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Novel Molecular Mechanisms and Pathophysiology of Human Embryos
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Novel Molecular Mechanisms and Pathophysiology of Human Embryos

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 June 2021) | Viewed by 29225

Special Issue Editor

Prof. Dr. Gábor L. Kovács

E-Mail Website
Guest Editor
Szentagothai Research Centre, University of Pecs, 7624 Pecs, Hungary
Interests: in vitro fertilization; biomarkers; molecular mechanisms; lab-on-a-chip
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Infertility is a global health problem. Early blastocysts are very adaptive to their environment, and embryonic development is a process of complex events orchestrated by the genome and later influenced by the maternal microenvironment. There have been recent efforts to clarify the shaded line between normal and pathological molecular behavior of the embryo and to enhance the effectiveness of IVF. The critical process is to assess the viability and the pathophysiological risks during culturing. Novel multi-omics approaches have been developed in order to gain a deeper understanding of the early stage of embryonal life. Artificial intelligence and machine learning algorithms are new scientific hotspots. Consideration of the ethical issues and challenges related to human embryonic investigation is a recent pioneering research area. NGS-based genomic and epigenomic technologies hold promise for improving the ability to predict pathophysiology prior to implantation, and non-invasive imaging will provide higher-resolution diagnostic modalities. These tools may identify novel molecular mechanisms, increasing the positive outcome of embryo transfer. The multidisciplinary design and interpretation of these studies need strict cooperation between researchers, clinicians, and bioinformaticians. We welcome manuscripts focusing on recent—preferably non-invasive—techniques, including time-lapse microscopy, biochemical markers, novel methods of evaluating embryo genomic profile, metabolism, and mitochondrial DNA.

Prof. Dr. Gábor L. Kovács
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • in vitro fertilization
  • biomarkers
  • molecular mechanisms
  • lab-on-a-chip

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Published Papers (6 papers)

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Editorial

Jump to: Research, Review

4 pages, 671 KiB  
Editorial
Novel Molecular Approaches to the Understanding of Pathophysiologal Mechanisms Acting in Human Embryos: An Editorial
by Gabor L. Kovacs and Katalin Gombos
Int. J. Mol. Sci. 2022, 23(8), 4327; https://doi.org/10.3390/ijms23084327 - 14 Apr 2022
Viewed by 1405
Abstract
Infertility is a rapidly evolving global health problem [...] Full article
(This article belongs to the Special Issue Novel Molecular Mechanisms and Pathophysiology of Human Embryos)
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Research

