In utero hyperthermia impacts the histological and transcriptomic signature of the mammary fat pad of newborn heifers

Abstract

Development of the mammary gland begins in utero and requires coordinated interactions between the epithelial rich parenchyma and the surrounding mammary fat pad (mFP). In this study we investigated how maternal heat stress (HS) during gestation impacts the development of the offspring mFP. Mammary fat pad tissue was collected from Holstein heifers at birth that were gestated under either HS or active cooling conditions for the last 54 days of gestation in a subtropical summer. Heifers exposed to in utero HS exhibited a higher number of small adipocytes and fewer large adipocytes. Additionally, there were 122 differentially expressed genes between in utero HS and in utero cooled heifers. Pathway and upstream regulator analysis was performed using a less stringent cutoff and included 662 genes. Overall, genes and pathways impacted by in utero HS were related to lipogenesis, intracellular signaling, extracellular matrix remodeling, insulin signaling, and cytoskeleton remodeling. Nuclear receptors, transcription factors, and growth factors were predicted to be inactivated due to in utero HS. These histological and transcriptomic results indicate a coordinated suppression of cell differentiation, lipid metabolism, hormone/nutrient sensing, and stress adaptation. Early-life disruptions of adipose development may ultimately compromise mammary gland development and future lactation performance.