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Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence

To increase the efficiency of assisted reproductive techniques (ART), molecular studies have been performed to identify the best predictive biomarkers for selecting the most suitable germ cells for fertilization and the best embryo for intra-uterine transfer. However, across different studies, no un...

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Autores principales: El-Maarri, Osman, Jamil, Muhammad Ahmer, Köster, Maria, Nüsgen, Nicole, Oldenburg, Johannes, Montag, Markus, van der Ven, Hans, van der Ven, Katrin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232172/
https://www.ncbi.nlm.nih.gov/pubmed/34203623
http://dx.doi.org/10.3390/ijms22126377
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author El-Maarri, Osman
Jamil, Muhammad Ahmer
Köster, Maria
Nüsgen, Nicole
Oldenburg, Johannes
Montag, Markus
van der Ven, Hans
van der Ven, Katrin
author_facet El-Maarri, Osman
Jamil, Muhammad Ahmer
Köster, Maria
Nüsgen, Nicole
Oldenburg, Johannes
Montag, Markus
van der Ven, Hans
van der Ven, Katrin
author_sort El-Maarri, Osman
collection PubMed
description To increase the efficiency of assisted reproductive techniques (ART), molecular studies have been performed to identify the best predictive biomarkers for selecting the most suitable germ cells for fertilization and the best embryo for intra-uterine transfer. However, across different studies, no universal markers have been found. In this study, we addressed this issue by generating gene expression and CpG methylation profiles of outer cumulus cells obtained during intra-cytoplasmic sperm injection (ICSI). We also studied the association of the generated genomic data with the clinical parameters (spindle presence, zona pellucida birefringence, pronuclear pattern, estrogen level, endometrium size and lead follicle size) and the pregnancy result. Our data highlighted the presence of several parameters that affect analysis, such as inter-individual differences, inter-treatment differences, and, above all, specific treatment protocol differences. When comparing the pregnancy outcome following the long protocol (GnRH agonist) of ovarian stimulation, we identified the single gene markers (NME6 and ASAP1, FDR < 5%) which were also correlated with endometrium size, upstream regulators (e.g., EIF2AK3, FSH, ATF4, MKNK1, and TP53) and several bio-functions related to cell death (apoptosis) and cellular growth and proliferation. In conclusion, our study highlighted the need to stratify samples that are very heterogeneous and to use pathway analysis as a more reliable and universal method for identifying markers that can predict oocyte development potential.
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spelling pubmed-82321722021-06-26 Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence El-Maarri, Osman Jamil, Muhammad Ahmer Köster, Maria Nüsgen, Nicole Oldenburg, Johannes Montag, Markus van der Ven, Hans van der Ven, Katrin Int J Mol Sci Article To increase the efficiency of assisted reproductive techniques (ART), molecular studies have been performed to identify the best predictive biomarkers for selecting the most suitable germ cells for fertilization and the best embryo for intra-uterine transfer. However, across different studies, no universal markers have been found. In this study, we addressed this issue by generating gene expression and CpG methylation profiles of outer cumulus cells obtained during intra-cytoplasmic sperm injection (ICSI). We also studied the association of the generated genomic data with the clinical parameters (spindle presence, zona pellucida birefringence, pronuclear pattern, estrogen level, endometrium size and lead follicle size) and the pregnancy result. Our data highlighted the presence of several parameters that affect analysis, such as inter-individual differences, inter-treatment differences, and, above all, specific treatment protocol differences. When comparing the pregnancy outcome following the long protocol (GnRH agonist) of ovarian stimulation, we identified the single gene markers (NME6 and ASAP1, FDR < 5%) which were also correlated with endometrium size, upstream regulators (e.g., EIF2AK3, FSH, ATF4, MKNK1, and TP53) and several bio-functions related to cell death (apoptosis) and cellular growth and proliferation. In conclusion, our study highlighted the need to stratify samples that are very heterogeneous and to use pathway analysis as a more reliable and universal method for identifying markers that can predict oocyte development potential. MDPI 2021-06-15 /pmc/articles/PMC8232172/ /pubmed/34203623 http://dx.doi.org/10.3390/ijms22126377 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
El-Maarri, Osman
Jamil, Muhammad Ahmer
Köster, Maria
Nüsgen, Nicole
Oldenburg, Johannes
Montag, Markus
van der Ven, Hans
van der Ven, Katrin
Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence
title Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence
title_full Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence
title_fullStr Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence
title_full_unstemmed Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence
title_short Stratifying Cumulus Cell Samples Based on Molecular Profiling to Help Resolve Biomarker Discrepancies and to Predict Oocyte Developmental Competence
title_sort stratifying cumulus cell samples based on molecular profiling to help resolve biomarker discrepancies and to predict oocyte developmental competence
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232172/
https://www.ncbi.nlm.nih.gov/pubmed/34203623
http://dx.doi.org/10.3390/ijms22126377
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