PMID- 22243401
OWN - NLM
STAT- MEDLINE
DCOM- 20121217
LR  - 20131121
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 39
IP  - 4
DP  - 2012 Apr
TI  - Role of p53-dependent placental apoptosis in the reproductive and developmental 
      toxicities of caffeine in rodents.
PG  - 357-63
LID - 10.1111/j.1440-1681.2012.05676.x [doi]
AB  - The aim of the present study was to evaluate the role of placental apoptosis in 
      mediating the reproductive and developmental toxicity of caffeine in rodents. 
      Female Kunming mice were treated with caffeine (60, 120 and 240 mg/kg per day) 
      before and during pregnancy. The conception rate, maternal bodyweight gain, 
      placental weight and indices of fetal developmental, including the rate of 
      intrauterine growth retardation (IUGR; i.e. the actual number of fetuses 
      exhibiting IUGR as a percentage of the total number of fetuses), were determined 
      on gestational day (GD) 18. Female Wistar rats were treated with caffeine (20, 60 
      and 180 mg/kg per day) from GD11 to GD20. The IUGR rate, maternal plasma 
      angiotensin (Ang) II and prolactin concentrations, placental pathology, 
      expression of angiotensin AT(1) and AT(2) receptors and apoptosis-related 
      proteins were measured on GD20. In mice, caffeine treatment dose-dependently 
      reduced the total conception rate, delayed conception and decreased maternal 
      bodyweight gain, placental weight, fetal bodyweight and fetal body and tail 
      lengths, whereas the IUGR rate was increased. In rats, caffeine treatment 
      dose-dependently decreased placental weight and fetal bodyweight and increased 
      the IUGR rate. Abnormal placental structures and decreased maternal plasma 
      prolactin concentrations were observed following 180 mg/kg per day caffeine 
      treatment, which resulted in increases in renin-angiotensin system (RAS) 
      activity, including maternal plasma AngII concentrations and placental AT(1B) and 
      AT(2) receptor expression, and Bax and p53 expression, but decreases in placental 
      Bcl-2 expression. On the basis of the results of the present study, it appears 
      that caffeine ingestion has detrimental effects on the reproductive system and 
      fetal development in rodents that are associated with chronic activation of the 
      maternal and placental RAS, and induction of p53-dependent placental apoptosis.
CI  - (c) 2012 The Authors Clinical and Experimental Pharmacology and Physiology (c) 2012 
      Blackwell Publishing Asia Pty Ltd.
FAU - Huang, Jing
AU  - Huang J
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, 185 Donghu 
      Road, Wuhan 430071, China.
FAU - Zhou, Shu
AU  - Zhou S
FAU - Ping, Jie
AU  - Ping J
FAU - Pan, Xiaoliang
AU  - Pan X
FAU - Liang, Gai
AU  - Liang G
FAU - Xu, Dan
AU  - Xu D
FAU - Kou, Hao
AU  - Kou H
FAU - Bao, Chong
AU  - Bao C
FAU - Wang, Hui
AU  - Wang H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 3G6A5W338E (Caffeine)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects/physiology
MH  - Caffeine/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fertilization/drug effects/physiology
MH  - Fetal Development/*drug effects/physiology
MH  - Mice
MH  - Placenta/*drug effects/physiology
MH  - Pregnancy
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
MH  - Reproduction/*drug effects/physiology
MH  - Tumor Suppressor Protein p53/*physiology
EDAT- 2012/01/17 06:00
MHDA- 2012/12/18 06:00
CRDT- 2012/01/17 06:00
PHST- 2012/01/17 06:00 [entrez]
PHST- 2012/01/17 06:00 [pubmed]
PHST- 2012/12/18 06:00 [medline]
AID - 10.1111/j.1440-1681.2012.05676.x [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2012 Apr;39(4):357-63. doi: 
      10.1111/j.1440-1681.2012.05676.x.