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At age 9, the methylome of assisted reproductive technology children that underwent embryo culture in different media is not significantly different on a genome-wide scale.

التفاصيل البيبلوغرافية
العنوان: At age 9, the methylome of assisted reproductive technology children that underwent embryo culture in different media is not significantly different on a genome-wide scale.
المؤلفون: Koeck RM; Department of Clinical Genetics, Maastricht University Medical Centre+, Maastricht, The Netherlands.; Department of Genetics and Cell Biology, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands., Busato F; Laboratory for Epigenetics & Environment, CEA-Centre National de Recherche en Genomique Humaine, Evry, France., Tost J; Laboratory for Epigenetics & Environment, CEA-Centre National de Recherche en Genomique Humaine, Evry, France., Zandstra H; Department of Obstetrics and Gynaecology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands., Remy S; Health Unit, Flemish Institute for Technological Research (VITO), Mol, Belgium., Langie S; Health Unit, Flemish Institute for Technological Research (VITO), Mol, Belgium.; Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands., Gielen M; Department of Epidemiology and Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, Maastricht, the Netherlands., van Golde R; Department of Obstetrics and Gynaecology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands., Dumoulin JCM; Department of Obstetrics and Gynaecology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands., Brunner H; Department of Clinical Genetics, Maastricht University Medical Centre+, Maastricht, The Netherlands.; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Zamani Esteki M; Department of Clinical Genetics, Maastricht University Medical Centre+, Maastricht, The Netherlands.; Department of Genetics and Cell Biology, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands., van Montfoort APA; Department of Obstetrics and Gynaecology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, The Netherlands.
المصدر: Human reproduction (Oxford, England) [Hum Reprod] 2022 Oct 31; Vol. 37 (11), pp. 2709-2721.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 8701199 Publication Model: Print Cited Medium: Internet ISSN: 1460-2350 (Electronic) Linking ISSN: 02681161 NLM ISO Abbreviation: Hum Reprod Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford, UK : Oxford University Press
Original Publication: Oxford ; Washington, DC : Published for the European Society of Human Reproduction and Embryology by IRL Press, [c1986-
مواضيع طبية MeSH: Epigenome* , Reproductive Techniques, Assisted*, Child ; Humans ; Birth Weight ; DNA Methylation ; Follow-Up Studies ; Randomized Controlled Trials as Topic
مستخلص: Study Question: Can we detect DNA methylation differences between ART children that underwent embryo culture in different media?
Summary Answer: We identified no significant differences in site-specific or regional DNA methylation between the different culture medium groups.
What Is Known Already: Embryo culture in G3 or K-SICM medium leads to differences in embryonic, neonatal and childhood outcomes, including growth and weight. The methylome may mediate this association as the period of in vitro culture of ART treatments coincides with epigenetic reprogramming.
Study Design, Size, Duration: This study was conducted as a follow-up to a previous culture medium comparison study in which couples were pseudo-randomized to embryo culture in G3 or K-SICM medium. Of the resultant singletons, 120 (n = 65 G3, n = 55 K-SICM), were recruited at age 9.
Participants/materials, Setting, Methods: The ART children provided a saliva sample from which the methylome was analysed using the Infinium MethylationEPIC array. After quality and context filtering, 106 (n = 57 G3, n = 49 K-SICM) samples and 659 708 sites were retained for the analyses. Differential methylation analyses were conducted using mixed effects linear models corrected for age, sex, sample plate and cell composition. These were applied to all cytosine-guanine dinucleotide (CpG) sites, various genomic regions (genes, promoters, CpG Islands (CGIs)) and as a targeted analysis of imprinted genes and birth weight-associated CpG sites. Differential variance was assessed using the improved epigenetic variable outliers for risk prediction analysis (iEVORA) algorithm and methylation outliers were identified using a previously defined threshold (upper or lower quartile plus or minus three times the interquartile range, respectively).
Main Results and the Role of Chance: After correcting for multiple testing, we did not identify any significantly differentially methylated CpG sites, genes, promoters or CGIs between G3 and K-SICM children despite a lenient corrected P-value threshold of 0.1. Targeted analyses of (sites within) imprinted genes and birth weight-associated sites also did not identify any significant differences. The number of DNA methylation outliers per sample was comparable between the culture medium groups. iEVORA identified 101 differentially variable CpG sites of which 94 were more variable in the G3 group.
Large Scale Data: Gene Expression Omnibus (GEO) GSE196432.
Limitations, Reasons for Caution: To detect significant methylation differences with a magnitude of <10% between the groups many more participants would be necessary; however, the clinical relevance of such small differences is unclear.
Wider Implications of the Findings: The results of this study are reassuring, suggesting that if there is an effect of the culture medium on DNA methylation (and methylation-mediated diseases risk), it does not differ between the two media investigated here. The findings concur with other methylome studies of ART neonates and children that underwent embryo culture in different media, which also found no significant methylome differences.
Study Funding/competing Interest(s): Study funded by March of Dimes (6-FY13-153), EVA (Erfelijkheid Voortplanting & Aanleg) specialty programme (grant no. KP111513) of Maastricht University Medical Centre (MUMC+) and the Horizon 2020 innovation (ERIN) (grant no. EU952516) of the European Commission. The authors do not report any conflicts of interest relevant to this study.
Trial Registration Number: Dutch Trial register-NL4083.
(© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)
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فهرسة مساهمة: Keywords: ART; ART children; culture medium; follow-up; methylome
تواريخ الأحداث: Date Created: 20221007 Date Completed: 20221108 Latest Revision: 20221130
رمز التحديث: 20221201
مُعرف محوري في PubMed: PMC9627755
DOI: 10.1093/humrep/deac213
PMID: 36206092
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2350
DOI:10.1093/humrep/deac213