The imprinted Phlda2 gene modulates a major endocrine compartment of the placenta to regulate placental demands for maternal resources
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE74318 | GEO | 2015/10/24
SECONDARY ACCESSION(S): PRJNA299659
REPOSITORIES: GEO
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Project description:Recent work suggests that imprinted genes may regulate the signalling function of the placenta by modulating the size of the endocrine compartment. Our work provides in vivo evidence that this hypothesis is well founded. Affymetrix Mouse Microarray analysis of E16.5 placneta was used to demonstrate gene expression changes in the mutant placenta. E16.5 Phlda2+/+(129) (non-transgenic; 1X), Phlda2-/+(129) (maternal KO; 0X) and Phlda2+/+BACx1(129) (single copy Phlda2 transgene; 2X) placenta were used (N=3-4 of each genotype, two independent litters) were used to extract RNA and hybridize to Affymetrix microarrays.
2015-10-24 | E-GEOD-74318 | biostudies-arrayexpress
Project description:Imprinted genes, which are expressed from a single parental allele in response to epigenetic marks first established in the germline, function in a myriad of processes to regulate mammalian development. Recent work suggests that imprinted genes may regulate the signalling function of the placenta by modulating the size of the endocrine compartment. Here we provide in vivo evidence that this hypothesis is well founded. Elevated expression of the imprinted Pleckstrin homology-like domain, family a, member 2 (Phlda2) gene drives a reduction of the spongiotrophoblast endocrine compartment, diminished placental glycogen and asymmetric foetal growth restriction. Using both loss-of-function and gain-in-expression mouse models, here we further show that Phlda2 exclusively modulates the spongiotrophoblast compartment of the placenta without significantly altering the composition of the trophoblast giant cell endocrine lineages that share a common progenitor with this lineage. Additionally, we show that Phlda2 loss-of-function placentae contain nearly three times more placental glycogen than non-transgenic placentae. Remarkably, relative to a fully wild type scenario, wild type placentae also accumulate excessive glycogen. While loss-of-function of Phlda2 increased both placental weight and placental glycogen, the weight of both mutant and non-transgenic fetuses was lower than that found in a fully wild type scenario indicating that excessive glycogen accumulation comes at the cost of foetal growth. This work firstly highlights a novel signalling function for the spongiotrophoblast in stimulating the global accumulation of placental glycogen. Furthermore, this work suggests that Phlda2 manipulates the placenta's demands for maternal resources, a process that must be tightly regulated by epigenetic marks to ensure optimal foetal growth.
| S-EPMC4684229 | biostudies-literature
Project description:The placenta acts as an interface between the mother and fetus, regulating nutrient transport and secreting hormones which impact maternal metabolism. Complications during pregnancy, such as placental endocrine malfunction, programme offspring to develop metabolic disease during adulthood, in part via changes in gene expression in critical metabolic organs, such as the liver, during fetal development. Placental endocrine malfunction was induced via the misexpression of two imprinted genes (Igf2 and H19) exclusively in the endocrine zone of the mouse placenta, to study the consequences this has on fetal hepatic gene expression.
2023-11-30 | E-MTAB-11457 | biostudies-arrayexpress
Project description:Background: Maternal iron deficiency (ID) is associated with poor pregnancy and fetal outcomes. The effect is thought to be mediated by the placenta but there is no comprehensive assessment of placental response to maternal ID. Additionally, whether the influence of maternal ID on the placenta differs by fetal sex is unknown. Objectives: Our primary aim was to identify gene and protein signatures of ID mouse placentas at mid-gestation. A secondary objective was to profile the expression of iron genes in mouse placentas across gestation. Methods: We used a real-time PCR based array to determine the mRNA expression of all known iron genes in mouse placentas at embryonic day (E) 12.5, E14.5, E16.5, and E19.5 (n=3 placentas/time point). To determine the effect of maternal ID, we performed RNA sequencing and proteomics in male and female placentas from ID and iron adequate mice at E12.5 (n=8 dams/diet). Results: In female placentas, six genes including transferrin receptor (Tfrc) and solute carrier family 11 member 2 were significantly changed by maternal ID. An additional 154 genes were altered in male ID placentas. Proteomic analysis quantified 7662 proteins in the placenta. Proteins translated from iron responsive element (IRE) containing mRNAs were altered in abundance; ferritin and ferroportin 1 decreased while TFRC increased in ID placenta. Less than 4% of the significantly altered genes in ID placentas occurred both at the transcriptional and translational levels. Conclusions: Our data demonstrate that the impact of maternal ID on placental gene expression in mice is limited in scope and magnitude at mid-gestation. We provide strong evidence for IRE-based transcriptional and translational coordination of iron gene expression in the mouse placenta. Finally, we discover sexually dimorphic effects of maternal ID on placental gene expression, with more genes and pathways altered in male compared with female mouse placentas.
