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Organellar responses to lactation-induced stress impact the fate of post-partum mammary glands.

ABSTRACT: Organellar responses to lactation-induced stress impact the fate of post-partum mammary glands.

PROVIDER: PRJNA1139167 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR29929771_1.fastq.gz	Fastqsanger.gz
	SRR29929771_2.fastq.gz	Fastqsanger.gz
	SRR29929773_1.fastq.gz	Fastqsanger.gz
	SRR29929773_2.fastq.gz	Fastqsanger.gz

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Organellar responses to lactation-induced stress impact the fate of post-partum mammary glands.

Project description:Breastfeeding protects against breast cancer, but not in all women and the mechanism remains elusive. Lactation implicates secretion of proteins through the endoplasmic reticulum (ER) and ER- mitochondria contacts for lipid metabolism. We show that in mice that share the same nuclear genome (BL/6) but differ in mitochondrial genomes (C57 or NZB) the outcome of lactation differs drastically. We analyzed the unfolded protein responses (UPR) of both organelles during lactation. In contrast to the BL/6C57mice, in BL/6NZB females, UPRs signaling is abruptly inhibited, no apoptosis is observed, post-partum hyperplasia develops and RNAseq demonstrates expression of pro-tumorigenic genes, which is consistent with increased post-partum tumor development. However, forced-induction of pro-apoptotic UPRER reverses this phenotype. Remarkably, milk fatty acids (FA) differ between genotypes and correlate with breast cancer risk in humans. These results indicate that mitochondrial genetics modulates organellar responses to lactation and its protective effect. Our results further raise the possibility of using milk FA-signature as a read-out of the underlying biology to predict risk of breast cancer in the future.

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2013-08-21 | E-GEOD-50056 | biostudies-arrayexpress

Expression profiles of microRNAs from lactating and non-lactating bovine mammary glands and identification of miRNA related to lactation.

Project description:miRNAs have been implicated in the regulation of milk protein synthesis and development of mammary gland. However, the function of miRNAs in regulating lactation is unclear. Therefore, the elucidation of miRNA expression profiles in MG provides a crucial entry into the understanding of the mechanisms of lactation initiation. Our present work is to examine miRNA expression profiles in bovine mammary gland, and to evaluate miRNAs function through the identification of differentially expressed miRNA between lactation and non-lactation mammary gland. Identification of novel miRNAs highlights the important function of low abundance and less conserved miRNAs. An interaction network of known miRNAs and their target genes around the lactation function was constructed to postulate the functional roles of miRNAs in mammary gland. This integrated analysis provides important information that will inspire further experimental investigations into the field of miRNAs and their targets during lactation.

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A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation. [human]

Project description:We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 100-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating lactation.

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A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation. [mouse]

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Expression data of porcine mammary glands from late pregnancy to peak lactation.

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