Human fetal membranes at term: Dead tissue or signalers of parturition?
Open accessAbstract
Various endocrine, immune, and mechanical factors produced by feto-maternal compartments at term increase intrauterine inflammatory loads to induce labor. The role of fetal (placental) membranes (amniochorion) as providers of parturition signals has not been well investigated. Fetal membranes line the intrauterine cavity and grow with and protect the fetus. Fetal membranes exist as an entity between the mother and fetus and perform unique functions during pregnancy. Membranes undergo a telomere-dependent p38 MAPK-induced senescence and demonstrate a decline in functional and mechanical abilities at term, showing signs of aging. Fetal membrane senescence is also allied with completion of fetal maturation at term as the fetus readies for delivery, which may also indicate the end of independent life and longevity of fetal membranes as their functional role concludes. Fetal membrane senescence is accelerated at term because of oxidative stress and increased stretching. Senescent fetal membranes cells produce senescence-associated secretory phenotype (SASP-inflammation) and also release proinflammatory damage-associated molecular patterns (DAMPs), namely HMGB1 and cell-free fetal telomere fragments. In a feedback loop, SASP and DAMPs increase senescence and enhance the inflammatory load to promote labor. Membranes increase the inflammatory load to disrupt homeostatic balance to transition quiescent uterine tissues toward a labor phenotype. Therefore, along with other well-described labor-promoting signals, senescent fetal membranes may also contribute to human term parturition.
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Trophoblast senescence is physiological, progresses with gestation and peaks at term; senescence is also described in maternal decidual cells and fetoplacental membranes, where it promotes parturition and placental detachment at term.
“In addition to trophoblast senescence, which is a physiological phenomenon that progresses with gestation and peaks at term, senescence is also extensively described in maternal decidual cells and fetoplacental membranes, where it has a pivotal role in the promotion of parturition and detachment of the placenta from the uterus at term257–262.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [257]
The sections on fetal membrane structure and biologic aging describe physiological membrane senescence during pregnancy and at term; the latter says signals from senescent membranes could trigger parturition. The copy does not establish the claimed gestational trajectory of trophoblast senescence, senescence in maternal decidual cells, or a role in placental detachment. It also presents the membrane contribution to labor as possible, rather than pivotal. (LLM, conf=0.88)
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Self-citationIL-27 induces a pro-inflammatory response in human fetal membranes mediating preterm birth
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- Authors
- Menon, R.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Menon, Ramkumar
- ORCID
- Menon, Ramkumar
- Venue
- Placenta
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 44
- Pages
- 1-5
- ISSN
- 0143-4004 (ISSN-L)
- PMC
- PMC5375105
- OpenAlex
- W2405957590
- Cited by
- 122
- References
- 58
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 6 · 2023: 12 · 2022: 19 · 2021: 15 · 2020: 19 · 2019: 10 · 2018: 12 · 2017: 11 · 2016: 1
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Placenta (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R03HD086354)
- Topics
- Health Sciences › Medicine › Epidemiology › Preterm Birth and Chorioamnionitis
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Keywords
- fetal membranes, amniochorion, p38 MAPK, senescence-associated secretory phenotype, damage-associated molecular patterns, HMGB1, oxidative stress, membrane stretching, metritis, labor induction, fetal maturity
- MeSH terms
- Female, Extraembryonic Membranes, Humans, Inflammation, Labor, Obstetric, Pregnancy, Cellular Senescence, Parturition
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