Elevated serum levels of biologically active omega-3 fatty acids are associated with better ovarian reserve


      Dietary omega-3 fatty acids (FA) delay ovarian aging,1 but it remains unclear if they affect ovarian reserve parameters. We sought to assess the relationship between the omega-3 FA and ovarian reserve in a mouse model, by evaluating essential FAs (linoleic and α-linolenic) and biologically active FAs (arachidonic (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)). We assessed significant correlations between the biologically active omega-6 to omega-3 FA ratio (AA/EPA+DHA) and primordial and growing (primary, preantral, antral) follicle count.


      Prospective laboratory animal study.

      Materials and Methods

      Ten 15 week-old chow-fed wild-type (WT; n=4) and hemizygous Fat-1 C57BL/6J female mice (n=6) were sacrificed for ovary and serum collection. Fat-1 mice overexpress an n-3 FA desaturase that converts certain omega-6 to omega-3 FAs, leading to increased n-3 FAs in their organs and tissues. Ovaries were assessed for primordial and growing follicle numbers. Serum levels of linoleic (LA, 18:2n-6), α-linolenic (ALA, 18:3n-3), AA, 20:4n-6; DHA, 22:6n-3; and EPA, 20:5n-3 acids from the total FA fraction were quantified by mass spectrometry and expressed as nmol/ug of protein. Pearson r correlation was used to assess correlation between FA levels and ovarian follicle numbers. P value < 0.05 was considered statistically significant.


      DHA and EPA serum amounts had a strong, positive correlation with primordial follicle count (r=0.66, p=0.03; and r = 0.72, p=0.01, respectively). There was also a significant and strong negative correlation between the AA/DHA+EPA ratio and primordial follicle count (p=0.02; r = -0.72). No correlation was observed between AA, LA, and ALA and primordial follicle numbers. No correlation was observed between FA levels and growing follicle pool.


      Our results indicate that quantities of biologically active omega-3 EPA and DHA strongly associate with primordial follicle pool. This effect is directionally consistent with dietary intervention studies showing that higher diet-derived DHA and EPA prolong reproductive lifespan and oocyte quality. Our preclinical model suggests that nutritional intervention using long-chain omega-3 FA supplements should be considered for women with diminished ovarian reserve in an attempt to promote oocyte quantity and quality.
      • 1.
        Nehra D, Le HD, Fallon EM, et al. Prolonging the female reproductive lifespan and improving egg quality with dietary omega-3 fatty acids. Aging Cell. 2012 Dec;11(6):1046-54.