Maternal cause of early-onset preeclampsia: excessive endometrial gland-derived apolipoprotein D induces placental ferroptosis and developmental abnormalities
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1213976 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32073158.fastq.gz | Fastqsanger.gz | |||
| SRR32073159.fastq.gz | Fastqsanger.gz | |||
| SRR32073160.fastq.gz | Fastqsanger.gz | |||
| SRR32073161.fastq.gz | Fastqsanger.gz | |||
| SRR32073162.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Early-onset pre-eclampsia (ePE) is a severe pregnancy complication affecting millions of pregnancies worldwide, resulting in significant maternal and fetal morbidity. The etiology of ePE is associated with defective trophoblast functions, leading to abnormal placental development. Regulatory factors released by endometrial glands are crucial for proper placental development. While circumstantial evidence indicates that defective endometrial gland development or function may lead to defective placental development and ePE in humans, direct evidence has been lacking. This study explored the role of endometrial gland-derived factors both in vitro and in vivo and correlated the findings with the clinical phenotypes of ePE. Our findings revealed that the secretome of organoids derived from the endometrial tissues of ePE patients impeded spiral artery remodeling and thus disrupted proper placental perfusion. Transcriptomic and proteomic analyses identified an increased apolipoprotein D (APOD) production in ePE organoids and decidual tissues compared to their normotensive (NT) counterparts. Overexpression of endometrial APOD impaired the vascular remodeling functions of extravillous trophoblasts (EVT) and endothelial cells in vitro. These findings were corroborated using an endometrial-specific APOD knock-in mouse model. APOD-induced ferroptosis through the PI3K/Akt pathway in both human ePE placentas and the mouse model. Moreover, elevated APOD levels were detected in the first-trimester serum of pregnant women who subsequently developed ePE. These results provide the first direct evidence that dysregulated endometrial gland secretome is a maternal cause of defective placental development and ePE. Clinically, APOD could serve as a biomarker for early detection of ePE, enabling early intervention with the potential to improve outcomes for both mothers and their babies.
2025-01-27 | GSE287645 | GEO
Project description:Preeclampsia is a severe placenta-related pregnancy disorder that is generally divided into two subtypes named early-onset preeclampsia (onset <34 weeks of gestation), and lateonset preeclampsia (onset ≥34 weeks of gestation), with distinct pathophysiological origins. Both forms of preeclampsia have been associated with maternal systemic inflammation. However, alterations in the placental immune system have been less well characterized. Here, we studied immunological alterations in early- and late-onset preeclampsia placentas using a targeted expression profile approach. RNA was extracted from snap-frozen placenta samples (healthy n=13, early-onset preeclampsia n=13, and late-onset preeclampsia n=6). The expression of 730 immune-related genes from the Pan Cancer Immune Profiling Panel was measured, and the data were analyzed Q10 in the advanced analysis module of nSolver software (NanoString Technology). The results showed that early-onset preeclampsia placentas displayed reduced expression of complement, and toll-like receptor (TLR) associated genes, specifically TLR1 and TLR4. Mast cells and M2 macrophages were also decreased in early-onset preeclampsia compared to healthy pl acentas. The findings were confirmed by an immunohistochemistry approach using 20 healthy, 19 early-onset preeclampsia, and 10 late-onset preeclampsia placentas. We conclude that the placental innate immune system is altered in early-onset preeclampsia compared to uncomplicated pregnancies. The absence of these alterations in late-onset preeclampsia placentas indicates dissimilar immunological profiles. The study revealed distinct pathophysiological processes in earlyonset and late-onset preeclampsia placentas and imply that a tailored treatment to each subtype is desirable.
