The Pivotal Role of Versican Turnover by ADAMTS Proteases in Mammalian Reproduction and Development

The chondroitin sulfate proteoglycan versican is an important component of the provisional extracellular matrix present in the early mammalian embryo and ovarian follicle. This matrix is highly dynamic and is remodeled by several members of a class of secreted metalloproteinases, the ADAMTS proteinases. Accordingly, analysis of mouse mutants of ADAMTS proteases capable of versican processing has demonstrated a strong association of versican accumulation with the specific mutant phenotypes. These phenotypes include female infertility resulting from anovulation, developmental defects, e.g., open neural tube, cleft palate, cardiac anomalies, soft tissue syndactyly, and umbilical cord anomalies, as well as impaired parturition. Thus, ADAMTS proteolysis of versican has crucial roles in mammalian reproduction and morphogenesis.