Maternal periconceptional smoking and alcohol consumption and risk for select congenital anomalies. 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. Introduction Gestational diabetes mellitus (GDM), defined as a glucose Best JD, Carey N. The epigenetics of normal pregnancy. 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]. Epigenetics 12 dibya nath 405 views23 slides. Yu S-L, Kim T-H, Han Y-H, Kang Y, Jeong D-U, Lee DC, Kang J, Park S-R. Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid-secretory phases. 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. In fact, neurobehavioral alterations have been related to pre-gestational stress. 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. PMC Brain development; Embryo and fetus development; Epigenetics; Pregnancy; Review; miRNA. 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. Greenberg MVC, Glaser J, Borsos M, Marjou FE, Walter M, Teissandier A, Bourchis D, Transient transcription in the early embryo sets an epigenetic state that programs postnatal growth. 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. VPA is a well-tolerated antiepileptic drug and mood stabilizer that is used for the treatment of epilepsy and other non-psychiatric diseases like Alzheimer, HIV, and cancer [178]. WebEpigenetic: Inherited changes in phenotype or gene expression that are caused by mechanisms other than changes in the underlying DNA sequence (eg, by methylation). Epigenetics in pregnancy Prenatal epigenetics diets play protective roles against Tung EWY, Winn LM. In utero tobacco exposure, even in the absence of fetal growth restriction, may alter the epigenome, contributing to global DNA hypomethylation. As pointed out by many groups, (Dunn et al., 2011; Gapp et al., 2014; Babenko et al., 2015), the maternal epigenetic contribution has been studied primarily during pregnancy, whereas the paternal input has been increasingly attributed to sperm, which has recently been demonstrated to be a crucial purveyor of epigenetic information. 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]. Monk D, Mackay DJG, Eggermann T, Maher ER, Riccio A. Genomic imprinting disorders: lessons on how genome, epigenome and environment interact. Regulation of the clustered genes is coordinated through short DNA sequences called imprinting control regions (ICRs). Epigenetics FOIA Maternal GDM can create different effects like global DNA hypermethylation or alteration of miRNA expressions. While it is known that most human transcripts are not translated, many of them actively participate in essential cellular functions nonetheless. Acetylating, methylating, phosphorylating, and ubiquitinating enzymes act alone or in combination to control chromatin compaction [1922]. See this image and copyright information in PMC. Pilsner JR, Liu X, Ahsan H, Ilievski V, Slavkovich V, Levy D, Factor-Litvak P, Graziano JH, Gamble MV. Unfortunately, smoking during pregnancy is still very widespread, especially in some populations where the level of attention to this teratogen is not so high. Mechanism for stable maintenance of gene expression that involves physically 'marking' DNA or its associated proteins. In male gametes, epigenetic patterns are established soon after the demethylation event has occurred in the primordial germ cells. Mechanisms of implantation: strategies for successful pregnancy. Kurdistani SK, Tavazoie S, Grunstein M. Mapping global histone acetylation patterns to gene expression. Nutritional epigenetics is a rapidly expanding field of research, to L-glutamate being the major excitatory neurotransmitter in the brain. Stewart KR, Veselovska L, Kelsey G. Establishment and functions of DNA methylation in the germline. Estrella et al. To date, the relationship between placental metabolism and epigenetic programming has been especially studied in animals (and only marginally in humans) with particular attention to sex development, as sex differences in epigenetic mechanisms such as DNA methylation have been described across placental development. Peschansky VJ, Wahlestedt C. Non-coding RNAs as direct and indirect modulators of epigenetic regulation. Alabduljabbar S, Zaidan SA, Lakshmanan AP, Terranegra A. Personalized nutrition approach in pregnancy and early life to tackle childhood and adult non-communicable diseases. Associations of existing diabetes, gestational diabetes, and glycosuria with offspring IQ and educational attainment: the Avon Longitudinal Study of Parents and Children. 