Jump to: Editorial, Review

16 pages, 2947 KiB  
Article
NGS-Based Application for Routine Non-Invasive Pre-Implantation Genetic Assessment in IVF
by Katalin Gombos, Bence Gálik, Krisztina Ildikó Kalács, Krisztina Gödöny, Ákos Várnagy, Donát Alpár, József Bódis, Attila Gyenesei and Gábor L. Kovács
Int. J. Mol. Sci. 2021, 22(5), 2443; https://doi.org/10.3390/ijms22052443 - 28 Feb 2021
Cited by 9 | Viewed by 3682
Abstract
Although non-invasive pre-implantation genetic testing for aneuploidy (NIPGT-A) is potentially appropriate to assess chromosomal ploidy of the embryo, practical application of it in a routine IVF centre have not been started in the absence of a recommendation. Our objective in this study was [...] Read more.
Although non-invasive pre-implantation genetic testing for aneuploidy (NIPGT-A) is potentially appropriate to assess chromosomal ploidy of the embryo, practical application of it in a routine IVF centre have not been started in the absence of a recommendation. Our objective in this study was to provide a comprehensive workflow for a clinically applicable strategy for NIPGT-A based on next-generation sequencing (NGS) technology with the corresponding bioinformatic pipeline. In a retrospective study, we performed NGS on spent blastocyst culture media of Day 3 embryos fertilised with intracytoplasmic sperm injection (ICSI) with quality score on morphology assessment using the blank culture media as background control. Chromosomal abnormalities were identified by an optimised bioinformatics pipeline applying copy number variation (CNV) detecting algorithm. In this study, we demonstrate a comprehensive workflow covering both wet- and dry-lab procedures supporting a clinically applicable strategy for NIPGT-A that can be carried out within 48 h, which is critical for the same-cycle blastocyst transfer. The described integrated approach of non-invasive evaluation of embryonic DNA content of the culture media can potentially supplement existing pre-implantation genetic screening methods. Full article
(This article belongs to the Special Issue Novel Molecular Mechanisms and Pathophysiology of Human Embryos)
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25 pages, 2234 KiB  
Article
Small Noncoding RNA Signatures for Determining the Developmental Potential of an Embryo at the Morula Stage
by Angelika Timofeeva, Yulia Drapkina, Ivan Fedorov, Vitaliy Chagovets, Nataliya Makarova, Maria Shamina, Elena Kalinina and Gennady Sukhikh
Int. J. Mol. Sci. 2020, 21(24), 9399; https://doi.org/10.3390/ijms21249399 - 10 Dec 2020
Cited by 23 | Viewed by 3540
Abstract
As part of the optimization of assisted reproductive technology programs, the aim of the study was to identify key small noncoding RNA (sncRNA) molecules that participate in maternal-to-zygotic transition and determine development potential and competence to form a healthy fetus. Small RNA deep [...] Read more.
As part of the optimization of assisted reproductive technology programs, the aim of the study was to identify key small noncoding RNA (sncRNA) molecules that participate in maternal-to-zygotic transition and determine development potential and competence to form a healthy fetus. Small RNA deep sequencing followed by quantitative real-time RT-PCR was used to profile sncRNAs in 50 samples of spent culture medium from morula with different development potentials (no potential (degradation/developmental arrest), low potential (poor-quality blastocyst), and high potential (good/excellent quality blastocyst capable of implanting and leading to live birth)) obtained from 27 subfertile couples who underwent in vitro fertilization. We have shown that the quality of embryos at the morula stage is determined by secretion/uptake rates of certain sets of piRNAs and miRNAs, namely hsa_piR_011291, hsa_piR_019122, hsa_piR_001311, hsa_piR_015026, hsa_piR_015462, hsa_piR_016735, hsa_piR_019675, hsa_piR_020381, hsa_piR_020485, hsa_piR_004880, hsa_piR_000807, hsa-let-7b-5p, and hsa-let-7i-5p. Predicted gene targets of these sncRNAs included those globally decreased at the 8-cell–morula–blastocyst stage and critical to early embryo development. We show new original data on sncRNA profiling in spent culture medium from morula with different development potential. Our findings provide a view of a more complex network that controls human embryogenesis at the pre-implantation stage. Further research is required using reporter analysis to experimentally confirm interactions between identified sncRNA/gene target pairs. Full article
(This article belongs to the Special Issue Novel Molecular Mechanisms and Pathophysiology of Human Embryos)
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Review

