Identifying placental epigenetic alterations in an intrauterine growth restriction (IUGR) rat model induced by gestational protein deficiency

Reamon-Buettner, Stella Marie; Buschmann, J.; Lewin, Geertje

doi:10.1016/j.reprotox.2014.02.009

Cited by 35 publications

(24 citation statements)

References 41 publications

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“…Epigenetics mechanisms have also been investigated in animal models of programmed hypertension. For example, methylation patterns were altered in placental tissue from IUGR rats from a maternal low protein diet model (319). In a maternal undernutrition rat model of programmed pulmonary hypertension, DNA methylation in the lung was altered in IUGR offspring compared with controls, which correlated with increased pulmonary vascular resistance (321).…”

Section: Developmental Programming Of Hypertensionmentioning

confidence: 99%

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

Morton

Cooke

Davidge³

2016

Physiological Reviews

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The developmental origins of health and disease theory is based on evidence that a suboptimal environment during fetal and neonatal development can significantly impact the evolution of adult-onset disease. Abundant evidence exists that a compromised prenatal (and early postnatal) environment leads to an increased risk of hypertension later in life. Hypertension is a silent, chronic, and progressive disease defined by elevated blood pressure (>140/90 mmHg) and is strongly correlated with cardiovascular morbidity/mortality. The pathophysiological mechanisms, however, are complex and poorly understood, and hypertension continues to be one of the most resilient health problems in modern society. Research into the programming of hypertension has proposed pharmacological treatment strategies to reverse and/or prevent disease. In addition, modifications to the lifestyle of pregnant women might impart far-reaching benefits to the health of their children. As more information is discovered, more successful management of hypertension can be expected to follow; however, while pregnancy complications such as fetal growth restriction, preeclampsia, preterm birth, etc., continue to occur, their offspring will be at increased risk for hypertension. This article reviews the current knowledge surrounding the developmental origins of hypertension, with a focus on mechanistic pathways and targets for therapeutic and pharmacologic interventions.

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Section: Developmental Programming Of Hypertensionmentioning

confidence: 99%

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

Morton

Cooke

Davidge³

2016

Physiological Reviews

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“…For example, high fat diets in utero are known to affect offspring epigenetic patterns and methylation status of particular genes, for example, adiponectin and leptin genes (Masuyama et al, 2016), while a high fat diet during pregnancy and lactation can induce epigenetic modifications and differential expression of the μ-opioid receptor, and corresponding hypomethylation of the promoter regions of the gene, in mouse offspring (Vucetic et al, 2010). Additionally, maternal protein restriction can cause hypomethylation of particular genes involved in metabolic processes in fetus and offspring (Lillycrop et al, 2007, Burdge et al, 2007a, van Straten et al, 2010, Burdge et al, 2004) and can also affect methylation in the developing placenta (Reamon-Buettner et al, 2014). Such epigenetic perturbation is not just limited to fetal and early life; the postnatal period is also susceptible to the epigenetic effects of nutrition.…”

Section: Introductionmentioning

confidence: 99%

A ‘phenotypic hangover’ – the predictive adaptive response and multigenerational effects of altered nutrition on the transcriptome ofDrosophila melanogaster

Osborne

Dearden

2017

Preprint

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The Developmental Origins of Health and Disease (DOHaD) hypothesis predicts that early-life environmental exposures can be detrimental to later-life health, and that mismatch between the pre- and postnatal environment may contribute to the growing non-communicable disease (NCD) epidemic. Within this is an increasingly recognised role for epigenetic mechanisms; epigenetic modifications can be influenced by, e.g., nutrition, and can alter gene expression in mothers and offspring. Currently, there are no whole-genome transcriptional studies of response to nutritional alteration. Thus, we sought to explore how nutrition affects the expression of genes involved in epigenetic processes in Drosophila melanogaster. We manipulated Drosophila food macronutrient composition at the F0 generation, mismatched F1 offspring back to a standard diet, and analysed the transcriptome of the F0 – F3 generations by RNA-sequencing. At F0, the altered (high protein, low carbohydrate, HPLC) diet increased expression of genes involved in epigenetic processes, with coordinated downregulation of genes involved in immunity, neurotransmission and neurodevelopment, oxidative stress and metabolism. Upon reversion to standard nutrition, mismatched F1 and F2 generations displayed multigenerational inheritance of altered gene expression. By the F3 generation, gene expression had reverted to F0 (matched) levels. These nutritionally-induced gene expression changes demonstrate that dietary alteration can upregulate epigenetic genes, which may influence the expression of genes with broad biological functions. Further, the multigenerational inheritance of the gene expression changes in F1 and F2 mismatched generations suggests a predictive adaptive response (PAR) to maternal nutrition. Our findings may help to understand the interaction between maternal diet and future offspring health, and have direct implications for the current NCD epidemic.

