Comparative proteomic analysis of malformed umbilical cords from somatic cell nuclear transfer-derived piglets: implications for early postnatal death.
BACKGROUND
Somatic cell nuclear transfer (scNT)-derived piglets have high rates of mortality, including stillbirth and postnatal death. Here, we examined severe malformed umbilical cords (MUC), as well as other organs, from nine scNT-derived term piglets.


RESULTS
Microscopic analysis revealed complete occlusive thrombi and the absence of columnar epithelial layers in MUC (scNT-MUC) derived from scNT piglets. scNT-MUC had significantly lower expression levels of platelet endothelial cell adhesion molecule-1 (PECAM-1) and angiogenesis-related genes than umbilical cords of normal scNT piglets (scNT-N) that survived into adulthood. Endothelial cells derived from scNT-MUC migrated and formed tubules more slowly than endothelial cells from control umbilical cords or scNT-N. Proteomic analysis of scNT-MUC revealed significant down-regulation of proteins involved in the prevention of oxidative stress and the regulation of glycolysis and cell motility, while molecules involved in apoptosis were significantly up-regulated. Histomorphometric analysis revealed severe calcification in the kidneys and placenta, peliosis in the liver sinusoidal space, abnormal stromal cell proliferation in the lungs, and tubular degeneration in the kidneys in scNT piglets with MUC. Increased levels of apoptosis were also detected in organs derived from all scNT piglets with MUC.


CONCLUSIONS
These results suggest that MUC contribute to fetal malformations, preterm birth and low birth weight due to underlying molecular defects that result in hypoplastic umbilical arteries and/or placental insufficiency. The results of the current study demonstrate the effects of MUC on fetal growth and organ development in scNT-derived pigs, and provide important insight into the molecular mechanisms underlying angiogenesis during umbilical cord development.
Park
Jong-Yi
JY
Animal Resource Research Center, College of Animal Bioscience and Technology, KonKuk University, Seoul, South Korea. cosmozen@hanmail.net
Kim
Jae-Hwan
JH
Choi
Yun-Jung
YJ
Hwang
Kyu-Chan
KC
Cho
Seong-Keun
SK
Park
Ho-Hyun
HH
Paik
Seung-Sam
SS
Kim
Teoan
T
Park
Chankyu
C
Lee
Hoon Taek
HT
Seo
Han Geuk
HG
Park
Soo-Bong
SB
Hwang
Seongsoo
S
Kim
Jin-Hoi
JH
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D019976:Cloning, Organism; D003643:Death; D015536:Down-Regulation; D042783:Endothelial Cells / Q000473:pathology; D047109:Fetal Development; D006019:Glycolysis; D006801:Humans; D020287:In Situ Nick-End Labeling; D018919:Neovascularization, Physiologic; D053652:Nuclear Transfer Techniques; D018384:Oxidative Stress; D040901:Proteomics; D013552:Swine; D013997:Time Factors; D014469:Umbilical Arteries / Q000098:blood supply / Q000378:metabolism; D014470:Umbilical Cord / Q000002:abnormalities* / Q000098:blood supply / Q000254:growth & development / Q000378:metabolism*; D015854:Up-Regulation