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40 pages, 2164 KiB  
Review
Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research
by Konstantinos Sfakianoudis, Evangelos Maziotis, Eleni Karantzali, Georgia Kokkini, Sokratis Grigoriadis, Amelia Pantou, Polina Giannelou, Konstantina Petroutsou, Christina Markomichali, Maria Fakiridou, Michael Koutsilieris, Byron Asimakopoulos, Konstantinos Pantos and Mara Simopoulou
Int. J. Mol. Sci. 2021, 22(15), 8353; https://doi.org/10.3390/ijms22158353 - 3 Aug 2021
Cited by 24 | Viewed by 6300
Abstract
Developmental arrest of the preimplantation embryo is a multifactorial condition, characterized by lack of cellular division for at least 24 hours, hindering the in vitro fertilization cycle outcome. This systematic review aims to present the molecular drivers of developmental arrest, focusing on embryonic [...] Read more.
Developmental arrest of the preimplantation embryo is a multifactorial condition, characterized by lack of cellular division for at least 24 hours, hindering the in vitro fertilization cycle outcome. This systematic review aims to present the molecular drivers of developmental arrest, focusing on embryonic and parental factors. A systematic search in PubMed/Medline, Embase and Cochrane-Central-Database was performed in January 2021. A total of 76 studies were included. The identified embryonic factors associated with arrest included gene variations, mitochondrial DNA copy number, methylation patterns, chromosomal abnormalities, metabolic profile and morphological features. Parental factors included, gene variation, protein expression levels and infertility etiology. A valuable conclusion emerging through critical analysis indicated that genetic origins of developmental arrest analyzed from the perspective of parental infertility etiology and the embryo itself, share common ground. This is a unique and long-overdue contribution to literature that for the first time presents an all-inclusive methodological report on the molecular drivers leading to preimplantation embryos’ arrested development. The variety and heterogeneity of developmental arrest drivers, along with their inevitable intertwining relationships does not allow for prioritization on the factors playing a more definitive role in arrested development. This systematic review provides the basis for further research in the field. Full article
(This article belongs to the Special Issue Novel Molecular Mechanisms and Pathophysiology of Human Embryos)
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13 pages, 1053 KiB  
Review
Current Advancements in Noninvasive Profiling of the Embryo Culture Media Secretome
by Raminta Zmuidinaite, Fady I. Sharara and Ray K. Iles
Int. J. Mol. Sci. 2021, 22(5), 2513; https://doi.org/10.3390/ijms22052513 - 3 Mar 2021
Cited by 27 | Viewed by 6055
Abstract
There have been over 8 million babies born through in vitro fertilization (IVF) and this number continues to grow. There is a global trend to perform elective single embryo transfers, avoiding risks associated with multiple pregnancies. It is therefore important to understand where [...] Read more.
There have been over 8 million babies born through in vitro fertilization (IVF) and this number continues to grow. There is a global trend to perform elective single embryo transfers, avoiding risks associated with multiple pregnancies. It is therefore important to understand where current research of noninvasive testing for embryos stands, and what are the most promising techniques currently used. Furthermore, it is important to identify the potential to translate research and development into clinically applicable methods that ultimately improve live birth and reduce time to pregnancy. The current focus in the field of human reproductive medicine is to develop a more rapid, quantitative, and noninvasive test. Some of the most promising fields of research for noninvasive assays comprise cell-free DNA analysis, microscopy techniques coupled with artificial intelligence (AI) and omics analysis of the spent blastocyst media. High-throughput proteomics and metabolomics technologies are valuable tools for noninvasive embryo analysis. The biggest advantages of such technology are that it can differentiate between the embryos that appear morphologically identical and has the potential to identify the ploidy status noninvasively prior to transfer in a fresh cycle or before vitrification for a later frozen embryo transfer. Full article
(This article belongs to the Special Issue Novel Molecular Mechanisms and Pathophysiology of Human Embryos)
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22 pages, 32916 KiB  
Review
MicroRNA–mRNA Networks in Pregnancy Complications: A Comprehensive Downstream Analysis of Potential Biomarkers
by Asghar Ali, Frieder Hadlich, Muhammad W. Abbas, Muhammad A. Iqbal, Dawit Tesfaye, Gerrit J. Bouma, Quinton A. Winger and Siriluck Ponsuksili
Int. J. Mol. Sci. 2021, 22(5), 2313; https://doi.org/10.3390/ijms22052313 - 25 Feb 2021
Cited by 52 | Viewed by 7362
Abstract
Pregnancy complications are a major cause of fetal and maternal morbidity and mortality in humans. The majority of pregnancy complications initiate due to abnormal placental development and function. During the last decade, the role of microRNAs (miRNAs) in regulating placental and fetal development [...] Read more.
Pregnancy complications are a major cause of fetal and maternal morbidity and mortality in humans. The majority of pregnancy complications initiate due to abnormal placental development and function. During the last decade, the role of microRNAs (miRNAs) in regulating placental and fetal development has become evident. Dysregulation of miRNAs in the placenta not only affects placental development and function, but these miRNAs can also be exported to both maternal and fetal compartments and affect maternal physiology and fetal growth and development. Due to their differential expression in the placenta and maternal circulation during pregnancy complications, miRNAs can be used as diagnostic biomarkers. However, the differential expression of a miRNA in the placenta may not always be reflected in maternal circulation, which makes it difficult to find a reliable biomarker for placental dysfunction. In this review, we provide an overview of differentially expressed miRNAs in the placenta and/or maternal circulation during preeclampsia (PE) and intrauterine growth restriction (IUGR), which can potentially serve as biomarkers for prediction or diagnosis of pregnancy complications. Using different bioinformatics tools, we also identified potential target genes of miRNAs associated with PE and IUGR, and the role of miRNA-mRNA networks in the regulation of important signaling pathways and biological processes. Full article
(This article belongs to the Special Issue Novel Molecular Mechanisms and Pathophysiology of Human Embryos)
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