The WNT signaling antagonist Dickkopf‐1 directs lineage commitment and promotes survival of the preimplantation embryo

Denicol, Anna C.; Block, J.; Kelley, Dale E.; Pohler, Ky G; Dobbs, Kyle B.; Mortensen, C.J.; Ortega, M. Sofía; Hansen, Peter J.

doi:10.1096/fj.14-253112

Cited by 98 publications

(130 citation statements)

References 55 publications

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“…Addition of DKK1 blocks the inhibitory actions of AMBMP on development (87). In addition, culture of embryos with DKK1 from day 5 to 8 of development increased the percent of cells in the blastocyst labeled as TE, decreased the percent of cells classified as ICM (CDX2 -), and increased the percent of cells in the ICM classified as hypoblasts (cells positive for labeling with the transcription factor GATA6 and negative for labeling with CDX2 and NANOG) (38). These actions of DKK1 are in contrast to the inhibition of TE cells caused by activation of WNT signaling (87).…”

Section: Dickkopf 1 and Regulation Of Wnt Signalingmentioning

confidence: 99%

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Maternal embryokines that regulate development of the bovine preimplantation embryo

Hansen¹,

Denicol²,

Dobbs³

2014

Turk J Vet Anim Sci

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The zygote contains within its genome and epigenome the program to direct development through the embryonic, fetal, and postnatal periods. The execution of that program is dependent on the embryo's nongenetic inheritance from the oocyte and sperm (1,2) as well as on the environment in which development proceeds. Variation in the maternal environment can affect the ability of the preimplantation embryo to establish pregnancy. In cattle, the focus of this review, competence of the preimplantation embryo for growth and survival can be affected by maternal parity (3), lactational status (4), and circulating concentrations of progesterone (5). Moreover, patterns of gene expression in the endometrium are associated with survival of an embryo transferred to the uterus in the next ovulatory cycle (6,7).Development of the bovine embryo to the blastocyst in the absence of maternal signals (i.e. through in vitro production procedures) results in embryos with aberrant gene expression (8,9), lipid content (10,11), DNA methylation (12), and, as shown in the Table, reduced competence to establish pregnancy after transfer into recipients (13-17). Additionally, an increased proportion of embryos produced in vitro have developmental abnormalities that lead to increased neonatal death losses (18-20). Some of the problems with the in vitro-produced embryo could result from selection of incompetent oocytes or inadequate oocyte maturation. However, the importance of the maternal environment during development is indicated by observations that transfer of in vitro-produced embryos to the oviduct after fertilization limits some of the abnormalities associated with in vitro production (9,21).One function of the reproductive tract is to secrete bioactive molecules that regulate the embryo, oviduct, or endometrium. Genes for 115 ligands expressed in the endometrium had the corresponding receptor gene expressed by the embryo (22). Regulatory molecules produced by the oviduct and endometrium, which include hormones, growth factors, and cytokines, are referred to as embryokines when they function to regulate embryonic growth and development (23).It is likely that some of the variation in the ability of the reproductive tract to support embryonic development represents variation in secretion of embryokines. Indeed, several genes that were overexpressed in the endometrium of cows that subsequently became pregnant after embryo transfer as compared to cows that did not establish pregnancy are potential embryokines. These include NGF,

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Section: Dickkopf 1 and Regulation Of Wnt Signalingmentioning

confidence: 99%

“…These effects of DKK1 likely result from a shift between pluripotency and differentiation, and are not reflective of an increased total cell number because DKK1 does not promote cell proliferation in the early embryo (38).…”

Section: Dickkopf 1 and Regulation Of Wnt Signalingmentioning

confidence: 99%

Maternal embryokines that regulate development of the bovine preimplantation embryo

