epigenetics in pregnancy ppt

Fertile sperm production requires effective epigenetic regulation. While most of the CpG sites in human DNA are methylated, the CpG-rich regions named CpG islands, that are located in approximately 60% of the promoters of human genes, display a baseline unmethylated pattern. Their role in broader effects on fetal and long-term human development is yet to be fully investigated and could represent a promising research field for future studies, which could even expand to the optimization of in vitro fertilization [37, 38]. The term decidualization defines the functional and morphological transition of the endometrial cells to form the cellular environment into which the blastocyst is able to implantitself. Cannarella R, Crafa A, Condorelli RA, Mongio LM, La Vignera S, Calogero AE. It is the comments and import statements in the code base of DNA. Ino T. Maternal smoking during pregnancy and offspring obesity: meta-analysis. Paquette AG, Chu T, Wu X, Wang K, Price ND, Sadovsky Y. The functions of endometrial miR-1792 during implantation are unclear. Histone acetylation generally results in higher gene expression, with rare exceptions [2325]. Additionally, the process of X-chromosome inactivation will occur in female embryos, leaving only one copy of almost all of the X-linked genes to be expressed [39]. An official website of the United States government. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. DNA methylation defects in spermatozoa of male partners from couples experiencing recurrent pregnancy loss. Messerschmidt DM, Knowles BB, Solter D. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Front Neuroendocrinol. Epigenetic reprogramming in mouse primordial germ cells. Epigenetics is defined as the study of heritable changes in gene expression that do not involve modifications to the underlying DNA sequence. Several authors demonstrated on murine models that early increases in histone acetylation occur within the embryo and in murine decidua following gestational VPA exposure [179, 180]. We have therefore chosen the most significant steps and those for which there is already literature data that allow a reasoned review of the causative mechanism. Before Quelhas D, Kompala C, Wittenbrink B, Han Z, Parker M, Shapiro M, Downs S, Kraemer K, Fanzo J, Morris S, Kreis K. The association between active tobacco use during pregnancy and growth outcomes of children under five years of age: a systematic review and meta-analysis. Xia W, Xu J, Yu G, Yao G, Xu K, Ma X, Zhang N, Liu B, Li T, Lin Z, Chen X, Li L, Wang Q, Shi D, Shi S, Zhang Y, Song W, Jin H, Hu L, Bu Z, Wang Y, Na J, Xie W, Sun Y-P. Resetting histone modifications during human parental-to-zygotic transition. Finally, by suppressing Dicer, miRNAs from the Lethal-7 family can regulate the expression of other miRNAs. Two events of extensive erasure occur in the primordial germ cells and pre-implantation embryo, followed by de novo DNA methylation, with differential kinetics and patterns during male and female gametogenesis and within cell lineage specification in post-implantation development. Histone methylation has both permissive or repressive effect on transcription, depending on the location of target amino acid residues in the histone tail or on the number of methyl groups attached [9, 26, 27]. These miRNAs primarily regulate placental processes such as the migration of the trophoblast and the placental morphogenesis, but evidence has emerged that they are transported to the fetal and maternal compartments as well, even though their role in such districts is still unclear [80, 82, 83]. Cardino VN, Goeden T, Yakah W, Ezeamama AE, Fenton JI. In fact, OGT represents a link between nutritional signals and chromatin regulation. Exposure to EDs starts during fetal life and continues after birth: the link between prenatal exposures and latent health outcomes suggests that these exposures may result in long-term epigenetic reprogramming. Distinct communication patterns of trophoblastic miRNA among the maternal-placental-fetal compartments. The plausibility of maternal nutritional status being a contributing factor to the risk for fetal alcohol spectrum disorders: the potential influence of zinc status as an example. Fetal membrane epigenetics. [92], hESC transfection of miR-542-3p suppressed IGFBP-1 (insulin-like growth factor-binding protein) expression, leading to PRL (prolactin) and WNT4 suppression and thus to the inhibition of decidualization in human endometrial stroma cells. One of the mostcommon pregnancy complications worldwide correlated to nutrition is gestational diabetes (GDM). This narrative review aims to recapitulate both the already established and the newly emerging environmental and parental factors that regulate pregnancy through epigenetic mechanisms. Jenkins TG, Carrell DT. Silver MJ. Shallie PD, Naicker T. The placenta as a window to the brain: a review on the role of placental markers in prenatal programming of neurodevelopment. Also, recent evidence is starting to highlight the contribution of post-translational histone modifications to the regulation of imprinting [42, 43]. 