102 - Insights Into the Molecular Underpinnings of Disrupted Mammary Development and Function Arising from Late-Gestation Heat Stress

Abstract: Exposure to heat stress during a dairy cow’s dry period disrupts mammary gland remodeling impairing milk production during the subsequent lactation. The dry period coincides with late gestation, and Intrauterine hyperthermia affects offspring growth, physiology, and performance into adulthood. This presentation will highlight histological and molecular adaptations of the mammary gland under heat stress, emphasizing the carry-over effects in the dam and her progeny. Pregnant dams were either cooled (CL, fans and water soakers) or heat-stressed (HS, lack of access to cooling devices) in a free-stall setting during the dry period (~46 d) in summer. Heifers gestated under maternal heat stress or cooling (in utero heat stressed, IUHS vs. in utero cooled, IUCL) were euthanized at birth or weaning, or were followed until the first lactation to collect mammary tissue for histological, proteomics, and methylation analyses. In the dam’s mammary gland, 251 proteins and 224 phosphorylated proteins were differentially abundant in HS compared to CL. Top functions were related to immune function, inflammation, amino acid metabolism, reactive oxygen species production, tissue remodeling, and stress response. Intrauterine hyperthermia derailed mammary gland development inducing alterations in the size and weight of the whole udder and parenchyma and fat pad mass. Epithelial structures within the parenchyma of IUHS heifers were significantly underdeveloped, with reduced proliferative capacity. These early-life alterations in tissue microstructure persist through the first lactation, evidenced by IUHS mammary glands with smaller alveoli and fewer mammary epithelial cells that exhibited reduced proliferation capacity. Further, in utero hyperthermia epigenetically programed the udder. Over 130 differentially methylated genes were identified in the IUHS mammary gland with roles in development, innate immune defense, cell signaling, and transcription and translation. These studies provide insights into the molecular underpinnings of disrupted mammary structure and function arising from prior exposure to dry period/late-gestation heat stress, which led to lower milk yields of the dam and her offspring.