Raised dietary n-6 polyunsaturated fatty acid intake increases 2-series prostaglandin production during labour in the ewe

Abstract

Preterm labour is the major cause of perinatal morbidity and mortality in humans. The incidence is around 10% and the causes are often unknown. Consumption of dietary n-6 polyunsaturated fatty acids (PUFAs) in western societies is increasing. These are metabolized to arachidonic acid, the precursor for 2-series prostaglandins (PGs), major signalling molecules during labour. This study investigated the effect of dietary supplementation with linoleic acid (LA, 18: 2, n-6) on parturition. Ewes were fed a control or LA-supplemented diet from 100 days gestation. Labour was induced using a standardized glucocorticoid challenge (dexamethasone, Dex) to the fetus, starting on day 139. Electromyographic (EMG) activity and fetal and maternal circulating PG concentrations were monitored. One third of LA-fed ewes delivered early (pre-Dex) although basal uterine EMG activity preceding Dex was higher in control ewes (P < 0.05). A steep increase in EMG activity occurred 18-38 h after the start of Dex infusion. Twice basal EMG activity (defined as established labour) occurred on average 7 h earlier in the LA-supplemented ewes (P < 0.05). The basal concentrations of maternal and fetal PGFM and fetal PGE(2) were approximately doubled in LA-supplemented ewes before the start of Dex infusion (P < 0.01). The rise in fetal PGE(2) and maternal oestradiol concentrations post-Dex occurred earlier in the LA-supplemented ewes. All PG measurements remained significantly higher in the LA-supplemented ewes during labour onset. This study suggests that consumption of a high LA diet in late pregnancy can enhance placental PG production and may thus increase the risk of preterm labour.

Figure 1. EMG traces from an LA-supplemented ewe

EMG traces from an LA-supplemented ewe over a 2 h window showing: A, basal activity and B, established labour. Four discrete uterine bursts are clearly seen in the basal trace. In B uterine bursts had exceeded twice basal activity, with 11 bursts in 2 h. This was defined as being in established labour.

Figure 2. Prostaglandin concentrations in the fetal and maternal circulation

Blood samples were taken in the post-operative recovery period following surgery to implant catheters and EMG recording electrodes on 132 day GA. PGE₂ was measured in the fetal circulation (A) and PGFM in both fetal (B) and maternal circulations (C). Values are the mean ± s.e.m. from control fed (open bars, n = 5) and LA-supplemented (black bars, n = 6) ewes which did not go into labour during this period. In these animals, PG values fell significantly between 132 and 138 day GA (*P < 0.05, paired Student's t test). In the LA-supplemented ewes that delivered early on 132–138 day GA PG values remained higher at 138 day GA, but as data were only available from 1 or 2 ewes (hatched bars), no statistical analysis was performed.

Figure 3. Uterine EMG activity during dexamethasone (Dex)-induced preterm labour

Individual data are shown from animals fed either a control or an LA-supplemented diet. Values are from 8 h before the start of Dex infusion to the fetus (at time 0 h) and were measured throughout the experimental period until scheduled death, 2 h after individuals animals were judged to be in established labour. This was defined as an increase in EMG activity to twice basal levels for 2 consecutive 2-h periods. See Table 2 for analysis.

Figure 4. Prostaglandin concentrations during dexamethasone (Dex)-induced preterm labour

Ewes were fed either a control diet (•, n = 5) or an LA-supplemented diet (•, n = 6). A, PGFM in the maternal circulation; B, PGFM in the fetal circulation; and C, PGE₂ in the fetal circulation. Values are from 6 h before the start of Dex infusion to the fetus (at time 0 h) and were measured throughout the experimental period until scheduled death 2 h after individual animals were judged to be in established labour (defined as an increase in EMG activity to twice basal levels for 2 consecutive 2-h periods). Data were grouped into the following time periods for analysis by repeated measures ANOVA: 139 day GA pre-Dex, 139 day GA post-Dex, 140 day GA and 141 day GA. Significance values between control and LA-supplemented ewes for individual time periods are indicated by the asterisks on the bar above each day: NS not significant, **P < 0.01, ***P < 0.001. The time of the first significant rise above baseline for each group is indicated by an arrow (assessed by ANOVA followed by multiple comparisons).

Figure 5. Maternal oestradiol-17β (A) and progesterone (B) concentrations after labour induction

Values are from the maternal jugular vein of control (n = 5) and LA-supplemented ewes (n = 6) during the 32 h prior to onset of Dex infusion (beginning at time 0, arrow) until scheduled killing during established labour. Values are mean ± s.e.m. The mean time of killing was 42 ± 1.1 h in control ewes and 34.7 ± 2.8 h in LA-supplemented ewes. Oestradiol concentrations had increased significantly above baseline in the LA-fed ewes from 16 h post-Dex, but in control ewes the first significant increase was not until labour (*P < 0.05, **P < 0.01 paired Student's t test in comparison with basal values at 0 h). Progesterone concentrations did not differ between dietary groups.