PMID- 34052757
OWN - NLM
STAT- MEDLINE
DCOM- 20210707
LR  - 20210707
IS  - 1090-2414 (Electronic)
IS  - 0147-6513 (Linking)
VI  - 220
DP  - 2021 Sep 1
TI  - Exposure to ethephon compromises endometrial decidualization in mice during early 
      pregnancy via GPR120.
PG  - 112361
LID - S0147-6513(21)00473-5 [pii]
LID - 10.1016/j.ecoenv.2021.112361 [doi]
AB  - Exposure to ethephon (ETH), a plant growth regulator commonly used for several 
      purposes, can potentially decrease sperm numbers and viability. Occasional 
      findings regarding ETH effects on female reproduction during early pregnancy have 
      also been reported. During early pregnancy, endometrial decidualization is a 
      critical event for embryo implantation and pregnancy maintenance. Thus, we aimed 
      to explore the effect and mechanism of ETH on endometrial decidualization both in 
      vivo and in vitro. Mice were gavaged with 0 and 285 mg/kg b.w. ETH from 
      gestational days (GD)1 until sacrifice, whereas pseudopregnant mice from 
      pseudopregnant day 1 (PPD-1) until PPD-8. Primary mouse endometrial stromal cells 
      (mESCs) received 640 ug/ml ETH and added E2 and P4 to induce decidualization. 
      Results indicated female albino CD1 mice exposed to high dose of ETH (285 mg/kg 
      b.w.) by oral gavage, the number of embryo implantation sites on GD6 and GD8 were 
      significantly decreased, the levels of serum E2 and P4 on GD8 were significantly 
      decreased. Compared with the control group, the decidualization response 
      artificially induced by corn oil in pseudopregnant mice and by E2 and P4 in 
      primary mouse endometrial stromal cells (mESCs) was weakened in the high dose of 
      ETH treated group. The high dose, 285 mg/kg b.w ETH treated group altered the 
      expression of endometrial decidual markers on GD6 and GD8. The triglyceride and 
      fatty acid metabolism-related genes were significantly increased after female 
      albino CD1 mice exposed to high does, 285 mg/kg b.w ETH on GD6 and GD8. GPR120 
      was substantially reduced after ETH treatment. When overexpression of GPR120, the 
      compromised decidualization induced by ETH treatment was rescued. Furthermore, 
      molecular docking presented Thr234 and His251 of GPR120 as preferred binding 
      sites for ETH. Mutation of these two sites rescued the compromised 
      decidualization induced by ETH. In conclusion, we demonstrated that ETH exposure 
      could impair decidualization during early pregnancy. GPR120 expression and 
      binding between GPR120 and ETH are crucial for impaired decidualization mediated 
      via ETH.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Huang, Chunling
AU  - Huang C
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China.
FAU - Wang, Dan
AU  - Wang D
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China.
FAU - Li, Na
AU  - Li N
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China.
FAU - Yang, Chengshun
AU  - Yang C
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China.
FAU - Chen, Xuemei
AU  - Chen X
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China.
FAU - Liu, Xueqing
AU  - Liu X
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China.
FAU - He, Junlin
AU  - He J
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China.
FAU - Ding, Yubin
AU  - Ding Y
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China.
FAU - Tong, Chao
AU  - Tong C
AD  - Department of Obstetrics and Gynecology, The First Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400016, China; Laboratory of Maternal and 
      Fetal Medicine, The First Affiliated Hospital of Chongqing Medical University, 
      Chongqing 400016, China.
FAU - Peng, Chuan
AU  - Peng C
AD  - Laboratory of Maternal and Fetal Medicine, The First Affiliated Hospital of 
      Chongqing Medical University, Chongqing 400016, China.
FAU - Li, Fangfang
AU  - Li F
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China.
FAU - Wang, Yingxiong
AU  - Wang Y
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China. Electronic address: yxwang@cqmu.edu.cn.
FAU - Gao, Rufei
AU  - Gao R
AD  - Laboratory of Reproductive Biology, School of Public Health and Management, 
      Chongqing Medical University, Chongqing 400016, China; Joint International 
      Research Laboratory of Reproduction & Development, Chongqing Medical University, 
      Chongqing 400016, China. Electronic address: gao_ru_fei@cqmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210527
PL  - Netherlands
TA  - Ecotoxicol Environ Saf
JT  - Ecotoxicology and environmental safety
JID - 7805381
RN  - 0 (FFAR4 protein, mouse)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Plant Growth Regulators)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - XU5R5VQ87S (ethephon)
SB  - IM
MH  - Animals
MH  - Decidua/drug effects/metabolism/pathology
MH  - Embryo Implantation/drug effects
MH  - Endometrium/*drug effects/metabolism/pathology
MH  - Female
MH  - Mice
MH  - Molecular Docking Simulation
MH  - Organophosphorus Compounds/chemistry/*toxicity
MH  - Plant Growth Regulators/chemistry/*toxicity
MH  - Pregnancy
MH  - Receptors, G-Protein-Coupled/chemistry/*metabolism
MH  - Stromal Cells/drug effects/metabolism/pathology
OTO - NOTNLM
OT  - Decidualization
OT  - Embryo implantation
OT  - Ethephon
OT  - G-protein-coupled receptor 120
OT  - Lipid metabolism
EDAT- 2021/05/31 06:00
MHDA- 2021/07/08 06:00
CRDT- 2021/05/30 21:01
PHST- 2021/01/05 00:00 [received]
PHST- 2021/05/17 00:00 [revised]
PHST- 2021/05/19 00:00 [accepted]
PHST- 2021/05/31 06:00 [pubmed]
PHST- 2021/07/08 06:00 [medline]
PHST- 2021/05/30 21:01 [entrez]
AID - S0147-6513(21)00473-5 [pii]
AID - 10.1016/j.ecoenv.2021.112361 [doi]
PST - ppublish
SO  - Ecotoxicol Environ Saf. 2021 Sep 1;220:112361. doi: 10.1016/j.ecoenv.2021.112361. 
      Epub 2021 May 27.