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]. This review will primarily focus on the causes and consequences of prenatal environment pollution exposure on the epigenome, and the potential protective role of the Federal government websites often end in .gov or .mil. Human endometrial stem cells (hESC) have been decidualized in vitro to explore the effects of decidualization on miRNA expression. 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]. Effects of prenatal exposure to endocrine disruptors and toxic metals on the fetal epigenome. Finally, regarding another known teratogen inducing limb reduction anomalies (5-aza-2-deoxycytidin or 5-aza), recent animal study focused the attention on miR-34 family, concluding that 5-aza and cyclophosphamide are able to activate miR-34 family in p53-independent fashion. [Epigenetics' implication in autism spectrum disorders: A review]. McEvoy CT, Spindel ER. ZAR1 and ZAR2 are required for oocyte meiotic maturation by regulating the maternal transcriptome and mRNA translational activation. Epigenetic Froggatt S, Covey J, Reissland N. Infant neurobehavioural consequences of prenatal cigarette exposure: a systematic review and meta-analysis. Mattick JS, Makunin IV (2006) Non-coding RNA. sharing sensitive information, make sure youre on a federal The lack of nutrients during pregnancy has been associated with various later-life consequences. Gueta K, Molotski N, Gerchikov N, Mor E, Savion S, Fein A, Toder V, Shomron N, Torchinsky A. Teratogen-induced alterations in microRNA-34, microRNA-125b and microRNA-155 expression: correlation with embryonic p53 genotype and limb phenotype. Carrell DT, Hammoud SS. WebWe used to think that a new embryo's epigenome was completely erased and rebuilt from scratch. doi: 10.1152/ajpregu.00310.2010. 8600 Rockville Pike Wallace AE, Fraser R, Cartwright JE. Epigenetics is concerned with this regulation. Cohort profile: Epigenetics in Pregnancy (EPIPREG) - PLOS The site is secure. Wang Y, Liu Q, Tang F, Yan L, Qiao J. Epigenetic regulation and risk factors during the development of human gametes and early embryos. Cold Spring Harb Perspect Biol a040188. 2019 Nov 5;25(6):777-801. doi: 10.1093/humupd/dmz025. Even if there is no specific time point during gestation when alcohol exposure is not accompanied by harmful consequences, the exposure during early embryonic stage is correlated with most severe birth defects [161]. Cells. Many of these transcripts are in fact necessary for proper targeting of histone modifying complexes or participate in the DNA methylation process and genomic imprinting. Any adverse factor altering the normal transcription program could therefore perturb the correct methylation patterns [60, 61]. sharing sensitive information, make sure youre on a federal DNA methylation dynamics in the female germline and maternal-effect mutations that disrupt genomic imprinting. Federal government websites often end in .gov or .mil. What is Epigenetics? DNA methylation profiling of acute chorioamnionitis-associated placentas and fetal membranes: insights into epigenetic variation in spontaneous preterm births. New research suggests that mammary glands retain an 'epigenetic memory' of pregnancy that changes the response to subsequent pregnancies. Both parental and environmental factors (such as nutrition, stress, socioeconomic status and exposure to teratogens and other environmental drivers) have been demonstrated to modulate prenatal development both in the preconception phase and afterwards during the pregnancy, via changes to the DNA methylation patterns (also known as methylome), histone modifications, and/or non-coding RNA (ncRNA) system. The sperm epigenome is well specialized because of its particular requirements in terms of motility and protection against the female reproductive tracts hostile environment, exhibiting a unique pattern of histone modifications that includes both activating and silencing marks in the promoters of genes associated with development [47, 48]; sperm chromatin is highly compacted and organized, and spermatogenesis has been associated with fluctuating level of ncRNAs, particularly endo-siRNAs [49]. Increased placental miR-16 expression is negatively associated with attention score. An official website of the United States government. The neurological condition known as amyotrophic lateral sclerosis (ALS), commonly referred to as Lou Gehrigs disease, or motor neuron disease (MND), is a progressive condition that affects the nerve cells that regulate voluntary muscles [].ALS is still considered one of the rare diseases and its incidence worldwide is 2.75 Further studies are definitely needed to understand the correlation in detail between fetal alcohol spectrum disorder and epigenetic changes [165]. 