Epigenetic regulation of placental endocrine lineages and complications of pregnancy

2013 ◽  
Vol 41 (3) ◽  
pp. 701-709 ◽  
Author(s):  
Rosalind M. John
Keyword(s):  
Genomic Imprinting ◽  
Giant Cells ◽  
In Utero ◽  
Imprinted Genes ◽  
Endocrine Organ ◽  
Fetal Physiology ◽  
Trophoblast Giant Cells ◽  
In Utero Development ◽  
Genetic Conflicts

A defining feature of mammals is the development in utero of the fetus supported by the constant flow of nutrients from the mother obtained via a specialized organ: the placenta. The placenta is also a major endocrine organ that synthesizes vast quantities of hormones and cytokines to instruct both maternal and fetal physiology. Nearly 20 years ago, David Haig and colleagues proposed that placental hormones were likely targets of the epigenetic process of genomic imprinting in response to the genetic conflicts imposed by in utero development [Haig (1993) Q. Rev. Biol. 68, 495–532]. There are two simple mechanisms through which genomic imprinting could regulate placental hormones. First, imprints could directly switch on or off alleles of specific genes. Secondly, imprinted genes could alter the expression of placental hormones by regulating the development of placental endocrine lineages. In mice, the placental hormones are synthesized in the trophoblast giant cells and spongiotrophoblast cells of the mature placenta. In the present article, I review the functional role of imprinted genes in regulating these endocrine lineages, which lends support to Haig's original hypothesis. I also discuss how imprinting defects in the placenta may adversely affect the health of the fetus and its mother during pregnancy and beyond.

scholarly journals Genomic imprinting, action, and interaction of maternal and fetal genomes

2014 ◽  
Vol 112 (22) ◽  
pp. 6834-6840 ◽  
Author(s):  
Eric B. Keverne
Keyword(s):  
Genomic Imprinting ◽  
Purifying Selection ◽  
Gene Families ◽  
In Utero ◽  
Imprinted Genes ◽  
Intrauterine Development ◽  
Leading Role ◽  
Expression Of Genes ◽  
In Utero Development ◽  
And Behavior

Mammalian viviparity (intrauterine development of the fetus) introduced a new dimension to brain development, with the fetal hypothalamus and fetal placenta developing at a time when the fetal placenta engages hypothalamic structures of the maternal generation. Such transgenerational interactions provide a basis for ensuring optimal maternalism in the next generation. This success has depended on genomic imprinting and a biased role of the matriline. Maternal methylation imprints determine parent of origin expression of genes fundamental to both placental and hypothalamic development. The matriline takes a further leading role for transgenerational reprogramming of these imprints. Developmental errors are minimized by the tight control that imprinted genes have on regulation of downstream evolutionary expanded gene families important for placental and hypothalamic development. Imprinted genes themselves have undergone purifying selection, providing a framework of stability for in utero development with most growth variance occurring postnatally. Mothers, not fathers, take the lead in the endocrinological and behavior adaptations that nurture, feed, and protect the infant. In utero coadaptive development of the placenta and hypothalamus has thus required a concomitant development to ensure male masculinization. Only placental male mammals evolved the sex determining SRY, which activates Sox9 for testes formation. SRY is a hybrid gene of Dgcr8 expressed in the developing placenta and Sox3 expressed in hypothalamic development. This hybridization of genes that take their origin from the placenta and hypothalamus has enabled critical in utero timing for the development of fetal Leydig cells, and hence testosterone production for hypothalamic masculinization.

scholarly journals Genomic imprinting in germ cells: imprints are under control

Reproduction ◽  
2010 ◽  
Vol 140 (3) ◽  
pp. 411-423 ◽  
Author(s):  
Philippe Arnaud
Keyword(s):  
Dna Methylation ◽  
Genomic Imprinting ◽  
Germ Cells ◽  
Imprinted Genes ◽  
Regulatory Sequences ◽  
Sequence Specificity ◽  
Maternal Allele ◽  
Primary Sequence ◽  
Chromatin Configuration

