Tomizawa S-I, Nowacka-Woszuk J, Kelsey G. DNA methylation establishment during oocyte growth: mechanisms and significance. Loss of miR-542-3p enhances IGFBP-1 expression in decidualizing human endometrial stromal cells. MicroRNA and embryo implantation. Bellanti JA. DNA methylation profiles may not persist into adulthood but could alter developmental trajectories and induce lasting alterations in brain structure, connectivity, and function [163]. The brain is an organ that consumes a lot of energy and absorbs a massive quantity of maternal resources during its growth and evolution. Interestingly, histone acetylation is also involved in the early endometrial processes, being implicated in the vascular endothelial growth factor pathway during angiogenesis. Epigenetics is concerned with this regulation. 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. See more. The earliest stages of embryonic development are characterized by major epigenetic remodeling events that include parental DNA methylation erasure and reprogramming (with the exception of DMRs), chromatin folding establishment, and spatial reorganization of the genome [6567]. Rush EC, Katre P, Yajnik CS. These compounds exhibit weak steroid-like activity and therefore can affect reproductive development along multiple points including the hypothalamus and the gonad. The placenta is known to be involved in the transfer of nutrients, hormones, and metabolites, but it is important to remember that it also produces neurotransmitters, including serotonin (5-HT), dopamine (DA), norepinephrine/epinephrine, which enter the maternalfetal circulation and interact with the development of the fetal brain. 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]. 2019 Nov 5;25(6):777-801. doi: 10.1093/humupd/dmz025. PPT DNA methylation in babies born to nonsmoking mothers exposed to secondhand smoke during pregnancy: an epigenome-wide association study. Epigenetics of pregnancy: looking beyond the DNA code On the other hand, poly-ubiquitination flags proteins as a mark for degradation or activation in some signaling pathways [22, 30]. Cold Spring Harb Perspect Biol a040188. Cuman C, Van Sinderen M, Gantier MP, Rainczuk K, Sorby K, Rombauts L, Osianlis T, Dimitriadis E. Human blastocyst secreted microRNA regulate endometrial epithelial cell adhesion. Kresowik JDK, Devor EJ, Van Voorhis BJ, Leslie KK. 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. 10.1101/cshperspect.a040188. 2020; other pictures obtained by. Hum Mol Genet 15 Spec No 1:R1729. Epigenetics in pregnancy. Knfler M, Haider S, Saleh L, Pollheimer J, Gamage TKJB, James J. Macklon NS, Brosens JJ. McEvoy CT, Spindel ER. Pathare ADS, Hinduja I. Aberrant DNA methylation profiling affecting the endometrial receptivity in recurrent implantation failure patients undergoing in vitro fertilization. Many signals regulate chromatin activation or repression; among these, those related to nutrient availability are relevant for epigenetic programming in the placenta. Aplin JD, Ruane PT. Barker DJ. Stage 1: from gametes to embryo-endometrium cross-talk; Stage 2: from placenta-fetus cross-talk to brain development, with an overview on environmental factors as well (nutrition and teratogens). 2023 Apr 17;15(8):1933. doi: 10.3390/nu15081933. Tung EWY, Winn LM. 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. Borchiellini M, Ummarino S, Di Ruscio A. 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. Many researches have also found that alcohol interferes with gene expression levels and epigenetic processes by altering DNA methylation (particularly the expression of two methyltransferase enzymes, DNMT1 and DNMT3A), histone regulation, and non-coding RNAs [162]. Extracellular vesicles mediated early embryo-maternal interactions. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Self-reported pregnancy exposures and placental DNA methylation in the MARBLES prospective autism sibling study. While the cells Mandal C, Kim SH, Chai JC, Oh SM, Lee YS, Jung KH, Chai YG. Epigenetic: New Insight in Gestational Diabetes Mellitus In vitro studies showed that stress hormones can increase excitability hippocampal cells [131]. Retis-Resendiz AM, Gonzlez-Garca IN, Len-Jurez M, Camacho-Arroyo I, Cerbn M, Vzquez-Martnez ER. A pivotal role in the fetal stage of pregnancy is played by the amniochorionic membranes, which act as the feto-maternal interface, as they exhibit characteristic chromatin modification patterns, DNA (CpG) methylation, histone modifications, and non-coding RNA transcriptomes, whose dynamic changes during normal and pathological pregnancies are an important contributor to gene regulation throughout pregnancy [31]. As a result, DNA methylation is mainly restricted to the transcribed gene bodies, while intergenic regions are hypomethylated [5759], as non-CpG hypermethylation plays an active role in gene expression regulation during oocyte maturation, potentially through the incorporation with transcription factors [57]. In particular, the study of miRNAs expression and transport appears to be the next frontier