Placental transcriptome adaptations to maternal nutrient restriction in sheep

Placental development is modified in response to maternal nutrient restriction (NR) resulting in a spectrum of fetal growth rates. Pregnant sheep carrying singleton fetuses and fed either 100% (n=8) or 50% (NR; n=28) of their National Research Council (NRC) recommended intake from Days 35 to 135 of pregnancy were used to elucidate placentome transcriptome alterations at both Day 70 and 135. NR fetuses were further designated into upper (NR NonSGA; n=7) and lower quartiles (NR SGA; n=7) based on Day 135 fetal weight. At Day 70 of pregnancy, there were 22 genes dysregulated between NR SGA and 100% NRC placentomes, 27 genes between NR NonSGA and 100% NRC placentomes, and 22 genes between NR SGA and NR NonSGA placentomes. These genes mediated molecular functions such as MHC class II protein binding, signaling receptor binding, and cytokine activity. Gene Set Enrichment Analysis (GSEA) revealed significant overrepresentation of genes for natural killer cell-mediated cytotoxicity in NR SGA compared to 100% NRC placentomes and alterations in nutrient utilization pathways between NR SGA and NR NonSGA placentomes at Day 70. Results identify novel factors associated with impaired function in SGA placentomes and potential for placentomes from NR NonSGA pregnancies to adapt to nutritional hardship. Samples from control pregnancies (n=8) as well as the upper (n=7) and lower (n=7) quartiles of the nutrient restricted pregnancies were analyzed at Days 70 and 135 of pregnancy. ***Please note that raw data are not provided because they were lost***