Author:
Biase Fernando H.,Rabel Chanaka,Guillomot Michel,Hue Isabelle,Andropolis Kalista,Olmstead Colleen A.,Oliveira Rosane,Wallace Richard,Le Bourhis Daniel,Richard Christophe,Campion Evelyne,Chaulot-Talmon Aurélie,Giraud-Delville Corinne,Taghouti Géraldine,Jammes Hélène,Renard Jean-Paul,Sandra Olivier,Lewin Harris A.
Abstract
A major unresolved issue in the cloning of mammals by somatic cell nuclear transfer (SCNT) is the mechanism by which the process fails after embryos are transferred to the uterus of recipients before or during the implantation window. We investigated this problem by using RNA sequencing (RNA-seq) to compare the transcriptomes in cattle conceptuses produced by SCNT and artificial insemination (AI) at day (d) 18 (preimplantation) and d 34 (postimplantation) of gestation. In addition, endometrium was profiled to identify the communication pathways that might be affected by the presence of a cloned conceptus, ultimately leading to mortality before or during the implantation window. At d 18, the effects on the transcriptome associated with SCNT were massive, involving more than 5,000 differentially expressed genes (DEGs). Among them are 121 genes that have embryonic lethal phenotypes in mice, cause defects in trophoblast and placental development, and/or affect conceptus survival in mice. In endometria at d 18, <0.4% of expressed genes were affected by the presence of a cloned conceptus, whereas at d 34, ∼36% and <0.7% of genes were differentially expressed in intercaruncular and caruncular tissues, respectively. Functional analysis of DEGs in placental and endometrial tissues suggests a major disruption of signaling between the cloned conceptus and the endometrium, particularly the intercaruncular tissue. Our results support a “bottleneck” model for cloned conceptus survival during the periimplantation period determined by gene expression levels in extraembryonic tissues and the endometrial response to altered signaling from clones.
Funder
U.S. Department of Agriculture
European Program SABRE
Publisher
Proceedings of the National Academy of Sciences
Cited by
46 articles.
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