Raised dietary n-6 polyunsaturated fatty acid intake increases 2-series prostaglandin production during labour in the ewe (original) (raw)
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Journal of Endocrinology, 2005
Polyunsaturated fatty acids derived from the diet are incorporated into cell membranes where they act as precursors for prostaglandin (PG) synthesis. Linoleic acid (LA; 18:2 n-6) is a major constituent of plant oils and its consumption in Westernized populations is increasing. This study investigated the influence of LA on PG production by the uterus and placenta. Pregnant ewes were fed a control or an LA-enriched diet. Oxytocin (OT) was injected on day 45 (early) or day 133 (late) of gestation to measure the release of 13,14-dihydro-15-keto PGF 2 (PGFM). Ewes were killed on day 46 or day 138 for collection of uterine intercaruncular endometrium and fetal allantochorion. Basal and stimulated PG release from explant cultures was assessed before and after in vitro treatment with OT, lipopolysaccharide (LPS), dexamethasone (DEX) or calcium ionophore (CaI). Expression of cyclooxygenase (COX)-1 and COX-2 was determined by Western blot in endometrium of late-gestation ewes. Circulating PGFM levels in vivo did not differ according to diet but there were highly significant differences in the release of PGs in vitro. Basal production of PGF 2 and PGE 2 by the endometrium and of PGE 2 by the allantochorion were all higher in tissues from LA-supplemented ewes. Endometrial tissues produced more PG following OT and CaI treatment, whereas DEX inhibited production of both PGs at both stages of gestation. In allantochorion collected at day 46 LPS did not significantly alter PGE 2 release and DEX increased output, whereas at day 138 LPS was stimulatory but DEX was inhibitory. These data show that a high-LA diet can significantly increase the ability of both endometrium and placental tissues to produce PGs in vitro. This effect of diet may only become apparent after a sustained period of PG release, so was not seen following the brief pulse caused by OT treatment in vivo. As COX protein levels were unaltered, the main influence was likely to be via conversion of LA to arachidonic acid, providing an increased supply of precursor. These results support previous studies which suggest that alterations in dietary polyunsaturated fatty acids may influence the time of labour.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2004
Linoleic acid (18:2n-6) is metabolised to arachidonic acid (20:4n-6), the precursor for 2-series prostaglandins (PGs). Increased consumption of 18:2n-6 during pregnancy may thus modify PG synthesis during labour. We have investigated whether increased 18:2n-6 composition during gestation altered the fatty acid consumption and PG synthesis of maternal and fetal tissues in the sheep. Ewes were fed a control diet or a diet providing 40% more 18:2n-6 from 96 days gestation. Half of each group received dexamethasone on day 136 to upregulate the PG synthetic pathways promoting parturition. Maternal and fetal tissues were collected at 138 days. The 18:2n-6 diet significantly increased the 20:4n-6 content of maternal plasma, fetal plasma and allantochorion (51-81%) phosphatidylcholine, and fetal liver (40%) and maternal caruncular endometrium (57%) phosphatidylethanolamine. Increased 18:2n-6 intake increased production of PGF 2a and PGE 2 in all placental tissues (maternal caruncular and intercaruncular endometrium and fetal allantochorion) by 23-98%, whereas dexamethasone increased it by 32-142%. This suggests that consumption of an 18:2n-6-enriched diet in late pregnancy enhanced placental PG production by increasing the supply of 20:4n-6. Variations in the extent to which the diet altered the polyunsaturated fatty acid (PUFA) content of the different tissues indicated complex interactions between nutrient availability and metabolic adaptation. D
Placenta, 2011
