PMID- 33983443
OWN - NLM
STAT- MEDLINE
DCOM- 20220121
LR  - 20220121
IS  - 1460-2407 (Electronic)
IS  - 1360-9947 (Linking)
VI  - 27
IP  - 6
DP  - 2021 May 29
TI  - Endometrial epithelial-mesenchymal transition (EMT) by menstruation-related 
      inflammatory factors during hypoxia.
LID - gaab036 [pii]
LID - 10.1093/molehr/gaab036 [doi]
AB  - Endometriosis is characterised by inflammation and fibrotic changes. Our previous 
      study using a mouse model showed that proinflammatory factors present in 
      peritoneal haemorrhage exacerbated inflammation in endometriosis-like grafts, at 
      least in part through the activation of prostaglandin (PG) E2 receptor and 
      protease-activated receptor (PAR). In addition, hypoxia is a well-known inducer 
      of fibrosis that may be associated with epithelial-mesenchymal transition (EMT). 
      However, the complex molecular interactions between hypoxia and proinflammatory 
      menstruation-related factors, PGE2 and thrombin, a PAR1 agonist, on EMT in 
      endometriosis have not been fully characterised. To explore the effects of 
      hypoxia and proinflammatory factors on EMT-like changes in endometrial cells, we 
      determined the effects of PGE2 and thrombin (P/T) on EMT marker expression and 
      cell migration in three dimensional cultured human endometrial epithelial cells 
      (EECs) and endometrial stromal cells (ESCs). Treatment of EECs with P/T under 
      hypoxia stimulated cell migration, increased the expression of mesenchymal 
      N-cadherin, vimentin and C-X-C chemokine receptor type 4 (CXCR4), and reduced the 
      expression of epithelial E-cadherin. Furthermore, treatment with C-X-C motif 
      chemokine ligand 12 (CXCL12), a ligand for CXCR4, increased EMT marker expression 
      and cell migration. In ESCs, P/T or oestrogen treatment under hypoxic conditions 
      increased the expression and secretion of CXCL12. Taken together, our data show 
      that hypoxic and proinflammatory stimuli induce EMT, cell migration and 
      inflammation in EECs, which was increased by CXCL12 derived from ESCs. These data 
      imply that inflammatory mediators in retrograde menstrual fluid contribute to 
      ectopic endometrial EMT and migration in the presence of peritoneal hypoxia.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of European 
      Society of Human Reproduction and Embryology. All rights reserved. For 
      permissions, please email: journals.permissions@oup.com.
FAU - Kusama, K
AU  - Kusama K
AUID- ORCID: 0000-0002-9120-0475
AD  - Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo 192-0392, Japan.
FAU - Fukushima, Y
AU  - Fukushima Y
AD  - Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo 192-0392, Japan.
FAU - Yoshida, K
AU  - Yoshida K
AD  - Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo 192-0392, Japan.
FAU - Sakakibara, H
AU  - Sakakibara H
AD  - Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo 192-0392, Japan.
FAU - Tsubata, N
AU  - Tsubata N
AD  - Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo 192-0392, Japan.
FAU - Yoshie, M
AU  - Yoshie M
AD  - Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo 192-0392, Japan.
FAU - Kojima, J
AU  - Kojima J
AD  - Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 
      160-0023, Japan.
FAU - Nishi, H
AU  - Nishi H
AD  - Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 
      160-0023, Japan.
FAU - Tamura, K
AU  - Tamura K
AUID- ORCID: 0000-0003-3351-895X
AD  - Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life 
      Sciences, Tokyo 192-0392, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mol Hum Reprod
JT  - Molecular human reproduction
JID - 9513710
RN  - 0 (Biomarkers)
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Inflammation Mediators)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 3.4.21.5 (Thrombin)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Adult
MH  - Biomarkers
MH  - Cell Culture Techniques, Three Dimensional
MH  - *Cell Hypoxia
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Chemokine CXCL12/metabolism/pharmacology
MH  - Dinoprostone/pharmacology
MH  - Endometriosis/*etiology/pathology
MH  - Endometrium/metabolism/*pathology
MH  - Epithelial Cells/drug effects
MH  - *Epithelial-Mesenchymal Transition
MH  - Estradiol/pharmacology
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Inflammation
MH  - Inflammation Mediators/metabolism
MH  - Menstruation/*physiology
MH  - Menstruation Disturbances/metabolism/*pathology
MH  - Spheroids, Cellular
MH  - Stromal Cells/drug effects
MH  - Thrombin/pharmacology
OTO - NOTNLM
OT  - CXCL12
OT  - CXCR4
OT  - endometrial cell
OT  - endometriosis
OT  - epithelial-mesenchymal transition
OT  - hypoxia
EDAT- 2021/05/14 06:00
MHDA- 2022/01/22 06:00
CRDT- 2021/05/13 12:35
PHST- 2021/02/06 00:00 [received]
PHST- 2021/04/27 00:00 [revised]
PHST- 2021/05/14 06:00 [pubmed]
PHST- 2022/01/22 06:00 [medline]
PHST- 2021/05/13 12:35 [entrez]
AID - 6275231 [pii]
AID - 10.1093/molehr/gaab036 [doi]
PST - ppublish
SO  - Mol Hum Reprod. 2021 May 29;27(6):gaab036. doi: 10.1093/molehr/gaab036.