Effect of bacterial cell wall and lipopolysaccharide on arachidonic acid metabolism by caruncular and allantochorionic tissues from cows that calved normally and those that retained fetal membranes

Immunoactive eicosanoids may have a role in both placental separation and uterine involution in cattle. In the present study, we examined the effects of bacterial cell wall preparation and endotoxins on in vitro prostaglandin synthesis and arachidonic acid (AA) metabolism by caruncular and allantochorionic tissues. Placentomes were obtained about 6 h post partum from cows that delivered normally (n = 10) or those with retained fetal membranes (n = 4); the tissue explants were incubated for 6 h in the presence of labeled or nonlabeled AA. Prostaglandin F(2alpha) (PGF(2alpha)) and E(2) (PGE(2)) were measured by radioimmunoassay, and labeled AA metabolites were separated by reverse phase-high pressure-liquid chromatography. There was no effect of bacterial cell wall preparations or endotoxins on in vitro caruncular PGF(2alpha) secretion. However, bacterial products increased caruncular PGE(2) secretion in both cows that delivered normally and those with retained fetal membranes. For normal delivery cows caruncular tissue, bacterial product also increased leukotriene B(4) (LTB(4)) and decreased both thromboxane B(2) (TXB(2)) and hydroxy-eicosatetranoic acids (HETE) in vitro secretion. For the allantochorion, bacterial products increased in vitro PGF(2alpha) secretion only in cows that delivered normally and increased PGE(2) secretion essentially in cows with retained fetal membranes. In general, 6 keto PGF(1alpha) was the main metabolite secreted by both allantochorionic and carucular tissues. However, in cows with retained fetal membranes, PGE(2) became the most important metabolite secreted by allantochorion, especially in the presence of endotoxin. In conclusion, these results suggest that bacteria found in the early postpartum uterus or their endotoxin affect primarily caruncular and allantochorionic PGE(2) synthesis.     

Effect of in vitro heat shock upon the synthesis and secretion of prostaglandins and protein by uterine and placental tissues of the sheep

The objectives of this study were to determine the secretion patterns of prostaglandins (PG) and protein during mid- (Day 100) and late- (Day 140) pregnancy in the ewe and to ascertain whether that pattern is altered by in vitro heat shock. Explant cultures were prepared from intercaruncular endometrium, caruncular endometrium, fetal cotyledon and interplacentomal placenta. Cultures were incubated at 39 or 42 degrees C for 18 h in the presence of arachidonic acid or L-[4,5(3)H]leucine. There were no effects of day of gestation or consistent effects of temperature upon de novo synthesis of tissue and secretory protein. Elevated temperature generally depressed PGE(2) secretion by maternal tissues and PGF secretion by caruncular endometrium but had little effect on PGE(2) release by fetal tissues or on PGF release by intercaruncular endometrium or fetal tissues. Day of gestation by tissue type interactions were found for PGF and PGE(2) release. At Day 100, maternal tissues secreted more PGF and PGE(2) than fetal tissues; at Day 140, PG secretion from fetal tissues was greater than at Day 100, and fetal PGE(2) release exceeded release from maternal tissues. Tissue proteins resolved by SDS-PAGE revealed the appearance in heat-shocked tissue of 93 and 72 kDa heat-shock proteins. In conclusion, elevated temperature depressed PGE(2) release, particularly from maternal tissues. Changes in PGE(2) suggest that the increase in utero-placental PGE(2) with increasing gestational age is due to changes in secretion of the fetal placenta.     

Maternal omega-3 fatty acids maintained positive maternal lipids and cytokines profile,and improved pregnancy outcomes of C57BL/6 mice

