title: Embryo implantation is closely associated with dynamic expression of proprotein convertase 5/6 in the rabbit uterus.
abstract: BACKGROUND
  Proprotein convertase 5/6 (PC5/6) is critical for embryo implantation in women, regulating both uterine epithelial receptivity and stromal cell decidualization. PC5/6 is likewise essential for implantation in mice, but involved only in decidualization. An alternative animal model is required to address the function of PC5/6 in the uterine epithelium. This study aimed to establish whether PC5/6 is associated with embryo implantation in rabbits.
  
  
  METHODS
  Virgin New-Zealand white rabbits aged 3-4 moths were mated with males of the same strain, or pseudo-pregnancy induced. After mating, uterine tissues were collected over a 10 day (d) period (n = 3 per time point) for RNA, protein and histological analyses to determine the temporal and spatial uterine expression pattern of PC5/6 during the initial stages of pregnancy or induced pseudo-pregnancy.
  
  
  RESULTS
  PC5/6 mRNA was up-regulated just prior to embryo attachment on d6, and the elevated expression was maintained throughout implantation on d6.5-10. Western analysis revealed a preferential up-regulation of PC5/6 in the implantation sites. Immunohistochemical analysis identified that both the amount and cellular localization of PC5/6 changed with increasing pregnancy stages. Before embryo attachment, PC5/6 was low and localised in the luminal and glandular epithelium. It increased on d6.5 in the basal glands and mucosal folds, and then strongly intensified on d7-10 in the multinucleated luminal symplasma and decidual cells at the site of embryo implantation. In contrast, the pseudo-pregnant uterus displayed relatively low and static PC6 mRNA expression throughout the 10 days, with no obvious changes in either PC5/6 level or cellular localization.
  
  
  CONCLUSIONS
  These findings demonstrate that embryo implantation in the rabbit is closely associated with dynamic expression of uterine PC5/6, and that the rabbit may be an appropriate model to investigate the function of PC5/6 in the uterine epithelium during embryo attachment.
authors.affiliation: Prince Henrys Institute of Medical Research, 246 Clayton Road, Clayton, Victoria 3168, Australia.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Nicholls
authors.forename: Zhaogui
authors.initials: Z
authors.lastname: Sun
authors.forename: Sophea
authors.initials: S
authors.lastname: Heng
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Guiying
authors.initials: G
authors.lastname: Nie
mesh_terms: D000818:Animals; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D023421:Models, Animal; D011247:Pregnancy / Q000378:metabolism*; D045702:Proprotein Convertase 5 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015854:Up-Regulation; D014599:Uterus / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D045702:Proprotein Convertase 5