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Comparative analysis of the human and mouse placental transcriptome and proteome

ABSTRACT: An important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human and mouse placenta show structural similarities but there have been no systematic attempt to assess their molecular similarities or differences. We built a comprehensive database of protein and microarray data for the highly vascular exchange region micro-dissected from the human and mouse placenta near-term. Abnormalities in this region are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting ~5% of all pregnancies. Over 7,000 orthologs were detected with 70% co-expressed and over 80% of genes known to cause placental phenotypes in mouse were co-expressed. These genes form a tight protein-protein interaction network with novel candidate genes likely to be important in placental structure and/or function. The entire data is available as a web-accessible database to guide the informed development of mouse models to study human disease. This experiment is now fully represented in the NCBI Peptidome database with accession PSE115.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE13299 | GEO | 2009/06/29

SECONDARY ACCESSION(S): PRJNA109871

REPOSITORIES: GEO

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Comparative analysis of the human and mouse placental transcriptome and proteome

Project description:An important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human and mouse placenta show structural similarities but there have been no systematic attempt to assess their molecular similarities or differences. We built a comprehensive database of protein and microarray data for the highly vascular exchange region micro-dissected from the human and mouse placenta near-term. Abnormalities in this region are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting ~5% of all pregnancies. Over 7,000 orthologs were detected with 70% co-expressed and over 80% of genes known to cause placental phenotypes in mouse were co-expressed. These genes form a tight protein-protein interaction network with novel candidate genes likely to be important in placental structure and/or function. The entire data is available as a web-accessible database to guide the informed development of mouse models to study human disease This experiment is now fully represented in NCBI Peptidome database with accession PSE115; http://www.ncbi.nlm.nih.gov/peptidome/search/index.shtml?acc=PSE115 Microdissection of human villous trees and mouse placental labyrinth. Tissues were split for microarray and protein analysis. For protein analysis samples were first fractionated by differential sucrose gradients into mitochrondria, cytosol, microsomes and nuclei. Mitochrondira and neuclei were each extracted by two different methods for soluble and insoluble material. Each subcellular fraction for each tissue was analysed in quintuplet by 9 step 2 dimensional LC/MSMS. This generated a total of 270 mzXML files for each tissue.

2009-06-29 | E-GEOD-13299 | biostudies-arrayexpress

Comparison of mouse placental labyrinth and human villus tree

2009-06-16 | GSE13155 | GEO

Transcription profiling of mouse placental labyrinth and human villus tree

Project description:An important question for the use of the mouse as a model for studying human disease is the degree of functional conservation of genetic control pathways from human to mouse. The human placenta and mouse placenta show structural similarities but there has been no systematic attempt to assess their molecular similarities or differences. We built a comprehensive database of protein and microarray data for the highly vascular exchange region micro-dissected from the human and mouse placenta near-term. Abnormalities in this region are associated with two of the most common and serious complications of human pregnancy, maternal preeclampsia (PE) and fetal intrauterine growth restriction (IUGR), each disorder affecting ~5% of all pregnancies. To compare the gene expression patterns in the vascular exchange regions of the human (villus tree) and mouse (labyrinth) placenta. Experiment Overall Design: Mouse labyrinth tissue was micro-dissected form naturally mated crosses of C57Bl/6J mice. Placentas were individually dissected on embryonic day 17.5. From each litter ¼ of the tissue were set aside for RNA extraction and microarray analysis and ¾ for cellular fractionation and proteomic analysis, as recently described (Kislinger et al., 2006). Human villous trees were dissected from term normal placenta delivered by cesarean section from a term pregnancy (~ 38 weeks). Tissue was divided for organellar fractionation and RNA extraction.

2009-06-22 | E-GEOD-13155 | biostudies-arrayexpress

Maternal iron deficiency modulates placental transcriptome and proteome in mid-gestation of mouse pregnancy

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

Alpha-1-Antitrypsin: A Novel Human High Temperature Requirement Protease A1 (HTRA1) Substrate in Human Placental Tissue

