Journal
GENES
Volume 12, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/genes12111704
Keywords
genomic imprinting; imprinting disorders; assisted reproductive technology; DNA methylation; mouse models; iPSCs
Categories
Funding
- European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant [812660, 739593]
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The review discusses the impact of ART on imprinting disorders, finding evidence from mouse models and human iPSC models that ART may contribute to certain imprinting disorders. The underlying molecular basis of this association needs further elucidation in order to understand the mechanisms of ART-linked imprinting disorders.
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.
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