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Title: Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism

Abstract

It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30–120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8–20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreasedmore » cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. - Highlights: • Caffeine reduced fetal blood leptin level. • Caffeine inhibited placental leptin production and transport. • Caffeine down-regulated placental leptin expression via antagonizing ADORA2. • Caffeine inhibited placental leptin transport via decreased OB-Ra expression.« less

Authors:
 [1];  [2];  [1];  [2]; ; ;  [1];  [3];  [1]
  1. Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China)
  2. Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)
  3. Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)
Publication Date:
OSTI Identifier:
22687816
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 289; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABUNDANCE; ADENOSINE; AMP; BLOOD; CAFFEINE; CONCENTRATION RATIO; CYCLASES; ECOLOGICAL CONCENTRATION; FETUSES; IN VITRO; IN VIVO; INHIBITION; LEPTIN; MESSENGER-RNA; PLACENTA; PREGNANCY; RATS; RECEPTORS; TIME DEPENDENCE; TRANSCRIPTION; TRANSCRIPTION FACTORS

Citation Formats

Wu, Yi-meng, Luo, Han-wen, Kou, Hao, Wen, Yin-xian, Shen, Lang, Pei, Ling-guo, Zhou, Jin, Zhang, Yuan-zhen, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, Wang, Hui, and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071. Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.09.007.
Wu, Yi-meng, Luo, Han-wen, Kou, Hao, Wen, Yin-xian, Shen, Lang, Pei, Ling-guo, Zhou, Jin, Zhang, Yuan-zhen, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, Wang, Hui, & Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071. Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism. United States. doi:10.1016/J.TAAP.2015.09.007.
Wu, Yi-meng, Luo, Han-wen, Kou, Hao, Wen, Yin-xian, Shen, Lang, Pei, Ling-guo, Zhou, Jin, Zhang, Yuan-zhen, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, Wang, Hui, and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071. Sun . "Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism". United States. doi:10.1016/J.TAAP.2015.09.007.
@article{osti_22687816,
title = {Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism},
author = {Wu, Yi-meng and Luo, Han-wen and Kou, Hao and Wen, Yin-xian and Shen, Lang and Pei, Ling-guo and Zhou, Jin and Zhang, Yuan-zhen and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 and Wang, Hui and Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071},
abstractNote = {It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30–120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8–20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. - Highlights: • Caffeine reduced fetal blood leptin level. • Caffeine inhibited placental leptin production and transport. • Caffeine down-regulated placental leptin expression via antagonizing ADORA2. • Caffeine inhibited placental leptin transport via decreased OB-Ra expression.},
doi = {10.1016/J.TAAP.2015.09.007},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 289,
place = {United States},
year = {2015},
month = {11}
}