Ewe undernutrition alters cotyledon development and function

Abstract

Undernutrition is common for animals maintained on rangelands, particularly during periods of drought. Undernutrition during gestation can be detrimental to offspring development. The placenta is a known mediator for maternal-fetal nutrient exchange, and developmental impacts to the placenta during nutritional stress contribute to poor offspring outcomes. The objective of this study was to determine the impacts of maternal nutrient restriction on the development and function of placental cotyledons. Targhee ewes were allocated into two dietary treatment groups for the entirety of gestation. The control group (CON; n = 10) was fed to meet 100% of NRC requirements and the nutrient restricted group (NR; n = 11) was fed to meet 60% of NRC requirements, to mimic the nutritional stress experienced by range ewes during drought. At the time of lambing total placental weight, total cotyledon number, and lamb birth weight was recorded. Cotyledons (n = 3 / placenta) were removed from multiple locations, weighed, and processed for RNA-sequencing. Total placental weight, total cotyledon number, and lamb birth weight were not affected by maternal diet restriction (P > 0.05). Average cotyledon weight was greater in the CON group compared to the NR group (P < 0.05). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathways (KEGG) analyses were performed to identify biological pathways involved in placental function and nutrient transfer. Cotyledons from NR singletons vs CON singletons expressed 470 differentially expressed genes (DEGs; P < 0.05; 187 up-regulated, 283 down-regulated). Gene ontology terms represented by DEGs include hormone activity (P = 0.0003) and antigen processing and presentation (P = 0.0004 ). KEGG pathways of interest include pyruvate metabolism, estrogen signaling, extracellular matrix receptor interaction, and antigen processing and presentation. There were also 426 DEGs (P < 0.05; 195 up-regulated, 231 down-regulated) in cotyledons of NR twins vs CON twins. Represented GO categories include heme binding (P = 0.003) and oxidoreductase activity (P = 0.03). These data show that prolonged nutrient restriction alters cotyledon development and gene expression indicating impacts to placental function. These changes in placental function likely mediate poor offspring developmental outcomes observed following gestational under nutrition.