Differential Regulation Mechanisms Of Placental Fatty Acid Transporters Mediate Maternal Cadmium-Induced Fetal Growth Restriction

Cadmium(Cd) is one of the most toxic environmental pollutants that cause fetal malformation and growth restriction.However,the molecular mechanisms underlying maternal Cd toxicity on fetal growth remain largely unknown.Specially,the role of placental fatty acid transporters,has been poorly characterized in the etiology of Cd-induced fetal growth restriction(FGR).In the present study,5 fatty acid transporting protein(FATP)genes and 4 fatty acid binding protein(FABP)genes were examined in the Cd-exposed placentas.To further clarify the regulation mechanisms of the differentially expressed genes in response to Cd,the upstream factors and(or)signaling pathways of these genes were also examined.The results showed that FATP1,FATP6 and FABP3 were significantly downregulated in the Cd-exposed placentas when compared to the normal ones.The expression levels of phosphor-p38 MAPK were significantly decreased in the Cd-exposed placentas;while the expression levels of the peroxisome proliferator-activated receptor-?(PPAR-?)and hypoxia-inducible factor-1?(HIF-1?)were significantly decreased in the Cd-exposed placentas.There were no significant differences of p38 MAPK or retinoid X receptor-?(RXR-?)between the Cd-exposed groups and the control group.The methylation levels of the promoter regions of these three genes showed no significant differences in the Cd-exposed placentas.The conclusions are as follow:Firstly,the decreased placental expression of FATP1,FATP6 and FABP3 may be involved in the etiology of Cd-induced FGR.Secondly,the decreased FATP1 expression may be associated with the p38 MAPK pathway,but not the PPAR-?/RXR-? signaling.The decreased FATP6 expression may be correlated with the stimuli of both phosphor-p38 MAPK and PPAR-?.The decreased FABP3 expression may be caused by the hypoxia/HIF-1? regulation.Thirdly,the dysregulation of these three genes(FATP1,FATP6 and FABP3)are not involved in the changes of the DNA methylation levels of promoter regions.