The cis-acting regulatory sequences of imprinted gene loci, called imprinting control regions (ICRs), acquire specific imprint marks in germ cells, including DNA methylation. These epigenetic imprints ensure that imprinted genes are expressed exclusively from either the paternal or the maternal allele in offspring. The last few years have witnessed a rapid increase in studies on how and when ICRs become marked by and subsequently maintain such epigenetic modifications. These novel findings are summarised in this review, which focuses on the germline acquisition of DNA methylation imprints and particularly on the combined role of primary sequence specificity, chromatin configuration, non-histone proteins and transcriptional events.

scholarly journals Aberrations of Genomic Imprinting in Glioblastoma Formation

2021 ◽  
Vol 11 ◽  
Author(s):  
Anna Lozano-Ureña ◽  
Esteban Jiménez-Villalba ◽  
Alejandro Pinedo-Serrano ◽  
Antonio Jordán-Pla ◽  
Martina Kirstein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genomic Imprinting ◽  
Current Knowledge ◽  
Small Population ◽  
Parental Origin ◽  
Imprinted Genes ◽  
Glioma Stem Cells ◽  
Epigenetic Changes ◽  
Human Gbm

In human glioblastoma (GBM), the presence of a small population of cells with stem cell characteristics, the glioma stem cells (GSCs), has been described. These cells have GBM potential and are responsible for the origin of the tumors. However, whether GSCs originate from normal neural stem cells (NSCs) as a consequence of genetic and epigenetic changes and/or dedifferentiation from somatic cells remains to be investigated. Genomic imprinting is an epigenetic marking process that causes genes to be expressed depending on their parental origin. The dysregulation of the imprinting pattern or the loss of genomic imprinting (LOI) have been described in different tumors including GBM, being one of the earliest and most common events that occurs in human cancers. Here we have gathered the current knowledge of the role of imprinted genes in normal NSCs function and how the imprinting process is altered in human GBM. We also review the changes at particular imprinted loci that might be involved in the development of the tumor. Understanding the mechanistic similarities in the regulation of genomic imprinting between normal NSCs and GBM cells will be helpful to identify molecular players that might be involved in the development of human GBM.

scholarly journals Plac1 Expression Pattern at the Mouse Fetomaternal Interface and Involvement in Trophoblast Differentiation

2017 ◽  
Vol 43 (5) ◽  
pp. 2001-2009 ◽  
Author(s):  
Yanli Gu ◽  
Junhui Wan ◽  
Lv Yao ◽  
Nan-Ni Peng ◽  
Wen-Lin Chang
Keyword(s):  
Expression Pattern ◽  
Giant Cells ◽  
Specific Gene ◽  
Trophoblast Differentiation ◽  
Spatiotemporal Expression ◽  
Trophoblast Stem Cell ◽  
Trophoblast Giant Cells ◽  
Ectoplacental Cone

Background/Aims: It is well known that Plac1 is a placenta-specific gene; however, its spatiotemporal expression pattern and exact role at t h e mouse fetomaternal interface r e m a i n s unclear. Methods: In situ hybridization (ISH) was used to localize the Plac1 mRNA at the mouse fetomaternal interface. A trophoblast stem cell (TS) differentiation model with Plac1 shRNA-overexpressing lentivirus was employed to investigate the possible role of Plac1 in placentation. Real-time RT-PCR was used to detect changes in gene expression. Results: Plac1 was exclusively expressed in the ectoplacental cone (EPC) as well as in 8.5 and 9.5 days post-coitum (dpc) embryos. Subsequently, Plac1 expression was abundant in the spongiotrophoblast layer and moderately in the labyrinth layer until 13.5 dpc, and declined thereafter. Interestingly, Plac1 was also expressed by secondary trophoblast giant cells and glycogen trophoblast cells, but not in primary trophoblast giant cells. Plac1 transcription was increased during the TS differentiation (P < 0.01), and knockdown of Plac1 significantly impaired TS differentiation. Conclusion: Plac1 is abundantly expressed at the fetomaternal interface and in all trophoblast subtypes except in primary trophoblast giant cells. Plac1 knockdown retarded the progress of TS differentiation, indicating that Plac1 is necessary for normal trophoblast differentiation into various trophoblast subpopulations.

