PARENT SESSION
IMPACT OF NUTRITION AND AGING ON REPRODUCTIVE FUNCTION
Kent
7:30 AM-10:00 AM

(598) THE EFFECT OF n-6 POLYUNSATURATED FATTY ACIDS (PUFAs) ON PROSTAGLANDIN PRODUCTION BY THE ENDOMETRIUM OF LATE PREGNANT EWES.

Wathes, Claire¹, Cheng, Zhangrui¹, Elmes, Matthew¹, Kirkup, Susan¹, Abayasekara, Robert¹, ¹ Reproduction and Development Group, Hatfield, GB

ABSTRACT- This study examined the effect of the n-6 PUFAs linoleic acid (LA), gamma linolenic acid (GLA) and arachidonic acid (AA) on prostaglandin (PG) production in the late pregnant ovine uterus. LA is elongated to GLA by -6 desaturase. Entire reproduction tracts were collected post mortem from 9 ewes on day 135 of gestation. Fetal and maternal tissues were separated. Strips of intercotyledonary endometrium were digested with trypsin-collagenase to yield mixed populations of epithelial and stromal cells. These were cultured for 7 days to confluence in 24 well plates in medium containing 10% FCS. This was replaced with serum free medium ± LA, GLA or AA at 20 and 100 M. After 72 h cultures were challenged with either: (1) control medium as before; (2) 250 nM oxytocin (OT); (3) 0.1 g/ml lipopolysaccharide (LPS) or (4) 5 M dexamethasone (DEX). Each treatment was performed in quadruplicate with tissue from at least 3 separate sheep. PGF₂ and PGE₂ production were measured in medium 24 h post challenge. Data were analysed using ANOVA via a mixed model (SAS 8.0). The addition of LA to control medium significantly reduced the production of both PGs at 24 h (P<0.05-0.01), whereas both GLA and AA stimulated the production of both PGs by up to 10 fold. Cells challenged with OT and LPS increased the concentration of both PGs at 24 h. Cells pre-treated with LA produced less PGF₂ in response to OT or LPS than cells in PUFA free medium, whereas those pre-treated with GLA or AA produced more (P<0.05-0.01). GLA and AA also increased the PGF₂ response to LPS. In PUFA free medium DEX inhibited the production of both PGF₂ and PGE₂ at 24 h. The addition of DEX to LA treated cells resulted in further inhibition of PGF₂ but not PGE₂. However in cells pre-treated with AA or GLA, the stimulatory effect of the PUFA was attenuated by DEX. In conclusion, n-6 PUFAs can alter both the basal production of uterine PGs and the responsiveness of the uterus to OT, DEX and LPS which are important activators in term and preterm delivery respectively. In terms of PG generation, LA, the most abundant n-6 PUFA in both diet and blood, was inhibitory whilst GLA and AA were stimulatory. -6 desaturase may therefore be important in controlling uterine responsiveness in animals on a high n-6 diet.

KEY WORDS: PUFAs, prostaglandins, endometrium, pregnancy