scholarly journals Effects of Plasma Choline Concentrations on Placental Development and Fetal Growth, With Potential Mechanistic Roles of Imprinted Genes

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 755-755
Author(s):  
Olivia Gutherz ◽  
Jia Chen ◽  
Qian Li ◽  
Maya Deyssenroth ◽  
Neil Dodge ◽  
...  
Keyword(s):  
Gene Expression ◽  
Drug Use ◽  
Fetal Growth ◽  
Regression Models ◽  
Alcohol Exposure ◽  
Interaction Effects ◽  
Placental Weight ◽  
Imprinted Genes ◽  
Placental Development ◽  
Imprinted Gene

Abstract Objectives Imprinted genes are epigenetically regulated and play critical roles in placental development and fetal growth. We aimed to examine (1) the impact of maternal one-carbon (methyl donor) nutrition on placental imprinted gene expression, placental development, and fetal growth; (2) whether imprinted gene expression alterations mediate effects of one-carbon nutrition on placental development and fetal growth; (3) interaction effects between one-carbon nutrients and imprinted genes in placental development and fetal growth. Methods Histopathology and expression of 109 imprinted genes (Nanostring) were assessed in placentas from 101 women recruited at initiation of antenatal care in a prospective cohort study examining developmental effects of prenatal alcohol exposure in South Africa. Women were interviewed prenatally about demographics, alcohol, smoking, and drug use, and erythrocyte folate, serum vitamin B12, and plasma choline concentrations were assayed at recruitment. Infant weight and height were assessed at age 2 wk. Results In limma tests, women with plasma choline concentrations below the median had lower placental expression of EPS15, IGF2R, LINC00657, SGCE, ZC3H12C, and ZNF264 than women above the median (p < .05, FDR < .10). In regression models adjusted for potential confounders (maternal age, gravidity, education, alcohol and drug use), plasma choline (μM) was associated with larger placental weight (g) (B = 14.0(1.9, 26.2)) and reduced maternal vascular underperfusion (MVU) prevalence (B = −.07(−.12, −.02). In causal inference analyses, there were trends for mediation of the relation between choline and MVU by decreased LINC00657, ZC3H12C, and ZNF264 expression. In regression models examining plasma choline X imprinted gene expression interaction effects, choline modified relations of EPS15, ZC3H12C, and ZNF264 to placental weight and fetal growth. Conclusions Maternal plasma choline was associated with decreased placental expression of 6 imprinted genes, 3 of which may mediate effects of choline on placental development. Choline modified effects of 3 genes on placental and fetal growth. These findings suggest maternal choline status may impact placental and fetal development, with imprinted genes playing mechanistic roles. Funding Sources NIH/NIAAA; Lycaki-Young Fund.

scholarly journals Placental imprinted gene expression mediates the effects of maternal psychosocial stress during pregnancy on fetal growth

2019 ◽  
Vol 10 (02) ◽  
pp. 196-205
Author(s):  
L. Lambertini ◽  
Q. Li ◽  
Y. Ma ◽  
W. Zhang ◽  
K. Hao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fetal Growth ◽  
Psychosocial Stress ◽  
Imprinted Genes ◽  
Economic Determinants ◽  
Imprinted Gene ◽  
Infant Gender ◽  
Maternal Resources ◽  
Gestational Age At Birth ◽  
Lower Birthweight

AbstractImprinted genes uniquely drive and support fetoplacental growth by controlling the allocation of maternal resources to the fetus and affecting the newborn’s growth. We previously showed that alterations of the placental imprinted gene expression are associated with suboptimal perinatal growth and respond to environmental stimuli including socio-economic determinants. At the same time, maternal psychosocial stress during pregnancy (MPSP) has been shown to affect fetal growth. Here, we set out to test the hypothesis that placental imprinted gene expression mediates the effects of MPSP on fetal growth in a well-characterized birth cohort, the Stress in Pregnancy (SIP) Study. We observed that mothers experiencing high MPSP deliver infants with lower birthweight (P=0.047). Among the 109 imprinted genes tested, we detected panels of placental imprinted gene expression of 23 imprinted genes associated with MPSP and 26 with birthweight. Among these genes, five imprinted genes (CPXM2, glucosidase alpha acid (GAA), GPR1, SH3 and multiple ankyrin repeat domains 2 (SHANK2) and THSD7A) were common to the two panels. In multivariate analyses, controlling for maternal age and education and gestational age at birth and infant gender, two genes, GAA and SHANK2, each showed a 22% mediation of MPSP on fetal growth. These data provide new insights into the role that imprinted genes play in translating the maternal stress message into a fetoplacental growth pattern.

