Effects of somatic cell nuclear transfer on transcripts related to IGF signaling, EGF signaling and cell adhesion during the peri-implantation period in cattle

Up to 70% of somatic cell nuclear transfer (SCNT)–derived bovine pregnancies are lost during the peri-implantation period of gestation. Given the physiology of blastocyst implantation and clinico-pathological features that characterize SCNT pregnancies, we hypothesized that insulin-like growth factor (IGF) signaling, epidermal growth factor (EGF) signaling, and cell adhesion are perturbed in bovine SCNT pregnancies during the peri-implantation period. To test this hypothesis, we analyzed transcriptomes of endometrial tissue and extra-embryonic tissue (EET) collected from gestation day (GD)-18 and GD-34 bovine pregnancies (SCNT and artificial insemination-derived pregnancies) using RNAseq, and endometrial transcription of 16 preselected genes using quantitative real time-PCR and/or in situ hybridization. Findings of our study suggest that IGF signaling, EGF signaling and cell adhesion are perturbed in SCNT pregnancies during the peri-implantation period. Findings of this study also extend our current knowledge on temporal regulation of these molecular functions during the peri-implantation period in cattle. On the basis of functional ontology enrichment analysis, integrin signaling, IGF1R signaling, EGFR/ERBB signaling, and PI3K/AKT and ERK1/2 signaling, two signal transduction pathways induced by integrin clustering and IGF1R and EGFR/ERBB activation, were significantly affected by both implantation and SCNT. In addition, expression levels of genes related to cell cycle G1/S transition, apoptosis/survival, glucose uptake, protein synthesis and energy metabolism, cellular functions regulated by growth factor and/or integrin signaling, were also affected by SCNT and/or implantation. Implantation-associated gene expression differences were observed in all tissues while SCNT-associated gene expression differences were observed mainly in GD-18 EET and GD-34 inter-caruncular tissues. Our findings on aberrant transcript levels of genes related to cell adhesion, IGF signaling and EGF signaling in SCNT pregnancies suggest that perturbations in these molecular functions may contribute to the high embryo mortalities and other clinico-pathological features observed during the peri-implantation period in cattle.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2012

Author dc:creator

• Rabel, Rathnaweera

Contributors dc:contributor

• Lewin, Harris A.
• Bagchi, Milan K.
• Stubbs, Lisa J.
• Tanaka, Tetsuya S.
• Wallace, Richard L.

• somatic cell nuclear transfer
• blastocyst implantation
• IGF signaling SCNT
• EGF signaling SCNT
• cell adhesion SCNT
• MTOR pathway SCNT
• bovine nuclear transfer
• SCNT peri-implantation period
• insulinlike growth factor (IGF)
• epidermal growth factor (EGF)
• somatic cell nuclear transfer (SCNT)
• Mammalian target of rapamycin (mTOR)

Statement dc:rights

• Copyright 2012 R. A. Chanaka Rabel

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/32068

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/32068