ArticleEBioMedicine2019
Estrogen receptor alpha isoform ERdelta7 in myometrium modulates uterine quiescence during pregnancy.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Transcription factors as essential regulators of myometrial smooth muscle cell function during pregnancy and labor.Cellular and molecular life sciences : CMLS · 2026Review
- Unveiling myometrial SP/Krüppel-like factors as drivers of parturition: insights from transcriptional and endocrine regulatory networks.Endocrine connections · 2025Review
- Alternative Splicing in Tumorigenesis and Cancer Therapy.Biomolecules · 2025Review
- Estrogen receptors in mitochondrial metabolism: age-related changes and implications for pregnancy complications.Aging advances · 2024Article
- Article
- Effect of aging on the human myometrium at single-cell resolution.Nature communications · 2024Article
- Hydrogen sulfide and its role in female reproduction.Frontiers in veterinary science · 2024Review
- Exploring myometrial microenvironment changes at the single-cell level from nonpregnant to term pregnant states.Physiological genomics · 2024Article
- Article
- Alternative promoters and splicing create multiple functionally distinct isoforms of oestrogen receptor alpha in breast cancer and healthy tissues.Cancer medicine · 2023Article
- Preterm Birth and Corticotrophin-Releasing Hormone as a Placental Clock.Endocrinology · 2022Review
- HIF-1α is essential for the augmentation of myometrial contractility during labor†.Biology of reproduction · 2022Article
- Molecular Mechanism of Mouse Uterine Smooth Muscle Regulation on Embryo Implantation.International journal of molecular sciences · 2022Article
- Female Reproductive Systems: Hormone Dependence and Receptor Expression.Advances in experimental medicine and biology · 2022Article
- Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth.Scientific reports · 2021Article
- Transcriptional control of parturition: insights from gene regulation studies in the myometrium.Molecular human reproduction · 2021Review
- Estrogen Regulates Local Cysteine Metabolism in Mouse Myometrium.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- Identification and Characterization of Hypothalamic Alternative Splicing Events and Variants in Ovine Fecundity-Related Genes.Animals : an open access journal from MDPI · 2020Article
- Pathogenesis of preterm birth: bidirectional inflammation in mother and fetus.Seminars in immunopathology · 2020Review
- Estrogen Receptors and Estrogen-Induced Uterine Vasodilation in Pregnancy.International journal of molecular sciences · 2020Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCirculating estrogen (E2) levels are high throughout pregnancy and increase towards term, however its local tissue specific actions vary across gestation. For example, myometrial E2 regulated uterotonic action is disabled until term, whereas it's proliferative function is maintained in the breast. We have identified gestationally regulated splicing events, mediated by hnRNPG and modulated by E2 that generate alternatively spliced estrogen receptor alpha (ERα) variants (ERΔ7 and ERα46) in the myometrium. These variants allow for differential, gestationally regulated, modulation of the uterotonic action of E2.
methodsHuman myometrium isolated from preterm and term non-laboring and laboring pregnant women were analyzed for ERα isoforms and splice factor levels. Lentiviral mediated shRNA knockdown of hnRNPG and overexpression of ERΔ7 were performed in human myometrial (hTERT-HM) cells. Functional 3D collagen contraction assays were executed.
findingsERΔ7 acts as a dominant negative repressor of the uterotonic action of ERα66 and ERα46 isoforms through the regulation of the myometrial gap junction protein GJA1. Elimination of hnRNPG inhibits the generation of ERΔ7 while overexpression of ERΔ7 inhibited GJA1 expression. Moreover in vivo human myometrial hnRNPG levels decline at term in an E2 dependent manner resulting in a withdrawal of ERΔ7 levels and its tocolytic action at term.
interpretationOur findings implicate the unique role of ERΔ7 as a modulator of myometrial quiescence and define the mechanism of ERΔ7 generation, through hormonally regulated splicing events. FUND: This study was supported by NIH OPRU U01 supplement (HD047905), University of Pittsburgh and Wayne State University Perinatal Research Initiative (USA).
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