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Cellular and Molecular Mechanisms in the Developmental Origins of Health and Disease

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 8500

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Special Issue Editors

Dr. Jean Pierre Segain

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Guest Editor

Nantes Université - INRAe, UMR 1280 Physiopathologies des Adaptations Nutritionnelle, IMAD, CRNHO, CHU-Hôtel Dieu, Place Alexis Ricordeau, F-44093 Nantes, France
Interests: DOHaD; perinatally; intestinal barrier; gut–brain axis; prebiotics; butyrate

Dr. Gwénola Le Dréan

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Guest Editor

Nantes Université - INRAe, UMR 1280 Physiopathologies des Adaptations Nutritionnelle, Institut des Maladies de l’Appareil Digestif, CHU-Hôtel Dieu, Place Alexis Ricordeau, F-44093 Nantes, France
Interests: DOHaD; perinatally; intestinal barrier; gut–brain axis; prebiotics; butyrate

Special Issue Information

Dear Colleagues,

The paradigm of the developmental origins of health and disease (DOHaD) is based on a large body of epidemiological and experimental evidence that suggests exposure to environmental factors during critical periods of development—the prenatal and postnatal periods—greatly influence health and disease in adult life. For example, maternal nutrition and the microbiome, stress, chemicals, endocrine disruptors, and infections have been reported to increase the risk of metabolic and cardiovascular diseases, cancer, and immune and cognitive function. The DOHaD concept suggests that the developmental plasticity of organisms allows them to mount adaptive responses to environmental cues, involving epigenetic regulation of gene expression in differentiating tissues. Epigenetic modifications, including DNA methylation, post-transcriptional modifications of histone, and noncoding RNAs, can permanently affect organ structure and function, resulting in the dysfunction of many systems, such as the metabolic, endocrine, nervous, and immune systems. At the cellular level, the acknowledged importance of epigenetic mechanisms in stem cell biology makes germinal and adult stem cells prime targets of the DOHaD. This Special Issue will cover recent advances in research on cellular and molecular mechanisms in the DOHaD field, revealing new insights into the development of new strategies in the prevention of adult diseases.

Dr. Jean Pierre Segain
Dr. Gwénola Le Dréan
Guest Editors

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

DOHaD
perinatal environment
development
epigenetics and epitranscriptomics
signaling pathways
metabolic programming
stem cells
omics

Published Papers (5 papers)

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Research

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20 pages, 3516 KiB

Open AccessArticle

DNA Methylation of Genes Participating in Hepatic Metabolisms and Function in Fetal Calf Liver Is Altered by Maternal Undernutrition during Gestation

by Susumu Muroya, Konosuke Otomaru, Kazunaga Oshima, Ichiro Oshima, Koichi Ojima and Takafumi Gotoh

Int. J. Mol. Sci. 2023, 24(13), 10682; https://doi.org/10.3390/ijms241310682 - 26 Jun 2023

Cited by 1 | Viewed by 1641

Abstract

This study aimed to elucidate the effects of maternal undernutrition (MUN) on epigenetic modification of hepatic genes in Japanese Black fetal calves during gestation. Using a previously established experimental design feeding the dams with 60% (LN) or 120% (HN) of their global nutritional requirements during the 8.5-month gestational period, DNA methylation in the fetal liver was analyzed with reduced representation bisulfite sequencing (RRBS). The promoters and gene bodies in the LN fetuses were hypomethylated compared to HN fetuses. Pathway analysis showed that the genes with DMR in the exon/intron in the LN group were associated with pathways involved in Cushing syndrome, gastric acid secretion, and aldosterone synthesis and secretion. Promoter hypomethylation in the LN group was frequently observed in genes participating in various signaling pathways (thyroid hormone, Ras/Rap1, PIK3-Akt, cAMP), fatty acid metabolism, and cholesterol metabolism. The promoter hypomethylated genes ALPL and GNAS were upregulated in the LN group, whereas the promoter hypermethylated genes GRB10 and POR were downregulated. The intron/exon hypomethylated genes IGF2, IGF2R, ACAD8, TAT, RARB, PINK1, and SOAT2 were downregulated, whereas the hypermethylated genes IGF2BP2, NOS3, and NR2F1 were upregulated. Collectively, MUN alters the promoter and gene body methylation of genes associated with hepatic metabolisms (energy, cholesterol, mitochondria) and function, suggesting an impact of altered gene methylation on the dysregulation of gene expression in the fetal liver. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in the Developmental Origins of Health and Disease)

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21 pages, 3352 KiB

Open AccessArticle

Modelling Microglial Innate Immune Memory In Vitro: Understanding the Role of Aerobic Glycolysis in Innate Immune Memory

by Morgan Towriss, Brian MacVicar and Annie Vogel Ciernia

Int. J. Mol. Sci. 2023, 24(10), 8967; https://doi.org/10.3390/ijms24108967 - 18 May 2023