2021-12-13 | GSE190639 | GEO
Project description:Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities are considered to play a key role. Mitochondrial abnormalities in preeclamptic placentae have been described, but the extent to which mitochondrial content and the molecular pathways controlling this (mitochondrial biogenesis and mitophagy) are affected in preeclamptic placentae is unknown. Therefore, in preeclamptic (n = 12) and control (n = 11) placentae, we comprehensively assessed multiple indices of placental antioxidant status, mitochondrial content, mitochondrial biogenesis, mitophagy, and mitochondrial fusion and fission. In addition, we also explored gene expression profiles related to inflammation and apoptosis. Preeclamptic placentae were characterized by higher levels of oxidized glutathione, a higher total antioxidant capacity, and higher mRNA levels of the mitochondrial-located antioxidant enzyme manganese-dependent superoxide dismutase 2 compared to controls. Furthermore, mitochondrial content was significantly lower in preeclamptic placentae, which was accompanied by an increased abundance of key constituents of glycolysis. Moreover, mRNA and protein levels of key molecules involved in the regulation of mitochondrial biogenesis were lower in preeclamptic placentae, while the abundance of constituents of the mitophagy, autophagy, and mitochondrial fission machinery was higher compared to controls. In addition, we found evidence for activation of apoptosis and inflammation in preeclamptic placentae. This study is the first to comprehensively demonstrate abnormalities at the level of the mitochondrion and the molecular pathways controlling mitochondrial content/function in preeclamptic placentae. These aberrations may well contribute to the pathophysiology of preeclampsia by upregulating placental inflammation, oxidative stress, and apoptosis. Graphical Abstract.
| S-EPMC8289780 | biostudies-literature
Project description:Preeclampsia (PE) is a major pregnancy complication leading to maternal and neonatal mortality. To investigate the spatial gene expression profile of preeclampsia, we performed the Visium FFPE spatial transcriptome analysis.
2025-11-25 | GSE266604 | GEO
Project description:The series is composed of thirty hybridizations for analysis of differentially expressed genes in normal placenta tissues from patients with normal labor and placenta tissues from patients with severe preeclampsia. Patients tissues samples were obtained from (Vasilis. Total RNA extraction was performed by using the MagNa Pure Compact RNA Isolation Kit (Roche Applied Science). Keywords: Gene expression study, Disease state Twenty-six out of 50 normal placentas were randomly selected to match with 17 preeclamptic placentas, accounting for parity. Microarrays were performed applying a direct comparison design.
2010-05-26 | E-GEOD-10588 | biostudies-arrayexpress
Project description:Analysis of genome-wide gene expression in placentas from women with preterm severe preeclampsia, with or without HELLP syndrome, compared to gestational age-matched controls. The hypothesis tested in the present study was that placental transcriptomic changes in preeclampsia are considerably different from controls. The results provide important information on placental transcriptomic changes in preeclampsia.
2018-12-30 | GSE66273 | GEO
Project description:We perform placental microRNA expression profiling to identify potential microRNAs involved in the development and pathogenesis of preeclampsia. microRNA expression profiling for serum was quantified by qPCR and evaluated at 12, 16, and 20 gestational weeks and at the time of preeclampsia diagnosis. Two groups were evaluated using TaqMan Low Density Array plates: a control group with 18 normotensive pregnant women and a preeclampsia group with 16 patients who developed preeclampsia during the follow-up period. The placental microRNA profile was assayed at delivery (7 cases and 7 controls) using the Illumina GAIIx sequencing platform.
2015-06-03 | GSE69452 | GEO
Project description:Placental Immune alterations in early-onset preeclampsia and late-onset preeclampsia
| PRJNA787896 | ENA
Project description:Dysregulated RNA editing is well documented in several diseases such as cancer. The extent to which RNA editing might be involved in diseases originated in the placenta such as preeclampsia remains unknown, because RNA editing has rarely been studied in the placenta. Here, the RNA editome is systematically profiled on placentae from 9 patients with early-onset severe preeclampsia (EOSPE) and 32 normal controls, and a widespread RNA editing dysregulation in EOSPE has been identified. The mis-edited gene set is enriched with known preeclampsia-associated genes and differentially expressed genes in EOSPE. The “RNA editing events” at two microRNA binding sites in 3’-UTR of the LEP mRNA have been generated, which leads to increased expression level of LEP in trophoblast cells. Upregulation of LEP is also observed in the placentae of PE patients. These results suggest that widespread placental RNA editing may be involved in placental development and dysregulation of RNA editing in the placenta may contribute to the pathogenesis of preeclampsia.
2020-04-20 | GSE148241 | GEO
Project description:The series is composed of thirty hybridizations for analysis of differentially expressed genes in normal placenta tissues from patients with normal labor and placenta tissues from patients with severe preeclampsia. Patients tissues samples were obtained from (Vasilis. Total RNA extraction was performed by using the MagNa Pure Compact RNA Isolation Kit (Roche Applied Science). Keywords: Gene expression study, Disease state
2008-06-20 | GSE10588 | GEO