Omega (n)-3 polyunsaturated fatty acids (PUFA) are known to regulate lipid metabolism and inflammation; however, the regulation of maternal lipid metabolism and cytokines profile by n-3 PUFA during different gestation stages, and its impact on fetal sustainability is not known. We investigated the effects of maternal diet varying in n-3 PUFA prior to, and during gestation, on maternal metabolic profile, placental inflammatory cytokines, and fetal outcomes. Female C57BL/6 mice were fed either a high, low or very low (9, 3 or 1% w/w n-3 PUFA) diet, containing n-6:n-3 PUFA of 5:1, 20:1 and 40:1, respectively for two weeks before mating, and throughout pregnancy. Animals were sacrificed prior to mating (NP), and during pregnancy at gestation days 6.5, 12.5 and 18.5. Maternal metabolic profile, placental cytokines and fetal outcomes were determined. Our results show for the first time that a maternal diet high in n-3 PUFA prevented dyslipidemia in NP mice, and maintained the expected lipid profile during pregnancy. However, females fed the very low n-3 PUFA diet became hyperlipidemic prior to pregnancy, and carried this profile into pregnancy. Maternal diet high in n-3 PUFA maintained maternal plasma progesterone and placental pro-inflammatory cytokines profile, and sustained fetal numbers throughout pregnancy, while females fed the low and very-low n-3 PUFA diet had fewer fetuses. Our findings demonstrate the importance of maternal diet before, and during pregnancy, to maintain maternal metabolic profile and fetus sustainability. These findings are important when designing dietary strategies to optimize maternal metabolism during pregnancy for successful pregnancy outcome.     

Effect of different contents of extruded linseed in the sow diet on piglet fatty acid composition and hepatic desaturase expression during the post-natal period

n-3 polyunsaturated fatty acids (n-3 PUFA) contribute to the normal growth and development of numerous organs in the piglet. The fatty acid composition of piglet tissues is linked to the fatty acid composition of sow milk and, consequently, to the composition of sow diet during the gestation and lactation period. In this study, we investigated the impact of different contents of extruded linseed in the sow diet on the fatty acid composition and desaturase gene expression of piglets. Sows received a diet containing either sunflower oil (low 18:3n-3 with 18:3n-3 representing 3% of total fatty acids) or a mixture of extruded linseed and sunflower oil (medium 18:3n-3 with 9% of 18:3n-3) or extruded linseed (high 18:3n-3 with 27% of 18:3n-3) during gestation and lactation. Fatty acid composition was evaluated on sow milk and on different piglet tissues at days 0, 7, 14, 21 and 28. The postnatal evolution of delta5 (D5D) and delta6 (D6D) desaturase mRNA expression was also measured in the liver of low 18:3n-3 and high 18:3n-3 piglets. The milk of high 18:3n-3 sows had higher proportions of n-3PUFA than that of low 18:3n-3 and medium 18:3n-3 sows. Piglets suckling the high 18:3n-3 sows had greater proportions of 18:3n-3, 20:5n-3, 22:5n-3 and 22:6n-3 in the liver, and of 22:5n-3 and 22:6n-3 in the brain than low 18:3n-3 and medium 18:3n-3 piglets. D5D and D6D mRNA expressions in piglet liver were not affected by the maternal diet at any age. In conclusion, extruded linseed in the sow diet modifies the n-3PUFA status of piglets during the postnatal period. However, a minimal content of 18:3n-3 in the sow diet is necessary to increase the n-3PUFA level in piglet liver and brain. Moreover, modifications in the n-3PUFA fatty acid composition of piglet tissue seem linked to the availability of 18:3n-3 in maternal milk and not to desaturase enzyme expression.     

Intestinal responsiveness to experimental colitis in young rats is altered by maternal diet

Increasing evidence suggests that fetal and neonatal nutrition impacts later health. Aims of the present study were to determine the effect of maternal dietary fat composition on intestinal phospholipid fatty acids and responsiveness to experimental colitis in suckling rat pups. Female rats were fed isocaloric diets varying only in fat composition throughout gestation and lactation. The oils used were high (8%) in n-3 [canola oil (18:3n-3)], n-6 (72%) [safflower oil (18:2n-6)], or n-9 (78%) [high oleic acid safflower oil (18:1n-9)] fatty acids, n = 6/group. Colitis was induced on postnatal day 15 by intrarectal 2,4-dinitrobenzene sulfonic acid (DNBS) administration with vehicle (50% ethanol) and procedure (0.9% saline) controls. Jejunal and colonic phospholipids and milk fatty acids were determined. The distal colon was assessed for macroscopic damage, histology, and MPO activity. The 18:2n-6 maternal diet increased n-6 fatty acids, whereas the 18:3n-3 diet increased n-3 fatty acids in milk and pup jejunal and colonic phospholipids. Maternal diet, milk, and pup intestinal n-6-to-n-3 fatty acid ratios increased significantly in order: high 18:3n-3 < high 18:1n-9 < high 18:2n-6. DNBS administration in pups in the high 18:2n-6 group led to severe colitis with higher colonic damage scores and MPO activity than in the 18:1n-9 and 18:3n-3 groups. High maternal dietary 18:3n-3 intake was associated with colonic damage scores and MPO activity, which were not significantly different from ethanol controls. We demonstrate that maternal dietary fat influences the composition of intestinal lipids and responsiveness to experimental colitis in nursing offspring.     

