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
N1 - Funding Information:
Funding information This study is supported by NIA/NIH grant award (1R21AG060356-01) to Bonney EA and Menon R. We would like to acknowledge the help provided by Jayshil Trivedi and Lauren Richardson in perfecting our IHC protocol. For graphic assistance, we thank UTMB Ob/Gyn Publications graphic artist: Regina Minton, BS. For editing assistance, we would like to thank the UTMB Ob/Gyn editing team, especially LeAnne Garcia and Goldie Tabor.
Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2020/3/1
Y1 - 2020/3/1
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 - GSK3β
KW - fetal membranes
KW - oxidative stress
KW - p38MAPK
KW - pre-term labor
KW - senescence
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U2 - 10.1111/aji.13214
DO - 10.1111/aji.13214
M3 - Article
C2 - 31814178
AN - SCOPUS:85077874713
VL - 83
JO - American Journal of Reproductive Immunology
JF - American Journal of Reproductive Immunology
SN - 1046-7408
IS - 3
M1 - e13214
ER -