Anti-inflammatory effects of fish oil in ovaries of laying hens target prostaglandin pathways

Abstract

BackgroundAn effective way to control cancer is by prevention. Ovarian cancer is the most lethal gynecological malignancy. Progress in the treatment and prevention of ovarian cancer has been hampered due to the lack of an appropriate animal model and absence of effective chemo-prevention strategies. The domestic hens spontaneously develop ovarian adenocarcinomas that share similar histological appearance and symptoms such as ascites and metastasis with humans. There is a link between chronic inflammation and cancer. Prostaglandin E2 (PGE2) is the most pro-inflammatory ecoisanoid and one of the downstream products of two isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. PGE2 exerts its effects on target cells by coupling to four subtypes of receptors which have been classified as EP1-4. Fish oil is a source of omega-3 fatty acids (OM-3FAs) which may be effective in prevention of ovarian cancer. Our objective was to assess the potential impact of fish oil on expression of COX enzymes, PGE2 concentration, apoptosis and proliferation in ovaries of laying hens.Methods48 white Leghorn hens were fed 50, 100, 175, 375 and 700 mg/kg fish oil for 21 days. The OM3-FAs and omega-6 fatty acids contents of egg yolks were determined by Gas Chromatography. Proliferation, apoptosis, COX-1, COX-2 and prostaglandin receptor subtype 4 (EP4) protein and mRNA expression and PGE2 concentration in ovaries were measured by PCNA, TUNEL, Western blot, quantitative real-time qPCR and ELISA, respectively.ResultsConsumption of fish oil increased the incorporation of OM-3FAs into yolks and decreased both COX-1 and COX-2 protein and mRNA expression. In correlation with COXs down-regulation, fish oil significantly reduced the concentrations of PGE2 in ovaries. EP4 protein and mRNA expression in ovaries of hens was not affected by fish oil treatment. A lower dose of fish oil increased the egg laying frequency. 175 and 700 mg/kg fish oil reduced proliferation and 700 mg/kg increased apoptosis in hen ovaries.ConclusionsOur findings suggest that the lower doses of fish oil reduce inflammatory PG and may be an effective approach in preventing ovarian carcinogenesis. These findings may provide the basis for clinical trials utilizing fish oil as a dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer.

Effects of different levels of clove bud (Syzygium aromaticum) on yolk biochemical parameters and fatty acids profile, yolk oxidative stability, and ovarian follicle numbers of laying hens receiving different n-6 to n-3 ratios

“…Our findings indicate that although feeding LRD induced higher lipid peroxidation in egg yolk, administration of 4 g/kg clove bud or 200 mg/kg vitamin E could improve fat stability in eggs under different storage conditions. Administration of LRD led to reduced n-6 to n-3 ratio in egg yolk as a result of fortifying DHA and EPA concentrations and suppressing C18:2, C20:2, and C20:4 fatty acids concentration (Table 4), as demonstrated by previous studies (Beynen, 2004;Carrillo-Dominguez et al, 2012;Eilati et al, 2013).…”

The relationship between dietary fat sources and immune response in poultry and pigs: An updated review

“…Correspondingly, Liu et al (2014) demonstrated that dietary fish oil, in comparison with maize oil, reduced concentrations of plasma PGE 2 in chickens; however, this modulatory effect was not reflected in growth performance. Eilati et al (2013), evaluated in a dose-response study, the effect of fish oil (0%, 0.5%, 1.0%, 1.75%, 3.75%, or 7.0% in the diet) on the expression of cyclooxygenase enzymes (COX-1, (2000) Maize (2%, 4%, or 6% in the diet), linseed (2%, 4%, or 6%), or fish oil (1%, 3%, or 5%)…”

“…The authors found that dietary fish oil reduced COX-1 and COX-2 protein and mRNA expression and concentrations of PGE 2 in ovaries, as well as improving laying performance. They concluded that the lower doses of fish oil reduce inflammatory PG and may be an effective tool in preventing ovarian carcinogenesis (Eilati et al, 2013). Chen et al (2012) reported that the modulating effect of decreasing the n-6:n-3 dietary fatty acid ratio (achieved by adding various amounts of linseed, soybean, and maize oils) on the functioning of immune cells was reflected in increases in body weight in broiler chickens during the first 3 weeks of age.…”

Flaxseed and its components differentially affect estrogen targets in pre-neoplastic hen ovaries

“…The decrease in PGE2 levels could be a result of the high alpha linoleic acid content of flaxseed oil which is partially converted to EPA (eicosapentanoic acid) and DHA (docosahexanoic acid) in the cells. EPA and DHA can get incorporated into the cell membrane and shift the equilibrium of PG (prostaglandin) synthesis to a less inflammatory type (PGE3) [28] as previously demonstrated by our group [29]. In addition, E-cadherin, a marker characteristically upregulated in human epithelial ovarian cancers as well as in the hen ovarian tumor [30], is significantly downregulated in ovarian tumors from hens fed a flaxseed supplemented diet [31].…”