Impact of maternal aging on the molecular signature of human cumulus cells.

OBJECTIVE

To investigate the impact of maternal aging on the molecular signature of cumulus cells.

DESIGN

Experimental study.

SETTING

Research laboratory.

PATIENT(S): Patients, young fertile oocyte donors (n = 40) and infertile women of advanced maternal age (40-45 years; n = 48), donated, with Institutional Review Board consent, cumulus cells during routine infertility treatment.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Proteomic and gene expression profiles of cumulus cells.

RESULT(S): Proteomic analysis identified a total of 1,423 cumulus cell proteins. Statistical analysis revealed 110 (7.7%) proteins to be differentially expressed in relation to female aging (>1.5-fold change). Pathway annotation revealed significant involvement in metabolism (ACAT2, HSD17B4, ALDH9A1, MVK, CYP11A1, and FDFT1), oxidative phosphorylation (OP; NDUFA1, UQCRC1, MT-ATP6, ATP5I, and MT-ATP8), and post-transcriptional mechanisms (KHSRP, SFPQ, DDX46, SNRPF, ADAR, NHPL1, and U2AF2) relative to advanced maternal age. Gene expression analysis also revealed altered profiles in cumulus cells from women in their early to mid-40s.

CONCLUSION(S): This novel study reveals that the cumulus cell molecular signature, at both the gene and protein level, is impacted by advanced maternal aging. A compromised follicular environment is evident with altered energy metabolism and post-transcriptional processes.