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Evidence for an Early Endometrial Response to Pregnancy in Cattle: Both Dependent Upon and Independent of Interferon Tau N Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau N. Forde, G.B. Duffy, P.A. Mcgettigan, J.A. Browne, J.P. Mehta, A.K. Kelly, N. Mansouri-Attia, Olivier Sandra, B.J. Loftus, M.A. Crowe, et al. To cite this version: N. Forde, G.B. Duffy, P.A. Mcgettigan, J.A. Browne, J.P. Mehta, et al.. Evidence for an early en- dometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau. Physiological Genomics, American Physiological Society, 2012, 44 (16), pp.799-810. 10.1152/physi- olgenomics.00067.2012. hal-01000912 HAL Id: hal-01000912 https://hal.archives-ouvertes.fr/hal-01000912 Submitted on 29 May 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau N. Forde, G. B. Duffy, P. A. McGettigan, J. A. Browne, J. P. Mehta, A. K. Kelly, N. Mansouri-Attia, O. Sandra, B. J. Loftus, M. A. Crowe, T. Fair, J. F. Roche, P. Lonergan and A. C. O. Evans Downloaded from Physiol. Genomics 44:799-810, 2012. First published 3 July 2012; doi: 10.1152/physiolgenomics.00067.2012 You might find this additional info useful... Supplementary material for this article can be found at: http://physiolgenomics.physiology.org/ http://physiolgenomics.physiology.org/http://physiolgenomics.physiology.org/content/suppl/2012/0 7/06/physiolgenomics.00067.2012.DC1.html This article cites 55 articles, 36 of which you can access for free at: http://physiolgenomics.physiology.org/content/44/16/799.full#ref-list-1 Updated information and services including high resolution figures, can be found at: http://physiolgenomics.physiology.org/content/44/16/799.full Additional material and information about Physiological Genomics can be found at: http://www.the-aps.org/publications/physiolgenomics This information is current as of January 4, 2013. at INRA Institut National de la Recherche Agronomique on January 4, 2013 Physiological Genomics publishes results of a wide variety of studies from human and from informative model systems with techniques linking genes and pathways to physiology, from prokaryotes to eukaryotes. It is published 24 times a year (twice monthly) by the American Physiological Society, 9650 Rockville Pike, Bethesda MD 20814-3991. Copyright © 2012 the American Physiological Society. ESSN: 1531-2267. Visit our website at http://www.the-aps.org/. Physiol Genomics 44: 799–810, 2012. First published July 3, 2012; doi:10.1152/physiolgenomics.00067.2012. Evidence for an early endometrial response to pregnancy in cattle: both dependent upon and independent of interferon tau 1 1 1 1 3 1 1 N. Forde, G. B. Duffy, P. A. McGettigan, J. A. Browne, J. P. Mehta, A. K. Kelly, N. Mansouri-Attia, Downloaded from O. Sandra,4 B. J. Loftus,3 M. A. Crowe,2,3 T. Fair,1 J. F. Roche,2 P. Lonergan,1,3 and A. C. O. Evans1,3 1School of Agriculture and Food Science, University College Dublin, Belfield, Dublin, Ireland; 2School of Veterinary Medicine, University College Dublin, Belfield, Dublin, Ireland; 3Conway Institute, University College Dublin, Belfield, Dublin, Ireland; 4Institut National de la Recherche Agronomique, Unite Mixté de Recherche, 1198 Biologie du Développement et Reproduction, Jouy en Josas, France Submitted 22 May 2012; accepted in final form 27 June 2012 http://physiolgenomics.physiology.org/ Forde N, Duffy GB, McGettigan PA, Browne JA, Mehta JP, Kelly nancy recognition signal in both cattle and sheep is interferon AK, Mansouri-Attia N, Sandra O, Loftus BJ, Crowe MA, Fair T, tau (IFNT) and in cattle, pregnancy recognition must occur by Roche JF, Lonergan P, Evans ACO. Evidence for an early endometrial day 16 to ensure luteolysis does not occur (6, 36). IFNT exerts response to pregnancy in cattle: both dependent upon and independent of its effects both locally on the uterus as well as in a paracrine interferon tau. Physiol Genomics 44: 799–810, 2012. First published July fashion on extra uterine tissues. A number of studies have 3, 2012; doi:10.1152/physiolgenomics.00067.2012.—The aims of this study were to 1) identify the earliest transcriptional response of the demonstrated that IFNT alters the transcriptome of the endo- bovine endometrium to the presence of the conceptus (using metrium during early pregnancy to increase expression of RNAseq), 2) investigate if these genes are regulated by interferon tau genes and/or transporters that enhance conceptus elongation (IFNT) in vivo, and 3) determine if they are predictive of the and to establish uterine receptivity to implantation (reviewed pregnancy status of postpartum dairy cows. RNAseq identified 459 by Ref. 46). These studies have shown that IFNT during the differentially expressed genes (DEGs) between pregnant and cyclic peri-implantation period of pregnancy in cattle induces the endometria