Requirement for ADAMTS-1 in extracellular matrix remodeling during ovarian folliculogenesis and lymphangiogenesis

被引:95
作者
Brown, Hannah M.
Dunning, Kylie R.
Robker, Rebecca L.
Pritchard, Melanie
Russell, Darryl L. [1 ]
机构
[1] Univ Adelaide, Sch Paediat & Reprod Hlth, Res Ctr Reprod Hlth, Adelaide, SA 5005, Australia
[2] Monash Univ, Med Res Inst, Ctr Funct Genom & Human Dis, Clayton, Vic, Australia
基金
英国医学研究理事会;
关键词
folliculogenesis; extracellular matrix remodeling; infertility; lymphangiogenesis; protease;
D O I
10.1016/j.ydbio.2006.10.012
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Murine ovarian folliculogenesis commences after birth involving oocyte growth, somatic cell differentiation and structural remodeling of follicle stromal boundaries. The extracellular metalloproteinase ADAMTS-1 has activity against proteoglycans and collagen and is produced by the granulosa cells of ovarian follicles. Mice with ADAMTS-1 gene disruption are subfertile due to an unknown mechanism resulting in severely reduced ovulation. Here we show that ADAMTS-1 is necessary for structural remodeling during ovarian follicle growth. A significant reduction in the number of healthy growing follicles and corresponding follicle dysmorphogenesis commencing at the stage of antrum formation was identified in ADAMTS-l(-/-) ovaries. Morphological analysis and immunostaining of basement membrane components identified stages of follicle dysgenesis from focal disruption in ECM integrity to complete loss of follicular structures. Cells expressing the thecal marker Cyp-17 were lost from dysgenic regions, while oocytes and dispersed cells expressing the granulosa cell marker anti-mullerian hormone persisted in ovarian stroma. Furthermore, we found that the ovarian lymphatic system develops coincidentally with follicular development in early postnatal life but is severely delayed in ADAMTS-l(-/-) ovaries. These novel roles for ADAMTS-1 in structural maintenance of follicular basement membranes and lyrnphangiogenesis provide new mechanistic understanding of folliculogenesis, fertility and disease. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:699 / 709
页数:11
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