Ovulation: New factors that prepare the oocyte for fertilization

Ovulation is a complex LH-induced process that allows the release of a fertilizable oocyte. Critical to ovulation is the proper formation of an extracellular hyaluronan (HA) rich matrix by the cumulus oocyte complex (COC), a process called expansion. During expansion genes associated matrix formation such as hyaluronan synthase 2 (HAS-2) are induced rapidly in COCs. To stabilize the long hyaluronan polymers, various HA binding proteins are covalently (or non-covalently) linked with hyaluronan. Some of the hyaluronan binding factors that have been identified in the COC matrix are the serum derived factor inter-a trypsin inhibitor (I alpha I) and tumor necrosis factor stimulated gene-6 (TSG-6). The latter is dependent on the induction in cumulus cells of cyclooxygenase-2 (COX-2) the limiting enzyme in the synthesis of prostaglandins (primarily PGE) that bind the PG receptor subtype EP2, leading to increased CAMP. TSG-6 and the heavy chains of I alpha I interact with each other and HA in a manner that is critical for the formation and/or stabilization of the expanded matrix. Another hyaluronan binding component of the expanded COC is the proteoglycan versican. Versican is induced by the LH surge and is a preferred substrate of the protease, a disintegrin and metalloproteinase with thrombospondin like repeats (ADAMTS-1), which co-localizes with versican and is coordinately induced in granulosa cells and COCs of ovulating follicles by LH and the progesterone receptor (PR). Mice null for COX-2 and EP2 fail to ovulate and exhibit impaired COC expression of TSG-6. Progesterone receptor knockout (PRKO) mice are also anovulatory and present impaired expression of ADAMTS-1. Thus. HA binding proteins and associated factors appear to be essential components of the matrix that is obligatory for release of the COCs through the ovulation pore. (c) 2005 Elsevier Ireland Ltd. All rights reserved.