Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally.
Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg·d) from gestational days (GD) 11 to 20, or 180 mg/kg·d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose-effect study and on GD11, 14 and 17 in the time-course study were analyzed by ¹H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR.
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
Hao
H
Kou
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
Yansong
Y
Liu
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
Gai
G
Liang
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
Jing
J
Huang
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
Jieqiong
J
Hu
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
You-e
YE
Yan
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.
Xiaojun
X
Li
Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, China.
Hong
H
Yu
Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, China.
Xiaohua
X
He
Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, China.
Baifang
B
Zhang
Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, China; Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Yuanzhen
Y
Zhang
Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China. Electronic address: jianghua.feng@xmu.edu.cn.
Jianghua
J
Feng
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China; Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
Hui
H
Wang
D000818:Animals; D002110:Caffeine / Q000009:adverse effects*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood* / Q000209:etiology / Q000473:pathology; D020567:Fetal Weight / Q000187:drug effects; D005333:Fetus / Q000187:drug effects; D005938:Glucocorticoids / Q000097:blood*; D008279:Magnetic Resonance Imaging; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D055442:Metabolome; D015999:Multivariate Analysis; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D005938:Glucocorticoids; D002110:Caffeine; D003345:Corticosterone
Caffeine; Intrauterine growth retardation; Maternal glucocorticoid; Metabolic programming; Metabonome