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Differential gene expression in lactating rats compared against age matched virgin controls

ABSTRACT: Gene level analysis of lactating day 10-11 16h Sprague-Dawley dams compared against age matched virgins. Lactation is a time of significantly increased energy demands imposed by the suckling young that requires a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules to meet the dietary needs of both the offspring and the dam. We have shown an increase in the size and hydrophobicity of the bile acid pool during lactation [1], implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the level of mRNA, we utilized an exon array and calculated gene level summaries to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE19175 | GEO | 2010/11/21

SECONDARY ACCESSION(S): PRJNA120591

REPOSITORIES: GEO

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Project description:Non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) plays some role in reducing obesity in mice overexpressing human NAG-1, even on a high fat diet. Male and female hNAG-1 expressing mice have reduced body weight, increased longevity and metabolic activity. This study investigates the role of hNAG-1 in female reproduction and finds that the female mice have reduced fertility and pup survival after birth. Examination of the mammary glands in these mice suggests that hNAG-1 overexpressing mice have altered mammary epithelial development during pregnancy, including reduced occupancy of the fat pad and increased apoptosis via TUNEL positive cells at lactation day 2. Pups nursing from hNAG-1 overexpressing dams have reduced milk spots compared to pups nursing from WT dams. When CD-1 pups were cross-fostered with hNAG-1 or WT dams; reduced milk volume was observed in pups nursing from hNAG-1 dams compared to pups nursing from WT dams in a lactation challenge study. Milk was isolated from WT and hNAG-1 dams, and the milk was found to have secreted NAG-1 protein (approximately 25ng/mL) from hNAG-1 dams compared to WT dams, which had no detectable NAG-1 in the milk. A decrease in non-esterified free fatty acids in the milk of hNAG-1 dams was observed. Altered milk composition suggests that the pups were receiving inadequate nutrients during perinatal development; to examine this hypothesis serum was isolated from pups and clinical chemistry points were measured. Male and female pups nursing from hNAG-1 dams had reduced serum triglyceride concentrations. Cidea/CIDEA expression was reduced in hNAG-1 mammary glands, and microarray analysis suggests that genes involved in lipid metabolism are differentially expressed in hNAG-1 mammary glands. This study suggests that overexpression of hNAG-1 impairs lactational differentiation and pup survival due to altered milk quality and quantity 4 WT mammary glands on lactation day 2 and 5 hNAG-1 transgenic mice mammary glands on lactation day 2 were used.

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Differential gene expression in lactating rats compared against age matched virgin controls

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