PMID- 29062003
OWN - NLM
STAT- MEDLINE
DCOM- 20190701
LR  - 20231112
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Oct 23
TI  - Maternal Glucocorticoid Elevation and Associated Fetal Thymocyte Apoptosis are 
      Involved in Immune Disorders of Prenatal Caffeine Exposed Offspring Mice.
PG  - 13746
LID - 10.1038/s41598-017-14103-7 [doi]
LID - 13746
AB  - Our previous study showed that prenatal caffeine exposure (PCE) could induce 
      intrauterine growth retardation (IUGR) and glucocorticoid elevation in the fetus. 
      Researchers suggested that IUGR is a risk factor for T helper cell (Th)1/Th2 
      deviation. However, whether PCE can induce these immune disorders and the 
      underlying mechanisms of that induction remain unknown. This study aimed to 
      observe the effects of PCE on the Th1/Th2 balance in offspring and further 
      explore the developmental origin mechanisms from the perspective of 
      glucocorticoid overexposure-induced thymocyte apoptosis. An IUGR model was 
      established by caffeine administration from gestational day (GD) 9 to GD 18, and 
      the offspring were immunized on postnatal day (PND) 42. The results show that 
      maternal glucocorticoid overexposure increased fetal thymocyte apoptosis by 
      activating both the Fas-mediated and the Bim-regulated apoptotic pathways. After 
      birth, accelerated thymocyte apoptosis and Th1 suppression were also found in the 
      PCE offspring at PND 14 and PND 49. Moreover, the PCE offspring showed immune 
      disorders after immunization, manifesting as increased IgG1/IgG2a ratio and IL-4 
      production in the serum. In conclusion, PCE could induce fetal overexposure to 
      maternal glucocorticoids and increase thymocyte apoptosis, which could persist 
      into postnatal life and be implicated in Th1 inhibition and further immune 
      disorders.
FAU - Liu, Han-Xiao
AU  - Liu HX
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Chen, Ting
AU  - Chen T
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Wen, Xiao
AU  - Wen X
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Qu, Wen
AU  - Qu W
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Liu, Sha
AU  - Liu S
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Yan, Hui-Yi
AU  - Yan HY
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Hou, Li-Fang
AU  - Hou LF
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China.
FAU - Ping, Jie
AU  - Ping J
AD  - Department of Pharmacology, Wuhan University School of Basic Medical Sciences, 
      Wuhan, 430071, China. pingjie@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171023
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cytokines)
RN  - 0 (Glucocorticoids)
RN  - 0 (RNA, Messenger)
RN  - 3G6A5W338E (Caffeine)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects/*immunology
MH  - Caffeine/*adverse effects
MH  - Cell Count
MH  - Cytokines/metabolism
MH  - Female
MH  - Fetus/immunology/metabolism
MH  - Glucocorticoids/blood/*metabolism
MH  - Maternal Exposure/*adverse effects
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Phenotype
MH  - Pregnancy
MH  - RNA, Messenger/genetics/metabolism
MH  - Signal Transduction/drug effects/immunology
MH  - Th1 Cells/cytology/drug effects
MH  - Th2 Cells/cytology/drug effects
MH  - Thymocytes/*cytology/*drug effects/immunology
MH  - Up-Regulation/drug effects/immunology
PMC - PMC5653827
COIS- The authors declare that they have no competing interests.
EDAT- 2017/10/25 06:00
MHDA- 2019/07/02 06:00
PMCR- 2017/10/23
CRDT- 2017/10/25 06:00
PHST- 2017/03/22 00:00 [received]
PHST- 2017/10/03 00:00 [accepted]
PHST- 2017/10/25 06:00 [entrez]
PHST- 2017/10/25 06:00 [pubmed]
PHST- 2019/07/02 06:00 [medline]
PHST- 2017/10/23 00:00 [pmc-release]
AID - 10.1038/s41598-017-14103-7 [pii]
AID - 14103 [pii]
AID - 10.1038/s41598-017-14103-7 [doi]
PST - epublish
SO  - Sci Rep. 2017 Oct 23;7(1):13746. doi: 10.1038/s41598-017-14103-7.