title: Massive dysregulation of genes involved in cell signaling and placental development in cloned cattle conceptus and maternal endometrium.
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.
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61820.
authors.forename: Fernando H
authors.initials: FH
authors.lastname: Biase
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61820.
authors.forename: Chanaka
authors.initials: C
authors.lastname: Rabel
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Guillomot
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hue
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61820.
authors.forename: Kalista
authors.initials: K
authors.lastname: Andropolis
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61820.
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Olmstead
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61820.
authors.forename: Rosane
authors.initials: R
authors.lastname: Oliveira
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61820.
authors.forename: Richard
authors.initials: R
authors.lastname: Wallace
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Le Bourhis
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.|Unité Commune d'Expérimentation Animale de Bressonvilliers (UCEA), INRA, 91030 Leudeville, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Richard
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Campion
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chaulot-Talmon
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Giraud-Delville
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Taghouti
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Jammes
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Renard
authors.affiliation: UMR Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), École Nationale Vétérinaire d'Alford (ENVA), Université Paris Saclay, 78350 Jouy en Josas, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sandra
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61820; lewin@ucdavis.edu.|Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61820.|Department of Evolution and Ecology and The Genome Center, University of California, Davis, CA 95616.
authors.forename: Harris A
authors.initials: HA
authors.lastname: Lewin
mesh_terms: D000818:Animals; D002417:Cattle; D019976:Cloning, Organism; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007315:Insemination, Artificial; D053652:Nuclear Transfer Techniques; D010920:Placenta / Q000378:metabolism*; D010929:Placentation; D011247:Pregnancy; D011270:Pregnancy, Animal; D015398:Signal Transduction; D013997:Time Factors; D059467:Transcriptome; D014327:Trophoblasts / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
keywords: conceptus; conceptus–maternal communication; placentation; somatic cell nuclear transfer