Replenishment of docosahexaenoic acid in n-3 fatty acid-deficient fetal rats by intraamniotic ethyl-docosahexaenoate administration

Green, Pnina; Kamensky, Batia; Yavin, Ephraïm

doi:10.1002/(sici)1097-4547(19970501)48:3<264::aid-jnr9>3.0.co;2-d

Cited by 12 publications

(14 citation statements)

References 57 publications

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“…Conversely, weanlings nursed on control dams had elevated levels of n-6 DPA in both plasma and brain lipids, despite the fact that the proportion of n-6 DPA in milk FA was not significantly different between milk derived from transgenic and control dams. Many other studies with n-3-deficient diets have reported that a decrease in DHA is accompanied by an increase in n-6 DPA, and the DHA:n-6 DPA ratio can be used as an indicator of n-3 FA deficiency (24). This ratio was 0.75 for the control pups' brains, as compared with 5.39 for the brains of pups nursed on transgenic dams.…”

Section: Discussionmentioning

confidence: 84%

Mice raised on milk transgenically enriched with n−3 PUFA have increased brain docosahexaenoic acid

Kao

DePeters

Eenennaam

2006

Lipids

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The brain contains high levels of the long-chain n-3 FA DHA (22:6n-3), mainly in the gray matter and synaptosomes. Adequate intake of DHA is crucial for optimal nervous system function, particularly in infants. Supplementation of infant formulas with DHA at levels similar to human breast milk is recommended for biochemical and functional benefits to neonates. We generated transgenic mice that produce elevated levels of n-3 PUFA in their milk by expressing the Caenorhabditis elegans n-3 FA desaturase under the control of a lactation-induced goat beta-casein promoter. To examine the postnatal effects of consuming the n-3-enriched milk, we compared the growth and brain and plasma FA composition of mouse pups raised on milk from transgenic dams with those observed for pups raised on milk from nontransgenic dams. A significant decrease in arachidonic acid (ARA, 20:4n-6) and concomitant increases in n-3 PUFA were observed in the phospholipid fraction of transgenic mouse milk. The n-6:n-3 FA ratios were 4.7 and 34.5 for the transgenic and control milk phospholipid fractions, respectively. DHA and DPA (22:5n-6) comprised 15.1% and 2.8% of brain FA from weanling mice nursed on transgenic dams, as compared with 6.9% and 9.2% for weanling mice nursed on control dams, respectively. This transgenic mouse model offers a unique approach to disassociate the effects and fetal programming resulting from a high n-6:n-3 FA ratio gestational environment from the postnatal nutritional effects of providing milk with differing n-6:n-3 FA ratios.

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Section: Discussionmentioning

confidence: 84%

Mice raised on milk transgenically enriched with n−3 PUFA have increased brain docosahexaenoic acid

Kao

DePeters

Eenennaam

2006

Lipids

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“…supply of lipids or FAs has not been done until very recently, when a method of DHA administration to late gestation fetal rats has been devised (Green and Yavin, 1995) by the intra-amniotic injection of Et-DHA in vivo. In rats fed both an n-3 FA-sufficient diet (Green and Yavin, 1995) or an n-3 FA-deficient diet (Green et al, 1997), fetal brain lipid DHA content increased significantly following a single intra-amniotic Et-DHA administration. In both studies, the DHA increase was steeper for the fetal liver than for the brain, suggesting that under certain conditions, the fetal liver may have an important role in the supply of DHA to the brain.…”

Section: The Fetal Gastrointestinal Route Of Brain Dha Supplymentioning

confidence: 98%

“…Animal studies have revealed direct correlations between the FA composition of the maternal diets and that of the brain and retina in the offsprings in several species (Bourre et al, 1984;Neuringer et al, 1986;Yonekubo et al, 1993). For example, feeding pregnant rats an n-3 FA-deficient diet for only the last 2 weeks of pregnancy resulted in a more than 30% decrease in fetal brain DHA and an almost 120% increase in DPA as compared to fetal brains from control, n-3 FA-sufficient diet-fed rats (Green et al, 1997). In a meticulous study in the pregnant guinea pig it was shown that a transient, mid-gestational increase in maternal liver concentration of 16:0/22:6 PC precedes the progressive increase in total PC concentration toward term (Burdge and Postle, 1994).…”

