almost 40,000 synapses/s [63]. Several approaches can be used to address the n-6 and n-3 fatty acid requirements of infants born during the third trimester of gestation. One approach is to match the blood levels of 20:4n-6 and 22:6n-3 of the fetus in utero. As described, the fetal plasma lipids are characterized by an abundance of 20:4n-6 and 22:6n-3, relatively low 18:2n-6, and triglyceride-rich lipoproteins of alimentary origin are very low. Following birth, the high 20:4n-6 and 22:6n-3 characteristic of fetal plasma lipids decline (Figure 2). Fat is provided as major source of energy in order to attain growth rates approaching that of the third trimester fetus, and the initiation of triglyceride-rich lipoproteins as a major lipid transport particle occurs, irrespective of whether nutritional support is provided by parenteral nutrition with intravenous lipids, human milk or infant formula. Although the increase in 18:2n-6 in infant plasma lipids may be partly explained by the considerable abundance of 18:2n-6 over 20:4n-6 and 22:6n-3 in human milk, infant formula and intravenous lipids, other physiological changes that accompany the provision of triglycerides as a major source of energy are likely to be involved. Another approach is to derive an estimate of need based on accretion of fatty acids in fetal tissue. Analyses of autopsy tissue from fetus from 22 weeks gestation to term birth has estimated intrauterine accretion of 552 mg/day n-6 fatty acids and 67 mg/day n-3 fatty acids (mostly 22:6n-3) during the last trimester of gestation, most of which is accumulated in white adipose tissue (368 mg n-6 and 52 mg n-3 fatty acids/day) [64], [65]. In these estimates, fetal brain accretion amounted to 5.8 mg n-6 and 3.1 mg n-3 fatty acids/day, equivalent to about 1.1% and 4.65% of the total body accretion of the n-6 and n-3 fatty acids, respectively. Whether the brain is protected during limited availability of 22:6n-3 is not known; however, the ease with which fetal brain 22:6n-3 is altered by maternal dietary n-3 fatty acid intakes suggests that the fetal brain is sensitive to perturbation of membrane lipid composition by changes in 22:6n-3 supply [19], [23]. Assuming an average of 3.7 g fat/dL human milk, milk with 0.2–0.4% fatty acids as 22:6n-3 [66] would provide the 1 kg preterm infant fed at full enteral feeds of 180 mL/day with only 13–25 mg 22:6n-3/day, an amount clearly below the in utero rate of accretion of 52 mg/day. Dose response studies to determine whether the provision of higher intakes of 22:6n-3 for preterm infants would facilitate development and tissue accretion of 22:6n-3 which more closely resembles those of the third trimester fetus and thus of infants at term birth is a subject for future research. Section snippetsConclusionAll of the n-6 and n-3 fatty acids accumulated in the fetus must ultimately be derived from the mother by placental transfer. However, despite pathways to facilitate transfer of 20:4n-6 and 22:6n-3 across the placenta, the maternal intake of essential fatty acids during pregnancy has a marked effect on the n-6 and n-3 fatty acid composition of blood lipids in human infants at birth, and on the accretion of 20:4n-6 and 22:6n-3 in fetal tissues in animals. The fetus and preterm infant are capable References (66)
Placental regulation of fatty acid delivery and its effect on fetal growth – a reviewPlacenta(2002) Long chain polyunsaturated fatty acid transport across the human placentaPlacenta(1997) Placental membrane fatty acid-binding protein preferentially binds arachidonic and docosahexaenoic acidsLife Sci(1998) Detection and cellular localization of plasma membrane-associated and cytoplasmic fatty acid-binding proteins in human placentaPlacenta(1998) Reduced G protein-coupled signaling efficiency in retinal rod outer segments in response to n-3 fatty acid deficiencyJ Biol Chem(2004) Lipid metabolism in vertebrate retinal rod outer segmentsProg Lipid Res(2000) Essential fatty acid metabolism during early developmentPerinatal biochemistry and physiology of long chain polyunsaturated fatty acidsJ Pediatr(2003) Lipids of nervous tissue, composition and metabolismProg Lipid Res(1985) Preferential uptake of long chain polyunsaturated fatty acids