Hansen¹,

Denicol²,

Dobbs³

2014

Turk J Vet Anim Sci

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“…Among the molecules in the cow that have been reported to affect development to the blastocyst stage are IGF1 [70], TGFB [71], LIF [71], and FGF2 [35]. Other embryokines, including IGF1 [72] and DKK1 [73], can improve competence of the bovine blastocyst to establish pregnancy after transfer to recipient females. Although each of these molecules can affect embryonic development, it is not known whether their actions on the embryo also depend upon sex.…”

Section: Sexually Dimorphic Programming By Csf2mentioning

confidence: 99%

Sexual Dimorphism in Developmental Programming of the Bovine Preimplantation Embryo Caused by Colony-Stimulating Factor 21

Dobbs

Gagné

Fournier

et al. 2014

Biology of Reproduction

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Physiology of the adult can be modified by alterations in prenatal development driven by the maternal environment. Developmental programming, which can be established before the embryo implants in the uterus, can affect females differently than males. The mechanism by which sex-specific developmental programming is established is not known. Here we present evidence that maternal regulatory signals change female embryos differently than male embryos. In particular, actions of the maternally derived cytokine CSF2 from Day 5 to Day 7 of development affected characteristics of the embryo at Day 15 differently for females than males. CSF2 decreased length and IFNT secretion of female embryos but increased length and IFNT secretion of male embryos. Analysis of a limited number of samples indicated that changes in the transcriptome and methylome caused by CSF2 also differed between female and males. Thus, sex-specific programming by the maternal environment could occur when changes in secretion of maternally derived regulatory molecules alter development of female embryos differently than male embryos.

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“…The only definitive marker identified for epiblast is NANOG (Kuijk et al . 2012; Denicol et al . 2014).…”

Section: Introductionmentioning

confidence: 99%

“…GATA6 can serve as a marker for hypoblast in bovine (Kuijk et al . 2012; Denicol et al . 2014) but interpretation of differences in gene expression for this transcription factor is complicated by the fact that expression can also occur for TE (Kuijk et al .…”

Section: Introductionmentioning

confidence: 99%

Single-cell gene expression of the bovine blastocyst

2017

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The first two differentiation events in the embryo result in three cell types – epiblast, trophectoderm (TE), and hypoblast. The purpose here was to identify molecular markers for each cell type in the bovine and evaluate differences in gene expression among individual cells of each lineage. The cDNA from 67 individual cells of dissociated blastocysts was used to determine transcript abundance for 93 genes implicated as cell lineage markers in other species or potentially involved in developmental processes. Clustering analysis indicated that the cells belonged to two major populations (clades A and B) with two subpopulations of clade A and four of clade B. Use of lineage-specific markers from other species indicated that the two subpopulations of clade A represented epiblast and hypoblast, respectively while the four subpopulations of clade B were TE. Among the genes upregulated in epiblast were AJAP1, DNMT3A, FGF4, H2AFZ, KDM2B, NANOG, POU5F1, SAV1 and SLIT2. Genes overexpressed in hypoblast included ALPL, FGFR2, FN1, GATA6, GJA1, HDAC1, MBNL3, PDGFRA and SOX17 while genes overexpressed in all four TE populations were ACTA2, CDX2, CYP11A1, GATA2, GATA3, IFNT, KRT8, RAC1 and SFN. The subpopulations of TE varied amongst each other for multiple genes including the prototypical TE marker IFNT. New markers for each cell type in the bovine blastocyst were identified. Results also indicate heterogeneity in gene expression among TE cells. Further studies are needed to confirm whether subpopulations of TE cells represent different stages in development of a committed TE phenotype.

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The WNT signaling antagonist Dickkopf‐1 directs lineage commitment and promotes survival of the preimplantation embryo

Cited by 98 publications

References 55 publications

Maternal embryokines that regulate development of the bovine preimplantation embryo

Maternal embryokines that regulate development of the bovine preimplantation embryo

Sexual Dimorphism in Developmental Programming of the Bovine Preimplantation Embryo Caused by Colony-Stimulating Factor 21

Single-cell gene expression of the bovine blastocyst

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