Endocrine Abstracts

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.