1Clinical Genetics Unit, Department of Womens and Childrens Health, University Hospital of Padova, Padua, Italy, 2Gynaecological Clinic, Department of Womens and Childrens Health, University of Padua, Padua, Italy. A significant inverse association has been found between miR-31 and both FOXP3, a transcription factor for T regulatory cells, and CXCL12, a chemoattractant for uterine natural killer cells, which participates in the creation of an immune-tolerant environment in the secretory phase [86]. Ivorra C, Fraga MF, Bayn GF, Fernndez AF, Garcia-Vicent C, Chaves FJ, Redon J, Lurbe E. DNA methylation patterns in newborns exposed to tobacco in utero. INTRODUCTION. High levels of progesterone in the post-ovulatory phase modulate the endometrial gene expression required for implantation by regulating DNA methylation [7577], and alterations in the DNA methylation of 448 sites have been associated with defective endometrial receptivity and consequently in recurrent pregnancy failure [75, 78]. Estella C, Herrer I, Moreno-Moya JM, Quionero A, Martnez S, Pellicer A, Simn C. miRNA signature and Dicer requirement during human endometrial stromal decidualization in vitro. National Library of Medicine MicroRNA-31 is significantly elevated in both human endometrium and serum during the window of implantation: a potential biomarker for optimum receptivity. Epigenetic and transgenerational reprogramming of brain development. The fetal and infant origins of adult disease. See this image and copyright information in PMC. Cai S, Quan S, Yang G, Chen M, Ye Q, Wang G, Yu H, Wang Y, Qiao S, Zeng X. Nutritional status impacts epigenetic regulation in early embryo development: a scoping review. Tomizawa S-I, Nowacka-Woszuk J, Kelsey G. DNA methylation establishment during oocyte growth: mechanisms and significance. Mishra A, Ashary N, Sharma R, Modi D. Extracellular vesicles in embryo implantation and disorders of the endometrium. Epigenetics: Expert Fetal and placental size and risk of hypertension in adult life. Yong HY, Mohd Shariff Z, Mohd Yusof BN, Rejali Z, Tee YYS, Bindels J, van der Beek EM. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. In contrast, miR-146a and miR-182 are positively related to quality of movement score [118]. in pregnancy Even second-hand smoke exposure among non-smoking women may alter DNA methylation in regions involved in development, carcinogenesis, and neuronal functioning. The lack of nutrients during pregnancy has been associated with various later-life consequences. Knowledge of the phenomena related to such regulatory mechanisms carries a huge relevance in both physiology and pathophysiology. This observation implies a scenario in which miR-34 family plays a regulatory role in the response to embryopathic stresses not activating the p53 pathway, but more studies are needed to explore these mechanisms. Maternal overeating and low protein consumption during pregnancy is associated with significant miRNA dysregulation in the offspring tissue, which may be associated with chronic inflammation status and metabolic health in offspring as early as the weaning age [145, 146]. Among the organogenetic processes that occur during fetal development, one of the most critically affected by maternal, environmental, and epigenetic factors is brain development. Weake VM, Workman JL. Some epigenetic tags remain in place as genetic Paquette AG, Lesseur C, Armstrong DA, Koestler DC, Appleton AA, Lester BM, Marsit CJ. Careers. In the host, the epigenetic machinery can regulate gene expression through a series of reversible epigenetic modifications, such as histone Cold Spring Harb Perspect Biol a040188. In male gametes, epigenetic patterns are established soon after the demethylation event has occurred in the primordial germ cells. The analysis of correlations between the expression pattern of the miRNAs tested in the study and cyclophosphamide induced limb phenotypes implies that miRNAs regulating apoptosis may differ from each other with respect to their functional role in teratogenesis [181]. Strutz J, Cvitic S, Hackl H, Kashofer K, Appel HM, Thringer A, Desoye G, Koolwijk P, Hiden U. Gestational diabetes alters microRNA signatures in human feto-placental endothelial cells depending on fetal sex. We present a case report of a 73-year-old woman suffering from bulbar onset ALS with a 4-month history of progressive dysphagia and dyspnea. [3741]. Tochigi H, Kajihara T, Mizuno Y, Mizuno Y, Tamaru S, Kamei Y, Okazaki Y, Brosens JJ, Ishihara O. In this way, GDM could represent a state of placental microbiota-driven altered immunologic tolerance that can be the target of a new therapy [153]. Argyraki M, Damdimopoulou P, Chatzimeletiou K, Grimbizis GF, Tarlatzis BC, Syrrou M, Lambropoulos A. Hum Reprod Update. Considerable evidence has gradually shown that the pregnancy environment regulates an extraordinary effect at the epigenetic level, with at least two diverse Cai S, Qiu A, Broekman BFP, Wong EQ, Gluckman PD, Godfrey KM, Saw SM, Soh S-E, Kwek K, Chong Y-S, Meaney MJ, Kramer MS, Rifkin-Graboi A, GUSTO study group The influence of gestational diabetes on neurodevelopment of children in the first two years of life: a prospective study. The https:// ensures that you are connecting to the Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. 