ArticleReproductive sciences (Thousand Oaks, Calif.)2021
Fetal Exosomal Platelet-activating Factor Triggers Functional Progesterone Withdrawal in Human Placenta.
Article in Reproductive sciences (Thousand Oaks, Calif.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Regulation of term and preterm labor: genetics and epigenetics.Frontiers in genetics · 2025Article
- Extracellular vesicles as markers and mediators of pregnancy complications: gestational diabetes, pre-eclampsia, preterm birth and fetal growth restriction.The Journal of physiology · 2023Review
- Events Leading to the Establishment of Pregnancy and Placental Formation: The Need to Fine-Tune the Nomenclature on Pregnancy and Gestation.International journal of molecular sciences · 2023Review
- Decreased level of TREM like Transcript 1 (TLT-1) is associated with prematurity and promotes the in-utero inflammatory response to maternal lipopolysaccharide (LPS) exposure.American journal of reproductive immunology (New York, N.Y. : 1989) · 2023Article
- Factors of Fetal Origin in the Regulation of Labor Initiation and Preterm Birth.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2023Article
- Preterm Birth: Screening and Prediction.International journal of women's health · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In most mammals, labor is heralded by the withdrawal of progesterone. In humans, circulating progesterone levels increase as gestation advances while placental expression of progesterone receptor A (PR-A) declines. As a result of PR-A downregulation, the non-canonical NF-κB pathway is activated, an event implicated in triggering labor. Here, we sought to identify fetal-derived mediator(s) that represses placental PR-A in human placenta leading to activation of pro-labor signaling. Lipidomic profiling demonstrated enrichment of platelet-activating factor (PAF) in exosomes originating from the human fetus. Exposure of primary cytotrophoblasts to fetal exosomes from term pregnancies reduced PR-A expression by > 50%, and PAF also reduced PR-A message levels in a dose-dependent manner. Notably, fetal exosomes from preterm pregnancies had lower PAF levels and no effect on PR-A expression. Synthetic PAF-induced DNA methylation increases by 20% at the PR-A promoter, leading to recruitment of corepressors and downregulation of PR-A in cytotrophoblast. Furthermore, suppression of PR-A by PAF-stimulated expression of the pro-labor genes, corticotropin-releasing hormone (CRH) and cyclooxygenase-2 (COX-2), which was reversed by disruption of the DNA methyltransferases 3B and 3L. Taken together, PAF represents a novel fetal-derived candidate for initiation of labor by stimulating methylation and repression of PR-A and activating pro-labor signaling in trophoblast.
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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.