in terms of improving the understanding of epigenetic mechanisms in fetal development and fetal-maternal crosstalk. Alabduljabbar S, Zaidan SA, Lakshmanan AP, Terranegra A. Personalized nutrition approach in pregnancy and early life to tackle childhood and adult non-communicable diseases. Any epigenetic tags or modifications that are made within a cell are carried through into the daughter cells when the cell divides. This is extremely important, as cells that have started down one functional path keep going down that path. In addition to protein-coding genes, these clusters typically contain lncRNA, which can regulate the imprinting of the nearby genes. Finally, it is probable that EDs alter the transcription factors activity, changing the availability of DNA to epigenetic machinery and giving rise to gene-specific patterning of epigenomic markers [159]. The lack of nutrients during pregnancy has been associated with various later-life consequences. Bekdash RA. 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. Angeloni A, Bogdanovic O. Enhancer DNA methylation: implications for gene regulation. Abraham M, Alramadhan S, Iniguez C, Duijts L, Jaddoe VWV, Den Dekker HT, Crozier S, Godfrey KM, Hindmarsh P, Vik T, Jacobsen GW, Hanke W, Sobala W, Devereux G, Turner S. A systematic review of maternal smoking during pregnancy and fetal measurements with meta-analysis. There are many epigenetic actions hot spots along the entire pregnancy process, and it would have been too long and purely didactic to analyze them all in detail. Cassidy FC, Charalambous M. Genomic imprinting, growth and maternal-fetal interactions. 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. Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies. 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]. Pulmonary effects of maternal smoking on the fetus and child: effects on lung development, respiratory morbidities, and life long lung health. One of the mostcommon pregnancy complications worldwide correlated to nutrition is gestational diabetes (GDM). Pathogenic variants in MEGs or the absence of MEG factors are correlated to adverse outcomes, like zygotic cleavage failure, imprinting disorders, and structural birth defects [6264]. Moreover, other EDs have been shown to interact with DNMTs and TETs enzymes, altering their activity in in vitro experiments [157]. WebEpigenetics definition, the study of the process by which genetic information is translated into the substance and behavior of an organism: specifically, the study of the way in Alcohol also induces alterations in the DNA methylome of the hypothalamus, including several differentially methylated regions (DMRs) that could underlie some of the deficits observed in FASD. Kim S-M, Kim J-S. A review of mechanisms of implantation. Lendvai , Deutsch MJ, Plsch T, Ensenauer R. Am J Physiol Endocrinol Metab. MicroRNA-31 is significantly elevated in both human endometrium and serum during the window of implantation: a potential biomarker for optimum receptivity. Tobi EW, Lumey LH, Talens RP, Kremer D, Putter H, Stein AD, Slagboom PE, Heijmans BT. Heerwagen MJ, Miller MR, Barbour LA, Friedman JE. Several association studies have evaluated miRNA expression levels in the receptive and pre-receptive endometrium in fertile women [8083]. Esteller M. Non-coding RNAs in human disease. Genomic methylation of peripheral blood leukocyte DNA: influences of arsenic and folate in Bangladeshi adults. 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 Such a brief but crucial phase represents a window of vulnerability towards interfering maternal and environmental factors (such as chronic metabolic disorders, polycystic ovary syndrome, diet, and teratogen exposure), as highlighted by an ever-increasing number of studies [6871]. Jaenisch R, Bird A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Stage 1: from gametes to embryo-endometrium cross-talk; Stage, MeSH 2019;8:E1559. A better comprehension of the underlying mechanisms and their consequences could therefore improve diagnosis and treatment of human infertility and diseases. Yong HY, Mohd Shariff Z, Mohd Yusof BN, Rejali Z, Tee YYS, Bindels J, van der Beek EM. Regarding substances universally recognized as teratogens, one of the most widespread is valproic acid (VPA). Maternal folic acid supplementation mediates offspring health via DNA methylation. Bridi A, Perecin F, da Silveira JC. Because folate deficiency in early pregnancy is associated with an increased risk of doi: 10.1152/ajpendo.00372.2015. The fetal and infant origins of adult disease. [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. Sex-specific associations between placental leptin promoter DNA methylation and infant neurobehavior. Studies found that miRNA expression profiles of decidualized hESC and control hESC departed from each other. While placental hyperserotonaemia can disrupt early neural development, hyposerotonaemia too appears to impair cognitive, motor, or sensory capacities [118, 124]. Epigenetics - National Institute of Environmental Health Sciences Epigenetic definition, of or relating to epigenesis, or the successive differentiation of undifferentiated cells in an embryo. Mandal C, Halder D, Jung KH, Chai YG. Messerschmidt DM, Knowles BB, Solter D. