Assisted reproduction causes intrauterus growth restriction by disrupting placental lipid metabolism

AbstractIVF related intrauterus growth restriction or low birth weight (LBW) is very common in ART clinic. This study is focus on the aberrant lipid metabolism induced by in vitro fertilization and its mechanism. Firstly, we investigated the effect of IVF on fetal weight and placenta efficiency at E18.5 (at birth) and E14.5 (middle gestation). Data shows that IVF caused LBW and low placenta efficiency. Then we studied the lipidomics of E18.5 placenta and E14.5 placenta. The IVF group has an eccentric lipid content compared toin vivogroup. All the 15 lipid classes are largely accumulated in E18.5 IVF placenta and are deficient in E14.5 IVF placenta. In detail, most of the 287 lipid species is accumulated at E18.5 and went short at E14.5. Using qRT-PCR we detected the expression level of genes related to lipid uptake, transport and metabolism. Most of these genes are down-regulated which indicated the metabolism function of placenta is disrupted seriously. To the imprinted genes for lipid metabolism regulation asGNASandGrb10, IVF not only disrupt their imprinting status (methylation level) but also disrupt their gene expression. The expression ofDNMTsandTetsare also disrupted in the placenta. These data demonstrate that IVF impaired the regulation network of lipid metabolism. These results prove the hypothesis: imperfect IVF condition of fertilization jeopardize the expressionDNMTs,Tetsand imprinting status of imprinted genes for lipid metabolism regulation. Then it causes to abnormal expression of genes for lipid metabolism and regulation. This leads to the significant differences in lipid species quantification and lipid metabolism. So it contributed to low lipid transport efficiency, restricted fetal growth and LBW. This study provides a renewed knowledge of lipid metabolism in placenta and its relation to imprinted genes and gave some clinical aware for optimizing the ART practice.FundingThis work was supported by grants from the National Basic Research Program of China (973 Program) and National Natural Science Foundation of China.Competing InterestsThe authors have declared that no competing interests exist.AbbreviationsARTartificial reproductive technologyIVFin vitro fertilizationLBWlow birth weightGNASGuanine Nucleotide Binding Protein AlphaGrb10Growth factor receptor-bound protein 10