Altering n-3 to n-6 polyunsaturated fatty acid ratios affects prostaglandin production by ovine uterine endometrium

Anim Reprod Sci. 2013 Dec;143(1-4):38-47. doi: 10.1016/j.anireprosci.2013.10.015. Epub 2013 Nov 1.


Consumption of n-3 polyunsaturated fatty acids (PUFAs) is considered beneficial to health but effects on fertility remain uncertain. This study investigated the effect of n-3 PUFA supplementation on endometrial prostaglandin (PG) production. Ovine uterine endometrial cells were cultured to confluence in DMEM/F12 medium containing 10% foetal bovine serum. Stromal and epithelial cell populations were confirmed by immunocytochemistry. Cultures were supplemented with 0, 20 or 100 μM of α-linolenic acid (ALA), stearidonic acid (SDA), eicosapentaenoic acid (EPA) with lipopolysaccharide (LPS) at 0 and 0.1 μg/ml, or different combinations of EPA with arachidonic acid (AA) in serum-free medium for 24h. PGs were quantified using radioimmunoassay and PG-endoperoxide synthase (PTGS) isoforms, PGE and PGF synthase (microsomal PGES1 and PGFS) mRNAs by qPCR. LPS increased PGE2 production significantly without changing PGF2α production, causing increased PGE2:PGF2α ratios. ALA and SDA increased PGE2, PGF2α and PGE2:PGF2α ratios (P<0.05-0.01) while EPA alone did not affect PG generation. AA significantly stimulated PTGS1 and PTGS2 mRNA expression and PGE2 and PGF2α production (P<0.01). The stimulatory effect of AA was attenuated by up to 80% (P<0.05) when AA was combined with EPA. The PGE2:PGF2α ratio was not affected by AA or EPA alone, but increased when these two PUFAs were combined (P<0.05). SDA and EPA decreased PTGS1 mRNA expression (P<0.05) but did not alter PTGS2 expression. EPA and AA up-regulated mPGES1 expression (P<0.05) without affecting PGFS expression. Since AA is preferentially incorporated in uterine endometrium to produce 2-series PGs, alteration of PG production by EPA may affect many reproductive processes.

Keywords: Endometrial cells; Ewe; Polyunsaturated fatty acid; Prostaglandin-endoperoxide synthase; Prostaglandins; Uterus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Endometrium / drug effects*
  • Endometrium / metabolism
  • Fatty Acids, Omega-3 / pharmacology*
  • Fatty Acids, Omega-6 / pharmacology*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hydroxyprostaglandin Dehydrogenases / genetics
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • Lipopolysaccharides / pharmacology
  • Prostaglandins / metabolism*
  • Sheep* / genetics
  • Sheep* / metabolism
  • Uterus / drug effects*
  • Uterus / metabolism


  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Lipopolysaccharides
  • Prostaglandins
  • Hydroxyprostaglandin Dehydrogenases
  • prostaglandin-F synthase
  • Cyclooxygenase 1
  • Cyclooxygenase 2