|Freking, Bradley - Brad|
|Nonneman, Danny - Dan|
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/21/2012
Publication Date: 1/31/2013
Publication URL: http://handle.nal.usda.gov/10113/57864
Citation: Bischoff, S.R., Tsai, S.Q., Hardison, N.E., Motsinger-Reif, A.A., Freking, B.A., Nonneman, D.J., Rohrer, G.A., Piedrahita, J.A. 2013. Differences in X-chromosome transcriptional activity and cholesterol metabolism between placentae from swine breeds from Asian and Western origins. PLoS One. 8(1):e55345. Interpretive Summary: Chinese Meishan germplasm has contributed greatly to many efforts in swine genomics and genetics. It has been successfully utilized in comparison to western breeds to develop genome linkage maps, identify and map quantitative trait loci for reproductive, growth, and carcass traits. They are a particularly useful model to study embryonic and placental growth with very large litter sizes yet improved fitness traits over western breeds. When compared to commercial western breeds, the Chinese Meishan farrow three to five more piglets per litter, and this greater litter size has been attributed to major differences in placental morphology and physiology. We investigated gene expression differences in placental tissue between a commercial white composite swine population and the prolific Chinese Meishan to potentially uncover candidate pathways influencing placental efficiency. The placenta serves as a critical transport organ between the developing fetus and mother to regulate nutrient exchange, excretion of waste, oxygen and hormones. Interactions among genes and environmental cues influence intrauterine growth and may lead to aberrant physiological programs in the adult through fetal programming. Identifying key physiology pathways, by identifying genes involved in those pathways, help to clarify how the fetus is sensitized to environmental inputs, such as under nutrition or uterine crowding. We used the Affymetrix porcine expression microarray to interrogate approximately 20,200 genes. The study surveyed placental gene expression throughout gestation at 20 day intervals (days 25, 45, 65, 85, and 105) to identify both breed differences and temporal differences throughout the gestational period. We identified cholesterol biosynthesis as a major functional pathway up-regulated in Chinese Meishan and down-regulated in the white composite breed. Furthermore, we identified different forms of XIST, a gene important in early development, expressed between the two breeds. This provides information to target physiological studies in any swine population to see if modulation of cholesterol biosynthetic pathways can favorably influence placental efficiency and fetal survival.
Technical Abstract: To gain insight into placental physiology differences between the Chinese Meishan and white composite (WC) swine breeds, short-oligonucleotide microarray gene expression profiles of gestational Day 25, 45, 65, 85, and 105 placental tissues were compared. Differential expression was determined by a gene-by-gene linear mixed model using a false-discovery rate q-value = 0.05. Both breed effects and breed x day effects were analyzed. Estimate statements were generated to exclude probe-by-breed interaction effects that may bias differential expression because of breed-specific single feature polymorphisms in probes. A total of 1596 differentially expressed genes were identified between the two breeds. Among these genes, X-linked inactivating transcript or XIST showed expression differences between the swine breeds, and this observation was attributed to the presence of breed-specific isoforms of XIST. We explored the interaction of placental gene expression and chromosomal location by the differential gene locus mapping method (DIGMAP). Our bioinformatic analyses revealed three Sus scrofa X chromosomal bands (Xq13, Xq21, Xp11) that were significantly different between the breeds and, notably, Xq11 contained XIST. Collective analyses using software by DAVID and Ingenuity, pathway tools indicated significant p < 0.02 upregulation of sterol biosynthesis (cholesterol) in the placentas of the Meishan breed. Taken together, this work provides a summary of transcriptome differences during feto-placental development between two breeds with marked differences in prolificacy, and fetal and placental birth weights. The data reported in this paper have been deposited in NCBI’s Gene Expression Omnibus (GEO) accession numbers GSE10446, GSE10447.