Project description:Substrate screening of the human protease HTRA1 in a placenta protein extract. The human serine protease high temperature requirement A1 (HTRA1) is highly expressed in the placental tissue, especially in the last trimester of gestation. This suggests that HTRA1 is involved in placental formation and function. With the aim of a better understanding of the role of HTRA1 in the placenta, candidate substrates were screened in a placenta protein extract using a gel-based mass spectrometric approach. Peptides were analysed using a nanoLC-ESI-IT-FTICR-MS instrument controlled by Xcalibur 2.07 software version (Thermo Scientific, Bremen). A by data-dependent acquisition method was used, where the five most intense precursor ions detected in the full MS scan (FTICR) were selected and fragmented in the IonTrap by collision induced dissociation (CID) (35% energy, 4 amu mass isolation width). Proteome Discoverer 1.3 and SEQUEST search engines (Thermo Scientific, Bremen) were used for data analysis. The MS/MS raw data were directly analysed with the Proteome Discoverer software using the following spectrum selector settings; minimum precursor mass 350 Da, maximum precursor mass 5000 Da, total intensity threshold 100, minimum peak count 10, signal-to-noise threshold 5 (FT-only). The identification searching parameters were: tryptic digestion, 2 missed cleavages, deamidated (N), oxidation (M) and propionamide (C) modifications, precursor mass tolerance 5 ppm and fragment mass tolerance 0.5 Da. The database UniProtKB/Swiss-Prot homo sapiens (September 2013, 20.267 Proteins) was chosen for protein identification. A list of contaminants was removed from this database, namely, Keratin, type I and type II cytoskeletal and trypsin. As discrimination criteria, protein identifications containing less than 2 peptides and SEQUEST scores lower than 40 were discarded.

2014-10-24 | PXD000473 | Pride

Comparison of gene expression in mouse placentas with different combination of MT1-MMP and MT2-MMP alleles

Project description:MT1-MMP and MT2-MMP double deficiency in mice leads to development of a placental defect resulting in embryonic death after E10.5. The protein substrate for these two proteases in placenta is unknown, which poses an obstacle in uncovering of molecular mechanism behind the observed placental defect. In search for a potential substrate for these two proteases in placenta we have employed whole genome microarray expression profiling as a discovery platform to identify genes, expression of which might be affected by double MMP deficiency. Fetal parts of mouse placentas were isolated from E10.5 placentas of different genotypes for MT1- and MT2-MMP.

2010-03-09 | E-GEOD-18604 | biostudies-arrayexpress

Inhibition of diacylglycerol lipase β modulates lipid and endocannabinoid levels in the ex vivo human placenta

Project description:This study utilized MS-based activity-based protein profiling to generate an activity landscape of placental catalytically active serine hydrolases, aiming to investigate the main 2-AGbiosynthetic enzyme in the human placenta

2023-03-10 | PXD039930 | Pride

Transcriptomic profile of human placenta derived trophoblast organoid cultures with its tissue of origin, human placental villi.

Project description:The aim of this microarray experiment was to compare the overall transcriptomic profile of human placenta derived trophoblast organoid cultures with its tissue of origin, human placental villi. As the placental villi contains both trophoblast and stromal populations, we have included placenta derived stromal cultures in this comparison.

2018-11-28 | E-MTAB-6683 | biostudies-arrayexpress

Immunological Sexual Dimorphism in Placenta and Its Response to Benzene Exposure

Project description:There is increasing concern regarding the adverse effects of air pollution on human health, and benzene is a major toxic compound in air pollution. Maternal benzene exposure has been associated with reproductive complications, such as preterm birth, low birth weight, and immunological and neurological complications in the offspring. However, it is poorly understood how benzene induces these complications. Our objective was to establish a full body inhalation mouse model for maternal benzene exposure that mimics clinical phenotypes observed in human populations, and characterize the maternal immune activation and placental response in our model. Here, we report that maternal immune activation triggered by benzene exposure during pregnancy leads to increased resorptions, abnormal placenta development and low birth weight of fetus. More importantly, there is a sexual dimorphic response to benzene exposure in female and male placentas. In the male placenta, the transcriptome changes reveal a more immunologically relevant profile, while females have a metabolically related profile. Furthermore, we discover the sexual dimorphic response could be a consequence of the sexual dimorphism of placenta at baseline, which indicates the significant difference between sexes in terms of the immunological processes in the placenta, both in human and mouse. Therefore, our findings established a benzene exposure mouse model and indicated the sexual dimorphism of placenta, which provides valuable reference for the future pregnancy studies.

2023-07-20 | PXD035085 | Pride

Placenta and uterus transcriptomes from transgenic mice expressing human corticotropin-releasing hormone in placenta

Project description:Purpose: Parturition is delayed by approximately 12 hours in transgenic mice expressing human corticotropin-releasing hormone (CRH) in placenta. The goal of the study was to identify the pathways in reproductive tissues (uterus and placenta) altered by placental expression of human CRH. Methods: Human BAC RP11-366K18 (CHORI) containing human CRH and cis-regulatory region was inserted into the mouse genome by microinjection and random integration to create the BAC1 line. The CRISPR/Cas9 system was used to delete a CRH regulatory element from the BAC1 line to create the CR1 line, eliminating expression of CRH in placenta. Total expression of uterus and placenta by RNA-seq at embryonic day 18.5 were compared between BAC1, CR1, and nontransgenic mice. Results: Genes known to be associated with luteolysis and initiation of parturition (Cav1, Gja1, Oxtr, Ptgs1, Ptgs2) were not differentially expressed in uterus of this model. Conclusions: CRH-mediated delay of parturition is likely independent of luteolysis.

2018-08-09 | GSE118283 | GEO

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