Abstract
Problem: Senescence of the fetal membranes and senescence-associated inflammation have been associated with parturition at term and pre-term in both mice and humans. Using a pregnant mouse model, we determined changes in multiple molecular signalers contributing to senescence and inflammation associated with parturition. Method of study: Fetal membranes were collected from timed-pregnant CD-1 mice on gestation days (E) 13, 15, 17, 18, and 19. Immunohistochemistry (IHC) localized pro-cell growth factors glycogen synthase kinase 3β (GSK3β) and β-catenin. Gestational age-associated changes in pro-cell growth vs senescence mediators (p38 mitogen-activated protein kinase [p38MAPK]), prooxidants (heme oxygenase-1 [HO-1], peroxisome proliferator-activated receptor γ [PPARγ]), and pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, and IL-1β) were determined by Western blots and Luminex assays. Results: Fetal membrane expressions of phosphorylated forms of GSK3β (inactivation) and p38MAPK (activation) increased, while β-catenin expression decreased, as gestation progressed. Antioxidant HO-1 expression decreased while PPARγ increased toward term gestation. IL-6 and IL-8 concentrations were highest on E19 (day of delivery), while IL-10 and IL-1β concentrations were highest on E15. Conclusion: Mouse fetal membranes showed a progressive senescence marker increase coincided with downregulation of cell growth factors. Development of senescence is associated with inflammation. Senescence-associated changes are natural and physiologic and indicative of fetal membranes' readiness for parturition.
| Original language | English (US) |
|---|---|
| Article number | e13214 |
| Journal | American Journal of Reproductive Immunology |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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Keywords
- fetal membranes
- GSK3β
- oxidative stress
- p38MAPK
- pre-term labor
- senescence
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Reproductive Medicine
- Obstetrics and Gynecology
Cite this
Changes in mediators of pro-cell growth, senescence, and inflammation during murine gestation. / Lavu, Narmada; Sheller-Miller, Samantha; Kechichian, Talar; Cayenne, Samir; Bonney, Elizabeth A.; Menon, Ramkumar.
In: American Journal of Reproductive Immunology, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Changes in mediators of pro-cell growth, senescence, and inflammation during murine gestation
AU - Lavu, Narmada
AU - Sheller-Miller, Samantha
AU - Kechichian, Talar
AU - Cayenne, Samir
AU - Bonney, Elizabeth A.
AU - Menon, Ramkumar
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Problem: Senescence of the fetal membranes and senescence-associated inflammation have been associated with parturition at term and pre-term in both mice and humans. Using a pregnant mouse model, we determined changes in multiple molecular signalers contributing to senescence and inflammation associated with parturition. Method of study: Fetal membranes were collected from timed-pregnant CD-1 mice on gestation days (E) 13, 15, 17, 18, and 19. Immunohistochemistry (IHC) localized pro-cell growth factors glycogen synthase kinase 3β (GSK3β) and β-catenin. Gestational age-associated changes in pro-cell growth vs senescence mediators (p38 mitogen-activated protein kinase [p38MAPK]), prooxidants (heme oxygenase-1 [HO-1], peroxisome proliferator-activated receptor γ [PPARγ]), and pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, and IL-1β) were determined by Western blots and Luminex assays. Results: Fetal membrane expressions of phosphorylated forms of GSK3β (inactivation) and p38MAPK (activation) increased, while β-catenin expression decreased, as gestation progressed. Antioxidant HO-1 expression decreased while PPARγ increased toward term gestation. IL-6 and IL-8 concentrations were highest on E19 (day of delivery), while IL-10 and IL-1β concentrations were highest on E15. Conclusion: Mouse fetal membranes showed a progressive senescence marker increase coincided with downregulation of cell growth factors. Development of senescence is associated with inflammation. Senescence-associated changes are natural and physiologic and indicative of fetal membranes' readiness for parturition.
AB - Problem: Senescence of the fetal membranes and senescence-associated inflammation have been associated with parturition at term and pre-term in both mice and humans. Using a pregnant mouse model, we determined changes in multiple molecular signalers contributing to senescence and inflammation associated with parturition. Method of study: Fetal membranes were collected from timed-pregnant CD-1 mice on gestation days (E) 13, 15, 17, 18, and 19. Immunohistochemistry (IHC) localized pro-cell growth factors glycogen synthase kinase 3β (GSK3β) and β-catenin. Gestational age-associated changes in pro-cell growth vs senescence mediators (p38 mitogen-activated protein kinase [p38MAPK]), prooxidants (heme oxygenase-1 [HO-1], peroxisome proliferator-activated receptor γ [PPARγ]), and pro- and anti-inflammatory cytokines (IL-6, IL-8, IL-10, and IL-1β) were determined by Western blots and Luminex assays. Results: Fetal membrane expressions of phosphorylated forms of GSK3β (inactivation) and p38MAPK (activation) increased, while β-catenin expression decreased, as gestation progressed. Antioxidant HO-1 expression decreased while PPARγ increased toward term gestation. IL-6 and IL-8 concentrations were highest on E19 (day of delivery), while IL-10 and IL-1β concentrations were highest on E15. Conclusion: Mouse fetal membranes showed a progressive senescence marker increase coincided with downregulation of cell growth factors. Development of senescence is associated with inflammation. Senescence-associated changes are natural and physiologic and indicative of fetal membranes' readiness for parturition.
KW - fetal membranes
KW - GSK3β
KW - oxidative stress
KW - p38MAPK
KW - pre-term labor
KW - senescence
UR - http://www.scopus.com/inward/record.url?scp=85077874713&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85077874713&partnerID=8YFLogxK
U2 - 10.1111/aji.13214
DO - 10.1111/aji.13214
M3 - Article
C2 - 31814178
AN - SCOPUS:85077874713
JO - American Journal of Reproductive Immunology and Microbiology
JF - American Journal of Reproductive Immunology and Microbiology
SN - 1046-7408
M1 - e13214
ER -