Location: Livestock Bio-Systems
Title: Chorionic somatomammotropin deficiency perturbs the metabolic transcriptome in the ruminant placentaAuthor
TANNER, AMELIA - Colorado State University | |
Cushman, Robert - Bob | |
ANTHONY, RUSSELL - Colorado State University |
Submitted to: Translational Animal Science
Publication Type: Proceedings Publication Acceptance Date: 9/23/2021 Publication Date: 12/1/2021 Citation: Tanner, A.R., Cushman, R.A., Anthony, R.V. 2021. Chorionic somatomammotropin deficiency perturbs the metabolic transcriptome in the ruminant placenta. Translational Animal Science. 5(Supplement S1):S67-S71. https://doi.org/10.1093/tas/txab175. DOI: https://doi.org/10.1093/tas/txab175 Interpretive Summary: Technical Abstract: In response to chorionic somatomammotropin (CSH) RNA interference (RNAi), two distinct phenotypes emerge: 1) pregnancies with intrauterine growth restriction (IUGR) and 2) pregnancies with normal fetal and placental weights. We hypothesized that CSH RNAi would result in placental transcriptional perturbations to cell function and metabolism in both CSH RNAi IUGR and non-IUGR phenotypes. To test this hypothesis, the trophectoderm of hatched blastocysts (9 days of gestational age; dGA) were infected with a lentivirus expressing either a scrambled control (CON; n=8) or CSH-specific shRNA (tg6; n=16) and subsequently transferred into synchronized recipient ewes. Cotyledons were then harvested at 135 dGA from pregnancies classified as CSH RNAi with IUGR (CSH-IUGR; n=5) or CSH RNAi normal weight (CSH-NW; n=5) based on fetal and placental weight reductions compared to control RNAi (CON; n=5). RNA-sequencing was performed on the Illumina NovaSEQ6000 platform and a total of 442 differentially expressed genes (DEGs) were identified with a Q = 0.10. 346 DEGs were found (Q = 0.10) between CON vs. CSH-IUGR and 96 DEGs (Q = 0.10) between CON vs. CSH-NW with 36 common DEGs between analyses. Functional analysis of DEGs was conducted for fit into functional categories impacting metabolism, nutrient transport and cell function. Analysis of CON vs CSH-IUGR pregnancies revealed perturbations (P= 0.05) in protein processing, regulation of cAMP, cell proliferation, carbon metabolism, and metabolic pathways. Furthermore, 185 genes in the following six functional categories were also identified (P=0.01): cell-to-cell signaling, cellular movement, protein synthesis, cell death, lipid metabolism and hematological development and function. Functional analysis of CON vs CSH-NW pregnancies revealed the unique functional categories (P=0.01) of post-translational modification, cell signaling, and connective tissue development. These results support our hypothesis that CSH RNAi perturbs metabolic and cellular function in both IUGR and non-IUGR phenotypes. These transcriptional changes combined with our previous in vivo physiology data support the idea that CSH RNAi pregnancies experience physiological and transcriptional ramifications regardless of fetal weight. Lastly, by continuing to examine and test unique transcriptional changes to functional groups and genes in both CSH RNAi phenotypes, we will elucidate pathways involved in the development of CSH RNAi dependent IUGR. |