Maternal dietary fat alters amniotic fluid and fetal intestinal membrane essential n-6 and n-3 fatty acids in the rat

We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% alpha-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 +/- 0.10 and 6.29 +/- 0.33 g/100 g fatty acid; DPA: 4.01 +/- 0.35 and 0.73 +/- 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 +/- 0.2 and 32.2 +/- 2.1 in PC and 2.4 +/- 0.03 and 17.1 +/- 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta.     

Effect of maternal fatty acid deficiency on lipid content and composition of rat liver during prenatal development

Two groups of female rats were fed a diet with high (5.9 cal % of linoleate + linolenate) or low (0.78 cal % of linoleate + linolenate) essential fatty acid (EFA) concentration. The effects of the EFA concentration during gestation on liver lipid and fatty acid composition were studied in the fetuses at 15 and 20 days of intrauterine life. Fetal and liver weights were identical in the two groups; at day 20 the contents of proteins, total cholesterol, phospholipids and glycolipids were significantly decreased (p less than 0.01) with the low EFA diet while at day 15 only total cholesterol was affected (p less than 0.05). At both gestational ages the triacylglycerol content was increased in the low EFA group (day 15 p less than 0.05, day 20 p less than 0.01). The maternal EFA deficiency resulted in higher levels of 16:1 n-7 in the phospholipid fractions and 16:1 n-7 and 18:1 n-7 in the neutral lipids. The increase in these monoenoic derivatives partially compensated the decrease of the polyunsaturated species 18:2 n-6 and 20:4 n-6. In conclusion the low EFA diet results in important modifications of the fetal hepatic lipids during intrauterine development.     

Effect of linseed supplementation of the gestation and lactation diets of dairy ewes on the growth performance and the intramuscular fatty acid composition of their lambs

In this study, we investigated the effects of maternal gestation and/or lactation diets supplemented with extruded linseed (rich in 18:3n-3) on growth performance and long-chain polyunsaturated faaty acid (PUFA) accumulation in muscle tissues of suckling lambs. A total of 36 dairy ewes were fed a control diet (CON) and a diet containing linseed (LIN) during the last 8 weeks of gestation and/or the first 4 weeks of lactation. The four dietary treatments consisted of the following gestation/lactation feeding treatments: CON/CON, CON/LIN, LIN/LIN or LIN/CON. The lambs born from ewes fed the aforementioned diets were reared exclusively on milk and were slaughtered at 4 weeks of age. Profiles of ewes’ milk fatty acids and that of intramuscular fat (IMF) of leg muscles from lambs were determined. Compared with the CON/CON, LIN/CON offspring tended to grow slower and to have reduced cold carcass weights. Moreover, the LIN supplementation only in the prepartum period (LIN/CON) resulted in greater PUFAn-3 accumulation in the IMF compared with the CON/CON offspring due to increased 20:5n-3 (1.20 v. 0.64 mg/100 mg of total FA), 22:5n-3 (1.91 v. 1.46;) and 22:6n-3 (1.25 v. 0.89) contents, respectively. Compared with the CON/CON diet, providing LIN only during lactation (CON/LIN) caused a greater PUFAn-3 content in the IMF mainly due to a greater 18:3n-3 (1.79 v. 0.75 mg/100 g total FA) concentration. Continuous PUFAn-3 exposure, both via the maternal gestation and lactation diet, had no additive effects on PUFAn-3 accumulation in tissues. The results suggest that linseed, as an 18:3n-3 source, seems to be more efficient in increasing long-chain PUFAn-3 in fetal than in suckling lamb tissues.     

Linoleic acid kinetics and conversion to arachidonic acid in the pregnant and fetal baboon.

