MicroRNA-21 as a regulator of human cumulus cell viability and its potential influence on the developmental potential of the oocyte.

Abstract

MicroRNA-21 is expressed in bovine, murine, and human cumulus cells with its expression in murine and bovine cumulus cells correlated with oocyte developmental potential. The aim of this study was to assess the relationship between cumulus cell MIR-21 and human oocyte developmental potential. These studies revealed that both the immature and mature forms of MicroRNA-21 (MIR-21-5p) were elevated in cumulus cells of oocytes that developed into blastocysts compared to cumulus cells of oocytes that arrested prior to blastocyst formation. This increase in MicroRNA-21 was observed regardless of whether the oocytes developed into euploid or aneuploid blastocysts. Moreover, MIR-21-5p levels in cumulus cells surrounding oocytes that either failed to mature or matured to metaphase II but failed to fertilize, were ≈50% less than the MIR-21-5p levels associated with oocytes that arrested prior to blastocyst formation. Why cumulus cells associated with oocytes of reduced developmental potential expressed less MIR-21-5p is unknown. It is unlikely due to reduced expression of either the receptors of growth differentiation factor 9 or rosha Ribonuclease III (DROSHA) and Dicer Ribonuclease III (DICER) which sequentially promote the conversion of immature forms of MicroRNA-21 to mature MicroRNA-21. Furthermore, cultured cumulus cells treated with a MIR-21-5p inhibitor had an increase in apoptosis and a corresponding increase in the expression of PTEN, a gene known to inhibit the AKT-dependent survival pathway in cumulus cells. These studies provide evidence for a role of MicroRNA-21 in human cumulus cells that influences the developmental potential of human oocytes.