TY - JOUR
T1 - Maternal inflammation leads to different mTORC1 activity varied by anatomic locations in mouse placenta
AU - Dong, Jie
AU - Shin, Na
AU - Lee, Ji Yeon
AU - Jia, Bei
AU - Chudnovets, Anna
AU - Mclane, Michael W.
AU - Li, Su
AU - Na, Quan
AU - Lei, Jun
AU - Burd, Irina
N1 - Funding Information:
† Dong Jie Shin Na Lee Ji Yeon Jia Bei Chudnovets Anna McLane Michael W Li Su Na Quan Lei Jun Burd Irina iburd@jhmi.edu Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine , Baltimore, MD, USA Reproductive Medical Center, Department of Obstetrics and Gynecology, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi Province , China Correspondence: Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Phipps 228, 600 N. Wolfe St, Baltimore, MD 21287-1228, USA. Tel: +410-955-8496; Fax: +410-614-8305; E-mail: iburd@jhmi.edu † Grant Support : This study was supported by the Integrated Research Center for Fetal Medicine Fund (Johns Hopkins School of Medicine 80037640) 11 2019 21 11 2019 12 08 2019 101 5 1046 1055 Supplemental_data_062019_ioz151 1 3 2019 21 6 2019 29 7 2019 ©The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2019 This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model )
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2019/11/21
Y1 - 2019/11/21
N2 - Maternal inflammation (MI) is associated with many adverse perinatal outcomes. The placenta plays a vital role in mediating maternal-fetal resource allocation. Studies have shown that MI contributes to placental dysfunction, which then leads to adverse birth outcomes and high health risks throughout childhood. Placental mammalian target of rapamycin complex 1 (mTORC1) signaling pathway links maternal nutrient availability to fetal growth; however, the impact of MI on mTORC1 signaling in the placenta remains unclear. In this study, we sought to explore the changes of mTORC1 signaling in the mouse placenta at late gestation by using two models of MI employing lipopolysaccharide (LPS) and interleukin-1β (IL-1β) to mimic acute (aMI) and sub-chronic (cMI) inflammatory states, respectively. We determined placental mTORC1 activity by measuring the activity of mTORC1 downstream molecules, including S6k, 4Ebp1, and rpS6. In the aMI model, we found that mTORC1 activity was significantly decreased in the placental decidual and junctional zone at 2 and 6 h after LPS surgery, respectively; however, mTORC1 activity was significantly increased in the placental labyrinth zone at 2, 6, and 24 h after LPS treatment, respectively. In the cMI model, we observed that mTORC1 activity was increased only in the placental labyrinth zone after consecutive IL-1β exposure. Our study reveals that different parts of the mouse placenta react differently to MI, leading to variable mTORC1 activity throughout the placenta. This suggests that different downstream molecules of mTORC1 from different parts of the mouse placenta may be used in clinical research to monitor the fetal well-being during MI.
AB - Maternal inflammation (MI) is associated with many adverse perinatal outcomes. The placenta plays a vital role in mediating maternal-fetal resource allocation. Studies have shown that MI contributes to placental dysfunction, which then leads to adverse birth outcomes and high health risks throughout childhood. Placental mammalian target of rapamycin complex 1 (mTORC1) signaling pathway links maternal nutrient availability to fetal growth; however, the impact of MI on mTORC1 signaling in the placenta remains unclear. In this study, we sought to explore the changes of mTORC1 signaling in the mouse placenta at late gestation by using two models of MI employing lipopolysaccharide (LPS) and interleukin-1β (IL-1β) to mimic acute (aMI) and sub-chronic (cMI) inflammatory states, respectively. We determined placental mTORC1 activity by measuring the activity of mTORC1 downstream molecules, including S6k, 4Ebp1, and rpS6. In the aMI model, we found that mTORC1 activity was significantly decreased in the placental decidual and junctional zone at 2 and 6 h after LPS surgery, respectively; however, mTORC1 activity was significantly increased in the placental labyrinth zone at 2, 6, and 24 h after LPS treatment, respectively. In the cMI model, we observed that mTORC1 activity was increased only in the placental labyrinth zone after consecutive IL-1β exposure. Our study reveals that different parts of the mouse placenta react differently to MI, leading to variable mTORC1 activity throughout the placenta. This suggests that different downstream molecules of mTORC1 from different parts of the mouse placenta may be used in clinical research to monitor the fetal well-being during MI.
KW - fetal development
KW - maternal inflammation
KW - nutrition
KW - placenta
KW - pregnancy
KW - stress
KW - trophoblast
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U2 - 10.1093/biolre/ioz151
DO - 10.1093/biolre/ioz151
M3 - Article
C2 - 31403169
AN - SCOPUS:85075813096
SN - 0006-3363
VL - 101
SP - 1046
EP - 1055
JO - Biology of reproduction
JF - Biology of reproduction
IS - 5
ER -