Linoleic acid plasma kinetics in pregnant baboons and its conversion to long chain polyunsaturates (LCP) in fetal organs is characterized over a 29-day period using stable isotope tracers. Pregnant baboons consumed an LCP-free diet and received [U-13C]linoleic acid (18:2*) in their third trimester of gestation. In maternal plasma, 18:2* dropped to near baseline by 14 days post-dose, while labeled arachidonic acid (20:4*) plateaued at 10 days at about 70% of total labeled fatty acids. After 2;-5 days, total tracer fatty acids decreased in visceral organs, but increased in the fetal brain. Maximal fetal incorporation of 18:2* was 1;-2 days post-dose; thereafter it dropped while 20:4* increased reciprocally. Labeled 20:4 replaced 18:2* in neural tissues by 5 days post-dose. In liver, kidney, and lung, 20:4* became dominant by 12 days, but in heart the crossover was >29 days. Fetal brain 20:4* plateaued by 21 days at 0. 025% of dose, while fetal liver 20:4* was constant from 1 to 29 days at 0.006% of dose. Under these dietary conditions we estimate that the fetus derives about 50% its 20:4 requirement from conversion of dietary 18:2, with the balance from maternal stores, and conclude that 1) fetal organs accumulate 18:2 within a day of a maternal dose and convert much of it to 20:4 within weeks, 2) modest dietary 18:2 levels may support fetal brain requirements for 20:4, and 3) the brain retains n;-6 fatty acids uniquely compared with major visceral organs.     

Production of prostaglandin by late-gestation porcine placental cells in vitro.

Fifteen sows were assigned to three groups of five each, according to gestational age (109 days, 114 days or labour). Two fetuses per sow were chosen at random, and amnion, allantochorion, amniochorion, amniotic fluid and fetal urine were collected. Tissues were enzymatically dispersed and incubated for 1, 2, 3 or 4 h and the prostaglandin (PG) content of the supernatant medium was measured by radioimmunoassay. In general, all placental cell types produced at least three times more prostaglandin E (PGE) and 6-keto-PGF1 alpha than PGF. Production did not vary across gestational age, except that production of 6-keto-PGF1 alpha was lower in cells collected during labour, resulting in a relative increase in PGF and PGE. Aminochorion cells had a lower de novo capacity to synthesize PG than did allantochorion or amniochorion, whereas treatment of allantochorion with preterm amniotic fluid, preterm or term fetal urine resulted in increased PG output. These results demonstrate that porcine placental cells can synthesize and metabolize prostaglandin in late gestation but suggest that their capacity to produce PGI2 (as measured by 6-keto-PGF1 alpha) is lower than for other prostaglandins during labour.     

Metabolic development in the liver and the implications of the n-3 fatty acid supply

The n-3 fatty acids contribute to regulation of hepatic fatty acid oxidation and synthesis in adults and accumulate in fetal and infant liver in variable amounts depending on the maternal diet fat composition. Using 2D gel proteomics and matrix-assisted laser desorption/ionization time of flight mass spectrometry, we recently identified altered abundance of proteins associated with glucose and amino acid metabolism in neonatal rat liver with increased n-3 fatty acids. Here, we extend studies on n-3 fatty acids in hepatic metabolic development to targeted gene and metabolite analyses and map the results into metabolic pathways to consider the role of n-3 fatty acids in glucose, fatty acid, and amino metabolism. Feeding rats 1.5% compared with <0.1% energy 18:3n-3 during gestation led to higher 20:5n-3 and 22:6n-3 in 3-day-old offspring liver, higher serine hydroxymethyltransferase, carnitine palmitoyl transferase, and acyl CoA oxidase and lower pyruvate kinase and stearoyl CoA desaturase gene expression, with higher cholesterol, NADPH and glutathione, and lower glycine (P < 0.05). Integration of the results suggests that the n-3 fatty acids may be important in facilitating hepatic metabolic adaptation from in utero nutrition to the postnatal high-fat milk diet, by increasing fatty acid oxidation and directing glucose and amino acids to anabolic pathways.     

