Late gestation hyperthermia: epigenetic programming of daughter's mammary development and function

Exposure to stressors during early developmental windows, such as prenatally (i.e., in utero), can have life-long implications for an animal's health and productivity. The mammary gland starts developing in utero and, like other developing tissues and organs, may undergo fetal programming. Previous research has implicated factors, such as prenatal exposure to endocrine disruptors or alterations in maternal diet (e.g., maternal over or undernutrition), that can influence the developmental trajectory of the offspring mammary gland in postnatal life. However, the direct links between prenatal insults and future productive outcomes are less documented in livestock species. Research on in utero hyperthermia effects on early-life mammary development is scarce. This review will provide an overview of key developmental milestones taking place in the bovine mammary gland during the pre- and postnatal stages. We will showcase how intrauterine hyperthermia, experienced by the developing fetus during the last trimester of gestation, derails postnatal mammary gland development and impairs its synthetic capacity later in life. We will provide insights into the underlying histological, cellular, and molecular mechanisms taking place at key postnatal developmental life stages, including birth, weaning and the first lactation, that might explain permanent detriments in productivity long after the initial exposure to hyperthermia. Collectively, our studies indicate that prenatal hyperthermia jeopardizes the normal developmental trajectory of the mammary gland from fetal development to lactation. Further, in utero hyperthermia epigenetically programs the udder, and possibly other organs critical to lactation, yielding a less resilient and less productive cow for multiple lactations.