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Prostaglandins (PG) have a regulatory influence on ovulation. α-Linolenic acid (ALA) vs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differently influence PG biosynthesis. Whereas high EPA/DHA reduces PGE₂, enhancing ovulation, we hypothesized that ALA would not affect ovulation. Our objective was to determine the effect of low and high ALA intake vs EPA/DHA on ovarian phospholipids, ovulation, and PG synthesis in rats. Following 27 days on diet and ovulation induction, ovaries were isolated and analyzed in 22 pups per diet. Ovarian phospholipid (n-3) polyunsaturated fatty acid (PUFA) incorporation increased with EPA/DHA ingestion. With significant ovarian (n-3) PUFA or EPA (P < .05) enrichment in the high-n-3 PUFA diets, ova release increased. Although high ALA did not enrich total (n-3), it increased ova release and tissue EPA over low ALA or control. Dietary EPA/DHA more effectively reduced ovarian arachidonic acid levels than dietary ALA. Dietary ALA increased PGF and very high intake reduced PGE, whereas EPA/DHA did not alter PGE or PGF. Enhanced ova release with high (n-3) PUFA intake may be induced via multiple mechanisms including reduced ovarian arachidonic acid. Significant ovarian retention of EPA and DHA enhanced ovulation with unchanged total PGE and PGF. Lack of change in PGE may have resulted from reduced PGE₂ combined with increased PGE₃. When EPA alone was elevated, PGE was reduced, whereas PGF was increased. Results indicate that very high ALA intake enhances ovulation similar to very high EPA/DHA ingestion, an effect potentially mediated via similar patterns of PGF₂α and PGE₂ synthesis., (Published by Elsevier Inc.)

The comparative effects of dietary alpha-linolenic acid and fish oil on eicosanoid metabolism was studied in vivo. Resident murine peritoneal cells were stimulated in vivo with opsonized zymosan in animals maintained on diets containing increasing amounts of alpha-linolenic acid or fish oil concentrate with projected n-3/n-6 ratios of 0.2, 0.4 and 1.0. While fish oil feeding resulted in significant changes in eicosapentaenoate tissue levels, alpha-linolenic acid was preferentially metabolized to docosahexaenoate. High performance liquid chromatographic analysis revealed the formation of leukotriene E5 (LTE5) in all the fish oil groups (19.8 +/- 3.5 ng/mouse to 83.3 +/- 13 ng/mouse), but only in the highest linolenic acid group (6.0 +/- 3.2 ng/mouse). Concomitantly, the 4-series sulfidopeptide leukotrienes and PGI2 were significantly reduced in the two highest fish oil containing dietary groups. Similar reductions were observed in the highest linolenic acid group, but the changes were not statistically different from the control values. In summary, this paper reports the de novo synthesis of 5-series sulfidopeptide leukotrienes in animals consuming alpha-linolenic acid. It also reveals that dietary fish oil is 2.5 to 5 times more effective than alpha-linolenic acid in modulating eicosanoid metabolism and altering tissue phospholipid fatty acid composition.

Resident mouse peritoneal cells, stimulated in vivo with opsonized zymosan, produced leukotriene C4 and E4, with LTE4 being the major (80-90%) product. When mice were placed on diets containing increasing amounts of fish oil, four additional sulfidopeptide leukotrienes (SP-LT), LTC5, LTE5, 11-trans LTC5 and 11-trans LTE5, were identified. The identity of LTE5 was confirmed by spectrophotometric, chromatographic and enzymatic methods. When equivalent amounts of n-6 and n-3 polyunsaturated fatty acids (PUFA) were included in the diet, the stimulated peritoneal cells (in vivo) produced higher quantities of LTE5 (30.2 +/- 5.4 ng/10(6) cells) than LTE4 (22.8 +/- 7.3 ng/10(6) cells). In addition, in vitro studies demonstrated a 60% reduction in LTC4 (42.0 +/- 10.8 ng/10(6) cells to 16.7 +/- 6.2 ng/10(6) cells) and the appearance of LTC5 (2.1 +/- 0.9 ng/10(6) cells) in resident macrophages (stimulated with A23187) from mice maintained on a fish oil diet compared to mice fed the control diet. This study demonstrated that formation of the pentaenyl SP-LT in vivo, in particular LTE5, by peritoneal cells can significantly contribute to the endogenous SP-LT pool in response to an inflammatory stimulus following a dietary regimen containing fish oil.