Developmental arrest of scNT-derived fetuses by disruption of the developing endometrial gland as a result of impaired trophoblast migration and invasiveness

Dev Dyn. 2011 Mar;240(3):627-39. doi: 10.1002/dvdy.22568. Epub 2011 Feb 8.

Abstract

Somatic cell nuclear transfer (scNT)-derived pig placenta tissues of gestational day 30 displayed avascularization and hypovascularization. Most of the cytotrophoblast-like cells of the developing scNT-derived placenta villi were improperly localized or exhibited impaired migration to their targeting loci. Id-2, Met, MMP-9, and MCM-7 were barely detectable in the cytotrophoblast cells of the scNT-derived placenta villi. Active MMP-2 and MMP-9 expression was significantly down-regulated in the scNT-embryo transferred recipient uteri. scNT clones exhibited a hypermethylated pattern within the pig MMP-9 promoter region and the significance of GC box in the regulation of MMP-9 promoter activity. Marked apoptosis was observed in the developing endometrial gland of scNT-embryo transferred recipient uteri. Collectively, our data strongly indicated that early gestational death of scNT clones is caused, at least in part, by disruption of the developing endometrial gland as a result of impaired trophoblast migration and invasiveness due to the down-regulation of active MMP-9 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Methylation / genetics
  • Endometrium / pathology*
  • Female
  • Immunoblotting
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Nuclear Transfer Techniques
  • Oocytes
  • Placenta / pathology
  • Pregnancy
  • Promoter Regions, Genetic / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Swine
  • Trophoblasts / pathology*
  • Uterus / metabolism

Substances

  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9