Document Detail

Requirement for ADAMTS-1 in extracellular matrix remodeling during ovarian folliculogenesis and lymphangiogenesis.
MedLine Citation:
PMID:  17097630     Owner:  NLM     Status:  MEDLINE    
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-1-/- 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-1-/- ovaries. These novel roles for ADAMTS-1 in structural maintenance of follicular basement membranes and lymphangiogenesis provide new mechanistic understanding of folliculogenesis, fertility and disease.
Hannah M Brown; Kylie R Dunning; Rebecca L Robker; Melanie Pritchard; Darryl L Russell
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-10-14
Journal Detail:
Title:  Developmental biology     Volume:  300     ISSN:  0012-1606     ISO Abbreviation:  Dev. Biol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-12-20     Completed Date:  2007-02-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  699-709     Citation Subset:  IM    
School of Paediatrics and Reproductive Health, Research Centre for Reproductive Health, The University of Adelaide, Adelaide, South Australia, 5005, Australia.
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MeSH Terms
ADAM Proteins / genetics,  physiology*
Extracellular Matrix / genetics,  physiology*
Lymphangiogenesis / genetics,  physiology*
Mice, Inbred C57BL
Mice, Knockout
Ovarian Follicle / growth & development*,  metabolism
Reg. No./Substance:
EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/Adamts1 protein, mouse

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