Advances in research into gamete and embryo-fetal origins of adult diseases

Zou, Kexin; Ding, Guo‐Lian; Huang, He‐Feng

doi:10.1007/s11427-018-9427-4

Cited by 27 publications

(12 citation statements)

References 73 publications

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“…Growing evidence suggests that the epigenetic patterns of gametes may impact the phenotypic health outcomes of offspring (Carrell & Hammoud, 2010;Hammoud et al, 2009;Jenkins & Carrell, 2012;Ryan & Kuzawa, 2020;Zou et al, 2019). Animal models have shown a number of exposures affecting DNAm in sperm including nutrition, endocrinedisrupting hormones, pollutants, and paternal stressors (Carone et al, 2010;Dias & Ressler, 2014;Gapp et al, 2014;Manikkam et al, 2013;Radford et al, 2014;Rodgers et al, 2013;Saavedra-Rodríguez & Feig, 2013;Wu et al, 2015).…”

Section: Epigenetic Associations Of Paternal Trauma With Offspring Bi...mentioning

confidence: 99%

Paternal adverse childhood experiences: Associations with infant DNA methylation

Merrill

Moore

Gladish

et al. 2021

Developmental Psychobiology

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Adverse childhood experiences (ACEs), or cumulative childhood stress exposures, such as abuse, neglect, and household dysfunction, predict later health problems in both the exposed individuals and their offspring. One potential explanation suggests exposure to early adversity predicts epigenetic modification, especially DNA methylation (DNAm), linked to later health. Stress experienced preconception by mothers may associate with DNAm in the next generation. We hypothesized that fathers’ exposure to ACEs also associates with their offspring DNAm, which, to our knowledge, has not been previously explored. An epigenome‐wide association study (EWAS) of blood DNAm (n = 45) from 3‐month‐old infants was regressed onto fathers’ retrospective ACEs at multiple Cytosine‐phosphate‐Guanosine (CpG) sites to discover associations. This accounted for infants’ sex, age, ethnicity, cell type proportion, and genetic variability. Higher ACE scores associated with methylation values at eight CpGs. Post‐hoc analysis found no contribution of paternal education, income, marital status, and parental postpartum depression, but did with paternal smoking and BMI along with infant sleep latency. These same CpGs also contributed to the association between paternal ACEs and offspring attention problems at 3 years. Collectively, these findings suggested there were biological associations with paternal early life adversity and offspring DNAm in infancy, potentially affecting offspring later childhood outcomes.

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Section: Epigenetic Associations Of Paternal Trauma With Offspring Bi...mentioning

confidence: 99%

Paternal adverse childhood experiences: Associations with infant DNA methylation

Merrill

Moore

Gladish

et al. 2021

Developmental Psychobiology

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“…Due to alterations in the peri-implantation environment and to key functions in placental development, such as cell fusion, embryo implantation, immune tolerance, and tissue remodeling, investigating the influence of IVF-ET on first-trimester placental development and function is particularly important [26,27]. In addition, according to maternal gestational physiology and the theory of fetal origins of adult disease [28,29], related research is needed to determine IVF-ET effects on placental gene expression and biological function as soon as possible, which would contribute toward developing strategies to prevent these diseases.…”

Section: Introductionmentioning

confidence: 99%

The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer

Zhao¹,

Zheng²,

Liu³

et al. 2019

Reprod Biol Endocrinol

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Background: The placenta is a highly specialized temporary organ that is related to fetal development and pregnancy outcomes, and epidemiological data demonstrate an increased risk of placental abnormality after in vitro fertilization and embryo transfer (IVF-ET). Methods: This study examines alterations in the transcriptome profile of first-trimester placentas from IVF-ET pregnancies and analyzes the potential mechanisms that play a role in the adverse perinatal outcomes associated with IVF-ET procedures. Four human placental villi from first-trimester samples were obtained through fetal bud aspiration from patients subjected to IVF-ET due to oviductal factors. An additional four control human placental villi were derived from a group of subjects who spontaneously conceived a twin pregnancy. We analyzed their transcriptomes by microarray. Then, RT-qPCR and immunohistochemistry were utilized to analyze several dysregulated genes to validate the microarray results. Biological functions and pathways were analyzed with bioinformatics tools. Results: A total of 3405 differentially regulated genes were identified as significantly dysregulated (> 2-fold change; P < 0.05) in the IVF-ET placenta in the first trimester: 1910 upregulated and 1495 downregulated genes. Functional enrichment analysis of the differentially regulated genes demonstrated that the genes were involved in more than 50 biological processes and pathways that have been shown to play important roles in the first trimester in vivo. These pathways can be clustered into coagulation cascades, immune response, transmembrane signaling, metabolism, cell cycle, stress control, invasion and vascularization. Nearly the same number of up-and downregulated genes participate in the same biological processes related to placental development and maintenance. Procedures utilized in IVF-ET altered the expression of first-trimester placental genes that are critical to these biological processes and triggered a compensatory mechanism during early implantation in vivo. Conclusion: These data provide a potential basis for further analysis of the higher frequency of adverse perinatal outcomes following IVF-ET, with the ultimate goal of developing safer IVF-ET protocols.

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“…Not surprisingly, researchers are still scratching the surface when it comes to discerning the biological relevance of RNA modifications. Several modifications have now been linked to disease pathologies [ 9 ], stress pathways [ 19 , 20 ], neuro-regulation [ 21 ], gene expression and regulation [ 22 ], and fetal development [ 23 ], amongst others. However, a mechanistic understanding of how modified nucleotides affect cellular processes and pathways has yet to be attained.…”

Section: Introductionmentioning

confidence: 99%

Challenges with Simulating Modified RNA: Insights into Role and Reciprocity of Experimental and Computational Approaches

D'Esposito

Myers

Chen

et al. 2022

Genes

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RNA is critical to a broad spectrum of biological and viral processes. This functional diversity is a result of their dynamic nature; the variety of three-dimensional structures that they can fold into; and a host of post-transcriptional chemical modifications. While there are many experimental techniques to study the structural dynamics of biomolecules, molecular dynamics simulations (MDS) play a significant role in complementing experimental data and providing mechanistic insights. The accuracy of the results obtained from MDS is determined by the underlying physical models i.e., the force-fields, that steer the simulations. Though RNA force-fields have received a lot of attention in the last decade, they still lag compared to their protein counterparts. The chemical diversity imparted by the RNA modifications adds another layer of complexity to an already challenging problem. Insight into the effect of RNA modifications upon RNA folding and dynamics is lacking due to the insufficiency or absence of relevant experimental data. This review provides an overview of the state of MDS of modified RNA, focusing on the challenges in parameterization of RNA modifications as well as insights into relevant reference experiments necessary for their calibration.

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Advances in research into gamete and embryo-fetal origins of adult diseases

Cited by 27 publications

References 73 publications

Paternal adverse childhood experiences: Associations with infant DNA methylation

Paternal adverse childhood experiences: Associations with infant DNA methylation

The placental transcriptome of the first-trimester placenta is affected by in vitro fertilization and embryo transfer

Challenges with Simulating Modified RNA: Insights into Role and Reciprocity of Experimental and Computational Approaches

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