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Frontiers in the Development of Germ Cells and Embryos

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 7451

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Prof. Dr. Gábor L. Kovács

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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

Dr. Katalin Gombos

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Guest Editor

Department of Laboratory Medicine, Medical School, University of Pecs, Pecs, Hungary
Interests: gene regulation; genetics; cancer diagnostics; cancer biology; DNA; gene expression; PCR; RNA isolation; epidemiology; epigenetics

Prof. Dr. József Bódis

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Guest Editor

National Laboratory on Human Reproduction and Department of Obstetrics and Gynecology, University of Pecs, Pecs, Hungary
Interests: reproductive endocrinology; gynecology; human reproduction; maternal health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advantages of single-cell technologies and data analysis provide new insight into early embryonic development and germ cell specification. Germ cells are responsible for the transfer of genetic information from one generation to another and facilitate variety between different progenies. Detailed molecular understanding of primordial germ cells including pluripotent stem cells (PSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), and their life-defining molecular qualities have become the research frontier of reproductive biology and reproductive health, opening a new perspective for understanding the mechanisms of gametogenesis and embryonic development. Advances in live imaging technologies combined with single-cell genome sequencing technologies, whole transcriptome analysis in early embryonic development, DNA methylation, histone modification and chromatin accessibility analysis of the epigenetic reprogramming of primordial germ cells and regulatory role of the micro-RNA or long noncoding RNA certainly contribute to the understanding molecular mechanisms regulating self-renewal, reproductive organ regeneration and differentiation of GSCs. In-depth understanding of the mechanisms underlying a germ cell’s multipotential differentiation properties establish the background of gene editing-based therapeutic strategies to address reproductive disorders.

The main objective of this Special Issue is to collect an update of basic and clinical research results on the field of primordial germ cell specification, PSCs, ESCs, iPSCs from any model system, germline stem cells or stem-cell-based humanized animal models, early embryonal development, genome activation and lineage specification of the blastocyst with the aim of promoting the comprehensive knowledge translation to reproductive medicine.

Prof. Dr. Gábor L. Kovács
Dr. Katalin Gombos
Prof. Dr. József Bódis
Guest Editors

Manuscript Submission Information

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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.

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Keywords

germ cells
embryo
pluripotent stem cells (PSCs)
embryonic stem cells (ESCs)
induced pluripotent stem cells (iPSCs)
genome sequencing technologies
whole transcriptome analysis
reproductive medicine

Published Papers (3 papers)

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Research

25 pages, 4986 KiB

Open AccessArticle

HMGXB4 Targets Sleeping Beauty Transposition to Germinal Stem Cells

by Anantharam Devaraj, Manvendra Singh, Suneel A Narayanavari, Guo Yong, Jiaxuan Chen, Jichang Wang, Mareike Becker, Oliver Walisko, Andrea Schorn, Zoltán Cseresznyés, Tamás Raskó, Kathrin Radscheit, Matthias Selbach, Zoltán Ivics and Zsuzsanna Izsvák

Int. J. Mol. Sci. 2023, 24(8), 7283; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087283 - 14 Apr 2023

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Abstract

Transposons are parasitic genetic elements that frequently hijack vital cellular processes of their host. HMGXB4 is a known Wnt signaling-regulating HMG-box protein, previously identified as a host-encoded factor of Sleeping Beauty (SB) transposition. Here, we show that HMGXB4 is predominantly maternally expressed, and marks both germinal progenitor and somatic stem cells. SB piggybacks HMGXB4 to activate transposase expression and target transposition to germinal stem cells, thereby potentiating heritable transposon insertions. The HMGXB4 promoter is located within an active chromatin domain, offering multiple looping possibilities with neighboring genomic regions. HMGXB4 is activated by ERK2/MAPK1, ELK1 transcription factors, coordinating pluripotency and self-renewal pathways, but suppressed by the KRAB-ZNF/TRIM28 epigenetic repression machinery, also known to regulate transposable elements. At the post-translational level, SUMOylation regulates HMGXB4, which modulates binding affinity to its protein interaction partners and controls its transcriptional activator function via nucleolar compartmentalization. When expressed, HMGXB4 can participate in nuclear-remodeling protein complexes and transactivate target gene expression in vertebrates. Our study highlights HMGXB4 as an evolutionarily conserved host-encoded factor that assists Tc1/Mariner transposons to target the germline, which was necessary for their fixation and may explain their abundance in vertebrate genomes. Full article

