Labor-Associated Gene Expression in the Human Uterine Fundus, Lower Segment, and Cervix
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BACKGROUND: Preterm labor, failure to progress, and postpartum hemorrhage are the common causes of maternal and neonatal mortality or morbidity. All result from defects in the complex mechanisms controlling labor, which coordinate changes in the uterine fundus, lower segment, and cervix. We aimed to assess labor-associated gene expression profiles in these functionally distinct areas of the human uterus by using microarrays. METHODS AND FINDINGS: Samples of uterine fundus, lower segment, and cervix were obtained from patients at term (mean +/- SD = 39.1 +/- 0.5 wk) prior to the onset of labor (n = 6), or in active phase of labor with spontaneous onset (n = 7). Expression of 12,626 genes was evaluated using microarrays (Human Genome U95A; Affymetrix) and compared between labor and non-labor samples. Genes with the largest labor-associated change and the lowest variability in expression are likely to be fundamental for parturition, so gene expression was ranked accordingly. From 500 genes with the highest rank we identified genes with similar expression profiles using two independent clustering techniques. Sets of genes with a probability of chance grouping by both techniques less than 0.01 represented 71.2%, 81.8%, and 79.8% of the 500 genes in the fundus, lower segment, and cervix, respectively. We identified 14, 14, and 12 those sets of genes in the fundus, lower segment, and cervix, respectively. This enabled networks of co-regulated and co-expressed genes to be discovered. Many genes within the same cluster shared similar functions or had functions pertinent to the process of labor. CONCLUSIONS: Our results provide support for many of the established processes of parturition and also describe novel-to-labor genes not previously associated with this process. The elucidation of these mechanisms likely to be fundamental for controlling labor is an important prerequisite to the development of effective treatments for major obstetric problems--including prematurity, with its long-term consequences to the health of mother and offspring.
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The direct actions of CRH on myometrial contractility involve distinct CRH receptor isoforms.
“The direct actions of CRH on myometrial contractility involve distinct CRH receptor isoforms.”
From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [65]
The Results and Discussion passages address labor-associated gene expression and other receptor pathways, but do not address CRH’s direct effects on myometrial contractility or distinct CRH receptor isoforms. Searches for “CRH” and “corticotropin-releasing hormone” found no passage establishing the claim. (LLM, conf=0.73)
Experimental — accuracy not yet measuredCRH-R2 expression increases in the upper segment of the uterus during labor.
“By contrast, CRH-R2 expression increases in the upper segment of the uterus during labor, although its function is still unclear [65].”
From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [65]
The Results discuss labor-associated gene expression in the fundus, but the genes named there do not include CRH-R2. Searches for “CRH-R2” and “corticotropin releasing hormone receptor 2” found no passage in our copy addressing whether its expression increases during labor. No page numbers are available in the indexed passages. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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Radek Bukowski appointed Editor of Computational Medicine for AJOG
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- Authors
- Bukowski, R., Hankins, G. D. V., Saade, G. R., Anderson, G. D., & Thornton, S.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- University of Warwick (GB)
- Corresponding author
- Bukowski, Radek
- Venue
- PLoS Medicine
- Publisher
- Public Library of Science (PLoS)
- Published
- 2006-06-13
- Volume
- 3
- Issue
- 6
- Pages
- e169
- ISSN
- 1549-1277 (ISSN-L)
- 1549-1676
- PMC
- PMC1475650
- OpenAlex
- W1982557352
- Cited by
- 77
- References
- 30
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 1 · 2013: 4 · 2012: 3
- FWCI
- 5.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Action Medical Research
- University of Warwick
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy-related medical research
- Keywords
- labor, childbirth, gene expression profiling, uterine fundus, lower uterine segment, uterine cervix, preterm labor, preterm birth, gene clusters, postpartum hemorrhage, failure to progress
- MeSH terms
- Prohibitins, Cervix Uteri, Female, Gene Expression Regulation, Humans, Labor, Obstetric, Pregnancy, Repressor Proteins, RNA, Messenger, Uterus, Reproducibility of Results, Cluster Analysis, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Parturition, Retinoid X Receptor alpha
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