Section: Maternal Dha Supplymentioning

confidence: 99%

Mechanisms of docosahexaenoic acid accretion in the fetal brain

Green

Yavin

1998

J. Neurosci. Res.

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Docosahexaenoic acid (DHA, 22:6 n-3) is the major polyunsaturated fatty acid (PUFA) in the adult mammalian brain. DHA is an essential fatty acid (FA) since it, or its short chain precursor, ␣-linolenic acid (LnA, 18:3 n-3), have to be obtained in the diet. Moreover, dietary n-3 FA deficiency is associated with biochemical changes in the brain and with disturbances in vision and other neurological parameters. Under normal nutritional conditions, fetal brain DHA accumulation is substantial, with a ''DHA accretion spurt'' being demonstrated in the last period of gestation. This accumulation is supported by the maternal supply of DHA or LnA, but selectivity of DHA accumulation is probably a placental function whose mechanism is lately being clarified. The fetal gastrointestinal (G-I) tract may be instrumental in supplying DHA to the fetal brain under certain conditions, such as following intra-amniotic administration of ethyldocosahexaenoate (Et-DHA). In this pathway, DHA is supplied independently of the maternal metabolism, and the fetal liver is apparently involved. The fetal G-I tract may be advantageous for DHA supply in cases of maternal-placental insufficiency resulting in intrauterine growth retardation. The fetal brain itself is capable of metabolizing LnA to DHA, without the participation of the fetal liver, thus contributing to the accumulation of its own DHA during one of the most crucial periods of its development.

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“…For these studies we used rats fed an n-3 FA sufficient or deficient diet. The state of deficiency, characterized by a 34% and 60% decrease in DHA content of fetal brain and liver, respectively, was attained by feeding pregnant rats from day 8 and up to 20 days gestation, with a n-3 LoA-deprived diet (Green et al, 1997). After a single intraamniotic administration of Et-DHA on day 18 or 19, a rapid increase in both fetal brain and liver DHA was achieved.…”

Section: The Intraamniotic Route For Brain Dha Enrichmentmentioning

confidence: 99%

Docosahexaenoic Acid Sources for the Developing Brain during Intrauterine Life

2001

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Docosahexaenoic acid (DHA, 22: 6n-3) and arachidonic acid (AA, 20: 4n-6) provision to the developing fetus, with emphasis towards brain and vascular system growth, is a subject of increasing concern particularly under pathological conditions associated with premature birth or in utero growth restriction following obstruction of the maternal-fetal blood flow. Most of DHA, but also AA accretion under physiological conditions, is maternally dependent and requires adequate maternal nutrition and normally functioning placental-fetal circulation. It has been demonstrated that unlike other fatty acids (FA), DHA is preferentially transported across the placenta into the fetal circulation. The selective transplacental DHA transfer is probably mediated by specific carrier proteins. While some of the latter may be acting in fetal organs, the mechanism(s) for the selective accumulation of DHA in brain is still unknown. The fetal brain and also the fetal liver are capable of producing DHA from linolenic (LnA, 18:3 n-3) acid. How effective this local elongation-desaturation mechanism for DHA provision is and to what degree this route is activated in premature births is not clear. Transfer of DHA via the fetal gastrointestinal tract is an additional route to provide DHA to other fetal organs. As indicated by animal model studies, it holds the potential for DHA supply when the maternal pathway is compromised.

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Replenishment of docosahexaenoic acid in n-3 fatty acid-deficient fetal rats by intraamniotic ethyl-docosahexaenoate administration

Cited by 12 publications

References 57 publications

Mice raised on milk transgenically enriched with n−3 PUFA have increased brain docosahexaenoic acid

Mice raised on milk transgenically enriched with n−3 PUFA have increased brain docosahexaenoic acid

Mechanisms of docosahexaenoic acid accretion in the fetal brain

Docosahexaenoic Acid Sources for the Developing Brain during Intrauterine Life

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