Dyslipidemia: negative effect on oocyte maturation and impact on ovarian intrafollicular lipid profile

Abstract

Dyslipidemia, defined as alterations in plasma lipid levels, shows high and increasing global prevalence. Ovarian follicular fluid (FF) is produced by granulosa cell (GC) secretion and by diffusion from the theca capillaries. The association between dyslipidemia and intrafollicular lipids or oocyte maturation competence remains unclear. This work aimed at analyzing: (I) the association between neutral plasma lipids and the percentage of metaphase II oocytes (% MII) and (ii) the influence of dyslipidemia on the lipid composition of FF and the hydrophobicity of intracellular lipid droplets in GC. We collected FF and GC from 109 women with no reproductive pathologies with dyslipidemia (n=57, age 32.3 ± 6.4 years) and without dyslipidemia (n=52; age 31.5 ± 5.5 years). These women include male factor infertility, donors, and women with the desire to gestate genetically related children. Follicular fluid lipids were quantified using enzymatic methods. Hydrophobicity of intracellular lipids was evaluated by fluorescence spectroscopy using the lipophilic dye Nile Red. To compare women with the most contrasting plasma lipid profiles, we selected the extreme quartiles (Q1 and Q3, women with the lowest and highest plasma lipid levels, respectively) based on principal component analysis. In Q3, the % MII oocytes negatively correlated (p<0.05) with total cholesterol and LDL-cholesterol in plasma. Both quartiles exhibited positive correlations between plasma and follicular lipids. Mean values of total cholesterol, HDL-cholesterol, and triglycerides of FF were statistically higher in Q3 than in Q1. Hydrophobicity of intracellular lipid droplets did not show differences between quartiles. Findings from our work showed that dyslipidemia exerts a negative effect on oocyte maturation and that dyslipidemic women have a distinctive lipid profile in the FF compatible with an “intrafollicular dyslipidemia”.