on day 16. Quantitative real-time PCR analysis of selected expression of large numbers of interferon-stimulated genes at INRA Institut National de la Recherche Agronomique on January 4, 2013 genes revealed PARP12, ZNFX1, HERC6, IFI16, RNF213, and (ISGs; Refs. 3, 14, 19, 26, 31, 52). Indeed, the transcriptional DDX58 expression increased in pregnant compared with cyclic endo- response of the endometrium to the developing conceptus can metria on day 16 and were directly upregulated by intrauterine Ͻ act as a sensor of the developmental competency of the infusion of IFNT in vivo for2h(P 0.05). On day 13 following conceptus (5, 32). However, the majority of these studies have estrous endometrial expression of nine genes increased [ARHGAP1, MGC127874, LIMS2, TBC1D1, FBXL7, C25H16orf71, LOC507810, focused on the peri-implantation period of pregnancy during or ZSWIM4, and one novel gene (ENSBTAT00000050193)] and seven after the period of pregnancy recognition in cattle (3, 14, 26, genes decreased (SERBP1, SRGAP2, AL7A1, TBK1, F2RL2, 31, 52). MGC128929, and WBSCR17; P Ͻ 0.05) in pregnant compared with Recent studies by our group and others sought to identify the cyclic heifers. Of these DEGs, significant differences in expression differences between the endometrial transcriptome of pregnant between pregnant and cyclic endometria were maintained on day 16 and cyclic heifers at distinct developmental stages of embryo for F2RL2, LIMS2, LOC507810, MGC127874, TBC1D1, WBSCR17, development. According to the Affymetrix microarray plat- and ZSWIM4 (P Ͻ 0.05) both their expression was not directly form the first detectable differences between the endometria of regulated by IFNT in vivo. Analysis of the expression of selected pregnant and cyclic heifers occurred on day 15 (4) and 16 (14). interferon-stimulated genes in blood samples from postpartum dairy Ͻ Despite this, interaction between the conceptus and the mater- cows revealed a significant increase (P 0.05) in expression of nal environment is required during the preimplantation stages ZXFX1, PARP12, SAMD9, and HERC6 on day 18 following artificial insemination in cows subsequently confirmed pregnant compared of pregnancy in cattle (45), and it is known that the bovine with cyclic controls. In conclusion, RNAseq identified a number of embryo expresses mRNA for IFNT as early as the blastocyst novel pregnancy-associated genes in the endometrium of cattle during stage of development (27, 29), indicating that the embryo may early pregnancy that are not regulated by IFNT in vivo. In addition, a elicit localized or subtle responses from the endometrium prior number of genes that are directly regulated by short term exposure to to pregnancy recognition. In addition, transcriptomic profiling IFNT in vivo are differentially expressed on day 18 following estrus of bovine embryos at the initiation of conceptus elongation detection in the blood of postpartum dairy cows depending on their (11) as well as trophoblast cells cultured in vitro (12, 50) pregnancy status. identified the expression of genes that code for secreted pro- RNA sequencing; uterine; gene expression; estrus cycle; interferon- teins. It is therefore reasonable to hypothesize that these stimulated gene conceptus-derived factors may stimulate more understated, localized gene expression changes in the endometrium during early pregnancy that are independent of IFNT. IN ORDER FOR SUCCESSFUL PREGNANCY to be established and Next-generation sequencing methods such as RNA sequenc- maintained in cattle, the corpus luteum (CL) must be main- ing (RNAseq) provide a far more precise measure of transcript tained beyond the time when luteolysis would normally occur. abundance than other methods developed to date; as it is It has been well established that the conceptus-derived preg- unbiased (no prior knowledge required), allowing complete coverage (i.e., very high sensitivity) and allowing true genome- Address for reprint requests and other correspondence: N. Forde, Veterinary wide discovery (33, 34). Data from human studies comparing Sciences Centre, Univ. College Dublin, Belfield, Dublin 4, Ireland (e-mail: the use of RNAseq and Affymetrix microarrays were highly [email protected]). correlated; however, the findings suggested that RNAseq was 1094-8341/12 Copyright © 2012 the American Physiological Society 799 800 EARLY RESPONSE OF THE BOVINE ENDOMETRIUM TO PREGNANCY the more sensitive of the two methods as it identified 30% more West Sussex, UK). RNA quality and quantity were determined with differentially expressed genes (DEGs) than the microarray the Agilent Bioanalyzer (Agilent Technologies, Santa Clara, CA), and platform, as validated by quantitative real-time PCR (qPCR) only samples with an RNA integrity number (RIN) of Ͼ8.5 were ϭ (33).
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