by isolated placental membranesMol Cell Biochem(1996) Transport mechanisms for long-chain polyunsaturated fatty acids in the human placentaAm J Clin Nutr(2000) Essential fatty acid requirements in pregnancy and lactation with special reference to brain developmentProg Lipid Res(1991) Newborn infant plasma trans, conjugated linoleic, n-6 and n-3 fatty acids are related to maternal plasma fatty acids, length of gestation and birth weight and lengthAm J Clin Nutr(2001) Implications of dietary fatty acids during pregnancy on placental, fetal and postnatal development – a reviewPlacenta(2002) Essential fatty acids interconversion in the human fetal liverBiol Neonate(1985) Hepatic microsomal and peroxisomal docosahexaenoate biosynthesis during piglet developmentLipids(2000) Comparison of the metabolism of linoleic and linolenic acids in the fetal ratAnn Nutr Metab(1987) Docosahexaenoic acid is transferred through maternal diet to milk and to tissues of natural milk-fed pigletsJ Nutr(1993) Brain docosahexaenoate accretion in fetal baboons, bioequivalence of dietary α-linolenic and docosahexaenoate acidsPediatr Res(1997) Bioequivalence of dietary α-linolenate and docosahexaenoate acids as possible sources of docosahexaenoate accretion in brain and associated organs of neonatal baboonsPediatr Res(1999) Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brainJ Nutr(2001) Alpha linolenic acid metabolism in men and women: nutritional and biological implicationsCurr Opin Nutr Metab Care(2004) The very low birth weight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linoleic and linolenic acidsPediatr Res(1996) 2022, Placenta Show abstractNavigate Down Pregnancy pathologies including gestational diabetes, intrauterine fetal growth restriction, and pre-eclampsia are common and significantly increase the risk of poor pregnancy outcomes. Research to better understand the pathophysiology and improve diagnosis and treatment is therefore crucial. The ex vivo placenta perfusion model offers a unique system to study pregnancy pathology without the risk of harm to mother or fetus. The presence of a maternal and fetal circulation and intact villus tree, facilitates investigations into maternal-fetal transfer, altered hemodynamics and vascular reactivity in the human placenta. It also provides a platform to test novel therapeutic agents. Here we review the key studies which have utilized the ex vivo placenta perfusion model to study different aspects of such pregnancy pathologies. 2022, Meat Science Show abstractNavigate Down This experiment evaluated growth, glucose metabolism, carcass characteristics, and meat quality of market lambs that were offered ad libitum or restricted (85% of ad libitum) feed intake following two different maternal fatty acid (FA) supplementations while in-utero. Ewes received either a diet supplemented with polyunsaturated FA or saturated/monounsaturated FA during mid- to late-gestation. Following weaning, progeny wethers were fed either ad libitum or a restricted level of feed intake. Ewe FA supplementation did not affect (P ≥ 0.11) growth, meat quality, nor plasma glucose or insulin concentrations of the progeny. Carcass body fat and yield grade of the progeny were affected (P = 0.01) by maternal FA supplementation and restricted feed intake. In summary, maternal FA supplementation did not affect progeny growth, while feed restriction during finishing did not affect meat quality. The interaction between maternal FA supplementation and finishing strategy for body fat accretion indicates that metabolism and the supply of FA during gestation may warrant further investigation. 