Cumulus cell acetyl-CoA metabolism from acetate is associated with maternal age but only partially with oocyte maturity

AbstractObjectiveTo use metabolism of cumulus cells (CCs) to predict oocyte competency.DesignCC clumps that associate with oocytes are thought to provide the oocytes with growth and signaling factors. Thus, the metabolism of the CCs may influence oocyte function. This was a prospective and blinded cohort study that analyzed 403 individual sets of CC clumps from 36 participants. Thirty-one of the participants had paired oocyte maturity data. CCs were removed from oocytes after oocyte retrieval procedure, transported individually in vials to the research laboratory, incubated with stable isotope labeled substrates for 60 minutes, and analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) for isotopologue enrichment of major metabolic intermediates, including acetyl-CoA derived from the stable isotope labeled substrates.ResultsMean enrichment of M+2 acetyl-CoA (mean, standard deviation), where M+0 is the unlabeled acetyl-CoA, M+1 contains 1 13C, M+2 contains 2 13C atoms, was for glucose (3.6, 7.7), for glutamine (9.4, 6.2), and for acetate (20.7, 13.9). Mean % enrichment of acetyl-CoA from acetate in CCs from women ≤34 (49.06, 12.73) decreased with age compared to CCs from women >34 (43.48, 16.20) (p=0.0004, t test). The CCs associated with the immature prophase I oocytes had significantly lower enrichment in M+2 acetyl CoA compared to the CCs associated with the metaphase I and metaphase II oocytes (difference: −6.02, CI: −1.74,−13.79, p=0.013). Limitations of this preliminary study include the difficulty in recovery of consistent numbers of CCs across oocytes, and the inability in this study to track oocyte function to the primary endpoint of successful birth.ConclusionAcetate metabolism in individual CC clumps was positively correlated with oocyte maturity and decreased with maternal age. These findings indicate that CC metabolism of short chain fatty acids like acetate should be investigated relative to oocyte function and age-related fertility.