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Initiation of a conserved trophectoderm program in human, cow and mouse embryos.

ABSTRACT: Current understandings of cell specification in early mammalian pre-implantation development are based mainly on mouse studies. The first lineage differentiation event occurs at the morula stage, with outer cells initiating a trophectoderm (TE) placental progenitor program. The inner cell mass arises from inner cells during subsequent developmental stages and comprises precursor cells of the embryo proper and yolk sac¹. Recent gene-expression analyses suggest that the mechanisms that regulate early lineage specification in the mouse may differ in other mammals, including human^2-5 and cow⁶. Here we show the evolutionary conservation of a molecular cascade that initiates TE segregation in human, cow and mouse embryos. At the morula stage, outer cells acquire an apical-basal cell polarity, with expression of atypical protein kinase C (aPKC) at the contact-free domain, nuclear expression of Hippo signalling pathway effectors and restricted expression of TE-associated factors such as GATA3, which suggests initiation of a TE program. Furthermore, we demonstrate that inhibition of aPKC by small-molecule pharmacological modulation or Trim-Away protein depletion impairs TE initiation at the morula stage. Our comparative embryology analysis provides insights into early lineage specification and suggests that a similar mechanism initiates a TE program in human, cow and mouse embryos.

SUBMITTER: Gerri C

PROVIDER: S-EPMC7116563 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Initiation of a conserved trophectoderm program in human, cow and mouse embryos.

Gerri Claudia C McCarthy Afshan A Alanis-Lobato Gregorio G Demtschenko Andrej A Bruneau Alexandre A Loubersac Sophie S Fogarty Norah M E NME Hampshire Daniel D Elder Kay K Snell Phil P Christie Leila L David Laurent L Van de Velde Hilde H Fouladi-Nashta Ali A AA Niakan Kathy K KK

Nature 20200923 7834

Current understandings of cell specification in early mammalian pre-implantation development are based mainly on mouse studies. The first lineage differentiation event occurs at the morula stage, with outer cells initiating a trophectoderm (TE) placental progenitor program. The inner cell mass arises from inner cells during subsequent developmental stages and comprises precursor cells of the embryo proper and yolk sac<sup>1</sup>. Recent gene-expression analyses suggest that the mechanisms that ...[more]

PMID: 32968278

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Project description:Study questionWhat is the predictive value of trophectoderm mitochondrial DNA (mtDNA) quantity for blastocyst reproductive potential?Summary answerThis study demonstrates that, within a given cohort, mtDNA quantitation does not distinguish between embryos that implant and embryos that do not implant after double embryo transfer (DET).What is already knownAn association between implantation failure and increased quantities of mtDNA has been observed in two studies but not in a third.Study design, size and durationA total of 187 patients (nine who received donor oocytes) with DET of one male and one female euploid blastocyst were included in this retrospective study, with 69 singleton deliveries providing the primary dataset to evaluate the predictive value of mtDNA for reproductive potential between January 2010 and July 2016.Participants/materials, setting and methodMtDNA was quantified in cell lines to validate the quantitative PCR assay on limited quantities of starting material and then applied to 374 blastocyst biopsies. Pregnancies resulting in a singleton outcome were analyzed and newborn gender was utilized as a means to identify the implanted embryo. MtDNA quantity was then compared between implanted and non-implanted embryos in order to define the predictive value of mtDNA content for reproductive potential in this subset of patients.Main results and the role of chanceAn initial comparison of mtDNA levels between all successful and unsuccessful embryos revealed no significant differences. In order to control for patient-specific variables, gender was subsequently used to identify the implanted embryo in DETs resulting in a singleton (n = 69). No systematic difference in relative mtDNA quantity was detected between implanted and non-implanted embryos.Limitations, reasons for cautionThis study was conducted at a single center and did not evaluate the entire cohort of embryos from each patient to evaluate cohort specific variation in mtDNA quantity. Although the largest of its kind so far, the sample size of DETs leading to a singleton was relatively small.Wider implications of the findingsThese data highlight the importance of control over patient-specific variables when evaluating candidate biomarkers of reproductive potential. All current available data suggest that mtDNA quantification needs further study before its clinical use to augment embryo selection.Study funding/competing interestsThe authors have no potential conflict of interest to declare. No external funding was obtained for this study.Trial registration numberNot applicable.

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Initiation of a conserved trophectoderm program in human, cow and mouse embryos.

Publications

Initiation of a conserved trophectoderm program in human, cow and mouse embryos.

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