1 Epigenetics Memory, Learning and BDNF gene expression 2 Epigenetics Overview I. official website and that any information you provide is encrypted 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. Suganuma T, Workman JL. Retis-Resendiz AM, Gonzlez-Garca IN, Len-Jurez M, Camacho-Arroyo I, Cerbn M, Vzquez-Martnez ER. 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. Epigenetic Definition & Meaning | Dictionary.com in pregnancy Histone acetylation generally results in higher gene expression, with rare exceptions [2325]. Messerschmidt DM, Knowles BB, Solter D. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Stress acts also on the amygdala and increases the incidence of anxiogenic and depressive-like behaviors [130]. Zijlmans MAC, Riksen-Walraven JM, de Weerth C. Associations between maternal prenatal cortisol concentrations and child outcomes: a systematic review. Nutrients. Warning JC, McCracken SA, Morris JM. Paquette AG, Lesseur C, Armstrong DA, Koestler DC, Appleton AA, Lester BM, Marsit CJ. Knowledge of the phenomena related to such regulatory mechanisms carries a huge relevance in both physiology and pathophysiology. Fetal and placental size and risk of hypertension in adult life. Epigenetics in Pregnancy (EPIPREG) is a population-based sample with the aim to study associations between DNA-methylation in pregnancy and Hot spots of epigenetic action. 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. Gil-Ibez P, Bernal J, Morte B. Thyroid hormone regulation of gene expression in primary cerebrocortical cells: role of thyroid hormone receptor subtypes and interactions with retinoic acid and glucocorticoids. Opposing roles of H3- and H4-acetylation in the regulation of nucleosome structurea FRET study. 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. Children prenatally exposed to moderate-high levels of alcohol showed increased DNA methylation of stress regulatory genes proopiomelanocortin (POMC) and period 2 (PER2) resulting in increased levels of stress hormone cortisol and adrenocorticotropic hormone (ACTH), compared to controls. Jirtle: BPA exposure during pregnancy increases the incidence of yellow offspring, but it does not result in all of the offspring having a yellow coat color and becoming obese. Distinct communication patterns of trophoblastic miRNA among the maternal-placental-fetal compartments. Received 2021 Nov 22; Accepted 2022 Mar 1. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternalfetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Bekdash RA. Extravillous trophoblast and decidual natural killer cells: a remodelling partnership. doi: 10.1093/humupd/dmz025. Epigenetics and Diet in Pregnancy Marian C. Aldhous, Kahyee Hor & Rebecca M. Reynolds Chapter First Online: 12 May 2018 2027 Accesses 2 Citations 1 [3741]. epigenetic Elbracht M, Mackay D, Begemann M, Kagan KO, Eggermann T. Disturbed genomic imprinting and its relevance for human reproduction: causes and clinical consequences. Early life nutrition and mental health: the role of DNA methylation. Genomic methylation of peripheral blood leukocyte DNA: influences of arsenic and folate in Bangladeshi adults. The first 1000days, which start from pre-conception until approximately two years of age, are considered the period during which early nutrition, thanks to its influence on epigenetic changes [133], can play a key role in developmental programming and can influence the individual susceptibility to diseases later in the life (cardiovascular diseases, obesity, diabetes, and other chronic condition). On the other hand, poly-ubiquitination flags proteins as a mark for degradation or activation in some signaling pathways [22, 30]. The secretion of exosomes from the apical surface of endometrial glands, which was confirmed by electron microscopy, is consistent with the existence of endosomes in epithelial cells and of embryo-derived extracellular vesicles [100]. Histone phosphorylation is regulated by kinases (that bind phosphate groups) and phosphatases (which detach the phosphates) and has at least three