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Special Issue "Epigenetic Safety after Assisted Reproductive Technologies"

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 21884

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Special Issue Editor

Prof. Dr. Martine De Rycke
E-Mail Website1 Website2
Guest Editor

Center for Medical Genetics, University Hospital Brussels, 1090 Brussels, Belgium
Interests: epigenetic safety after ART; preimplantation genetic testing for monogenic disorders and chromosomal aberrations

Special Issue Information

Dear Colleagues,

We would like to invite you to participate in this Special Issue, “Epigenetic Safety after Assisted Reproductive Technologies”.

Assisted reproductive technologies (ART) provide great benefits for many couples struggling with infertility problems. Although the vast majority of children born as a result of ART are healthy, an association between ART and epigenetic changes has been documented. Human and animal studies indicate that certain aspects of ART, such as hormonal stimulation or in vitro culture systems, may cause epigenetic deregulation during the periconceptional period of gamete maturation and early embryonic development, which may lead to phenotypic changes such as low birth weight or an increased prevalence of metabolic and cardiovascular disease later in adult life (the Developmental Origins of Health and Disease (DOHaD) concept).

Epidemiological studies in human also suggest that subfertility predisposes to epigenetic deregulation. As the use of ART increases worldwide, it is crucial to understand the mechanism(s) underlying the association between ART and epigenetics as this would allow for taking precautions in order to realize the safe and ethical use of ART. So far, most studies have focused on DNA methylation analysis. Now, technological advances allow an integrated multi-omics approach that may provide new insights into the underlying mechanisms.

The purpose of this Special Issue is to host research and review papers on our molecular understanding of the influence of ART on the epigenome. New results, confirmatory results, and contradictory results from both human and animal models will be considered for publication.

Prof. Dr. Martine De Rycke
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. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). 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

Assisted reproduction technologies (ART)
IVF and ICSI
Epigenetics
DNA methylation
Histone modifications
Genomic imprinting
Developmental Origins of Health and Disease
Epigenome-wide association study
Integrated multi-omics

Published Papers (7 papers)

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Research

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Open AccessArticle

Genome-Wide Analysis of DNA Methylation in Buccal Cells of Children Conceived through IVF and ICSI

and

Genes 2021, 12(12), 1912; https://doi.org/10.3390/genes12121912 - 28 Nov 2021

Cited by 4 | Viewed by 1509

Abstract

Early life periconceptional exposures during assisted reproductive technology (ART) procedures could alter the DNA methylation profiles of ART children, notably in imprinted genes and repetitive elements. At the genome scale, DNA methylation differences have been reported in ART conceptions at birth, but it is still unclear if those differences remain at childhood. Here, we performed an epigenome-wide DNA methylation association study using Illumina InfiniumEPIC BeadChip to assess the effects of the mode of conception on the methylome of buccal cells from 7- to 8-year-old children (48 children conceived after ART or naturally (control, CTL)) and according to the embryo culture medium in which they were conceived. We identified 127 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) (FDR < 0.05) with low delta beta differences between the two groups (ART vs. CTL). DMPs were preferentially located inside promoter proximal regions and CpG islands and were mostly hypermethylated with ART. We highlighted that the use of distinct embryo culture medium was not associated with DNA methylation differences in childhood. Overall, we bring additional evidence that children conceived via ART display limited genome-wide DNA methylation variation compared with those conceived naturally. Full article

(This article belongs to the Special Issue Epigenetic Safety after Assisted Reproductive Technologies)

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Review

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Open AccessReview

Network Approaches for Charting the Transcriptomic and Epigenetic Landscape of the Developmental Origins of Health and Disease

Salvo Danilo Lombardo

Ivan Fernando Wangsaputra

Jörg Menche

and

Adam Stevens

Genes 2022, 13(5), 764; https://doi.org/10.3390/genes13050764 - 26 Apr 2022

Cited by 1 | Viewed by 1895

Abstract

The early developmental phase is of critical importance for human health and disease later in life. To decipher the molecular mechanisms at play, current biomedical research is increasingly relying on large quantities of diverse omics data. The integration and interpretation of the different datasets pose a critical challenge towards the holistic understanding of the complex biological processes that are involved in early development. In this review, we outline the major transcriptomic and epigenetic processes and the respective datasets that are most relevant for studying the periconceptional period. We cover both basic data processing and analysis steps, as well as more advanced data integration methods. A particular focus is given to network-based methods. Finally, we review the medical applications of such integrative analyses. Full article

(This article belongs to the Special Issue Epigenetic Safety after Assisted Reproductive Technologies)

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Open AccessReview

Epigenetics in the Uterine Environment: How Maternal Diet and ART May Influence the Epigenome in the Offspring with Long-Term Health Consequences

Irene Peral-Sanchez

Batoul Hojeij

Diego A. Ojeda

Régine P. M. Steegers-Theunissen

and

Sandrine Willaime-Morawek

Genes 2022, 13(1), 31; https://doi.org/10.3390/genes13010031 - 23 Dec 2021

Cited by 15 | Viewed by 5102

Abstract

The societal burden of non-communicable disease is closely linked with environmental exposures and lifestyle behaviours, including the adherence to a poor maternal diet from the earliest preimplantation period of the life course onwards. Epigenetic variations caused by a compromised maternal nutritional status can affect embryonic development. This review summarises the main epigenetic modifications in mammals, especially DNA methylation, histone modifications, and ncRNA. These epigenetic changes can compromise the health of the offspring later in life. We discuss different types of nutritional stressors in human and animal models, such as maternal undernutrition, seasonal diets, low-protein diet, high-fat diet, and synthetic folic acid supplement use, and how these nutritional exposures epigenetically affect target genes and their outcomes. In addition, we review the concept of thrifty genes during the preimplantation period, and some examples that relate to epigenetic change and diet. Finally, we discuss different examples of maternal diets, their effect on outcomes, and their relationship with assisted reproductive technology (ART), including their implications on epigenetic modifications. Full article

