Identification of gene sets and pathways associated with lactation performance in mice

Abstract

-Mammary transcriptome analyses across the lactation cycle and transgenic animal studies have identified candidate genes for mammogenesis, lactogenesis and involution; however, there is a lack of information on pathways that contribute to lactation performance. Previously we have shown significant differences in lactation performance, mammary gland histology, and gene expression profiles during lactation [lactation day 9 (L9)] between CBA/CaH (CBA) and the superior performing QSi5 strains of mice. In the present study, we compared these strains at midpregnancy [pregnancy day 12 (P12)] and utilized these data along with data from a 14th generation of intercross (AIL) to develop an integrative analysis of lactation performance. Additional analysis by quantitative reverse transcription PCR examined the correlation between expression profiles of lactation candidate genes and lactation performance across six inbred strains of mice. The analysis demonstrated that the mammary epithelial content per unit area was similar between CBA and QSi5 mice at P12, while differential expression was detected in 354 mammary genes (false discovery rate Ͻ 0.1). Gene ontology and functional annotation analyses showed that functional annotation terms associated with cell division and proliferation were the most enriched in the differentially expressed genes between these two strains at P12. Further analysis revealed that genes associated with neuroactive ligand-receptor interaction and calcium signaling pathways were significantly upregulated and positively correlated with lactation performance, while genes associated with cell cycle and DNA replication pathways were downregulated and positively correlated with lactation performance. There was also a significant negative correlation between Grb10 expression and lactation performance. In summary, using an integrative genomic approach we have identified key genes and pathways associated with lactation performance. gene sets; lactation performance; mammary transcriptome; microarray; qRT-PCR LACTATION IS A COMPLEX PROCESS involving biosynthesis, secretory activation, and metabolic regulation. However, compared with the physiological events of mammary (alveolar) development, secretory differentiation during pregnancy, secretory activation at parturition, and involution (48, 56), genetically determined variation in lactation performance can be relatively subtle, and thus genetic variation in expression of the key genes for regulating milk production can be difficult to detect. A strategy employing inbred mouse strains to identify candidate genes and pathways associated with lactation performance has been developed in our laboratory (52). Comparison of gene expression profiles of lactating mammary glands between the highperformance QSi5 strain and the relatively low-performance

DanQi Pill protects against heart failure through the arachidonic acid metabolism pathway by attenuating different cyclooxygenases and leukotrienes B4

“…These significantly enriched biological pathways provided important information on the mechanism of DQP. Many of these enriched pathways have been associated with HF, e.g., the importance of neuroactive ligand–receptor interaction in the development and progress of cardiovascular diseases [26]. The key proteins in this pathway, such as adrenergic, angiotensin, and calcitonin receptor-like neurotensin receptors, are closely related to cardiac function [27-29].…”

Genome-wide association and pathway-based analysis using latent variables related to milk protein composition and cheesemaking traits in dairy cattle

“…Overall, some of the identified GO and KEGG categories have been previously detected in gene-set enrichment studies using the individual CF t , CY, and REC phenotypes (Dadousis et al, 2016), milk yield traits (Iso-Touru et al, 2016), or gene expression studies of the mammary gland in mice (Ramanathan et al, 2008;Wei et al, 2013) and humans (Maningat et al, 2009).…”

“…Some of these terms have been previously connected with milk production in mice. More precisely, the GO _BP: 0006811 (ion transport), GO _MF: 0005216 (ion channel activity), GO_MF: 0022838 (substrate-specific channel activity), and GO _MF: 0015267 (channel activity) were upregulated in mice with increased milk yield (Wei et al, 2013). Moreover, it is known that in the cheese process the caseins react with calcium ions.…”

Anesthetic Propofol-Induced Gene Expression Changes in Patients Undergoing Coronary Artery Bypass Graft Surgery Based on Dynamical Differential Coexpression Network Analysis

“…Significantly, in the current study, pathway enrichment results indicated that genes in key modules 1, 2, 3, 5, 6, and 7 were simultaneously enriched in the pathway of neuroactive ligand-receptor interaction. As documented, the pathway of neuroactive ligand-receptor interaction has been demonstrated to be associated with the development and progress of cardiovascular diseases [ 46 ]. The key proteins in this pathway, such as angiotensin, adrenergic, and calcitonin receptor-like neurotensin receptors, have also been indicated to be closely related to cardiac function [ 47 , 48 ].…”