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“…Microarray analysis indicated a number of genes that were up- or down-regulated by the miR-518b mimic. Among the 124 target genes down-regulated more than 2-fold (Supplementary Table S1), two genes (tyrosine hydroxylase: TH and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1: HSD3B1 ) were previously demonstrated to be involved in the pathogenesis of preeclampsia202122, and five genes (endothelin receptor type A: EDNRA , advanced glycosylation end product-specific receptor: AGER , wingless-type MMTV integration site family member 2: WNT2 , complement component 9: C9 , and transient receptor potential cation channel, subfamily M, member 2: TRPM2 ) play roles in preeclampsia with foetal growth restriction23242526272829303132 (Table 1). Likewise, among the 112 target genes up-regulated over 2-fold by the miR-518b mimic (Supplementary Table S2), four genes [hemopexin: HPX , serpin peptidase inhibitor, clade B (ovalbumin), member 2: SERPINB2 , lipoprotein, Lp(a): LPA , and tumour necrosis factor superfamily, member 10: TNFSF10 ] show involvement in preeclampsia35363738, and two genes (CD69 molecule: CD69 and stanniocalcin 1: STC1 ) are involved in preeclampsia with foetal growth restriction333439 (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…miR-518b seems to control multiple target genes located on various chromosomes. Interestingly, some miR-518b target genes were previously demonstrated to associate with preeclampsia (e.g., TH and HSD3B1 for down-regulated genes, and HPX, SERPINB2, LPA and TNFSF10 for up-regulated genes)20212235363738 and with preeclampsia with foetal growth restriction (e.g., EDNRA, AGER, WNT2, C9 , and TRPM2 for down-regulated genes, and CD69 and STC1 for up-regulated genes)23242526272829303132333439. However, further experiments are needed to demonstrate a causal relationship between the expression of pregnancy-associated miRNAs and pregnancy-related disorders.…”

Section: Discussionmentioning

confidence: 99%

Feasibility of placenta-derived mesenchymal stem cells as a tool for studying pregnancy-related disorders

Fuchi

Miura

Doi

et al. 2017

Sci Rep

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The cellular and molecular mechanisms responsible for pregnancy-related disorders remain unclear. We investigated the feasibility of using placenta-derived mesenchymal stem cells (MSCs) as a tool to study such pregnancy-related disorders. We isolated and expanded adequate numbers of cells with characteristic features of MSCs from the chorionic plate (CP-MSCs), chorionic villi (CV-MSCs), and decidua basalis (DB-MSCs) of human term placental tissues. All placenta-derived MSCs expressed pregnancy-associated C14MC microRNA (miRNA) (miR-323-3p). Interestingly, the placenta-specific C19MC miRNAs (miR-518b and miR517a) were clearly expressed in CP-MSCs and CV-MSCs of foetal origin, but were barely expressed in DB-MSCs of maternal origin. Furthermore, expression levels of placenta-specific C19MC miRNAs in CV-MSCs remained stable during the ex vivo expansion process and across different pregnancy phases (first trimester versus third trimester). High-efficiency siRNA transfection was confirmed in twice-passaged CV-MSCs with little toxicity, and microarray analysis was used to screen for miR-518b target genes. Placenta-derived MSCs, especially CV-MSCs, are a potential tool for investigating the role of placental miRNAs in pregnancy-related disorders.

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Identifying placental epigenetic alterations in an intrauterine growth restriction (IUGR) rat model induced by gestational protein deficiency

Cited by 35 publications

References 41 publications

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

In Utero Origins of Hypertension: Mechanisms and Targets for Therapy

A ‘phenotypic hangover’ – the predictive adaptive response and multigenerational effects of altered nutrition on the transcriptome ofDrosophila melanogaster

Feasibility of placenta-derived mesenchymal stem cells as a tool for studying pregnancy-related disorders

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