scholarly journals Divergence among rice cultivars reveals roles for transposition and epimutation in ongoing evolution of genomic imprinting

2021 ◽  
Vol 118 (29) ◽  
pp. e2104445118
Author(s):  
Jessica A. Rodrigues ◽  
Ping-Hung Hsieh ◽  
Deling Ruan ◽  
Toshiro Nishimura ◽  
Manoj K. Sharma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Genomic Imprinting ◽  
Small Rnas ◽  
Imprinted Genes ◽  
Dna Hypomethylation ◽  
Transcription Start ◽  
Specific Expression ◽  
Parent Of Origin

Parent-of-origin–dependent gene expression in mammals and flowering plants results from differing chromatin imprints (genomic imprinting) between maternally and paternally inherited alleles. Imprinted gene expression in the endosperm of seeds is associated with localized hypomethylation of maternally but not paternally inherited DNA, with certain small RNAs also displaying parent-of-origin–specific expression. To understand the evolution of imprinting mechanisms in Oryza sativa (rice), we analyzed imprinting divergence among four cultivars that span both japonica and indica subspecies: Nipponbare, Kitaake, 93-11, and IR64. Most imprinted genes are imprinted across cultivars and enriched for functions in chromatin and transcriptional regulation, development, and signaling. However, 4 to 11% of imprinted genes display divergent imprinting. Analyses of DNA methylation and small RNAs revealed that endosperm-specific 24-nt small RNA–producing loci show weak RNA-directed DNA methylation, frequently overlap genes, and are imprinted four times more often than genes. However, imprinting divergence most often correlated with local DNA methylation epimutations (9 of 17 assessable loci), which were largely stable within subspecies. Small insertion/deletion events and transposable element insertions accompanied 4 of the 9 locally epimutated loci and associated with imprinting divergence at another 4 of the remaining 8 loci. Correlating epigenetic and genetic variation occurred at key regulatory regions—the promoter and transcription start site of maternally biased genes, and the promoter and gene body of paternally biased genes. Our results reinforce models for the role of maternal-specific DNA hypomethylation in imprinting of both maternally and paternally biased genes, and highlight the role of transposition and epimutation in rice imprinting evolution.

scholarly journals Use of the progesterone (P4) receptor antagonist aglepristone to characterize the role of P4 withdrawal for parturition and placental release in cows

Reproduction ◽  
2010 ◽  
Vol 140 (4) ◽  
pp. 623-632 ◽  
Author(s):  
Sima Shenavai ◽  
Bernd Hoffmann ◽  
Marc Dilly ◽  
Christiane Pfarrer ◽  
Gözde R Özalp ◽  
...  
Keyword(s):  
Cesarean Section ◽  
Receptor Antagonist ◽  
Tissue Remodeling ◽  
Giant Cells ◽  
Normal Term ◽  
Estrogen Synthesis ◽  
Placental Membranes ◽  
Limited Spectrum ◽  
Trophoblast Giant Cells

In late pregnant cows, progesterone (P4) is mainly of luteal origin. However, the trophoblast may provide high local P4concentrations in the uterus. To test for the importance of a complete P4withdrawal for parturition-related processes and placental release, the P4receptor (PGR) blocker aglepristone (Ap) was administered to three cows on days 270 and 271 of pregnancy. A complete opening of the cervix was observed 46.5±7.3 h after the start of treatment. However, expulsion of the calves was impaired obviously because of insufficient myometrial activity, and placental membranes were retained for at least 10 days. Measurement of P4concentrations indicated that PGR blockage induced luteolysis. To investigate the role of P4withdrawal for the prepartal tissue remodeling of the placentomes, the caruncular epithelium was evaluated by morphometry, and the percentage of trophoblast giant cells (TGCs) relative to the total number of trophoblast cells were assessed. Caruncular epithelium in Ap-treated cows (D272+Ap) was immature (30.5±3.3%) and not different from untreated controls (elected cesarean section (CS) on day 272; D272-CS; 31.5±1.4%), whereas it was significantly reduced at normal term (D280.5±1.3; 21.0±6.1%;P=0.011). Correspondingly, the percentage of TGCs were 20.1±1.4 in D272+Ap, 22.1±4.8 in D272-CS, and 9.8±3.9 at term (P=0.001). No effect was detected on placental estrogen synthesis. The results showed that in late pregnant cows, P4withdrawal only induces a limited spectrum of the processes related to normal parturition and is not a crucial factor for the prepartal tissue remodeling in placentomes and the timely release of the placenta.