scholarly journals Differences in Placental Imprinted Gene Expression across Preeclamptic and Non-Preeclamptic Pregnancies

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1146
Author(s):  
Maya A. Deyssenroth ◽  
Qian Li ◽  
Carlos Escudero ◽  
Leslie Myatt ◽  
Jia Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fetal Growth ◽  
Pregnancy Complications ◽  
Fetal Growth Restriction ◽  
Late Onset ◽  
Critical Role ◽  
Growth Restriction ◽  
Imprinted Genes ◽  
Imprinted Gene ◽  
Expression Levels

Preeclampsia is a multi-systemic syndrome that presents in approximately 5% of pregnancies worldwide and is associated with a range of subsequent postpartum and postnatal outcomes, including fetal growth restriction. As the placenta plays a critical role in the development of preeclampsia, surveying genomic features of the placenta, including expression of imprinted genes, may reveal molecular markers that can further refine subtypes to aid targeted disease management. In this study, we conducted a comprehensive survey of placental imprinted gene expression across early and late onset preeclampsia cases and preterm and term normotensive controls. Placentas were collected at delivery from women recruited at the Magee-Womens Hospital prenatal clinics, and expression levels were profiled across 109 imprinted genes. We observed downregulation of placental Mesoderm-specific transcript (MEST) and Necdin (NDN) gene expression levels (false discovery rate (FDR) < 0.05) among early onset preeclampsia cases compared to preterm controls. No differences in placental imprinted gene expression were observed between late onset preeclampsia cases and term controls. While few studies have linked NDN to pregnancy complications, reductions in MEST expression levels, as observed in our study, are consistently reported in the literature in relation to various pregnancy complications, including fetal growth restriction, suggesting a potential role for placental MEST expression as a biosensor of an adverse in utero environment.

scholarly journals Associations between imprinted gene expression in the placenta, human fetal growth and preeclampsia

2017 ◽  
Vol 13 (11) ◽  
pp. 20170643 ◽  
Author(s):  
Julian K. Christians ◽  
Katherine Leavey ◽  
Brian J. Cox
Keyword(s):  
Gene Expression ◽  
Genomic Imprinting ◽  
Fetal Growth ◽  
Placental Insufficiency ◽  
Imprinted Genes ◽  
Nutrient Allocation ◽  
Imprinted Gene ◽  
Expression Levels ◽  
Kinship Theory ◽  
Coordinated Regulation

Genomic imprinting is essential for normal placental and fetal growth. One theory to explain the evolution of imprinting is the kinship theory (KT), which predicts that genes that are paternally expressed will promote fetal growth, whereas maternally expressed genes will suppress growth. We investigated the expression of imprinted genes using microarray measurements of expression in term placentae. Correlations between birthweight and the expression levels of imprinted genes were more significant than for non-imprinted genes, but did not tend to be positive for paternally expressed genes and negative for maternally expressed genes. Imprinted genes were more dysregulated in preeclampsia (a disorder associated with placental insufficiency) than randomly selected genes, and we observed an excess of patterns of dysregulation in preeclampsia that would be expected to reduce nutrient allocation to the fetus, given the predictions of the KT. However, we found no evidence of coordinated regulation among these imprinted genes. A few imprinted genes have previously been shown to be associated with fetal growth and preeclampsia, and our results indicate that this is true for a broader set of imprinted genes.

scholarly journals Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3

2016 ◽  
Vol 46 (14) ◽  
pp. 2999-3011 ◽  
Author(s):  
A. B. Janssen ◽  
L. E. Capron ◽  
K. O'Donnell ◽  
S. J. Tunster ◽  
P. G. Ramchandani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Maternal Depression ◽  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Growth Restriction ◽  
Prenatal Depression ◽  
Placental Lactogen ◽  
Maternal Behaviour ◽  
Imprinted Genes ◽  
Neurodevelopmental Outcomes

BackgroundMaternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression.MethodA diagnosis of depression during pregnancy was recorded from Manchester cohort participants’ medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression.ResultsIn a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively).ConclusionsThis study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.

scholarly journals Early prenatal alcohol exposure alters imprinted gene expression in placenta and embryo in a mouse model

PLoS ONE ◽  
2018 ◽  
Vol 13 (5) ◽  
pp. e0197461 ◽  
Author(s):  
Heidi Marjonen ◽  
Mia Toivonen ◽  
Laura Lahti ◽  
Nina Kaminen-Ahola
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Imprinted Gene ◽  
Prenatal Alcohol

scholarly journals Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Basilia Acurzio ◽  
Ankit Verma ◽  
Alessia Polito ◽  
Carlo Giaccari ◽  
Francesco Cecere ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neural Differentiation ◽  
Embryonic Stem ◽  
Imprinted Genes ◽  
Wild Type ◽  
Mouse Escs ◽  
Biallelic Expression ◽  
Imprinted Gene ◽  
Expression Levels ◽  
Mutant Cells