Objective: To use an in vitro model of the ovine placenta to determine effects of n-6 polyunsaturated fatty acid (PUFA) supplementation on prostaglandin (PG) production. PGs are key regulators of fetal maturation and parturition. Study design: Fetal allantochorion tissue (FC) was collected in late pregnancy (day 135). FC cells were isolated and cultured with 0e100 mM of linoleic acid (LA), g-linolenic acid (GLA) or arachidonic acid (AA) in serum free medium and challenged with control medium, lipopolysaccharide (LPS, 0.1 mg/ml), dexamethasone (DEX, 5 mM) or a combination of LPS (0.1 mg/ml) with DEX (5 mM). Spent medium was harvested at 2 h and 24 h post challenge for measuring PGs. Main outcome measures: To assess the effects of treatment on placental 1-and 2-series PGE production. Results: LA supplementation inhibited both PGE 1 and PGE 2 production. GLA predominantly stimulated PGE 1 generation, although it also increased PGE 2 production. AA supplementation predominantly increased PGE 2 production, but also stimulated PGE 1 . DEX treatment with or without LPS inhibited PG production. Supplementation with n-6 PUFAs attenuated or neutralised the stimulatory effect of LPS challenge on FC cells for both PGE 1 and PGE 2 production. Conclusion: These data show that supplementation with n-6 PUFAs alters placental PG production, but their precise effects depend on their position in the biosynthetic pathway for PG synthesis. This study supports the possibility that GLA containing oils, widely promoted as dietary supplements, might reduce the risk of pre-term labour by inhibiting the responsiveness of PGE 2 production to LPS challenge in the placenta.
Journal of Endocrinology, 2004
We investigated the effect of n-6 polyunsaturated fatty acids (PUFAs) on prostaglandin (PG) production by the uterus. A mixed population of endometrial cells (epthelium and stroma) from late-gestation ewes were cultured in defined medium containing linoleic acid (LA, 18:2, n-6), -linolenic acid (GLA, 18:3, or arachidonic acid (AA, 20:4, in concentrations of 0 (control), 20 or 100 µM. After 45 h in test medium with or without added PUFAs, cells were challenged with control medium (CM), oxytocin (OT, 250 nM), lipopolysaccharide (LPS, 0·1 µg/ml) or dexamethasone (DEX, 5 µM) for 22 h in the continued presence of the same concentration of PUFA and the medium was collected for measurement of PGF 2 and PGE 2 . Supplementation with LA inhibited the production of PGF 2 but did not alter PGE 2 , whereas GLA and AA increased production of both PGs. All PUFA supplements thus increased the ratio of PGE 2 to PGF 2 (E:F ratio) two-to threefold. In control cells, OT and LPS challenges stimulated the production of PGF 2 and PGE 2 . In all challenge groups, the concentrations of PGF 2 in response to PUFAs followed the same pattern -LA<control<GLA<AA -but there were significant alterations in responsiveness as a result of PUFA treatment. In the cells supplemented with 100 µM AA, there was no further increase in PGF 2 output in the presence of OT or LPS and when 100 µM GLA was present neither LPS nor OT stimulated PGE 2 significantly. When LPS was given to AA-supplemented cells, the E:F ratio was increased. DEX did not change PGE 2 production in control or LA-treated cells, but the cells produced significantly less PGF 2 , so the E:F ratio was increased. In contrast, in GLA-and AA-treated cells, DEX reduced the production of both PGF 2 and PGE 2 , so the E:F ratio was unaltered. In summary, the study showed altered production of PGs in the presence of different PUFAs according to their position in the n-6 metabolic pathway. The type of PUFA present affected responsiveness to OT, LPS and DEX and also changed the ratio of PGE 2 to PGF 2 produced. The possible implications of this work are discussed in relation to the effect of diet on term and pre-term labour, which both require upregulation of the endometrial PG synthetic pathway.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2003
