PMID- 18829104
OWN - NLM
STAT- MEDLINE
DCOM- 20090109
LR  - 20181113
IS  - 0143-4004 (Print)
IS  - 0143-4004 (Linking)
VI  - 29
IP  - 11
DP  - 2008 Nov
TI  - Maternal di-(2-ethylhexyl)-phthalate exposure influences essential fatty acid 
      homeostasis in rat placenta.
PG  - 962-9
LID - 10.1016/j.placenta.2008.08.011 [doi]
AB  - Maintaining essential fatty acid (EFA) homeostasis during pregnancy is critical 
      for fetal development. As the organ that controls the maternal-to-fetal supply of 
      nutrients, the placenta plays a significant role in guiding EFA transfer to the 
      fetus. Many EFA homeostasis proteins are regulated by peroxisome 
      proliferator-activated receptors (PPARs). The metabolites of 
      di-(2-ethylhexyl)-phthalate (DEHP), a ubiquitous environmental contaminant, might 
      influence EFA homeostasis via trans-activation of PPARs with subsequent 
      downstream effects on EFA transporters and enzymes. To investigate DEHP's effect 
      on placental/fetal EFA homeostasis, female Sprague-Dawley rats were orally 
      gavaged with either vehicle or DEHP at 750 or 1500 mg/kg/day from gestational day 
      (GD) 0 to GD 19. Changes in the expression of several EFA homeostasis regulating 
      proteins were determined in the junctional (JXN) and labyrinthine (LAB) zones of 
      the placenta, including PPAR isoforms (alpha, beta and gamma), fatty acid 
      translocase (FAT/CD36), fatty acid transport protein 1 (FATP1), plasma membrane 
      fatty acid binding protein (FABPpm), heart cytoplasmic fatty acid binding protein 
      (HFABP), cytochrome P450 (CYP) 4A1, and cyclooxygenase (COX)-1 and -2. 
      Additionally, effects of DEHP maternal exposure on the placental transfer and 
      fetal distribution of representative EFAs, arachidonic acid (AA) and 
      docosahexaenoic acid (DHA), and the placental production of prostaglandins (PGs) 
      were investigated. Expression of PPARalpha, PPARgamma, FAT/CD36, FATP1, HFABP and 
      CYP4A1 was up-regulated in JXN and/or LAB while COX-2 was down-regulated in JXN. 
      PPARbeta, FABPpm, and COX-1 demonstrated variable expression. Reduced directional 
      maternal-to-fetal placental transfer and altered fetal distribution of AA and DHA 
      were observed in concordance with a decreased total placental PG production. 
      These results correlate with previous in vitro data, suggesting that DEHP could 
      influence placental EFA homeostasis with potential downstream effects in the 
      developing fetus.
FAU - Xu, Y
AU  - Xu Y
AD  - Department of Pharmaceutics, Rutgers University, Piscataway, NJ 08854, USA.
FAU - Agrawal, S
AU  - Agrawal S
FAU - Cook, T J
AU  - Cook TJ
FAU - Knipp, G T
AU  - Knipp GT
LA  - eng
GR  - R03CA121403/CA/NCI NIH HHS/United States
GR  - R01 GM065448-04/GM/NIGMS NIH HHS/United States
GR  - R01 GM065448-03/GM/NIGMS NIH HHS/United States
GR  - R01 GM065448/GM/NIGMS NIH HHS/United States
GR  - R01GM065448/GM/NIGMS NIH HHS/United States
GR  - R03CA105465/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080930
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Fatty Acid Transport Proteins)
RN  - 0 (Fatty Acids)
RN  - 0 (PPAR alpha)
RN  - 0 (PPAR gamma)
RN  - 0 (PPAR-beta)
RN  - 0 (Plasticizers)
RN  - 0 (Prostaglandins)
RN  - 10028-17-8 (Tritium)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - C42K0PH13C (Diethylhexyl Phthalate)
RN  - EC 1.14.15.3 (Cytochrome P-450 CYP4A)
RN  - EC 1.14.99.1 (Cyclooxygenase 1)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/pharmacokinetics
MH  - Carbon Radioisotopes
MH  - Cyclooxygenase 1/genetics
MH  - Cytochrome P-450 CYP4A/genetics
MH  - Diethylhexyl Phthalate/*toxicity
MH  - Docosahexaenoic Acids/pharmacokinetics
MH  - Fatty Acid Transport Proteins/genetics
MH  - Fatty Acids/*metabolism
MH  - Female
MH  - Gene Expression/drug effects
MH  - Homeostasis/drug effects
MH  - PPAR alpha/genetics
MH  - PPAR gamma/genetics
MH  - PPAR-beta/genetics
MH  - Placenta/*drug effects/*physiology
MH  - Plasticizers/*toxicity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/metabolism/physiopathology
MH  - Prostaglandins/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tritium
PMC - PMC2680757
MID - NIHMS79847
EDAT- 2008/10/03 09:00
MHDA- 2009/01/10 09:00
PMCR- 2009/11/01
CRDT- 2008/10/03 09:00
PHST- 2008/05/29 00:00 [received]
PHST- 2008/07/24 00:00 [revised]
PHST- 2008/08/11 00:00 [accepted]
PHST- 2008/10/03 09:00 [pubmed]
PHST- 2009/01/10 09:00 [medline]
PHST- 2008/10/03 09:00 [entrez]
PHST- 2009/11/01 00:00 [pmc-release]
AID - S0143-4004(08)00248-8 [pii]
AID - 10.1016/j.placenta.2008.08.011 [doi]
PST - ppublish
SO  - Placenta. 2008 Nov;29(11):962-9. doi: 10.1016/j.placenta.2008.08.011. Epub 2008 
      Sep 30.