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Logo of bmcgenoBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Genomics
 
BMC Genomics. 2009; 10: 511.
Published online Nov 5, 2009. doi:  10.1186/1471-2164-10-511
PMCID: PMC2783166
Comparative proteomic analysis of malformed umbilical cords from somatic cell nuclear transfer-derived piglets: implications for early postnatal death
Jong-Yi Park,#1,3 Jae-Hwan Kim,#2 Yun-Jung Choi,1 Kyu-Chan Hwang,1 Seong-Keun Cho,3 Ho-Hyun Park,4 Seung-Sam Paik,4 Teoan Kim,5 ChanKyu Park,1 Hoon Taek Lee,1 Han Geuk Seo,6 Soo-Bong Park,7 Seongsoo Hwang,7 and Jin-Hoi Kimcorresponding author1
1Animal Resource Research Center, College of Animal Bioscience and Technology, KonKuk University, Seoul 143-701, South Korea
2Department of Biomedical Science, College of Life Science, CHA University, Pochon-si, Gyeonggi-do 487-010, South Korea
3CHO-A Biotechnology Research Institute, CHO-A Pharmaceutical Co. Ltd., Seoul 150-992, South Korea
4Department of Pathology, College of Medicine, Hanyang University, Seoul 133-791, South Korea
5Department of Physiology, Catholic University of Daegu School of Medicine, Daegu 705-718, South Korea
6Department of Pharmacology, Gyeongsang National University School of Medicine, Jinju, GyeongNam 660-701, South Korea
7Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon 441-706, South Korea
corresponding authorCorresponding author.
#Contributed equally.
Jong-Yi Park: cosmozen/at/hanmail.net; Jae-Hwan Kim: jaehwan_k/at/cha.ac.kr; Yun-Jung Choi: choi_yunjung/at/nate.com; Kyu-Chan Hwang: skc1998/at/hanmail.net; Seong-Keun Cho: skcho67/at/hanmail.net; Ho-Hyun Park: hhpark/at/hanyang.ac.kr; Seung-Sam Paik: sspaik/at/hanyang.ac.kr; Teoan Kim: takim/at/cu.ac.kr; ChanKyu Park: chankyu/at/konkuk.ac.kr; Hoon Taek Lee: htl3675/at/konkuk.ac.kr; Han Geuk Seo: hgseo/at/gnu.ac.kr; Soo-Bong Park: psb292/at/rda.go.kr; Seongsoo Hwang: hwangss/at/rda.go.kr; Jin-Hoi Kim: jhkim541/at/konkuk.ac.kr
Received June 9, 2009; Accepted November 5, 2009.
Abstract
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.
Conclusion
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.
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