(This article belongs to the Special Issue Epigenetic Safety after Assisted Reproductive Technologies)

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Open AccessReview

Developmental Effects of (Pre-)Gestational Diabetes on Offspring: Systematic Screening Using Omics Approaches

Bachuki Shashikadze

Florian Flenkenthaler

and

Genes 2021, 12(12), 1991; https://doi.org/10.3390/genes12121991 - 15 Dec 2021

Cited by 6 | Viewed by 2603

Abstract

Worldwide, gestational diabetes affects 2–25% of pregnancies. Due to related disturbances of the maternal metabolism during the periconceptional period and pregnancy, children bear an increased risk for future diseases. It is well known that an aberrant intrauterine environment caused by elevated maternal glucose levels is related to elevated risks for increased birth weights and metabolic disorders in later life, such as obesity or type 2 diabetes. The complexity of disturbances induced by maternal diabetes, with multiple underlying mechanisms, makes early diagnosis or prevention a challenging task. Omics technologies allowing holistic quantification of several classes of molecules from biological fluids, cells, or tissues are powerful tools to systematically investigate the effects of maternal diabetes on the offspring in an unbiased manner. Differentially abundant molecules or distinct molecular profiles may serve as diagnostic biomarkers, which may also support the development of preventive and therapeutic strategies. In this review, we summarize key findings from state-of-the-art Omics studies addressing the impact of maternal diabetes on offspring health. Full article

(This article belongs to the Special Issue Epigenetic Safety after Assisted Reproductive Technologies)

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Open AccessReview

Epigenetic Mechanisms of ART-Related Imprinting Disorders: Lessons From iPSC and Mouse Models

Alex Horánszky

Jessica L. Becker

Melinda Zana

Anne C. Ferguson-Smith

and

András Dinnyés

Genes 2021, 12(11), 1704; https://doi.org/10.3390/genes12111704 - 26 Oct 2021

Cited by 6 | Viewed by 2847

Abstract

The rising frequency of ART-conceived births is accompanied by the need for an improved understanding of the implications of ART on gametes and embryos. Increasing evidence from mouse models and human epidemiological data suggests that ART procedures may play a role in the pathophysiology of certain imprinting disorders (IDs), including Beckwith-Wiedemann syndrome, Silver-Russell syndrome, Prader-Willi syndrome, and Angelman syndrome. The underlying molecular basis of this association, however, requires further elucidation. In this review, we discuss the epigenetic and imprinting alterations of in vivo mouse models and human iPSC models of ART. Mouse models have demonstrated aberrant regulation of imprinted genes involved with ART-related IDs. In the past decade, iPSC technology has provided a platform for patient-specific cellular models of culture-associated perturbed imprinting. However, despite ongoing efforts, a deeper understanding of the susceptibility of iPSCs to epigenetic perturbation is required if they are to be reliably used for modelling ART-associated IDs. Comparing the patterns of susceptibility of imprinted genes in mouse models and IPSCs in culture improves the current understanding of the underlying mechanisms of ART-linked IDs with implications for our understanding of the influence of environmental factors such as culture and hormone treatments on epigenetically important regions of the genome such as imprints. Full article

(This article belongs to the Special Issue Epigenetic Safety after Assisted Reproductive Technologies)

Open AccessReview

Maternal One-Carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

Régine P. M. Steegers-Theunissen

and

Melek Rousian

Genes 2021, 12(10), 1634; https://doi.org/10.3390/genes12101634 - 17 Oct 2021

Cited by 12 | Viewed by 3997

Abstract

The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B₆, vitamin B₁₂, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (>17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (<7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases. Full article

(This article belongs to the Special Issue Epigenetic Safety after Assisted Reproductive Technologies)

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Open AccessReview

Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes

Federica Lamberto

Irene Peral-Sanchez

Suchitra Muenthaisong

Melinda Zana

Sandrine Willaime-Morawek

and

András Dinnyés

Genes 2021, 12(10), 1564; https://doi.org/10.3390/genes12101564 - 30 Sep 2021

Cited by 2 | Viewed by 2641

Abstract

Non-communicable diseases (NCDs) sauch as diabetes, obesity and cardiovascular diseases are rising rapidly in all countries world-wide. Environmental maternal factors (e.g., diet, oxidative stress, drugs and many others), maternal illnesses and other stressors can predispose the newborn to develop diseases during different stages of life. The connection between environmental factors and NCDs was formulated by David Barker and colleagues as the Developmental Origins of Health and Disease (DOHaD) hypothesis. In this review, we describe the DOHaD concept and the effects of several environmental stressors on the health of the progeny, providing both animal and human evidence. We focus on cardiovascular diseases which represent the leading cause of death worldwide. The purpose of this review is to discuss how in vitro studies with pluripotent stem cells (PSCs), such as embryonic and induced pluripotent stem cells (ESC, iPSC), can underpin the research on non-genetic heart conditions. The PSCs could provide a tool to recapitulate aspects of embryonic development “in a dish”, studying the effects of environmental exposure during cardiomyocyte (CM) differentiation and maturation, establishing a link to molecular mechanism and epigenetics. Full article

(This article belongs to the Special Issue Epigenetic Safety after Assisted Reproductive Technologies)

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