2022, Journal of Affective Disorders Show abstractNavigate Down Evaluate the influence of maternal consumption of safflower oil on reflex maturation, memory and offspring hippocampal oxidative stress. Two groups were formed: control group (C), whose mothers received a standard diet, and Safflower group (SF), whose mothers received a normolipidic diet with safflower oil as lipid source. Treatment was given from the 14th day of gestation and throughout lactation. To evaluate newborn development, the reflex ontogeny indicators between the 1st and the 21st days of life were evaluated; to assess memory, from the 42nd day of life on these animals were examined on open field habituation and novel object recognition test. Following behavioral analysis, the animals were anesthetized and decapitated. Hippocampus was rapidly dissected. In the hippocampal tissues, we evaluated the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione S transferase (GST) and reduced glutathione (GSH). SF offspring showed delayed maturation of reflexes and improvement of novel object recognition in short-term and long-term (p < 0.05). Safflower oil decreases lipid peroxidation evaluated by MDA levels (p < 0.001) and increases antioxidant defenses as shown by SOD, CAT, GST and GSH levels (p < 0.05). In our study, the composition of flavonoids present in the oil was not evaluated. Furthermore, in a future study, the effect of maternal consumption on female offspring should be verified. Maternal intake of safflower oil could: (1) change neonate reflex parameters, (2) promote improvement of cognitive development in adolescence (3) improve antioxidant enzymatic and non-enzymatic defenses in the hippocampus. 2022, Placenta Show abstractNavigate Down Preeclampsia (PE) is a leading condition threatening pregnant women and their offspring. The offspring of PE pregnancies have a high risk of poor neurodevelopmental outcomes and neuropsychological diseases later in life. However, the pathophysiology and pathogenesis of poor neurodevelopment remain undetermined. Abnormal placental functions are at the core of most PE cases, and recent research evidence supports that the placenta plays an important role in fetal brain development. Here, we summarize the relationship between abnormal fetal brain development and placental dysfunction in PE conditions, which include the dysfunction of nutrient and gas-waste exchange, impaired angiogenesis stimulation, abnormal neurotransmitter regulation, disrupted special protectors, and immune disorders. All these factors could lead to poor neurodevelopmental outcomes. 2022, eBioMedicine Show abstractNavigate Down We aimed to investigate plasma phospholipid PUFA levels in early pregnancy and fetal growth trajectories throughout pregnancy. Within the NICHD Fetal Growth Studies–Singleton Cohort, we enrolled 2,802 pregnant women at gestational weeks 8–13 and randomly assigned them to four ultrasonogram schedules to capture weekly fetal growth throughout pregnancy. Eleven plasma phospholipid PUFAs were measured at early pregnancy using blood samples collected from a subsample of 321 pregnant women. We modeled fetal growth trajectories across tertiles of PUFAs with cubic splines using linear mixed models after adjusting for major confounders. We then compared pairwise weekly fetal growth biometrics referencing the lowest tertile in each PUFA using the Wald test. Among plasma n-3 PUFAs in early pregnancy, docosahexaenoic acid (DHA, 22:6n3) and alpha-linolenic acid (ALA, 18:3n3) showed positive associations with all fetal growth measurements. For instance, compared with the lowest tertile, the highest tertile of DHA had greater estimated fetal growth (EFW) and abdominal circumference (AC), starting at 13 weeks of gestation and throughout pregnancy (at gestational week 38: 3235.3 vs. 3089.0 g for EFW; 344.6 vs. 339.2 mm for AC). As for plasma n-6 PUFAs, some showed positive associations (e.g., linoleic acid [LA], 18:2n6) while others (e.g., docosatetraenoic acid [DTA], 22:4n6) showed inverse associations with fetal growth measures. Our data suggested that higher plasma levels of DHA and ALA in the first trimester were associated with increased fetal size and weight throughout subsequent pregnancy. National Institute of Child Health and Human Development intramural funding. Effects of Omega-3-6-9 fatty acid supplementation on behavior and sleep in preterm toddlers with autism symptomatology: Secondary analysis of a randomized clinical trial2022, Early Human Development Show abstractNavigate Down Children born extremely preterm disproportionately experience sequelae of preterm birth compared to those born at later gestational ages, including higher prevalence of autism spectrum disorder (ASD) and associated behaviors. Explore effects of combined dietary docosahexaenoic acid, eicosapentaenoic