DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?

Zhou, Qi; Xiong, Yunhe; Qu, Bing; Bao, Anyu; Zhang, Yan

doi:10.3389/fimmu.2021.738962

Cited by 36 publications

(17 citation statements)

References 198 publications

(249 reference statements)

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“…During the regulation of epigenetic modification processes, DNA methylation and histone modification interact with each other. DNA methylation is the earliest and most extensively studied epigenetic modification, which takes the CpG island as the central link (Zhou et al, 2021). Recent studies have indicated that methylation of CpG islands is related to the methylation status of H3K4 (Zardo, 2021), and the levels of methylated H3K4 (H3K4me3) tend to be inversely correlated with DNA methylation (Okitsu Cindy and Hsieh, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have indicated that methylation of CpG islands is related to the methylation status of H3K4 (Zardo, 2021), and the levels of methylated H3K4 (H3K4me3) tend to be inversely correlated with DNA methylation (Okitsu Cindy and Hsieh, 2007). DNA methylation is mainly established and maintained by DNA methyltransferases (DNMTs) that transfer a methyl group from S-adenyl methionine (SAM) to the fifth carbon of a cytosine residue to form 5mC (Zhou et al, 2021) (Chen and Zhang, 2020), while the active removal of methylation marks relies on the activity of ten-eleven translocation (TET) enzymes and thymine DNA glycosylase (TDG) (Parry et al, 2021). After fertilization, including the deletion of most methylation marks inherited from the gametes and the subsequent establishment of the embryonic methylation pattern, they show dynamic changes during development (Zeng and Chen, 2019).…”

Section: Introductionmentioning

confidence: 99%

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LncRNA affects epigenetic reprogramming of porcine embryo development by regulating global epigenetic modification and the downstream gene SIN3A

et al. 2022

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The study of preimplantation development is of great significance to reproductive biology and regenerative medicine. With the development of high-throughput deep sequencing technology, it has been found that lncRNAs play a very important role in the regulation of embryonic development. In this study, key lncRNAs that regulate embryonic development were screened by analyzing the expression pattern of lncRNAs in porcine in vivo fertilization (IVV) embryos. By knocking down lncRNA expression in in vitro fertilization (IVF) embryos, we investigated its function and mechanism of regulating embryonic development. The results showed that the expression pattern of lncRNA was consistent with the time of gene activation. The lncRNAs were highly expressed in the 4-cell to blastocyst stage but barely expressed in the oocytes and 2-cell stage. So we speculated this part of lncRNAs may regulate gene expression. The lncRNA LOC102165808 (named lncT because the gene near this lncRNA is TFAP2C) was one of them. The knockdown (KD) of lncT inhibited embryonic development, resulting in decreased H3K4me3, H3K4me2, and H3K9me3, and increased DNA methylation. Meanwhile, RNAseq showed SIN3A was the top decreased gene in lncT-KD embryos. There was a severe blastocyst formation defect in SIN3A-KD embryos. Both lncT and SIN3A could affect NANOG and induce more cell apoptosis. In conclusion, the knockdown of lncT inhibits embryonic development by regulating H3K4me3, H3K4me2, DNA methylation, pluripotency gene, and apoptosis, and SIN3A is one of the downstream genes of lncT in regulating embryonic development.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LncRNA affects epigenetic reprogramming of porcine embryo development by regulating global epigenetic modification and the downstream gene SIN3A

et al. 2022

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“…The most pivotal epigenetic modifications are DNA methylation, histone modifications and nucleosome remodeling. The current epigenetic studies investigating RPL mainly focus on DNA methylation ( 15 ). The main methods of DNA methylation analyses are bisulfite sequencing, array or bead hybridization, pyrosequencing, methylation-specific polymerase chain reaction (PCR), high -performance liquid chromatography-ultraviolet, and mass spectrometry (MS)-based approaches ( 16 ).…”

Section: Overview Of Omicsmentioning

confidence: 99%

Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration

Wang

Ding

et al. 2022

Front. Immunol.