activities: DNA damage repair, control of chromatin compaction connected with mitosis and meiosis, and modulation of transcriptional function [28, 29]. MicroRNA-31 is significantly elevated in both human endometrium and serum during the window of implantation: a potential biomarker for optimum receptivity. Self-reported pregnancy exposures and placental DNA methylation in the MARBLES prospective autism sibling study. For instance, 5-HT promotes various processes during fetal brain growth: neuronal migration, cell division, and differentiation and synaptogenesis. Cannarella R, Crafa A, Condorelli RA, Mongio LM, La Vignera S, Calogero AE. Sperm epigenetic abnormalities are associated with infertility, reduced embryogenesis capability, and alterations in early embryo development [50, 51], and the study of sperm epigenome is being evaluated as a potential diagnostic tool for idiopathic recurrent pregnancy loss and infertility [47, 5055]. But this isn't completely true. While the cells 2020; other pictures obtained by Vecteezy.com. Daniela Zuccarello and Ugo Sorrentino contributed equally to this work. and transmitted securely. Xia W, Xie W. Rebooting the epigenomes during mammalian early embryogenesis. fetal epigenetics found throughout pregnancy 10.18632/aging.102864. 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]. Regulation of nutrient transport across the placenta. Embryoepithelium interactions during implantation at a glance. Early life nutrition can modulate the epigenome through different mechanisms: the change in the structure of chromatin through histone modifications and the supply ofmethyl donors (i.e., methionine, choline, folate), the activity of DNA methyltransferases, and of specific transcription factors. Garry D. Lasaga 4K views38 slides. Keywords: 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. 2017 Aug;43(4):374-381. doi: 10.1016/j.encep.2016.07.007. 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. Epub 2016 Feb 9. 2023 Apr 17;15(8):1933. doi: 10.3390/nu15081933. The https:// ensures that you are connecting to the The addition of a methyl group to the fifth carbon of the pyrimidine cytosine ring determines long-term silencing in processes such as genomic imprinting, tissue-specific regulation of gene expression, X-chromosome inactivation, and silencing of repetitive DNA elements. This mechanism of action is known to result in teratogenicity and cell toxicity, causing a wide range of fetal alterations, both malformative and neurological. Unauthorized use of these marks is strictly prohibited. Among the organogenetic processes that occur during fetal development, one of the most critically affected by maternal, environmental, and epigenetic factors is brain development. Rong Y, Ji S-Y, Zhu Y-Z, Wu Y-W, Shen L, Fan H-Y. Regarding substances universally recognized as teratogens, one of the most widespread is valproic acid (VPA). There is also growing evidence that variants in the maternal genome affecting the imprinting status of the oocyte could cause MLID [44]. These effects are regulated by alteration in theepigenetic programming. 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]. Lifestyle, pregnancy and epigenetic effects - PubMed 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. A key implication of the ongoing research is that dietitians should encourage clients to take diet seriously both during pregnancy and before conception. 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. Also, members of the miR-1792 cluster (including miR-17, miR-18a, miR-19a, miR-20a, miR-19b-1, and miR-92a-1) are upregulated at the implantation sites of the receptive uterus in humans. It is Bridi A, Perecin F, da Silveira JC. Maternal effect genes: update and review of evidence for a link with birth defects. 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. This site needs JavaScript to work properly. The brain is an organ that consumes a lot of energy and absorbs a massive quantity of maternal resources during its growth and evolution. Moreover, some nutrients, such as vitamin B and polyphenols, can modulate the function of the methylation enzymes [140]. Lee TW, Katz DJ. MicroRNA and embryo implantation. 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]. 1990;301:1111. doi: 10.1136/bmj.301.6761.1111. 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. The site is secure. 