AbstractZFP57 is required to maintain the germline-marked differential methylation at imprinting control regions (ICRs) in mouse embryonic stem cells (ESCs). Although DNA methylation has a key role in genomic imprinting, several imprinted genes are controlled by different mechanisms, and a comprehensive study of the relationship between DMR methylation and imprinted gene expression is lacking. To address the latter issue, we differentiated wild-type and Zfp57-/- hybrid mouse ESCs into neural precursor cells (NPCs) and evaluated allelic expression of imprinted genes. In mutant NPCs, we observed a reduction of allelic bias of all the 32 genes that were imprinted in wild-type cells, demonstrating that ZFP57-dependent methylation is required for maintaining or acquiring imprinted gene expression during differentiation. Analysis of expression levels showed that imprinted genes expressed from the non-methylated chromosome were generally up-regulated, and those expressed from the methylated chromosome were down-regulated in mutant cells. However, expression levels of several imprinted genes acquiring biallelic expression were not affected, suggesting the existence of compensatory mechanisms that control their RNA level. Since neural differentiation was partially impaired in Zfp57-mutant cells, this study also indicates that imprinted genes and/or non-imprinted ZFP57-target genes are required for proper neurogenesis in cultured ESCs.

scholarly journals Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation

2019 ◽  
Vol 2 (2) ◽  
pp. e201800252 ◽  
Author(s):  
Alexander M Tseng ◽  
Amanda H Mahnke ◽  
Alan B Wells ◽  
Nihal A Salem ◽  
Andrea M Allan ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Fetal Growth Restriction ◽  
Epithelial Mesenchymal Transition ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Growth Restriction ◽  
Circulating Mirnas ◽  
Placental Development ◽  
Mesenchymal Transition ◽  
Pregnant Mice

Prenatal alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, although the linking causal mechanisms are unclear. We previously identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) that predicted infant growth deficits following PAE. Here, we investigated whether theseHEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial–mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and thatHEamiRNAs collectively, but not individually, mediate placental EMT inhibition.HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intravascular administration of the pooled murine-expressedHEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited the expression of pro-EMT transcripts in the placenta. Our data suggest thatHEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction.

79 UTERINE AND PLACENTAL INTERACTIONS DURING NECROTIC TIP DEVELOPMENT IN THE PIG FROM DAY 22 TO 42 OF GESTATION

2014 ◽  
Vol 26 (1) ◽  
pp. 153
Author(s):  
E. C. Wright ◽  
J. R. Miles ◽  
C. A. Lents ◽  
L. A. Rempel
Keyword(s):  
Fetal Growth ◽  
Fetal Death ◽  
Morphological Changes ◽  
Placental Weight ◽  
Placental Development ◽  
Dynamic Architecture ◽  
Uterine Endometrium ◽  
Hematoxylin And Eosin ◽  
Fold Formation ◽  
Size And Morphology

Placental development is important for fetal development and nutrient and waste transport. The pig, a litter bearing animal, has an epitheliochorial placenta that forms a noninvasive attachment with the uterine endometrium. Insufficient placental development is one of the primary causes of fetal death and reduced fetal growth after 35 days of gestation. Necrotic tips develop at the distal ends of each allantochorion between Day 22 and 42 of gestation. During this same period, placenta attaches to the uterine endometrium and establish fetal blood supplies and nutrient exchange. The attached placenta is composed of a central highly vascular placental (HVP) region adjacent to the fetus and less vascular placental (LVP) regions on either side to the fetus, the paraplacenta and necrotic tips, which form after 27 days of gestation. The objective of this study was to comprehensively evaluate uterine–placental interactions and necrotic tip development from 22 to 42 days of gestation in the gilt. Gilts (n = 25) were bred by AI at first detection of oestrus (Day 0) and harvested at 22, 27, 32, 37, or 42 days of gestation. Each conceptus was counted and weighed to identify the large, medium, and small fetus in each litter. From these fetuses, HVP and LVP sections of tissue and necrotic tip (no placental attachment) were collected. Intact attached uterus and placenta were collected for histology and preserved in paraformaldehyde. Placentas were then stripped from the endometrium and individually weighed. Hematoxylin and eosin staining of uterine : placental sections was used to identify uterine fold development in the HVP, LVP, and uterine endometrial morphology in the necrotic tip regions. Three folds were measured for depth, width, and area using BQ Nova Prime software (Bioquant Image Analysis, Nashville, TN, USA). Data were analysed using PROC MIXED in SAS (SAS Institute Inc., Cary, NC, USA). Litter size, 12.1 ± 3.4, was similar (P = 0.86) for all days of gestation. Fetal and placental weight increased (P < 0.05) as day of gestation increased. Average fetal weight was similar (P = 0.30) for Day 27 and 32 with a tendency (P = 0.09) to increase by Day 37 before a significant increase at Day 42 (P = 0.002). The placenta increased (P = 0.02) in weight throughout this period of gestation, with the greatest increase in weight between 37 and 42 days of gestation. The LVP zones had no measureable fold formation until Day 32 from most conceptuses, and all LVP zones displayed microfold formation by Day 37. Necrotic tips became apparent after 27 days of gestation. Necrotic tip areas of the uterus had observable modifications from Day 32 to 42 of gestation, developing folds with dramatic changes in endometrial cell size and morphology. This work demonstrated fundamental time points in placental development that correspond to fetal growth and microfold formation. Gestation Day 27 through 32 show limited changes in either fetal growth or increased placental weight; however, significant morphological changes occur throughout the placenta, and even necrotic tips demonstrating the dynamic architecture of the establishing porcine placenta during early gestation.

