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      Is Open Access

      Developmental perturbation in human embryos: Clinical and biological significance learned from time‐lapse images

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          Abstract

          Background

          Time‐lapse technology (TLT) has gained widespread adoption worldwide. In addition to facilitating the undisturbed culture of embryos, TLT offers the unique capability of continuously monitoring embryos to detect spatiotemporal changes. Although these observed phenomena play a role in optimal embryo selection/deselection, the clinical advantages of introducing TLT remain unclear. However, manual annotation of embryo perturbation could facilitate a comprehensive assessment of developmental competence. This process requires a thorough understanding of embryo observation and the biological significance associated with developmental dogma and variation. This review elucidates the typical behavior and variation of each phenomenon, exploring their clinical significance and research perspectives.

          Methods

          The MEDLINE database was searched using PubMed for peer‐reviewed English‐language original articles concerning human embryo development.

          Main findings

          TLT allows the observation of consecutive changes in embryo morphology, serving as potential biomarkers for embryo assessment. In assisted reproductive technology laboratories, several phenomena have not revealed their mechanism, posing difficulties such as fertilization deficiency and morula arrest.

          Conclusion

          A profound understanding of the biological mechanisms and significance of each phenomenon is crucial. Further collaborative efforts between the clinical and molecular fields following translational studies are required to advance embryonic outcomes and assessment.

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          Most cited references185

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          The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.

          Many variations in oocyte and embryo grading make inter-laboratory comparisons extremely difficult. This paper reports the proceedings of an international consensus meeting on oocyte and embryo morphology assessment. Background presentations about current practice were given. The expert panel developed a set of consensus points to define the minimum criteria for oocyte and embryo morphology assessment. It is expected that the definition of common terminology and standardization of laboratory practice related to embryo morphology assessment will result in more effective comparisons of treatment outcomes. This document is intended to be referenced as a global consensus to allow standardized reporting of the minimum data set required for the accurate description of embryo development.
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            TEAD mediates YAP-dependent gene induction and growth control.

            The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent gene expression. TEAD is also required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition. CTGF is identified as a direct YAP target gene important for cell growth. Moreover, the functional relationship between YAP and TEAD is conserved in Drosophila Yki (the YAP homolog) and Scalloped (the TEAD homolog). Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP.
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              Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells.

              Micronuclei (MN) and other nuclear anomalies such as nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) are biomarkers of genotoxic events and chromosomal instability. These genome damage events can be measured simultaneously in the cytokinesis-block micronucleus cytome (CBMNcyt) assay. The molecular mechanisms leading to these events have been investigated over the past two decades using molecular probes and genetically engineered cells. In this brief review, we summarise the wealth of knowledge currently available that best explains the formation of these important nuclear anomalies that are commonly seen in cancer and are indicative of genome damage events that could increase the risk of developmental and degenerative diseases. MN can originate during anaphase from lagging acentric chromosome or chromatid fragments caused by misrepair of DNA breaks or unrepaired DNA breaks. Malsegregation of whole chromosomes at anaphase may also lead to MN formation as a result of hypomethylation of repeat sequences in centromeric and pericentromeric DNA, defects in kinetochore proteins or assembly, dysfunctional spindle and defective anaphase checkpoint genes. NPB originate from dicentric chromosomes, which may occur due to misrepair of DNA breaks, telomere end fusions, and could also be observed when defective separation of sister chromatids at anaphase occurs due to failure of decatenation. NBUD represent the process of elimination of amplified DNA, DNA repair complexes and possibly excess chromosomes from aneuploid cells.
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                Author and article information

                Contributors
                k-kato@towako.net
                Journal
                Reprod Med Biol
                Reprod Med Biol
                10.1111/(ISSN)1447-0578
                RMB2
                Reproductive Medicine and Biology
                John Wiley and Sons Inc. (Hoboken )
                1445-5781
                1447-0578
                09 July 2024
                Jan-Dec 2024
                : 23
                : 1 ( doiID: 10.1111/rmb2.v23.1 )
                : e12593
                Affiliations
                [ 1 ] Kato Ladies Clinic Tokyo Japan
                Author notes
                [*] [* ] Correspondence

                Keiichi Kato, Kato Ladies Clinic, 7‐20‐3 Nishishinjuku, Shinjuku‐ku, Tokyo 160‐0023, Japan.

                Email: k-kato@ 123456towako.net

                Author information
                https://orcid.org/0000-0002-3778-2259
                https://orcid.org/0000-0003-0563-5358
                https://orcid.org/0000-0002-1394-4532
                Article
                RMB212593 RMB-2024-0053.R2
                10.1002/rmb2.12593
                11232294
                38983691
                e4c5e469-51d8-40e3-b586-488a4a428eb1
                © 2024 The Author(s). Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 May 2024
                : 05 March 2024
                : 07 June 2024
                Page count
                Figures: 2, Tables: 4, Pages: 17, Words: 12800
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                January/December 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.5 mode:remove_FC converted:09.07.2024

                assisted reproductive technology,developmental competence,embryo development,embryo selection,time‐lapse imaging

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