acid, gamma-linolenic acid, and oleic acid (omega 3-6-9) on caregiver-reported behavior and sleep in toddlers born at ≤29 weeks' gestation who were exhibiting symptoms commonly seen with ASD. 90-day randomized (1:1), double blinded, placebo-controlled trial. Thirty-one children aged 18–38 months received omega 3-6-9 (n = 15) or canola oil placebo (n = 16). Mixed effects regression analyses followed intent to treat and explored treatment effects on measures of caregiver-reported behavior (Child Behavior Checklist 1.5–5, Toddler Behavior Assessment Questionnaire – Short Form, Vineland Adaptive Behavior Scales, 2nd Edition) and sleep (Children's Sleep Habits Questionnaire, Brief Infant Sleep Questionnaire). Twenty-nine of 31 (94%; ntx = 13, nplacebo = 16) children randomized had data available for at least one outcome measure, 27 (87%; ntx = 12, nplacebo = 15) had complete outcome data. Children randomized to omega 3-6-9 experienced a medium magnitude benefit of supplementation on anxious and depressed behaviors (ΔDifference = −1.27, d = −0.58, p = 0.049) and internalizing behaviors (ΔDifference = −3.41, d = −0.68, p = 0.05); and a large magnitude benefit on interpersonal relationship adaptive behaviors (ΔDifference = 7.50, d = 0.83, p = 0.01), compared to placebo. No effects were observed on other aspects of behavior or sleep. Findings provide preliminary support for further exploration of omega 3-6-9 during toddlerhood to improve socioemotional outcomes among children born preterm, especially for those showing early symptoms commonly seen with ASD. Results need to be replicated in a larger sample. Registered with ClinicalTrials.gov: NCT01683565. Research article Gene, Volume 549, Issue 1, 2014, pp. 7-23 Show abstractNavigate Down During pregnancy and lactation, metabolic adaptations involve changes in expression of desaturases and elongases (Elovl2 and Elovl5) in the mammary gland and liver for the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid (AA) required for fetal and postnatal growth. Adipose tissue is a pool of LC-PUFAs. The response of adipose tissue for the synthesis of these fatty acids in a lipid-deficient diet of dams is unknown. The aim of this study was to explore the role of maternal tissue in the synthesis of LC-PUFAs in rats fed a low-lipid diet during pregnancy and lactation. Fatty acid composition (indicative of enzymatic activity) and gene expression of encoding enzymes for fatty acid synthesis were measured in liver, mammary gland and adipose tissue in rats fed a low-lipid diet. Gene expression of desaturases, elongases, fatty acid synthase (Fasn) and their regulator Srebf-1c was increased in the mammary gland, liver and adipose tissue of rats fed a low-lipid diet compared with rats from the adequate-lipid diet group throughout pregnancy and lactation. Genes with the highest (P < 0.05) expression in the mammary gland, liver and adipose tissue were Elovl5 (1333%), Fads2 (490%) and Fasn (6608%), respectively, in a low-lipid diet than in adequate-lipid diet. The percentage of AA in the mammary gland was similar between the low-lipid diet and adequate-lipid diet groups during the second stage of pregnancy and during lactation. The percentage of monounsaturated and saturated fatty acids was significantly (P < 0.05) increased throughout pregnancy and lactation in all tissues in rats fed a low-lipid diet than in rats fed an adequate-lipid diet. Results suggest that maternal metabolic adaptations used to compensate for lipid-deficient diet during pregnancy and lactation include increased expression of genes involved in LC-PUFAs synthesis in a stage- and tissue-specific manner and elevated lipogenic activity (saturated and monounsaturated fatty acid synthesis) of maternal tissues including adipose tissue. Research article Placenta, Volume 35, Issue 7, 2014, pp. 523-525 Show abstractNavigate Down Fatty acids can function as signaling molecules, acting through receptors in the cytosol or on the cell surface. G-Protein Receptor (GPR)120 is a membrane-bound receptor mediating anti-inflammatory and insulin-sensitizing effects of the omega-3 fatty acid docohexaenoic acid (DHA). GPR120 dysfunction is associated with obesity in humans. Cellular localization of GPR120 and the