Differential senescence in feto-maternal tissues during mouse pregnancy

Elizabeth A. Bonney, Kendall Krebs, George Saade, Talar Kechichian, Jayshil Trivedi, Yin Huaizhi, Ramkumar Menon

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background Human studies show that fetal membranes have a limited lifespan and undergo telomere-dependent cellular senescence that is augmented by oxidative stress and mediated by p38 mitogen activated protein kinase (MAPK). Further, these studies suggest that fetal membranes are anatomically and physiologically positioned to transmit senescence signals that may initiate parturition at term. Methods Longitudinal evaluation of feto-maternal tissues from mouse pregnancies was undertaken to determine the molecular progression of senescence during normal pregnancy. On days 10-18 of gestation, C57BL/6 mice were euthanized. Fetal membranes, placenta, and decidua/uterus were collected. Tissues were examined for Telomere length (TL) and the presence of Phosphorylated (P) p38MAPK and p53, p21 and senescence associated β-Galactosidase (SA- β-Gal). Findings Linear regression modeling of observed telomere length as a function of gestational age revealed that beta (β), the slope of the linear regression was negative and significantly different from zero for each tissue (fetal membranes, β = -0.1901 ± 0.03125, p <0.0001; placenta β = -0.09000 ± 0.03474, p = 0.0135; decidua/uterus β = -0.1317 ± 0.03264, p = 0.0003). Progressive activation p38MAPK was observed in all tissues from days 10 to day18, with the highest activation observed in fetal membranes. Activation of p53 was progressive in fetal membranes. In contrast, active p53 was constitutive in placenta and decidua/uterus throughout gestation. Detection of p21 indicated that pro-senescent change was higher in all compartments on day 18 as compared to other days. The number of SA-β-Gal positive cells increased in fetal membranes as gestation progressed. However, in placenta and uterus and decidua/uterus SA-β-Gal was seen only in days 15 and 18. Conclusions Telomere dependent p38 and p53 mediated senescence progressed in mouse fetal membranes as gestation advanced. Although senescence is evident, telomere dependent events were not dominant in placenta or decidua/uterus. Fetal membrane senescence may significantly contribute to mechanisms of parturition at term.

Original languageEnglish (US)
Pages (from-to)26-34
Number of pages9
JournalPlacenta
Volume43
DOIs
StatePublished - Jul 1 2016

Fingerprint

Extraembryonic Membranes
Mothers
Decidua
Pregnancy
Telomere
Uterus
Placenta
Linear Models
Galactosidases
Parturition
Cell Aging
p38 Mitogen-Activated Protein Kinases
Inbred C57BL Mouse
Gestational Age
Oxidative Stress

Keywords

  • Aging
  • Fetal membranes
  • Mouse
  • p38MAPK
  • p53
  • Parturition
  • Telomere

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Reproductive Medicine
  • Developmental Biology

Cite this

Differential senescence in feto-maternal tissues during mouse pregnancy. / Bonney, Elizabeth A.; Krebs, Kendall; Saade, George; Kechichian, Talar; Trivedi, Jayshil; Huaizhi, Yin; Menon, Ramkumar.

In: Placenta, Vol. 43, 01.07.2016, p. 26-34.

Research output: Contribution to journalArticle

Bonney, Elizabeth A. ; Krebs, Kendall ; Saade, George ; Kechichian, Talar ; Trivedi, Jayshil ; Huaizhi, Yin ; Menon, Ramkumar. / Differential senescence in feto-maternal tissues during mouse pregnancy. In: Placenta. 2016 ; Vol. 43. pp. 26-34.
@article{f93dd31b6dee4dd7aaf0124dbdd82daf,
title = "Differential senescence in feto-maternal tissues during mouse pregnancy",
abstract = "Background Human studies show that fetal membranes have a limited lifespan and undergo telomere-dependent cellular senescence that is augmented by oxidative stress and mediated by p38 mitogen activated protein kinase (MAPK). Further, these studies suggest that fetal membranes are anatomically and physiologically positioned to transmit senescence signals that may initiate parturition at term. Methods Longitudinal evaluation of feto-maternal tissues from mouse pregnancies was undertaken to determine the molecular progression of senescence during normal pregnancy. On days 10-18 of gestation, C57BL/6 mice were euthanized. Fetal membranes, placenta, and decidua/uterus were collected. Tissues were examined for Telomere length (TL) and the presence of Phosphorylated (P) p38MAPK and p53, p21 and senescence associated β-Galactosidase (SA- β-Gal). Findings Linear regression modeling of observed telomere length as a function of gestational age revealed that beta (β), the slope of the linear regression was negative and significantly different from zero for each tissue (fetal membranes, β = -0.1901 ± 0.03125, p <0.0001; placenta β = -0.09000 ± 0.03474, p = 0.0135; decidua/uterus β = -0.1317 ± 0.03264, p = 0.0003). Progressive activation p38MAPK was observed in all tissues from days 10 to day18, with the highest activation observed in fetal membranes. Activation of p53 was progressive in fetal membranes. In contrast, active p53 was constitutive in placenta and decidua/uterus throughout gestation. Detection of p21 indicated that pro-senescent change was higher in all compartments on day 18 as compared to other days. The number of SA-β-Gal positive cells increased in fetal membranes as gestation progressed. However, in placenta and uterus and decidua/uterus SA-β-Gal was seen only in days 15 and 18. Conclusions Telomere dependent p38 and p53 mediated senescence progressed in mouse fetal membranes as gestation advanced. Although senescence is evident, telomere dependent events were not dominant in placenta or decidua/uterus. Fetal membrane senescence may significantly contribute to mechanisms of parturition at term.",
keywords = "Aging, Fetal membranes, Mouse, p38MAPK, p53, Parturition, Telomere",
author = "Bonney, {Elizabeth A.} and Kendall Krebs and George Saade and Talar Kechichian and Jayshil Trivedi and Yin Huaizhi and Ramkumar Menon",
year = "2016",
month = "7",
day = "1",
doi = "10.1016/j.placenta.2016.04.018",
language = "English (US)",
volume = "43",
pages = "26--34",
journal = "Placenta",
issn = "0143-4004",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Differential senescence in feto-maternal tissues during mouse pregnancy

AU - Bonney, Elizabeth A.