scholarly journals In-utero stress and mode of conception: impact on regulation of imprinted genes, fetal development and future health

2019 ◽  
Vol 25 (6) ◽  
pp. 777-801 ◽  
Author(s):  
Maria Argyraki ◽  
Pauliina Damdimopoulou ◽  
Katerina Chatzimeletiou ◽  
Grigoris F Grimbizis ◽  
Basil C Tarlatzis ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Psychological Stress ◽  
Genomic Imprinting ◽  
Fetal Growth ◽  
Fetal Development ◽  
Environmental Chemicals ◽  
Imprinted Genes ◽  
Epigenetic Patterns

AbstractBACKGROUNDGenomic imprinting is an epigenetic gene regulatory mechanism; disruption of this process during early embryonic development can have major consequences on both fetal and placental development. The periconceptional period and intrauterine life are crucial for determining long-term susceptibility to diseases. Treatments and procedures in assisted reproductive technologies (ART) and adverse in-utero environments may modify the methylation levels of genomic imprinting regions, including insulin-like growth factor 2 (IGF2)/H19, mesoderm-specific transcript (MEST), and paternally expressed gene 10 (PEG10), affecting the development of the fetus. ART, maternal psychological stress, and gestational exposures to chemicals are common stressors suspected to alter global epigenetic patterns including imprinted genes.OBJECTIVE AND RATIONALEOur objective is to highlight the effect of conception mode and maternal psychological stress on fetal development. Specifically, we monitor fetal programming, regulation of imprinted genes, fetal growth, and long-term disease risk, using the imprinted genes IGF2/H19, MEST, and PEG10 as examples. The possible role of environmental chemicals in genomic imprinting is also discussed.SEARCH METHODSA PubMed search of articles published mostly from 2005 to 2019 was conducted using search terms IGF2/H19, MEST, PEG10, imprinted genes, DNA methylation, gene expression, and imprinting disorders (IDs). Studies focusing on maternal prenatal stress, psychological well-being, environmental chemicals, ART, and placental/fetal development were evaluated and included in this review.OUTCOMESIGF2/H19, MEST, and PEG10 imprinted genes have a broad developmental effect on fetal growth and birth weight variation. Their disruption is linked to pregnancy complications, metabolic disorders, cognitive impairment, and cancer. Adverse early environment has a major impact on the developing fetus, affecting mostly growth, the structure, and subsequent function of the hypothalamic–pituitary–adrenal axis and neurodevelopment. Extensive evidence suggests that the gestational environment has an impact on epigenetic patterns including imprinting, which can lead to adverse long-term outcomes in the offspring. Environmental stressors such as maternal prenatal psychological stress have been found to associate with altered DNA methylation patterns in placenta and to affect fetal development. Studies conducted during the past decades have suggested that ART pregnancies are at a higher risk for a number of complications such as birth defects and IDs. ART procedures involve multiple steps that are conducted during critical windows for imprinting establishment and maintenance, necessitating long-term evaluation of children conceived through ART. Exposure to environmental chemicals can affect placental imprinting and fetal growth both in humans and in experimental animals. Therefore, their role in imprinting should be better elucidated, considering the ubiquitous exposure to these chemicals.WIDER IMPLICATIONSDysregulation of imprinted genes is a plausible mechanism linking stressors such as maternal psychological stress, conception using ART, and chemical exposures with fetal growth. It is expected that a greater understanding of the role of imprinted genes and their regulation in fetal development will provide insights for clinical prevention and management of growth and IDs. In a broader context, evidence connecting impaired imprinted gene function to common diseases such as cancer is increasing. This implies early regulation of imprinting may enable control of long-term human health, reducing the burden of disease in the population in years to come.

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