influence of maternal obesity on GPR120 protein expression in the placenta are unknown. Herein we demonstrate that GPR120 is predominantly expressed in the microvillous membrane (MVM) of human placenta and that the expression level of this receptor in MVM is not altered by maternal body mass index (BMI). Research article Nutrition, Volume 50, 2018, pp. 91-96 Show abstractNavigate Down The aim of this cohort study was to investigate the relationship between maternal fat consumption during pregnancy and behavioral problems in 1199 Japanese children at age 5 y. Dietary intake of mothers during pregnancy was assessed using a diet history questionnaire. Emotional, conduct, hyperactivity, and peer problems in children were assessed using the Strengths and Difficulties Questionnaire; the four scale scores were dichotomized, comparing children with borderline and abnormal scores to children with normal scores. Logistic regression analysis was applied to estimate adjusted odds ratios and 95% confidence intervals for each behavioral problem according to the quartile of dietary factors under study, adjusting for potential confounding factors. Higher maternal intake of monounsaturated fatty acids, α-linolenic acid, ω-6 polyunsaturated fatty acids, and linoleic acid during pregnancy was independently associated with an increased risk for childhood emotional problems. The adjusted odds ratios between extreme quartiles (95% confidence intervals, Ptrend) were 1.85 (1.11 − 3.17, 0.04), 1.60 (0.99 − 2.60, 0.03), 2.06 (1.24 − 3.46, 0.002), and 2.09 (1.26 − 3.51, 0.002), respectively. No such positive associations were observed for the other outcomes. No relationships were found between maternal intake of total fat, saturated fatty acids, ω-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, or cholesterol, or the ratio of ω-3 to ω-6 polyunsaturated fatty acid intake during pregnancy and any of the outcomes. Maternal consumption of monounsaturated fatty acids, α-linolenic acid, ω-6 polyunsaturated fatty acids, and linoleic acid during pregnancy may increase the risk for childhood emotional problems. Research article Placenta, Volume 57, 2017, pp. 144-151 Show abstractNavigate Down Placental fatty acid (FA) uptake and metabolism depend on maternal supply which may be altered when women have a high pre-pregnancy body mass index (BMI) or develop gestational diabetes (GDM). Consequently, an impaired FA transport to the fetus may negatively affect fetal development. While placental adaptation of maternal-fetal glucose transfer in mild GDM has been described, knowledge on placental FA acid metabolism and possible adaptations in response to maternal obesity or GDM is lacking. We aimed to analyze the FA composition and the expression of key genes involved in FA uptake and metabolism in placentas from women with pre-pregnancy normal weight (18.5 ≤ BMI<25 kg/m2), overweight (25 ≤ BMI<30 kg/m2), obesity (BMI ≥ 30 kg/m2), and lean pregnant women with GDM. Placental FA content was determined by gas liquid chromatography. Placental mRNA expression of FA transport proteins (FATP1, FATP4, FATP6), FA binding proteins (FABP3, FABP4, FABP7), FA translocase (FAT/CD36) and enzymes (Endothelial lipase (EL) and lipoprotein lipase (LPL)) were quantified by qRT-PCR. High pre-pregnancy BMI and GDM were associated with decreased placental FATP1, FATP4, EL and increased FAT/CD36 and FATP6 expressions. LPL mRNA levels and placental total FA content were similar among groups. Specific FA, including some long-chain polyunsaturated FA, were altered. Our results demonstrate that high pre-pregnancy BMI or GDM independently alter mRNA expression levels of genes involved in FA uptake and metabolism and the placental FA profile, which could affect fetal development and long-term health. Research article Prostaglandins, Leukotrienes and Essential Fatty Acids, Volume 165, 2021, Article 102233 Show abstractNavigate Down Long-chain polyunsaturated fatty acids (LCPUFAs) required for infant development are produced by Δ6 desaturase (D6D) and Δ5 desaturase (D5D). The D6D index and D5D index are calculated based on their respective precursor/product ratios. The D5D and D6D indices are related to obesity and lifestyle-related diseases. The aim