PMID- 31827696
OWN - NLM
STAT- MEDLINE
DCOM- 20200504
LR  - 20200505
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2019
DP  - 2019
TI  - Obeticholic Acid Protects against Gestational Cholestasis-Induced Fetal 
      Intrauterine Growth Restriction in Mice.
PG  - 7419249
LID - 10.1155/2019/7419249 [doi]
LID - 7419249
AB  - Gestational cholestasis is a common disease and is associated with adverse 
      pregnancy outcomes. However, there are still no effective treatments. We 
      investigated the effects of obeticholic acid (OCA) on fetal intrauterine growth 
      restriction (IUGR) during 17alpha-ethynylestradiol- (E2-) induced gestational 
      cholestasis in mice. All pregnant mice except controls were subcutaneously 
      injected with E2 (0.625 mg/kg) daily from gestational day (GD) 13 to GD17. Some 
      pregnant mice were orally administered with OCA (5 mg/kg) daily from GD12 to 
      GD17. As expected, OCA activated placental, maternal, and fetal hepatic FXR 
      signaling. Additionally, exposure with E2 during late pregnancy induced 
      cholestasis, whereas OCA alleviated E2-induced cholestasis. Gestational 
      cholestasis caused reduction of fetal weight and crown-rump length and elevated 
      the incidence of IUGR. OCA decreased the incidence of IUGR during cholestasis. 
      Interestingly, OCA attenuated reduction of blood sinusoid area in placental 
      labyrinth layer and inhibited downregulation of placental sodium-coupled neutral 
      amino acid transporter- (SNAT-) 2 during cholestasis. Additional experiment found 
      that OCA attenuated glutathione depletion and lipid peroxidation in placenta and 
      fetal liver and placental protein nitration during cholestasis. Moreover, OCA 
      inhibited the upregulation of placental NADPH oxidase-4 and antioxidant genes 
      during cholestasis. OCA activated antioxidant Nrf2 signaling during cholestasis. 
      Overall, we demonstrated that OCA treatment protected against gestational 
      cholestasis-induced placental dysfunction and IUGR through suppressing placental 
      oxidative stress and maintaining bile acid homeostasis.
CI  - Copyright (c) 2019 Wei Chen et al.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Histology and Embryology, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, 
      Anhui Medical University, Hefei, China.
FAU - Gao, Xing-Xing
AU  - Gao XX
AD  - Department of Histology and Embryology, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, 
      Anhui Medical University, Hefei, China.
FAU - Ma, Li
AU  - Ma L
AD  - Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, 
      Anhui Medical University, Hefei, China.
FAU - Liu, Zhi-Bing
AU  - Liu ZB
AD  - Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, 
      Anhui Medical University, Hefei, China.
FAU - Li, Li
AU  - Li L
AD  - The First Affiliated Hospital, Anhui Medical University, Hefei, China.
FAU - Wang, Hua
AU  - Wang H
AD  - Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, 
      Anhui Medical University, Hefei, China.
FAU - Gao, Lan
AU  - Gao L
AD  - Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, 
      Anhui Medical University, Hefei, China.
FAU - Xu, De-Xiang
AU  - Xu DX
AUID- ORCID: 0000-0002-5126-4335
AD  - Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, 
      Anhui Medical University, Hefei, China.
FAU - Chen, Yuan-Hua
AU  - Chen YH
AUID- ORCID: 0000-0001-7344-4436
AD  - Department of Histology and Embryology, Anhui Medical University, Hefei, China.
AD  - Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, 
      Anhui Medical University, Hefei, China.
LA  - eng
PT  - Journal Article
DEP - 20191115
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (Estrogens)
RN  - 0462Z4S4OZ (obeticholic acid)
RN  - 0GEI24LG0J (Chenodeoxycholic Acid)
RN  - 423D2T571U (Ethinyl Estradiol)
RN  - Intrahepatic Cholestasis of Pregnancy
SB  - IM
MH  - Animals
MH  - Chenodeoxycholic Acid/*analogs & derivatives/pharmacology
MH  - Cholestasis, Intrahepatic/chemically induced/*complications
MH  - Estrogens/toxicity
MH  - Ethinyl Estradiol/toxicity
MH  - Female
MH  - Fetal Growth Retardation/etiology/metabolism/pathology/*prevention & control
MH  - Fetus/*drug effects/metabolism
MH  - Lipid Peroxidation/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Oxidative Stress/drug effects
MH  - Pregnancy
MH  - Pregnancy Complications/chemically induced
MH  - Signal Transduction/drug effects
PMC - PMC6885290
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/12/13 06:00
MHDA- 2020/05/06 06:00
PMCR- 2019/11/15
CRDT- 2019/12/13 06:00
PHST- 2019/02/21 00:00 [received]
PHST- 2019/04/25 00:00 [revised]
PHST- 2019/09/23 00:00 [accepted]
PHST- 2019/12/13 06:00 [entrez]
PHST- 2019/12/13 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2019/11/15 00:00 [pmc-release]
AID - 10.1155/2019/7419249 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2019 Nov 15;2019:7419249. doi: 10.1155/2019/7419249. 
      eCollection 2019.