Glucosamine supplementation during in vitro maturation inhibits subsequent embryo development: Possible role of the hexosamine pathway as a regulator of developmental competence

M. SUTTON-MCDOWALL, M. MITCHELL, P. CETICA, G. DALVIT, M. PANTALEON, M. LANE, R. GILCHRIST AND J. THOMPSON

BIOLOGY OF REPRODUCTION

Stanford University Libraries´

Año: 2006 vol. 74 p. 881 - 888

0006-3363

Glucose concentration during cumulus-oocyte complex (COC) maturation influences several functions, induding progression of oocyte meiosis, oocyte developmental competence, and cumulus mucification. Glucosamine (GIcN) is an altemative hexose substrate, specifically metabolized through the hexosamine biosynthesis pathway, which provides the intermediates for extracellular matrix formation during cumulus cell mucification. The aim of this study was to determine the influence of GIcN on meiotic progression and oocyte developmental competence following in vitro maturation (IVM).The presence of GIcN during bovine IVM did not affect the completion of nuclear maturation and early cleavage, but severely perturbed b1astocyst development. lhis effect was subsequently shown to be dose-dependent and was also observed for porcine oocytes matured in vitro. Hexosamine biosynthesis up regulation using GIcN supplementation is well known to increase O-linked glycosylation of many intracellular signaling molecules, the best characterized being the phosphoinositol-3-kinase (PI3K)signaling pathway. We observed extensive O-linked glycosylation in bovine cumulus cells, but not oocytes, following IVM in either the presence or the absence of GIcN. Inhibition of O-linked glycosylation significantly reversed the effect of GIcN-induced reduction in developmental competence, but inhibition of PI3K signaling had no effect. Our data are the first to link hexosamine biosynthesis, involved in cumulus cell mucification, to oocyte developmental competence during in vitro maturation.