187 IMPRINTED GENE EXPRESSION IN IN VIVO-AND IN VITRO-PRODUCED BOVINE FETUSES AND PLACENTAS

2008 ◽  
Vol 20 (1) ◽  
pp. 173
Author(s):  
F. Perecin ◽  
S. C. Méo ◽  
W. Yamazaki ◽  
C. R. Ferreira ◽  
F. H. Biase ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Rna Extraction ◽  
Imprinted Genes ◽  
Total Rna ◽  
Imprinted Gene ◽  
Bovine Fetuses ◽  
Low Efficiency

Some gestational alterations associated with bovine somatic cell nuclear transfer (SCNT) are presumably consequences of abnormal imprinted gene expression. This work aimed to evaluate the expression patterns of imprinted genes IGF2 and IGF2R in bovine fetuses and chorioallantoic membranes derived from in vivo- and in vitro-produced embryos. Fetuses were produced by AI (in vivo group, n = 3), IVF (n = 3), parthenogenesis (n = 3), or SCNT (n = 2). Cows with positive pregnancy diagnosis after ultrasonographic examination were slaughtered between Days 33 and 36 of gestation. The reproductive tract was transported on ice to the laboratory, where fetuses and chorioallantoic fragments were collected and stored in liquid nitrogen. Total RNA extraction was performed using TRIzol, according to manufacturer's instructions, and the reverse transcription reaction was carried out with 1 µg of total RNA, 6.75 µm oligo pd(T)12–18, and 50 U of reverse transcriptase (Improm-II, Promega, Madison, WI, USA). The relative quantification of IGF2 and IGF2R transcripts was done using real-time PCR with SYBR Green dye. The average efficiency of PCR amplifications was estimated for each gene using a linear regression on the logarithm of fluorescence per cycle (Ramakers et al. 2003 Neurosci. Lett. 339, 62–66), and the expression ratios were calculated according to the method described previously by Livak and Schmittgen (2001 Methods 25, 402–408). To verify statistical differences, a pair-wise fixed reallocation randomization test (Pfaffl et al. 2002 Nucl. Acids Res. 30, e36) was used. All expression ratios were normalized by glyceraldehyde 3-phosphate dehydrogenase expression and calibrated by the in vivo group (expression assumed as 1.00 for all genes and tissues). The analysis of relative differences on transcript levels of imprinted genes in fetuses revealed IGF2 down-regulation (P < 0.05) in the SCNT (0.19) and parthenogenetic (0.02) groups when compared to the in vivo group and IVF fetuses (2.02). In chorioallantois, IGF2 was down-regulated (P < 0.001) in parthenotes (0.001) when compared to the in vivo, IVF (3.13), and SCNT (0.98) groups. IGF2R was down-regulated (P < 0.001) in SCNT chorioallantois (0.25) when compared to the in vivo group. Low expression of IGF2 in parthenogenetic fetuses and chorioallantois confirms its imprinted status in bovine. Alterations in the relative frequency of IGF2 and IGF2R transcripts were observed in bovine SCNT-derived fetuses and chorioallantoic membranes, respectively, supporting the hypothesis that abnormalities in the expression of imprinted genes are causes for the low efficiency of SCNT procedures in this species. Such alterations suggest modifications in DNA methylation patterns at IGF2 and IGF2R imprinting centers.

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