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

• Published in: Developmental dynamics 2011-03, Vol.240 (3), p.627-639
• Main Authors: Kim, Jae‐Hwan, Park, Jong‐Yi, Park, Mi‐Rung, Hwang, Kyu‐Chan, Park, Keun‐Kyu, Park, Chankyu, Cho, Seong‐Keun, Lee, Hwi‐Cheul, Song, Hyuk, Park, Soo‐Bong, Kim, Teoan, Kim, Jin‐Hoi
• Format: Article
• Language: English
• Subjects: 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; pig; placenta; Placenta - pathology; Pregnancy; Promoter Regions, Genetic - genetics; Reverse Transcriptase Polymerase Chain Reaction; somatic cell nuclear transfer; Swine; Trophoblasts - pathology; Uterus - metabolism
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.22568

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. Developmental Dynamics 240:627–639, 2011. © 2011 Wiley‐Liss, Inc.