The anticarcinogenic properties of conjugated linoleic acid (CLA) are, at least partially, attributed to its ability to interrupt the n-6 polyunsaturated fatty acid (PUFA) metabolic pathway for the biosynthesis of eicosanoids, including prostaglandins (PG). Both PGE 2 and PGF 2a play key roles in parturition. In the present study, we compared the effects of CLA (a mixture of cis-and trans-9, 11-and -10, 12octadecadienoic acid) and linoleic acid (LA) on PG production by cells isolated from maternal intercotyledonary endometrium, fetal allantochorion and amnion from late pregnant ewes. The results demonstrated that supplementation of LA and CLA significantly affected both the proportions and the amounts of PGs produced by all three tissue types. The ability of the uterus and placenta to respond to oxytocin (OT, endometrium only) and lipopolysaccharide (LPS) was also affected. LA inhibited PGE 2 and PGF 2a production in the absence or presence of either oxytocin or LPS. In endometrial cells with or without oxytocin or LPS, CLA dose-dependently suppressed PGF 2a generation, whereas low doses of CLA (20 AM) increased PGE 2 generation. Supplementation with CLA therefore increased the PGE 2 /PGF 2a ratio in the endometrial cells. These results suggest that dietary supplementation of LA or CLA may affect both the initiation and progression of parturition. D
Polyunsaturated fatty acid supplementation during pregnancy alters neonatal behaviour in sheep
The objectives of the study were to determine whether supplementation of pregnant ewes with long-chain (n-3) fatty acids present in fish oil, in combination with dietary vitamin E, would alter neonatal behavior in sheep. Twin- (n ¼ 36) and triplet- (n ¼ 12) bearing ewes were allocated at d 103 of gestation to 1 of 4 dietary treatments containing 1 of 2 fat sources [Megalac, a calcium soap of palm fatty acid distillate or a fish oil mixture, high in 20:5(n-3) and 22:6(n-3)] and 1 of 2 dietary vitamin E concentrations (50 or 500 mg/kg) in a 2 3 2 factorial design. Feeding fish oil increased gestation length by 2 d and increased the proportion of 22:6(n-3) within neonatal plasma by 5.1-fold and brain by 10%, whereas brain 20:5(n-3) was increased 5-fold. Supranutritional dietary vitamin E concentrations decreased the latency of lambs to stand in ewes fed fish oil but not Megalac, whereas latency to suckle was decreased from 43 to 34 min by fish oil supplementation. Supplementation with fish oil also substantially decreased the secretion rate (mL/h) of colostrum and the yield (g/h) of fat and protein. We conclude that supplementation of ewes with fish oil decreases the latency to suckle, increases gestation length and the 22:6(n-3):20:4(n-6) ratio in the neonatal brain, and may improve lamb survival rate. However, further work is required to determine how to mitigate the negative effects of fish oil on colostrum production.
Long-chain ??-3 fatty acid supply in pregnancy and lactation
Current Opinion in Clinical Nutrition and Metabolic Care, 2008
Purpose of review Long-chain v-3 fatty acids are essential for the developing fetus. Docosahexaenoic acid, the most important v-3 fatty acid, is an important component of neural and retinal membranes, and rapidly accumulates in the brain during gestation and the postnatal period. Positive associations have been shown between maternal intake of fish, seafood and v-3 fatty acids during pregnancy and/or lactation and visual and cognitive development. Recent findings The review focuses on new findings by both observational and interventional studies on the influence of v-3 fatty acids during pregnancy or lactation on gestation length and birth weight, preterm delivery, preeclampsia, maternal depression and infant visual function and neural development. Summary Omega-3 fatty acids have been associated with reduced risk of cardiovascular and other diseases. Observational and interventional studies indicate a significant association with prolonging gestation and reducing the risk of preterm delivery both in low-risk and in high-risk pregnancies. Further benefits have been suggested for intrauterine growth restriction, preeclampsia and postpartum depression, but the evidence is inconclusive. Higher maternal docosahexaenoic acid intake both in pregnancy and lactation is associated with positive infant neurodevelopmental outcomes. Women of reproductive age should achieve an average dietary docosahexaenoic acid intake of at least 200 mg/day.