GSE67386
An epigenetic memory of pregnancy in the mouse mammary gland
Pregnancy is the major modulator of mammary gland activity. It induces a tremendous expansion of the mammary epithelium and the generation of alveolar structures for milk production. Anecdotal evidence from multiparous humans indicates that the mammary gland may react less strongly to the first pregnancy than it does to subsequent pregnancies. Here we verify that the mouse mammary gland responds more robustly to a second pregnancy, indicating that the gland retains a long-term memory of pregnancy. A comparison of genome-wide profiles of DNA methylation in isolated mammary cell types revealed substantial and long lasting alterations.  The majority of these alterations affect sites occupied by the Stat5a transcription factor and mark specific genes that are upregulated during pregnancy.  We postulate that the epigenetic memory of a first pregnancy primes the activation of gene expression networks that promote mammary gland function in subsequent reproductive cycles.  More broadly, our data indicate that physiological experience can broadly alter epigenetic states, functionally modifying the capacity of the affected cells to respond to later stimulatory events. Overall design: Mammary gland cells (six distinct cell types) from nulliparous and parous female mice were FACS-sorted using a combination of cell surface markers. Genomic DNA was bisulfite converted and used to obtain genome-wide DNA methylation profiles. The current work focuses on the analysis of the first 12 samples (GSM1646785-96) and uses the other two samples to confirm some properties of the analysis results based on samples 1-12. Consequently, samples GSM1646797, GSM1646798 were analyzed in a much more limited manner compared to the other 12 samples, generating two plots included in the associated manucript.