Secretion of angiogenic activity by placental tissues of cows at several stages of gestation

Samples of maternal and fetal placental tissues were obtained from cows on Days 100 (N = 4), 150 (N = 5), 200 (N = 6) and 250 (N = 6) of gestation and incubated for 24 h. Conditioned media from caruncular explants were mitogenic for bovine aortic endothelial cells (BAEC) on all days of gestation. Media from intercaruncular endometrium were stimulatory for proliferation of BAEC on Day 100 but inhibitory on Days 150, 200 and 250. Media from cotyledonary and intercotyledonary tissues inhibited proliferation of BAEC on all days. Caruncular-conditioned media stimulated migration of BAEC on Days 150, 200 and 250. Cotyledonary-conditioned media inhibited migration of BAEC on all days. Effects of media from intercaruncular and intercotyledonary tissues on migration of BAEC varied with stage of gestation. Angiogenic activity of media from caruncular (all stages) and intercaruncular (Day 100) tissues appeared to have an Mr greater than 100,000. In cows, therefore, the maternal placentome (caruncle) appears to be the primary source of placental angiogenic activity throughout gestation. The fetal placentome (cotyledon) secretes activity which inhibits two major components of angiogenesis (proliferation and migration of endothelial cells) throughout gestation. Intercaruncular and intercotyledonary tissues may modulate placental angiogenesis throughout gestation. Placental vascular development in the cow is therefore probably controlled by an interaction between stimulatory and inhibitory factors produced by the placenta itself.     

Effects of conjugated linoleic acids and docosahexaenoic acid on rat liver and reproductive tissue fatty acids, prostaglandins and matrix metalloproteinase production

Long chain n-6 and n-3 fatty acids play important roles in labor and delivery. These effects may be mediated by prostaglandin (PG) synthesis and by regulation of matrix metalloproteinases (MMPs), both of which play roles in uterine contraction, cervical ripening and rupture of fetal membranes. The effects of altering dietary n-6:n-3 long chain fatty acid ratios, and the addition of dietary conjugated linoleic acids (CLA) and docosahexaenoic acid (DHA) on fatty acid composition of reproductive tissues, PG synthesis in liver and reproductive tissue and serum MMP levels were examined in pregnant rats. Modified AIN-96G diets with n-6:n-3 ratios of 7:1 and 34:1 with and without added 1.1% (by weight) conjugated linoleic acid (CLA) and/or 0.3% (by weight) DHA were fed through day 20 of gestation. Reproductive tissues readily incorporated both DHA and CLA. CLA significantly (P<0.05) depressed PGF(2 alpha)synthesis in placenta, uterus and liver by 50% when the n-6:n-3 ratio was 7:1 and by 66% at 34:1 ratio. Significant differences (P<0.05) in PGE(2)synthesis in uterus and liver were seen only between groups fed the high ratio of n-6:n-3 without CLA, and the low ratio with CLA. Addition of CLA to DHA containing diets depressed PGF(2alpha) by one-third in uterus and liver (P<0.05). Serum MMP-9 and active MMP-2 were suppressed (P<0.05) by addition of either CLA or DHA.     

Fat supplementation to the gestation diet of older sows and its effect on maternal and fetal fat metabolism

Sows that had had 3 previous litters were fed either a diet with no added fat (low fat) which was rich in linoleic acid (56.7% 18:2n-6), or a high fat diet containing lard, high in total saturates (28.9%) and oleic acid (37.8% 18:1n-9) during gestation. Backfat build-up in the sows on the high fat diet was accelerated compared to the low fat group. On day 110 of gestation, fetuses were removed. The fat content of the diet had no significant effect on sow weight gain during gestation, and the number or body weight of fetuses. Activities of sow liver and adipose and fetal liver malic enzyme, glucose-6-phosphate dehydrogenase (G-6-P) and acetyl-CoA-carboxylase (ACoABx) were measured. Only fetal liver ACoABx and sow adipose G-6-P were significantly affected by the sow's diet.     

Maternal high fat diet is associated with decreased plasma n-3 fatty acids and fetal hepatic apoptosis in nonhuman primates

To begin to understand the contributions of maternal obesity and over-nutrition to human development and the early origins of obesity, we utilized a non-human primate model to investigate the effects of maternal high-fat feeding and obesity on breast milk, maternal and fetal plasma fatty acid composition and fetal hepatic development. While the high-fat diet (HFD) contained equivalent levels of n-3 fatty acids (FA's) and higher levels of n-6 FA's than the control diet (CTR), we found significant decreases in docosahexaenoic acid (DHA) and total n-3 FA's in HFD maternal and fetal plasma. Furthermore, the HFD fetal plasma n-6:n-3 ratio was elevated and was significantly correlated to the maternal plasma n-6:n-3 ratio and maternal hyperinsulinemia. Hepatic apoptosis was also increased in the HFD fetal liver. Switching HFD females to a CTR diet during a subsequent pregnancy normalized fetal DHA, n-3 FA's and fetal hepatic apoptosis to CTR levels. Breast milk from HFD dams contained lower levels of eicosopentanoic acid (EPA) and DHA and lower levels of total protein than CTR breast milk. This study links chronic maternal consumption of a HFD with fetal hepatic apoptosis and suggests that a potentially pathological maternal fatty acid milieu is replicated in the developing fetal circulation in the nonhuman primate.     