of the present study was to examine the associations of umbilical cord fatty acid profiles, D6D index, and D5D index in appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA) infants. This was a nested case-control study, and the relationship between case and control maternal blood and umbilical cord blood fatty acid compositions was examined. Cases were small for gestational age (SGA; n = 55) and large for gestational age (LGA; n = 149) infants, whereas controls were appropriate for gestational age (AGA; n = 204) infants. Fatty acid profiles in maternal blood and umbilical cord plasma were analyzed by gas-liquid chromatography. The D6D index was calculated as dihomo-γ-linolenic acid (DGLA 20: 3 n-6) / linoleic acid (18: 2 n - 6), and the D5D index was calculated as arachidonic acid (20: 4 n - 6) / DGLA (20: 3 n - 6). Statistical analysis of umbilical cord blood fatty acids was performed with multiple comparisons. SGA infants showed high umbilical cord values for α-linolenic acid and DHA and lower values for DGLA compared to AGA infants. SGA infants showed a higher D5D index but a lower D6D index than AGA infants. LGA infants showed high values for α-linolenic acid and DGLA and lower values for arachidonic acid than AGA infants. LGA infants showed a high D6D index and a low D5D index relative to AGA infants. No significant differences in maternal blood fatty acid profiles, the D6D index, and D5D index desaturase activities were found among the three groups. There were differences in umbilical cord fatty acid profiles and D6D and D5D indices among AGA, SGA, and LGA infants, but further study is needed. Research article Domestic Animal Endocrinology, Volume 67, 2019, pp. 42-53 Show abstractNavigate Down Peroxisome proliferator–activated receptors (PPARs) are members of a nuclear receptor family of ligand-dependent transcription factors. Three isoforms of PPAR named PPARα, PPARβ/δ, and PPARγ have been described, each encoded by a separate gene: PPARA, PPARD, and PPARG, respectively. In the present study, we examined the profiles of PPAR and retinoid X receptor (RXR; PPAR heterodimer partner) mRNA expression and PPAR DNA binding activity in porcine trophoblast tissue collected on days 15, 20, 25, and 30 of pregnancy and in day-20 embryos. Placenta trophoblast cells isolated on day 25 of pregnancy were used to determine effects of (1) cytokines on PPAR and RXR mRNA expression and (2) PPAR agonists on prostaglandin (PG) E2 synthesis and the expression of genes involved in steroidogenesis, fatty acid binding, and PG transport, as well as on cell proliferation. The mRNA expression of PPARA and RXRB was greater in trophoblast tissue collected on days 25 and 30 of pregnancy compared with day 15 (P < 0.05), while DNA binding activity of PPARα decreased between day 15 and 25 (P < 0.05). Increased concentrations of PPARD and RXRA transcripts were observed in trophoblasts collected on day 20 compared to trophoblasts from days 15 and 30 (P < 0.05). Moreover, concentrations of DNA-bound PPARβ/δ and PPARγ proteins increased in day-30 trophoblasts compared to day 15 (P < 0.01) and day 20 (P < 0.05), respectively. On day 20 of gestation, the mRNA expression of PPARD, PPARG, and RXRA and protein levels of PPARα and PPARγ isoforms were greater in trophoblast than embryonic tissue (P < 0.01). Interleukin 1β and/or interferon γ, but not IL6 and leukemia inhibitory factor, upregulated PPAR and RXR mRNA expression in placenta trophoblast cells in vitro (P < 0.05). Rosiglitazone (a PPARγ agonist) stimulated prostaglandin E synthase mRNA expression in trophoblast cells and PGE2 accumulation in incubation medium (P < 0.05). Moreover, activation of PPAR isoforms differentially affected the expression of genes involved in steroidogenesis, fatty acid binding, and PG transport in studied cells. Finally, PPARα and PPARγ agonists stimulated trophoblast cell proliferation (P < 0.05), and this effect was abolished by the addition of a respective PPAR antagonist (P < 0.05). Overall, these results point to a role of PPAR isoforms in porcine placenta development and function. |
Which of the following fatty acids is critical to fetal brain and development?
zusammenhängende Posts
Urheberrechte © © 2024 membukakan Inc.