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]. Statistical and integrative system-level analysis of DNA methylation data. Biomedical research is currently focused on identifying placental biomarkers useful for identifying fetuses at risk of developing neurodevelopmental disorders, for starting an early clinical management [118, 125129]. Knfler M, Haider S, Saleh L, Pollheimer J, Gamage TKJB, James J. in pregnancy Epigenetics in fertilization and preimplantation embryo development. Methylation of CpG islands located in the promoter region of a gene usually inhibits the transcription of that gene due to binding of methyl-CpG binding proteins, as they recruit chromatin remodelers, histone deacetylases, and methylases to the promoter of the gene, thereby blocking transcription [17, 18]. Skvortsova K, Iovino N, Bogdanovi O. Hanna CW, Kelsey G. Genomic imprinting beyond DNA methylation: a role for maternal histones. He Y, Chen J, Zhu L-H, Hua L-L, Ke F-F. Maternal smoking during pregnancy and ADHD: results from a systematic review and meta-analysis of prospective cohort studies. Rivera RM, Ross JW. Epigenetic definition, of or relating to epigenesis, or the successive differentiation of undifferentiated cells in an embryo. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Rossetto D, Avvakumov N, Ct J. Histone phosphorylation: a chromatin modification involved in diverse nuclear events. 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. Extensive epidemiological studies have Keen CL, Uriu-Adams JY, Skalny A, Grabeklis A, Grabeklis S, Green K, Yevtushok L, Wertelecki WW, Chambers CD. Cigarette smoke creates alterations in DNA methylation of cord blood and placenta, histone modifications, and miRNA expression. Inter- and transgenerational epigenetic inheritance: evidence in Because folate deficiency in early pregnancy is associated with an increased risk of Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. Epigenetics epigenetic maternal complications fetal complications Author Information Show + 1. Gansen A, Tth K, Schwarz N, Langowski J. 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. New Perspectives on the Associations between Blood Fatty Acids, Growth Parameters, and Cognitive Development in Global Child Populations. Xu R, Li C, Liu X, Gao S. Insights into epigenetic patterns in mammalian early embryos. 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). Another type of epigenetic modification that can occur in the placenta and may regulate infant neurobehavioral patterns is represented by the alterations in miRNA expression profiles. Agricola E, Verdone L, Di Mauro E, Caserta M. H4 acetylation does not replace H3 acetylation in chromatin remodelling and transcription activation of Adr1-dependent genes. FOIA High levels of vitamin B12 in the maternal blood was correlated with the reduction in the total level of DNA methylation of the neonate, while the elevated concentration of serum vitamin B12 in the new-born correlated with decrease methylation levels of the insulin-like growth factor-binding protein3 (IGFBP-3) gene, which is one of the candidate genes for intrauterine growth [142]. Anvar Z, Chakchouk I, Demond H, Sharif M, Kelsey G, Van den Veyver IB. This phenomenon, that allows parent-oforigin specific gene expression, is defined as genomic imprinting. Oster M, Nuchchanart W, Trakooljul N, Murni E, Zeyner A, Wirthgen E, Hoeflich A, Ponsuksili S, Wimmers K. Methylating micronutrient supplementation during pregnancy influences foetal hepatic gene expression and IGF signalling and increases foetal weight. Accessibility Expression arrays demonstrated that embryos treated with miR-30d exhibited increased expression of ten genes, including those encoding adhesion molecules such as ITGB3 (Integrin Subunit Beta 3), ITGA7 (Integrin Subunit Alpha 7), and CDH5 (Cadherin 5) [85]. Glaser J, Mundlos S (2021) 3D or not 3D: shaping the genome during development. Coronary heart disease after prenatal exposure to the Dutch famine, 194445. The .gov means its official. 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]. Mishra A, Ashary N, Sharma R, Modi D. Extracellular vesicles in embryo implantation and disorders of the endometrium. 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. Sex-specific associations between placental leptin promoter DNA methylation and infant neurobehavior. A balancing act: mechanisms by which the fetus avoids rejection by the maternal immune system.
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