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. WebAbstract Rapidly growing evidences link maternal lifestyle and prenatal factors with serious health consequences and diseases later in life. 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. But this isn't completely true. In humans, excess amounts of corticotropin releasing hormones (CRH) and cortisol reaching the fetal brain can alter personality and predispose to attention deficits and depressive illness through changes in neurotransmitter activity [9, 73]. Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. During gametogenesis and then again in the early moments after fertilization, mammals undergo a two-step DNA methylation reprogramming that affects more than 80% of the genome. GDM increases the incidence of short-term (i.e., large for gestational age, shoulder dystocia, higher body fat) and long-term complications (i.e., obesity, metabolic syndrome, diabetes mellitus type 2, attention problems, and depression) observed in the offspring [150, 151]. Monoamine Neurotransmitters Control Basic Emotions and Affect Major Depressive Disorders. Ino T. Maternal smoking during pregnancy and offspring obesity: meta-analysis. Altme S, Martinez-Conejero JA, Esteban FJ, Ruiz-Alonso M, Stavreus-Evers A, Horcajadas JA, Salumets A. MicroRNAs miR-30b, miR-30d, and miR-494 regulate human endometrial receptivity. FOIA 113,114 High dose folate supplementation during pregnancy has shown to alter synaptic transmission, lowering the threshold and increasing the susceptibility for seizure in offspring. -, Kurian NK, Modi D. Extracellular vesicle mediated embryo-endometrial cross talk during implantation and in pregnancy. Diabetes and congenital malformations. Homer H, Rice GE, Salomon C. Review: Embryo- and endometrium-derived exosomes and their potential role in assisted reproductive treatments-liquid biopsies for endometrial receptivity. Altered levels of many nutrients (i.e., vitamin B, folic acid, zinc) can increase the risk of developing fetal disorders [134, 135]. Zhao L-Y, Song J, Liu Y, Song C-X, Yi C. Mapping the epigenetic modifications of DNA and RNA. These novel findings suggest that even low levels of smoke exposure during pregnancy may be sufficient to alter DNA methylation of the fetus [177]. It is the comments and import statements in the code base of DNA. Bethesda, MD 20894, Web Policies Cratty MS, Ward HE, Johnson EA, Azzaro AJ, Birkle DL. Expression of imprinted genes in placenta is associated with infant neurobehavioral development. Epigenetics and Pregnancy: Conditional Snapshot or Rolling Event 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. Is there a way to reduce the negative consequences? Recent literature revealed the presence, in the endometrial fluid of both fertile and infertile women, of 12 sncRNAs strongly associated with biological functions related to immune response, extracellular matrix and cell junction, highlighting the different expression patterns in the two subpopulations and suggesting that sncRNA could be used as biomarkers of endometrial receptivity and implantation success [102]. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal-fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. -, Argyraki M, Damdimopoulou P, Chatzimeletiou K, Grimbizis GF, Tarlatzis BC, Syrrou M, Lambropoulos A. In-utero stress and mode of conception: impact on regulation of imprinted genes, fetal development and future health. In the early pregnancy, the brain is extraordinarily plastic, but also exposed to environmental fluctuations which can influence long-term programming. The epigenetic modulation of gene expression begins in the gametes and zygote through genomic imprinting and then continues throughout the whole gestation with changes to the fetal and maternal methyloma and the specific action of the ncRNA system. Epigenetic mechanisms, such as VPA interacts with the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA) and blocks voltage-gated ion channels. Statistical and integrative system-level analysis of DNA methylation data. Casati L, Sendra R, Sibilia V, Celotti F. Endocrine disrupters: the new players able to affect the epigenome. Regulation of the clustered genes is coordinated through short DNA sequences called imprinting control regions (ICRs). Cohort profile: Epigenetics in Pregnancy (EPIPREG) - PLOS MicroRNAs targeting the immunomodulatory HLA-G gene: a new survey searching for microRNAs with potential to regulate HLA-G. Liu W, Niu Z, Li Q, Pang RTK, Chiu PCN, Yeung WS-B. Any adverse factor altering the normal transcription program could therefore perturb the correct methylation patterns [60, 61]. The developing brain tissue requires considerable nutritional intake and it is particularly susceptible to overabundance or insufficiency of specific nutrients and growth factors [108, 110, 111]. Wallace AE, Fraser R, Cartwright JE.