title: Gubernaculum as icebreaker: do matrix metalloproteinases in rodent gubernaculum and inguinal fat pad permit testicular descent?
abstract: OBJECTIVE
  Cryptorchidism is the most common male congenital abnormality. The rodent gubernaculum steers the testis from abdomen to scrotum postnatally by eversion and migration through the developing inguinal fat pad (IFP). We hypothesize that extracellular matrix remodeling in/around the gubernaculum is necessary for eversion and migration and is permitted by timed IFP maturation and aimed to examine regional development and matrix metalloproteinase (MMP) content.
  
  
  METHODS
  Embryonic day 19 (E19) and postnatal days 0 and 2 (P0, P2) wild-type Sprague-Dawley rats (n = 10) were prepared for histologic examination (trichrome) and immunohistochemistry (membrane-type MMP-1 [MT1-MMP], MMP2) and analyzed using light/confocal microscopy.
  
  
  RESULTS
  At E19, IFP contained fibroblasts and immature cells in an extensive collagenous extracellular matrix. Cells in the gubernaculum base were cytoplasmic-MT1-MMP-positive (inactive). At P0, the gubernaculum had everted, and adjacent cells were membranous-MT1-MMP-positive (active). At P2, the gubernaculum was migrating through the IFP, and adjacent cells were membranous-MT1-MMP-positive. Adipocyte maturation began cranially in the IFP and proceeded in a craniocaudal gradient until more uniformly mature at P2.
  
  
  CONCLUSIONS
  The MT1-MMP-positive cells may remodel the gubernaculum for eversion and provide the collagenolysis necessary for migration, like an icebreaking ship, through the IFP, which matures to permit migration through collagen-rich tissue. Disruption of these processes may cause cryptorchidism.
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Victoria 3052, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Churchill
authors.forename: Silverton
authors.initials: S
authors.lastname: Buraundi
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Farmer
authors.forename: Ruili
authors.initials: R
authors.lastname: Li
authors.forename: Bridget R
authors.initials: BR
authors.lastname: Southwell
authors.forename: John M
authors.initials: JM
authors.lastname: Hutson
authors.forename: Adam
authors.initials: A
authors.lastname: Balic
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D003456:Cryptorchidism / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000201:enzymology*; D005260:Female; D005865:Gestational Age; D050152:Intra-Abdominal Fat / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D008022:Ligaments / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development / Q000502:physiology; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012611:Scrotum / Q000196:embryology / Q000254:growth & development; D012727:Sex Characteristics; D013737:Testis / Q000196:embryology* / Q000254:growth & development
chemical_list: D003094:Collagen; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14