2021-03-12 | PXD023454 | Pride
Project description:Previous work has suggested that the imprinted gene Phlda2 regulates the signalling function of the placenta by modulating the size of the endocrine compartment. This study investigated the affect that Phlda2 mutant placenta has upon the brains of the wildtype dams carrying different placenta and consequently offspring. Affymetrix Mouse Microarray analysis of maternal hippocampus and hypothalamus was used to demonstrate gene expression changes in the maternal brains of wildtype dams carrying mutant placenta at E16.5.
2018-06-06 | GSE115276 | GEO
Project description:Cell atlas of the human placenta
| EGAS00001004187 | EGA
Project description:Advanced paternal age has been shown to be a significant risk factor for neurodevelopmental psychiatric disorders, particularly autism. We have recently shown that mice conceived by old fathers display behavioral abnormalities which resemble key diagnostic symptoms of human autism. De novo mutations and epigenetic alterations increase in the male germ line during ageing and are thought to mediate the effect of paternal age on occurrence of diseases occurrence. Because the placenta carry a predominantly fetal genetic background, age-related mutagenesis and epigenetic errors might negatively influence placental physiology and in turn perturb fetal brain development. Here, we examined the impact of paternal age on placental mRNA transcriptome. This work was supported by Programme FP7-KBBE-2012.1.3-04, GA no. 312097 Acronym: FECUND, to GEP; MIUR/CNR, Programme FIRB. GA n. B81J12002520001 Acronym: GenHome, to PL. This study was also partially financed by the IGAB PAS project (S.III.1.3), Polish Scientific Committee Grant 2011/03/N/NZ29/05222, Polish Ministry of Science and Higher Education Grants N N519 657940 and N N311 604938. We compared gene expression patterns of mouse placentas harvested from either advanced paternal age model (APA) of autism or control animals. We included 2 comparisons: 1) placenta of female APA vs placenta of female control; 2) placenta of male APA vs placenta of male control. Each comparison was composed of 3 biological replicates. To minimize family bias, poolings contained at most one placenta per sex from each dam to a minimum of one and a maximum of three placentas per group/sex.
2015-07-25 | E-GEOD-71322 | biostudies-arrayexpress
Project description:The human placenta is a dynamic and cellular heterogeneous organ, which is critical in fetomaternal homeostasis and the development of preeclampsia. Previous work has shown that placenta-derived cell-free RNA increases during pregnancy. We applied large-scale microfluidic single-cell transcriptomic technology to comprehensively characterize cellular heterogeneity of the human placentas and identified multiple placental cell-type–specific gene signatures. Analysis of the cellular signature expression in maternal plasma enabled noninvasive delineation of the cellular dynamics of the placenta during pregnancy and the elucidation of extravillous trophoblastic dysfunction in early preeclampsia.
| EGAS00001002449 | EGA
Project description:MicroRNAs (miRNAs) represent small noncoding RNAs that are involved in physiologic and developmental processes by negatively regulating expression of target genes. They exist as individual miRNA genes or as polycistronically transcribed gene clusters. The largest miRNA cluster in mice is located in intron 10 of the Sfmbt2 gene, and contains 72 miRNA precursor sequences within approximately 50 kb. Although this miRNA cluster emerged recently in the rodent genome, probably coincidentally with the acquisition of the imprinted control of Sfmbt2, very little is known about its functions. In this study, we generated mice lacking the entire Sfmbt2 miRNA cluster to elucidate its functions during development. Like the Sfmbt2 gene, the Sfmbt2 miRNAs were expressed in the placenta predominantly from the paternal allele. Loss of the paternal allele resulted in severely impaired development of the spongiotrophoblast layer, which usually comprises about half of the fetal placenta. This phenotype was associated with fetal developmental delay or lethality, leading to significant decreases in the number of fetuses and their weights at term. Microarray analysis identified that at least 30 miRNAs in the cluster were actively transcribed in wild-type placentas. Among the predicted targets of these miRNAs, 132 genes were upregulated in the miRNA-deleted placentas. Some of the genes most significantly upregulated, including Gkn2 and Runx1, are known to inhibit cell proliferation by inducing cell cycle arrest or apoptosis. Thus, the Sfmbt2 miRNAs play essential roles in promoting trophoblastic cell proliferation in the placenta, cooperating with the host gene under the same paternal expression control.
2017-02-01 | GSE82054 | GEO
Project description:The purpose of this article is to provide a systematic review of leadership and Job Demands-Resources (JD-R) theory. We have analyzed 139 studies that study the relationship between leadership and Job Demands-Resources (JD-R) theory. Based on our analysis, we highlight ways forward. First, research designs can be improved by eliminating endogeneity problems. Regarding leadership concepts, proper measurements should be used. Furthermore, we point toward new theory building by highlighting three main ways in which leadership may affect employees, namely by: (1) directly influencing job demands and resources, (2) influencing the impact of job demands and resources on well-being; and (3) influencing job crafting and self-undermining. We hope this review helps researchers and practitioners analyze how leadership and JD-R theory can be connected, ultimately leading to improved employee well-being and organizational performance.
| S-EPMC8514935 | biostudies-literature