Arachidonic acid metabolism by bovine placental tissue during the last month of pregnancy

Conversion of tritiated arachidonic acid (AA) into metabolites of the cyclo- and lipoxygenase pathways by bovine fetal placental tissue (200 mg) and fetal plus maternal placental tissue (400 mg) of Days 255, 265, 275 of gestation and at parturition (n = 5) during a 30 min incubation was measured using reverse-phase high pressure liquid chromatography. Fetal placental tissue produced 13,14-dihydro-15-keto-prostaglandin E2 (PGEM) as the major metabolite, the synthesis of which increased from Day 265 to Day 275 and parturition by 150% and 475%, respectively. In tissues collected at parturition, PGE2 synthesis was also detected. On Day 275 and at parturition fetal placental tissue synthesized the metabolite 12-hydroxyheptadecatrienoic acid (HHT), and throughout the experimental period the lipoxygenase product 15-HETE was detected with synthesis rates increasing over time of gestation. In addition, an unidentified metabolite was regularly found in the radiochromatograms which eluted at 1 h and 1 min (U101), between HHT and 15-HETE. The synthesis of this metabolite decreased as pregnancy progressed. Furthermore, various other polar and nonpolar metabolites pooled under the heading UNID were eluted, the production of which increased over time of gestation. The presence of maternal placental tissue did not influence the synthesis of PGEM, 15-HETE and U101, but the production of HHT was decreased when maternal tissue was present. Also, as pregnancy progressed, maternal placental tissue seemed to contribute to the pool of unidentified metabolites. In conclusion, fetal placental tissue seems to be the major source of the AA metabolites when compared with maternal placental tissue, and AA metabolism by bovine placental tissue is markedly increased throughout the last month of pregnancy, suggesting a role for AA metabolites in mechanisms controlling parturition.     

Dietary low linolenic acid compared with docosahexaenoic acid alter synaptic plasma membrane phospholipid fatty acid composition and sodium-potassium ATPase kinetics in developing rats

The objective of this study was to investigate if maternal dietary 20:4n-6 arachidonic acid (AA) and 22:6n-3 compared with adequate or low levels of 18:3n-3 linolenic acid (LNA) increases synaptic plasma membrane (SPM) cholesterol and phospholipid content, phospholipid 20:4n-6 and 22:6n-3 content, and Na,K-ATPase kinetics in rat pups at two and five weeks of age. At parturition, Sprague-Dawley rats were fed semi-purified diets containing either AA + docosahexaenoic acid (DHA), adequate LNA (control; 18:2n-6 : 18:3n-3 ratio of 7.1 : 1) or low LNA (18:2n-6 : 18:3n-39 ratio of 835 : 1). During the first two weeks of life, the rat pups received only their dams' milk. After weaning, pups received the same diet as their respective dams to five weeks of age. No significant difference was observed among rat pups fed the diet treatments for SPM cholesterol or total and individual phospholipid content at two and five weeks of age. Fatty acid analysis revealed that maternal dietary AA + DHA, compared with feeding the dams the control diet or the low LNA diet, increased 20:4n-6 in phosphatidylserine and 22:6n-3 content of SPM phospholipids. Rats fed dietary AA + DHA or the control diet exhibited a significantly increased Vmax for SPM Na,K-ATPase. Diet treatment did not alter the Km (affinity) of SPM Na,K-ATPase in rat pups at two and five weeks of age. It is concluded that dietary AA + DHA does not alter SPM cholesterol and phospholipid content but increases the 22:6n-3 content of SPM phospholipids modulating activity of Na,K-ATPase.     