AU - Krebs, Kendall

AU - Saade, George

AU - Kechichian, Talar

AU - Trivedi, Jayshil

AU - Huaizhi, Yin

AU - Menon, Ramkumar

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Background Human studies show that fetal membranes have a limited lifespan and undergo telomere-dependent cellular senescence that is augmented by oxidative stress and mediated by p38 mitogen activated protein kinase (MAPK). Further, these studies suggest that fetal membranes are anatomically and physiologically positioned to transmit senescence signals that may initiate parturition at term. Methods Longitudinal evaluation of feto-maternal tissues from mouse pregnancies was undertaken to determine the molecular progression of senescence during normal pregnancy. On days 10-18 of gestation, C57BL/6 mice were euthanized. Fetal membranes, placenta, and decidua/uterus were collected. Tissues were examined for Telomere length (TL) and the presence of Phosphorylated (P) p38MAPK and p53, p21 and senescence associated β-Galactosidase (SA- β-Gal). Findings Linear regression modeling of observed telomere length as a function of gestational age revealed that beta (β), the slope of the linear regression was negative and significantly different from zero for each tissue (fetal membranes, β = -0.1901 ± 0.03125, p <0.0001; placenta β = -0.09000 ± 0.03474, p = 0.0135; decidua/uterus β = -0.1317 ± 0.03264, p = 0.0003). Progressive activation p38MAPK was observed in all tissues from days 10 to day18, with the highest activation observed in fetal membranes. Activation of p53 was progressive in fetal membranes. In contrast, active p53 was constitutive in placenta and decidua/uterus throughout gestation. Detection of p21 indicated that pro-senescent change was higher in all compartments on day 18 as compared to other days. The number of SA-β-Gal positive cells increased in fetal membranes as gestation progressed. However, in placenta and uterus and decidua/uterus SA-β-Gal was seen only in days 15 and 18. Conclusions Telomere dependent p38 and p53 mediated senescence progressed in mouse fetal membranes as gestation advanced. Although senescence is evident, telomere dependent events were not dominant in placenta or decidua/uterus. Fetal membrane senescence may significantly contribute to mechanisms of parturition at term.

AB - Background Human studies show that fetal membranes have a limited lifespan and undergo telomere-dependent cellular senescence that is augmented by oxidative stress and mediated by p38 mitogen activated protein kinase (MAPK). Further, these studies suggest that fetal membranes are anatomically and physiologically positioned to transmit senescence signals that may initiate parturition at term. Methods Longitudinal evaluation of feto-maternal tissues from mouse pregnancies was undertaken to determine the molecular progression of senescence during normal pregnancy. On days 10-18 of gestation, C57BL/6 mice were euthanized. Fetal membranes, placenta, and decidua/uterus were collected. Tissues were examined for Telomere length (TL) and the presence of Phosphorylated (P) p38MAPK and p53, p21 and senescence associated β-Galactosidase (SA- β-Gal). Findings Linear regression modeling of observed telomere length as a function of gestational age revealed that beta (β), the slope of the linear regression was negative and significantly different from zero for each tissue (fetal membranes, β = -0.1901 ± 0.03125, p <0.0001; placenta β = -0.09000 ± 0.03474, p = 0.0135; decidua/uterus β = -0.1317 ± 0.03264, p = 0.0003). Progressive activation p38MAPK was observed in all tissues from days 10 to day18, with the highest activation observed in fetal membranes. Activation of p53 was progressive in fetal membranes. In contrast, active p53 was constitutive in placenta and decidua/uterus throughout gestation. Detection of p21 indicated that pro-senescent change was higher in all compartments on day 18 as compared to other days. The number of SA-β-Gal positive cells increased in fetal membranes as gestation progressed. However, in placenta and uterus and decidua/uterus SA-β-Gal was seen only in days 15 and 18. Conclusions Telomere dependent p38 and p53 mediated senescence progressed in mouse fetal membranes as gestation advanced. Although senescence is evident, telomere dependent events were not dominant in placenta or decidua/uterus. Fetal membrane senescence may significantly contribute to mechanisms of parturition at term.

KW - Aging

KW - Fetal membranes

KW - Mouse

KW - p38MAPK

KW - p53

KW - Parturition

KW - Telomere

UR - http://www.scopus.com/inward/record.url?scp=84964412476&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84964412476&partnerID=8YFLogxK

U2 - 10.1016/j.placenta.2016.04.018

DO - 10.1016/j.placenta.2016.04.018

M3 - Article

C2 - 27324096

AN - SCOPUS:84964412476

VL - 43

SP - 26

EP - 34

JO - Placenta

JF - Placenta

SN - 0143-4004

ER -