ArticleThe Journal of clinical endocrinology and metabolism2014
Long-acting progestin-only contraceptives enhance human endometrial stromal cell expressed neuronal pentraxin-1 and reactive oxygen species to promote endothelial cell apoptosis.
Article in The Journal of clinical endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Integrative genetic and multi-omics analysis reveals the interleukin-6 receptor's role in recurrent spontaneous abortion.Frontiers in immunology · 2025Article
- Gene expression associated with unfavorable vaginal bleeding in women using the etonogestrel subdermal contraceptive implant: a prospective study.Scientific reports · 2024Article
- Enhanced ZBTB16 Levels by Progestin-Only Contraceptives Induces Decidualization and Inflammation.International journal of molecular sciences · 2023Article
- Tryptophan Metabolites Regulate Neuropentraxin 1 Expression in Endothelial Cells.International journal of molecular sciences · 2022Article
- The role of extracellular vesicle miRNAs and tRNAs in synovial fibroblast senescence.Frontiers in molecular biosciences · 2022Article
- Preeclampsia is Associated With ReducedFrontiers in cell and developmental biology · 2022Article
- Systems level insights into the impact of airborne exposure on SARS-CoV-2 pathogenesis and COVID-19 outcome - A multi-omics big data study.Gene reports · 2021Article
- [Expression and Diagnostic Value of NPTX1 in Thymoma Patients].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Article
- Polyethylene Glycol-Coated Graphene Oxide Loaded with Erlotinib as an Effective Therapeutic Agent for Treating Nasopharyngeal Cancer Cells.International journal of nanomedicine · 2020Article
- The Basic Characteristics of the Pentraxin Family and Their Functions in Tumor Progression.Frontiers in immunology · 2020Review
- As a downstream target of the AKT pathway, NPTX1 inhibits proliferation and promotes apoptosis in hepatocellular carcinoma.Bioscience reports · 2019Article
- Identification of differential gene expression in endothelial cells from young and aged mice using RNA-Seq technique.American journal of translational research · 2019Article
- The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding.Human reproduction update · 2016Review
- Cigarette smoke but not electronic cigarette aerosol activates a stress response in human coronary artery endothelial cells in culture.Drug and alcohol dependence · 2016Article
- Long-acting progestin-only contraceptives impair endometrial vasculature by inhibiting uterine vascular smooth muscle cell survival.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
contextDespite the absence of progesterone receptor protein in human endometrial endothelial cells (HEECs), endometria of women receiving long-acting progestin-only contraceptives (LAPCs) display reduced uterine blood flow, elevated reactive oxygen species generation, increased angiogenesis, and irregularly distributed, enlarged, fragile microvessels resulting in abnormal uterine bleeding.
objectiveWe propose that paracrine factors from LAPC-treated human endometrial stromal cells (HESCs) impair HEEC functions by shifting the balance between HEEC viability and death in favor of the latter. DESIGN AND
settingProliferation, apoptosis, and transcriptome analyses were performed in HEECs treated with conditioned medium supernatant (CMS) derived from HESCs treated with estradiol (E2) ± medroxyprogesterone acetate or etonogestrel under normoxia or hypoxia. Mass spectrometry interrogated the CMS secretome while immunostaining for neuronal pentraxin-1 (NPTX1), cleaved caspase-3, and cytochrome c was performed in cultured HEECs and paired endometria from women using LAPCs. MAIN OUTCOME: HEEC apoptosis and its underlying mechanism.
resultsHESC CMS from E2 + medroxyprogesterone acetate or E2 + etonogestrel incubations under hypoxia induced HEEC apoptosis (P < .05), whereas mass spectrometry of the CMS revealed increased NPTX1 secretion (P < .05). Endothelial cleaved caspase-3 and stromal NPTX1 immunoreactivity were significantly higher in LAPC-treated endometria (P < .001). Transcriptomics revealed AKT signaling inhibition and mitochondrial dysfunction in HEECs incubated with HESC CMS. In vitro analyses proved that CMS decreased HEEC AKT phosphorylation (P < .05) and that recombinant NPTX1 (P < .05) or NPTX1 + H2O2 (P < .001) increase HEEC apoptosis and cytosolic cytochrome c levels.
conclusionsLAPC-enhanced NPTX1 secretion and reactive oxygen species generation in HESCs impair HEEC survival resulting in a loss in vascular integrity, demonstrating a novel paracrine mechanism to explain LAPC-induced abnormal uterine bleeding.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.