Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization.
Early embryo miscarriage is linked to inadequate endometrial decidualization, a cellular transformation process that enables deep blastocyst invasion into the maternal compartment. Although much of the cellular events that underpin endometrial stromal cell (ESC) decidualization are well recognized,...
Main Authors: | , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-10-01
|
Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC3812085?pdf=render |
id |
doaj-556bd8b7edd443d5b7e4875980f1b43d |
---|---|
record_format |
Article |
spelling |
doaj-556bd8b7edd443d5b7e4875980f1b43d2020-11-24T21:44:21ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-10-01910e100390010.1371/journal.pgen.1003900Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization.Ramakrishna KommaganiMaria M SzwarcErtug KovanciWilliam E GibbonsNagireddy PutluriSuman MaityChad J CreightonArun SreekumarFrancesco J DeMayoJohn P LydonBert W O'MalleyEarly embryo miscarriage is linked to inadequate endometrial decidualization, a cellular transformation process that enables deep blastocyst invasion into the maternal compartment. Although much of the cellular events that underpin endometrial stromal cell (ESC) decidualization are well recognized, the individual gene(s) and molecular pathways that drive the initiation and progression of this process remain elusive. Using a genetic mouse model and a primary human ESC culture model, we demonstrate that steroid receptor coactivator-2 (SRC-2) is indispensable for rapid steroid hormone-dependent proliferation of ESCs, a critical cell-division step which precedes ESC terminal differentiation into decidual cells. We reveal that SRC-2 is required for increasing the glycolytic flux in human ESCs, which enables rapid proliferation to occur during the early stages of the decidualization program. Specifically, SRC-2 increases the glycolytic flux through induction of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3), a major rate-limiting glycolytic enzyme. Similarly, acute treatment of mice with a small molecule inhibitor of PFKFB3 significantly suppressed the ability of these animals to exhibit an endometrial decidual response. Together, these data strongly support a conserved mechanism of action by which SRC-2 accelerates the glycolytic flux through PFKFB3 induction to provide the necessary bioenergy and biomass to meet the demands of a high proliferation rate observed in ESCs prior to their differentiation into decidual cells. Because deregulation of endometrial SRC-2 expression has been associated with common gynecological disorders of reproductive-age women, this signaling pathway, involving SRC-2 and PFKFB3, promises to offer new clinical approaches in the diagnosis and/or treatment of a non-receptive uterus in patients presenting idiopathic infertility, recurrent early pregnancy loss, or increased time to pregnancy.http://europepmc.org/articles/PMC3812085?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ramakrishna Kommagani Maria M Szwarc Ertug Kovanci William E Gibbons Nagireddy Putluri Suman Maity Chad J Creighton Arun Sreekumar Francesco J DeMayo John P Lydon Bert W O'Malley |
spellingShingle |
Ramakrishna Kommagani Maria M Szwarc Ertug Kovanci William E Gibbons Nagireddy Putluri Suman Maity Chad J Creighton Arun Sreekumar Francesco J DeMayo John P Lydon Bert W O'Malley Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization. PLoS Genetics |
author_facet |
Ramakrishna Kommagani Maria M Szwarc Ertug Kovanci William E Gibbons Nagireddy Putluri Suman Maity Chad J Creighton Arun Sreekumar Francesco J DeMayo John P Lydon Bert W O'Malley |
author_sort |
Ramakrishna Kommagani |
title |
Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization. |
title_short |
Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization. |
title_full |
Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization. |
title_fullStr |
Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization. |
title_full_unstemmed |
Acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization. |
title_sort |
acceleration of the glycolytic flux by steroid receptor coactivator-2 is essential for endometrial decidualization. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2013-10-01 |
description |
Early embryo miscarriage is linked to inadequate endometrial decidualization, a cellular transformation process that enables deep blastocyst invasion into the maternal compartment. Although much of the cellular events that underpin endometrial stromal cell (ESC) decidualization are well recognized, the individual gene(s) and molecular pathways that drive the initiation and progression of this process remain elusive. Using a genetic mouse model and a primary human ESC culture model, we demonstrate that steroid receptor coactivator-2 (SRC-2) is indispensable for rapid steroid hormone-dependent proliferation of ESCs, a critical cell-division step which precedes ESC terminal differentiation into decidual cells. We reveal that SRC-2 is required for increasing the glycolytic flux in human ESCs, which enables rapid proliferation to occur during the early stages of the decidualization program. Specifically, SRC-2 increases the glycolytic flux through induction of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3), a major rate-limiting glycolytic enzyme. Similarly, acute treatment of mice with a small molecule inhibitor of PFKFB3 significantly suppressed the ability of these animals to exhibit an endometrial decidual response. Together, these data strongly support a conserved mechanism of action by which SRC-2 accelerates the glycolytic flux through PFKFB3 induction to provide the necessary bioenergy and biomass to meet the demands of a high proliferation rate observed in ESCs prior to their differentiation into decidual cells. Because deregulation of endometrial SRC-2 expression has been associated with common gynecological disorders of reproductive-age women, this signaling pathway, involving SRC-2 and PFKFB3, promises to offer new clinical approaches in the diagnosis and/or treatment of a non-receptive uterus in patients presenting idiopathic infertility, recurrent early pregnancy loss, or increased time to pregnancy. |
url |
http://europepmc.org/articles/PMC3812085?pdf=render |
work_keys_str_mv |
AT ramakrishnakommagani accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT mariamszwarc accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT ertugkovanci accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT williamegibbons accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT nagireddyputluri accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT sumanmaity accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT chadjcreighton accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT arunsreekumar accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT francescojdemayo accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT johnplydon accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization AT bertwomalley accelerationoftheglycolyticfluxbysteroidreceptorcoactivator2isessentialforendometrialdecidualization |
_version_ |
1725911005905551360 |