Endocrine Abstracts (2004) 7 OC6

Effect of a high n-6 polyunsaturated fatty acid (PUFA) diet on COX expression and PGE2 synthesis in the ovine amnion during gestation

SE Kirkup, Z Cheng, E Chin, M Elmes, DC Wathes & DRE Abayasekara

Reproduction and Development Group, Veterinary Basic Sciences, Royal Veterinary College; London; UK.

Cervical dilatation and myometrial contractions are essential processes of both pre-term and term labour. These processes are associated with enhanced production of 2-series prostaglandins (PGs) from polyunsaturated fatty acids (PUFAs), by feto-placental tissues. Some human epidemiological studies suggest that specific PUFAs can alter the length of gestation. The amnion is a prime site for PG synthesis in the feto-placental unit. Thus perturbations of PG synthesis in this tissue may influence the timing of parturition, which is dependant on up-regulation of PG synthesis. Hence in this study we have investigated the effect of feeding a diet high in n-6 PUFA in vivo, on PGE2 production in vitro, by ovine amnion tissue at Day 135 of gestation. Corresponding changes in expression of both constitutive and inducible isoforms of the key PG synthetic enzyme [cyclooxygenase (COX)] were also evaluated.

PGE2 synthesis in ovine amnion tissue explants increased from Day 45 (D45) to Day 135 (D135) of gestation (D45: undetectable; D135: 62.06 plus/minusSD 13.78 picograms/per/milligram/tissue/per/hour; n=7). Whilst no COX protein was detected in lysed amnion tissues at D45; both isoforms of COX were expressed at D135 as detected by Western blotting. Supplementation of the diet with excess n-6 PUFA during the last 4 weeks of pregnancy had no effect on either COX expression or basal PGE2 synthesis in amnion explants at D135 of gestation. However, in tissues from sheep that had been artificially induced in vivo with Dexamethasone, PGE2 synthesis was enhanced 2-fold in tissues from sheep on the high n-6 diet (control: 53.5 plus/minusSD 46.5; high n-6: 109.7 plus/minusSD 25.4; picograms/per/milligram/tissue/per/hour. n=7, P<0.05). These results demonstrate that a high n-6 diet may not pre-dispose subjects to pre-term delivery. However, in the event of a physiological challenge, intrauterine tissues will have the capability to respond far more significantly in terms of increased PG synthesis.

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