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Patients with recurrent pregnancy loss (RPL) account for approximately 1%-5% of women aiming to achieve childbirth. Although studies have shown that RPL is associated with failure of endometrial decidualization, placental dysfunction, and immune microenvironment disorder at the maternal-fetal interface, the exact pathogenesis remains unknown. With the development of high-throughput technology, more studies have focused on the genomics, transcriptomics, proteomics and metabolomics of RPL, and new gene mutations and new biomarkers of RPL have been discovered, providing an opportunity to explore the pathogenesis of RPL from different biological processes. Bioinformatics analyses of these differentially expressed genes, proteins and metabolites also reflect the biological pathways involved in RPL, laying a foundation for further research. In this review, we summarize the findings of omics studies investigating decidual tissue, villous tissue and blood from patients with RPL and identify some possible limitations of current studies.

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“…DNA methylation has been shown to play a key role in regulating genes involved in metabolic adaptation during pregnancy, and aberrant DNA methylation has been demonstrated during pregnancy complications such as preeclampsia, hypertension, GDM, early pregnancy loss and preterm birth (24)(25)(26)(27). Moreover, altered DNA methylation patterns have been observed in the placenta and cord blood of women with GDM, and have been identified as potential factors that mediate in utero fetal programming (26,(28)(29)(30)(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

The role of maternal DNA methylation in pregnancies complicated by gestational diabetes

Dias¹,

Willmer²,

Adam³

2022

Front. Clin. Diabetes Healthc.

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Diabetes in pregnancy is associated with adverse pregnancy outcomes and poses a serious threat to the health of mother and child. Although the pathophysiological mechanisms that underlie the association between maternal diabetes and pregnancy complications have not yet been elucidated, it has been suggested that the frequency and severity of pregnancy complications are linked to the degree of hyperglycemia. Epigenetic mechanisms reflect gene-environment interactions and have emerged as key players in metabolic adaptation to pregnancy and the development of complications. DNA methylation, the best characterized epigenetic mechanism, has been reported to be dysregulated during various pregnancy complications, including pre-eclampsia, hypertension, diabetes, early pregnancy loss and preterm birth. The identification of altered DNA methylation patterns may serve to elucidate the pathophysiological mechanisms that underlie the different types of maternal diabetes during pregnancy. This review aims to provide a summary of existing knowledge on DNA methylation patterns in pregnancies complicated by pregestational type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). Four databases, CINAHL, Scopus, PubMed and Google Scholar, were searched for studies on DNA methylation profiling in pregnancies complicated with diabetes. A total of 1985 articles were identified, of which 32 met the inclusion criteria and are included in this review. All studies profiled DNA methylation during GDM or impaired glucose tolerance (IGT), while no studies investigated T1DM or T2DM. We highlight the increased methylation of two genes, Hypoxia‐inducible Factor‐3α (HIF3α) and Peroxisome Proliferator-activated Receptor Gamma-coactivator-Alpha (PGC1-α), and the decreased methylation of one gene, Peroxisome Proliferator Activated Receptor Alpha (PPARα), in women with GDM compared to pregnant women with normoglycemia that were consistently methylated across diverse populations with varying pregnancy durations, and using different diagnostic criteria, methodologies and biological sources. These findings support the candidacy of these three differentially methylated genes as biomarkers for GDM. Furthermore, these genes may provide insight into the pathways that are epigenetically influenced during maternal diabetes and which should be prioritized and replicated in longitudinal studies and in larger populations to ensure their clinical applicability. Finally, we discuss the challenges and limitations of DNA methylation analysis, and the need for DNA methylation profiling to be conducted in different types of maternal diabetes in pregnancy.

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DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?

Cited by 36 publications

References 198 publications

LncRNA affects epigenetic reprogramming of porcine embryo development by regulating global epigenetic modification and the downstream gene SIN3A

LncRNA affects epigenetic reprogramming of porcine embryo development by regulating global epigenetic modification and the downstream gene SIN3A

Multiomics Studies Investigating Recurrent Pregnancy Loss: An Effective Tool for Mechanism Exploration

The role of maternal DNA methylation in pregnancies complicated by gestational diabetes

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