Viewed by 2167

Abstract

Microglia, the resident macrophages of the central nervous system, play important roles in maintaining brain homeostasis and facilitating the brain’s innate immune responses. Following immune challenges microglia also retain immune memories, which can alter responses to secondary inflammatory challenges. Microglia have two main memory states, training and tolerance, which are associated with increased and attenuated expression of inflammatory cytokines, respectively. However, the mechanisms differentiating these two distinct states are not well understood. We investigated mechanisms underlying training versus tolerance memory paradigms in vitro in BV2 cells using B-cell-activating factor (BAFF) or bacterial lipopolysaccharide (LPS) as a priming stimulus followed by LPS as a second stimulus. BAFF followed by LPS showed enhanced responses indicative of priming, whereas LPS followed by LPS as the second stimulus caused reduced responses suggestive of tolerance. The main difference between the BAFF versus the LPS stimulus was the induction of aerobic glycolysis by LPS. Inhibiting aerobic glycolysis during the priming stimulus using sodium oxamate prevented the establishment of the tolerized memory state. In addition, tolerized microglia were unable to induce aerobic glycolysis upon LPS restimulus. Therefore, we conclude that aerobic glycolysis triggered by the first LPS stimulus was a critical step in the induction of innate immune tolerance. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in the Developmental Origins of Health and Disease)

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14 pages, 2168 KiB

Open AccessArticle

Iodomethylcholine Inhibits Trimethylamine-N-Oxide Production and Averts Maternal Chronic Kidney Disease-Programmed Offspring Hypertension

by You-Lin Tain, Guo-Ping Chang-Chien, Sufan Lin, Chih-Yao Hou and Chien-Ning Hsu

Int. J. Mol. Sci. 2023, 24(2), 1284; https://doi.org/10.3390/ijms24021284 - 9 Jan 2023

Cited by 5 | Viewed by 1877

Abstract

Chronic kidney disease (CKD) affects 10% of the global population, including pregnant women. Adverse maternal conditions determine the developmental programming of many diseases later in life. We previously demonstrated that adult rat offspring born to dams with CKD developed hypertension and renal hypertrophy. Trimethylamine-N-oxide (TMAO), a uremic toxin derived from the gut microbiota, has been linked to hypertension. This study assesses the effects of TMAO inhibition by iodomethylcholine (IMC) treatment on offspring hypertension programmed by maternal CKD. Female rats were fed either a control or a 0.5% adenine diet before conception, with or without IMC treatment during pregnancy and lactation. Maternal IMC treatment averted maternal CKD-primed offspring hypertension and renal hypertrophy in 12-week-old offspring. Offspring hypertension is associated with increases in the plasma TMAO concentration and oxidative stress and shifts in gut microbiota. The beneficial effects of IMC are related to a reduction in TMAO; increases in genera Acetatifactor, Bifidobacterium, and Eubacterium; and decreases in genera Phocacecola and Bacteroides. Our findings afford insights into the targeting of the gut microbiota to deplete TMAO production, with therapeutic potential for the prevention of offspring hypertension programmed by maternal CKD, although these results still need further clinical translation. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in the Developmental Origins of Health and Disease)

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Review

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21 pages, 1268 KiB

Open AccessReview

The Effect of Maternal Exposure to a Diet High in Fats and Cholesterol on the Placental Function and Phenotype of the Offspring in a Rabbit Model: A Summary Review of About 15 Years of Research

by Delphine Rousseau-Ralliard, Pascale Chavatte-Palmer and Anne Couturier-Tarrade

Int. J. Mol. Sci. 2023, 24(19), 14547; https://doi.org/10.3390/ijms241914547 - 26 Sep 2023

Cited by 2 | Viewed by 913

Abstract

The rates of obesity and being overweight are increasing all around the world, especially among women of childbearing age, in part due to overconsumption of lipids. The aim of this summary review was to present the cellular and molecular effects of a hyperlipidic high-cholesterol (H) diet on the maternal and offspring phenotype at the early embryonic, neonatal, weaning and adult stages while considering the effects of sex and to identify the window(s) of vulnerability linked to this exposure in a rabbit model. Before breeding, the H diet induced dyslipidemia and aortic atherosclerosis lesions and increased the number of atretic follicles. In the offspring, the H diet disrupted the embryonic phenotype and induced fetal hypotrophy associated with sex-specific disturbances of the feto-placental unit. In adulthood, the offspring of the H dams were heavier and hyperphagic and had increased blood pressure associated with disturbed gonadal development in both sexes. Vulnerability windows were explored via embryo transfers. The maternal gestational diet was shown to play a key role in the feto-placental phenotype, and preconception programming was unquestionably also observed. These two periods could represent windows of intervention in the context of obesity or being overweight to limit fetal and placental consequences. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in the Developmental Origins of Health and Disease)

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27 pages, 2213 KiB

Open AccessReview

Imprinted Long Non-Coding RNAs in Mammalian Development and Disease

by Flavio Di Michele, Isabel Chillón and Robert Feil

Int. J. Mol. Sci. 2023, 24(17), 13647; https://doi.org/10.3390/ijms241713647 - 4 Sep 2023

Cited by 3 | Viewed by 1237

Abstract

Imprinted genes play diverse roles in mammalian development, homeostasis, and disease. Most imprinted chromosomal domains express one or more long non-coding RNAs (lncRNAs). Several of these lncRNAs are strictly nuclear and their mono-allelic expression controls in cis the expression of protein-coding genes, often developmentally regulated. Some imprinted lncRNAs act in trans as well, controlling target gene expression elsewhere in the genome. The regulation of imprinted gene expression—including that of imprinted lncRNAs—is susceptible to stochastic and environmentally triggered epigenetic changes in the early embryo. These aberrant changes persist during subsequent development and have long-term phenotypic consequences. This review focuses on the expression and the cis- and trans-regulatory roles of imprinted lncRNAs and describes human disease syndromes associated with their perturbed expression. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in the Developmental Origins of Health and Disease)

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