8600 Rockville Pike When established on promoters or enhancers, methylation can repress transcription either directly, by inhibition of transcription factor binding, or indirectly, through recruitment of methyl-binding proteins and chromatin modifiers [1115]. However, specific differentially methylated regions (DMRs), in which DNA is methylated on one specific parental allele, escape the reprogramming process that happens in the pre-implantation embryo [37]. Bassols J, Serino M, Carreras-Badosa G, Burcelin R, Blasco-Baque V, Lopez-Bermejo A, Fernandez-Real J-M. Gestational diabetes is associated with changes in placental microbiota and microbiome. Main epigenetic processes involved in the regulation of pregnancy, -Transcription silencing (sporadically transcription permissive), -Protein recruitment (scaffolding &/or sponging), DNMT, DNA methyltransferase; TET, ten-eleven translocation methylcytosine dioxygenases; MBD4, methyl-CpG binding protein 4; TDG, thymine DNAglycosylase; (A), acetylation; (M), methylation; (P), phosphorylation; (U), ubiquitination; HATs, histone acetyltransferases; HDACs, histone deacetylases; HMTs, histone methyltransferases; HDMs, histone demethylases; DUBs, deubiquitinating enzymes; ncRNAs, non-coding RNAs; sncRNAs, short ncRNAs; siRNAs, short interfering RNAs; miRNAs, microRNAs; piRNAs, piwi interacting RNAs; lncRNAs, long ncRNAs; lincRNAs, long intergenic ncRNAs; ilncRNAs, intronic long ncRNAs; eRNAs, enhancer long ncRNAs; DMRs, differentially methylated regions; ICRs, imprinting control regions. There is also growing evidence that variants in the maternal genome affecting the imprinting status of the oocyte could cause MLID [44]. Maternal tobacco smoking is associated with smaller birth weight and head circumference, as well as reduced length for gestational age [166, 167]. In particular, it has been suggested that the association between assisted reproductive treatment (ART) procedures and slightly higher frequences of imprinting syndromes may be due to ART causing an abnormal epigenome in the offspring [71]. Investigation towards miRNA and downstream transcriptional regulation are growing, while studies investigating histone modifications are still sparse [176]. Cells. BMJ. The disruption of genomic imprinting leads to largely established human diseases with recognizable clinical features such as Beckwith-Wiedemann syndrome (MIM 130,650), Silver-Russell syndrome (MIM 180,860), Prader-Willi syndrome (MIM 176,270), and Angelman syndrome (MIM 105,830), but less dramatic and more subtle changes in the imprinted patterns, especially concerning multi-locus imprinting disturbances (MLID), can instead modulate fetal growth, resource acquisition, and organogenesis [4446]. Addresses issues of where, when how gene is expressed B. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders. According to Tochigi et al. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders. WebEpigenetic: Inherited changes in phenotype or gene expression that are caused by mechanisms other than changes in the underlying DNA sequence (eg, by methylation). Rossetto D, Avvakumov N, Ct J. Histone phosphorylation: a chromatin modification involved in diverse nuclear events. WebEpigenetics is the study of non-genotoxic, reversible, heritable mechanisms that influence gene expression without changing the DNA sequence. The human endometrium as a sensor of embryo quality. Interestingly, histone acetylation is also involved in the early endometrial processes, being implicated in the vascular endothelial growth factor pathway during angiogenesis. Alabduljabbar S, Zaidan SA, Lakshmanan AP, Terranegra A. Personalized nutrition approach in pregnancy and early life to tackle childhood and adult non-communicable diseases. Hot spots of epigenetic action. The British epidemiologist David Barker first introduced the concept that the womb may be more important than the home, emphasizing the role of the gestational environment as a regulatory staple in the development of the embryo, of the fetus and, ultimately, of the adult [1]. Expression and trafficking of placental microRNAs at the feto-maternal interface. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. PPT Hopefully, in the future, DNA methylation status could be used as a biomarker of prenatal insults for tobacco exposure as well. Beyond food, there are many substances which influence epigenetic programming. Normal development of brain circuits. Howerton CL, Bale TL. Sarkar DK, Gangisetty O, Wozniak JR, Eckerle JK, Georgieff MK, Foroud TM, Wetherill L, Wertelecki W, Chambers CD, Riley E, Zymak-Zakutnya N, Yevtushok L. Persistent changes in stress-regulatory genes in pregnant women or children exposed prenatally to alcohol. Epigenetics and Public Health: Why What is Epigenetics? Extracellular vesicles mediated early embryo-maternal interactions. The endometrial epigenome and its response to steroid hormones. Alaskhar Alhamwe B, Khalaila R, Wolf J, von Blow V, Harb H, Alhamdan F, Hii CS, Prescott SL, Ferrante A, Renz