(This article belongs to the Special Issue Frontiers in the Development of Germ Cells and Embryos)

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19 pages, 5252 KiB

Open AccessArticle

Scd1 Deficiency in Early Embryos Affects Blastocyst ICM Formation through RPs-Mdm2-p53 Pathway

by Huimin Niu, Anmin Lei, Huibin Tian, Weiwei Yao, Ying Liu, Cong Li, Xuetong An, Xiaoying Chen, Zhifei Zhang, Jiao Wu, Min Yang, Jiangtao Huang, Fei Cheng, Jianqing Zhao, Jinlian Hua, Shimin Liu and Jun Luo

Int. J. Mol. Sci. 2023, 24(2), 1750; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021750 - 16 Jan 2023

Cited by 2 | Viewed by 1965

Abstract

Embryos contain a large number of lipid droplets, and lipid metabolism is gradually activated during embryonic development to provide energy. However, the regulatory mechanisms remain to be investigated. Stearoyl-CoA desaturase 1 (Scd1) is a fatty acid desaturase gene that is mainly involved in intracellular monounsaturated fatty acid production, which takes part in many physiological processes. Analysis of transcripts at key stages of embryo development revealed that Scd1 was important and expressed at an increased level during the cleavage and blastocyst stages. Knockout Scd1 gene by CRISPR/Cas9 from zygotes revealed a decrease in lipid droplets (LDs) and damage in the inner cell mass (ICM) formation of blastocyst. Comparative analysis of normal and knockout embryo transcripts showed a suppression of ribosome protein (RPs) genes, leading to the arrest of ribosome biogenesis at the 2-cell stage. Notably, the P53-related pathway was further activated at the blastocyst stage, which eventually caused embryonic development arrest and apoptosis. In summary, Scd1 helps in providing energy for embryonic development by regulating intra-embryonic lipid droplet formation. Moreover, deficiency activates the RPs-Mdm2-P53 pathway due to ribosomal stress and ultimately leads to embryonic development arrest. The present results suggested that Scd1 gene is essential to maintain healthy development of embryos by regulating energy support. Full article

(This article belongs to the Special Issue Frontiers in the Development of Germ Cells and Embryos)

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21 pages, 2586 KiB

Open AccessArticle

LC-MS Analysis Revealed the Significantly Different Metabolic Profiles in Spent Culture Media of Human Embryos with Distinct Morphology, Karyotype and Implantation Outcomes

by Chupalav Eldarov, Alina Gamisonia, Vitaliy Chagovets, Luiza Ibragimova, Svetlana Yarigina, Veronika Smolnikova, Elena Kalinina, Nataliya Makarova, Victor Zgoda, Gennady Sukhikh and Mikhail Bobrov

Int. J. Mol. Sci. 2022, 23(5), 2706; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23052706 - 28 Feb 2022

Cited by 7 | Viewed by 2855

Abstract

In this study we evaluated possible differences in metabolomic profiles of spent embryo culture media (SECM) of human embryos with distinct morphology, karyotype, and implantation outcomes. A total of 153 samples from embryos of patients undergoing in vitro fertilization (IVF) programs were collected and analyzed by HPLC-MS. Metabolomic profiling and statistical analysis revealed clear clustering of day five SECM from embryos with different morphological classes and karyotype. Profiling of day five SECM from embryos with different implantation outcomes showed 241 significantly changed molecular ions in SECM of successfully implanted embryos. Separate analysis of paired SECM samples on days three and five revealed 46 and 29 molecular signatures respectively, significantly differing in culture media of embryos with a successful outcome. Pathway enrichment analysis suggests certain amino acids, vitamins, and lipid metabolic pathways to be crucial for embryo implantation. Differences between embryos with distinct implantation potential are detectable on the third and fifth day of cultivation that may allow the application of culture medium analysis in different transfer protocols for both fresh and cryopreserved embryos. A combination of traditional morphological criteria with metabolic profiling of SECM may increase implantation rates in assisted reproductive technology programs as well as improve our knowledge of the human embryo metabolism in the early stages of development. Full article

(This article belongs to the Special Issue Frontiers in the Development of Germ Cells and Embryos)

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