Histology and Transcriptome Profiles of the Mammary Gland across Critical Windows of Development in Sprague Dawley Rats

Abstract

Breast development occurs through well-defined stages representing ‘windows of susceptibility’ to adverse environmental exposures that potentially modify breast cancer risk. Systematic characterization of morphology and transcriptome during normal breast development lays the foundation of our understanding of cancer etiology. We examined mammary glands in female Sprague Dawley rats across six developmental stages – pre-pubertal, peri-pubertal, pubertal, lactation, adult parous and adult nulliparous. We investigated histology by Hematoxylin and Eosin and Mallory’s Trichrome stain, proliferative and apoptotic rate by immunohistochemistry and whole-transcriptome by microarrays. We identified differentially expressed genes between adjacent developmental stages by linear models, underlying pathways by gene ontology analysis and gene networks and hubs active across developmental stages by coexpression network analysis. Mammary gland development was associated with large-scale changes in the transcriptome; particularly from pre-pubertal to peri-pubertal period and the lactation period were characterized by distinct patterns of gene expression with unique biological functions such as immune processes during pre-pubertal development and cholesterol biosynthesis during lactation. These changes were reflective of the shift in mammary gland histology, from a rudimentary organ during early stages to a secretory organ during lactation followed by regression with age. Hub genes within mammary gene networks included metabolic genes such as Pparg during the pre-pubertal stage and tight junction-related genes claudins and occludins in lactating mammary glands. Transcriptome profile paired with histology enhanced our understanding of mammary development, which is fundamental in understanding the etiologic mechanism of breast cancer, especially pertaining to windows of susceptibility to environmental exposures that may alter breast cancer risk.

Polyscias scutellaria Aqueous Leaves Extract Increases Insulin Levels and Improves Mammary Gland Histology in Lactating Rats

“…The mammary glands of the lactating rats also filled with lobule-alveolar structures that play an important role in milk production. (18,19) In this study, the mammary glands of the lactating rats treated with distilled water merely had less lobule-alveolar structures than those of Asifit or PSAE-treated lactating rats. These results suggested that PSAE treatment, especially at a dosage of 250 mg/kg BW, had a similar effect on the mammary gland histoarchitecture as Asifit treatment.…”

Cannabinoids accumulate in mouse breast milk and differentially regulate lipid composition and lipid signaling molecules involved in infant development

“…During the limited period when milk must be produced and secreted, a host of morphological and transcriptional changes occur that result in increased transcription for proteins involved in fatty acid synthesis and decreased transcription for proteins involved in fatty acid degradation [ 20 , 21 ]. Lipids are secreted from mammary tissue through cytoplasmic lipid droplets (CLD), and CLDs contain lipids either derived from maternal stores and circulation or synthesized de novo in mammary epithelial cells (reviewed; [ 22 ]).…”

Cannabinoids accumulate in mouse breast milk and differentially regulate lipid composition and lipid signaling molecules involved in infant development

“…During the limited period when milk must be produced and secreted, a host of morphological and transcriptional changes occur that result in increased transcription for proteins involved in fatty acid synthesis and decreased transcription for proteins involved in fatty acid degradation [19,20]. Lipids are secreted from mammary tissue through cytoplasmic lipid droplets (CLD), and CLDs contain lipids either derived from maternal stores and circulation or synthesized de novo in mammary epithelial cells (reviewed; [21]).…”