ADAMTS1 cleavage of versican mediates essential structural remodeling of the ovarian follicle and cumulus-oocyte matrix during ovulation in mice

Hannah M Brown, Kylie R Dunning, Rebecca L Robker, Derek Boerboom, Melanie April Pritchard, Michelle Lane, Darryl L Russell

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Remodeling of ovarian follicle extracellular matrix is essential for ovulation and vascularization of the corpus luteum (CL). Formation of the cumulus matrix around oocytes also plays an important role in ovulation and subsequent fertilization of oocytes. ADAMTS1 is an extracellular metalloprotease induced in ovarian follicles by ovulatory hormones and required for fertility. In this study we identified ADAMTS1-mediated structural and morphological changes in remodeling of the follicle and cumulus oocyte complex (COC). In Adamts1(-/-) mice ovulation rate was 77 reduced and fertilization of ovulated oocytes was reduced a further 63 resulting in reduced number of litters and pups per litter. Morphological assessment of peri-ovulatory ovaries revealed abnormal morphogenesis with a lack of thecal/vascular invagination in the basal region of follicles. Cleavage of the ADAMTS1-substrate, versican, at these invaginating regions was abundant in Adamts1(+/-), but undetectable in Adamts1(-/-) ovaries indicating that processing of versican by ADAMTS1 is involved in ovulating follicle remodeling. Versican and hyaluronan localization was abnormal during COC matrix expansion and versican persisted beyond the expected time of fertilization in Adamts1(-/-) but was catabolized and cleared from control COC. The results demonstrate that ADAMTS1 is critical in both ovulation and fertilization processes in vivo. The protease activity of ADAMTS1 mediates neomorphogenesis of the ovulating follicle wall and COC matrix necessary for successful ovulation and fertilization as well as subsequent catabolism of versican required for degradation of COC matrix after fertilization.
Original languageEnglish
Pages (from-to)549 - 557
Number of pages9
JournalBiology of Reproduction
Issue number4
Publication statusPublished - 2010

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