Low linoleic acid may facilitate Δ6 desaturase activity and docosahexaenoic acid accretion in human fetal development

The n-3 and n-6 fatty acids are transferred across the placenta with consistently higher 22:6n-3 and lower 18:2n-6 in fetal than maternal plasma. This study sought to determine whether maternal and fetal cord blood red blood cell (RBC) phospholipid fatty acids show similar saturation with 22:6n-3, and also addressed the relationship between 18:2n-6 and Δ6 desaturase product/precursor ratios for 97 mothers and newborns. Despite higher fetal than maternal plasma phospholipid 22:6n-3, the maternal and fetal RBC phospholipid 22:6n-3 showed similar curvilinear relationships to the plasma phospholipid 22:6n-3. Risk of failure to achieve high RBC phospholipid 22:6n-3 increased sharply below a plasma phospholipid 22:6n-3 of 6.5g/100g fatty acids. Higher maternal and fetal 18:2n-6 was associated with lower RBC phospholipid 22:6n-3/22:5n-3, 22:5n-6/22:4n-6 and 18:3n-6/18:2n-6. These findings suggest low placental transfer of 18:2n-6 may be a specific mechanism to prevent inhibition of fetal Δ6 desaturase and facilitate fetal cellular phospholipid 22:6n-3 accretion.     

n-6 and n-3 Long-chain polyunsaturated fatty acids in the erythrocyte membrane of Brazilian preterm and term neonates and their mothers at delivery

Placental transfer of the long-chain polyunsaturated fatty acids (LCPUFA) arachidonic (AA) and docosahexaenoic (DHA) acids is selectively high to maintain accretion to fetal tissues, especially the brain. The objectives of the present study were to investigate the essential fatty acid (EFA) and LCPUFA status at birth of preterm and term Brazilian infants and their mothers, from a population of characteristically low intake of n-3 LCPUFA, and to evaluate the association between fetal and maternal status, by the determination of the fatty acid composition of the erythrocyte membrane. Blood samples from umbilical cord of preterm (26-36 weeks of gestation; n = 30) and term (37-42 weeks of gestation; n = 30) infants and the corresponding maternal venous blood were collected at delivery. The LCPUFA composition of the erythrocyte membrane and DHA status were similar for mothers of preterm and term infants. Neonatal AA was higher (P < 0.01) whereas its precursor 18:2n-6 was lower (P < 0.01) than maternal levels, as expected. There was no difference in LCPUFA erythrocyte composition between preterm and term infants, except for DHA. Term infants presented a worse DHA status than preterm infants (P < 0.01) and than their mothers (P < 0.01) at delivery. There was a negative correlation of neonatal DHA with maternal AA and a positive correlation between neonatal AA and maternal AA and 18:2n-6 only at term. These results suggest that the persistent low DHA maternal status, together with the comparatively better AA and 18:2n-6 status, might have affected maternal-fetal transfer of DHA when gestation was completed up to term, and possibly contributed to the worse DHA status of term neonates compared with the preterm neonates.     

Angiogenic activity of maternal and fetal placental tissues of ewes throughout gestation

In Study 1, explants of caruncular and intercaruncular endometrium and fetal membrane were collected from ewes (5-6/day) on Days 11-13, 16-18 and 21-23 after mating and Days 10-12 after oestrus, and incubated for 24 h. Explant-conditioned media were evaluated for their effects on endothelial cell proliferation. Both caruncular and intercaruncular endometrium secreted factor(s) which stimulated endothelial cell proliferation, and which appeared to be greater than 100 x 10(3) Mr and heat-labile. In Study 2, conditioned media from explant incubations of caruncular and intercaruncular endometrium, cotyledon and intercotyledonary fetal membrane obtained from ewes (6-7/day) on Days 40, 65, 90, 115 and 140 after mating were evaluated for their effects on endothelial cell proliferation. Caruncular and intercaruncular endometrium and intercotyledonary fetal membrane secreted factor(s) which inhibited endothelial cell proliferation. Media from cotyledonary explants tended to stimulate endothelial cell proliferation on Day 115. Conditioned media from cotyledonary explants obtained from 3 additional ewes at Day 120 of gestation stimulated endothelial cell proliferation, and this activity also appeared to be greater than 100 x 10(3) Mr. Placental angiogenesis in ewes therefore appears to be modulated by both maternal and fetal placental tissues via stimulatory and inhibitory factors.