Changes in mediators of pro-cell growth, senescence, and inflammation during murine gestation

Narmada Lavu, Samantha Sheller-Miller, Talar Kechichian, Samir Cayenne, Elizabeth A. Bonney, Ramkumar Menon

Research output: Contribution to journalArticle

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 languageEnglish (US)
Article numbere13214
JournalAmerican Journal of Reproductive Immunology
DOIs
StateAccepted/In press - Jan 1 2019

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Cell Aging
Extraembryonic Membranes
Inflammation
Pregnancy
Growth
Glycogen Synthase Kinase 3
Catenins
Peroxisome Proliferator-Activated Receptors
Heme Oxygenase-1
Parturition
p38 Mitogen-Activated Protein Kinases
Interleukin-8
Interleukin-1
Interleukin-10
Interleukin-6
Intercellular Signaling Peptides and Proteins
Gestational Age
Anti-Inflammatory Agents
Down-Regulation
Antioxidants

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 journalArticle

Lavu, Narmada ; Sheller-Miller, Samantha ; Kechichian, Talar ; Cayenne, Samir ; Bonney, Elizabeth A. ; Menon, Ramkumar. / Changes in mediators of pro-cell growth, senescence, and inflammation during murine gestation. In: American Journal of Reproductive Immunology. 2019.
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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.",
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