H, Garn H, Potaczek DP. Zhang S, Lin H, Kong S, Wang S, Wang H, Wang H, Armant DR. Physiological and molecular determinants of embryo implantation. Altered methylation patterns of 10 imprinted genes (DLX5, DHCR24, VTRNA2-1, PHLDA2, NPA1, FAM50B, GNAS-AS1, PAX8-AS1, SHANK2, and COPG2IT1) have been also associated with reduced quality of movement, elevated indices of asymmetrical and non-optimal reflexes, and increased likelihood of physiological stress [126]. Vilella F, Moreno-Moya JM, Balaguer N, Grasso A, Herrero M, Martnez S, Marcilla A, Simn C. Hsa-miR-30d, secreted by the human endometrium, is taken up by the pre-implantation embryo and might modify its transcriptome. Carrell DT, Hammoud SS. Silver MJ, Saffari A, Kessler NJ, Chandak GR, Fall CHD, Issarapu P, Dedaniya A, Betts M, Moore SE, Routledge MN, Herceg Z, Cuenin C, Derakhshan M, James PT, Monk D, Prentice AM. Pregnancy and early life are believed to be periods when environmental impacts on the epigenome can have long-lasting implications on health. Experimental models have shown that some in utero exposures can impact offspring methylation, leading to altered phenotypes. DNA methylation is the mostly commonly studied epigenetic modification in humans. It is also undoubtedly important to reveal whether other teratogens can affect offspring in this way [182]. McEvoy CT, Spindel ER. The brain is an organ that consumes a lot of energy and absorbs a massive quantity of maternal resources during its growth and evolution. Is there a way to reduce the negative consequences? Genetic and non-genetic influences during pregnancy on infant global and site specific DNA methylation: role for folate gene variants and vitamin B12. Therefore, these epigenetic changes represent a critical mechanism essential to understand the changes of fetal epigenome causing adverse outcomes at birth and later in life, warranting further study. Because folate deficiency in early pregnancy is associated with an increased risk of The most severe form of FASD is called fetal alcohol syndrome (FAS) and manifests as growth retardation, facial abnormalities, and central nervous system deficiencies. Defects in decidualization can lead to recurrent implantation failure and recurrent spontaneous abortion [90, 91]. Journal of Assisted Reproduction and Genetics, http://creativecommons.org/licenses/by/4.0/. Epigenetics is the level of control that sits above the genes and helps determine which genes are turned on and which genes are turned off. Chemical modifications to either the DNA, or structures associated with DNA, alter gene expression, without changes to the DNA sequence. Dong T, Hu W, Zhou X, Lin H, Lan L, Hang B, Lv W, Geng Q, Xia Y. Prenatal exposure to maternal smoking during pregnancy and attention-deficit/hyperactivity disorder in offspring: a meta-analysis. epigenetic maternal complications fetal complications Author Information Show + 1. Gallou-Kabani C, Gabory A, Tost J, Karimi M, Mayeur S, Lesage J, Boudadi E, Gross M-S, Taurelle J, Vig A, Breton C, Reusens B, Remacle C, Vieau D, Ekstrm TJ, Jais J-P, Junien C. Sex- and diet-specific changes of imprinted gene expression and DNA methylation in mouse placenta under a high-fat diet. Pregnancy-associated miRNA-clusters. For such reasons, it has been proposed that a contemporary definition of epigenetics should also include the gene silencing or upregulation mediated by ncRNAs [3436]. Zeng Y, Chen T. DNA methylation reprogramming during mammalian development. Martin EM, Fry RC. Numerous miRNAs are predominantly or exclusively expressed by the placenta and can be found clustered in specific chromosomal regions; they may be also controlled by the same promoters, have similar seed regions and targets, and work synergistically. Skvortsova K, Iovino N, Bogdanovi O. Munro SK, Farquhar CM, Mitchell MD, Ponnampalam AP. Histone ubiquitination: triggering gene activity. DNA methylation establishment in the oocyte is dynamically controlled during oocyte growth andit is proximally regulated by transcription events. Independent and combined effects of age, body mass index and gestational weight gain on the risk of gestational diabetes mellitus. Furthermore, primary human endometrial endothelial cells (hEECs) were found to actively secrete large quantities of exosomes into the conditioned media, and labelling experiments with miR30-d revealed that miRNAs are internalized in vesicles and secreted in exosomes. Please enable it to take advantage of the complete set of features! Hot spots of epigenetic action. Placental DNA methylation levels at CYP2E1 and IRS2 are associated with child outcome in a prospective autism study. The initial steps of nervous system development start as early as 23weeks post fertilization in humans; however, neuronal proliferation begins later in the first trimester and synaptogenesis and neural migration mainly occur in the later stages of pregnancy, during the second and third trimesters. Epigenetics is concerned with this regulation. Regulation of nutrient transport across the placenta. Inter- and transgenerational epigenetic inheritance: evidence in
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