Ensuring quality maternal care in an adverse environment

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A critically important adaptation during the mammalian pregnancy is the induction of maternal care. Maternal care is vitally important for the survival of the newborn and the withdrawal of maternal care or poor quality maternal care can result in adverse behavioural and metabolic outcomes later in life. Importantly, prenatal adversities such as suboptimal diet or stress can influence the quality of maternal care. Consequently, understanding how maternal care is induced and how the maternal environment influences the induction of maternal care is of paramount importance.There is some evidence that the placenta plays a role in instructing the mother to care for her newborns. The placenta is a transient organ of pregnancy that plays a key role in transferring nutrients to the growing fetus. The placenta is also a super endocrine organ that manufactures hormones that flood the maternal system to induce the changes required for a successful, health pregnancy. Studies suggest that some of these hormones, the placental lactogens, may induce maternal care. Given this proposed role for the placenta, placental dysfunction could contribute to poor maternal care. We have identified a gene called Phlda2 that is important for the production of these placental hormones. Phlda2 regulates the amount of placental hormones that are manufactured by regulating the size of the placental endocrine compartment. Transgenic over expression of Phlda2 results in a smaller endocrine compartment. Mouse mothers exposed to placenta with this much smaller endocrine compartment exhibit changes in gene expression and neurogenesis in the maternal brain during pregnancy and poor maternal care of their offspring, even though they themselves are not mutant for Phlda2. Phlda2 is an imprinted gene whose expression is regulated by epigenetic marks. Remarkably, expression of Phlda2 is altered in the placenta in response to the two different suboptimal maternal diets that have previously been linked to poor maternal care. This leads us to believe that a suboptimal maternal diet may contribute to poor maternal care by altering the expression of Phlda2 in the placenta and thus reducing exposure of the maternal brain to placental lactogens. In this study, we will use a variety of existing experimental models and techniques to test this hypothesis first asking whether we can restore maternal care by manipulating placental expression of Phlda2 in a dietary model, and then by exploring the mechanism initially focusing on placental lactogen signaling via the maternal prolactin receptor. We will also develop a novel imaging tool based on infrared luciferase, to ask whether we can longitudinally bioimage ongoing maternal neurogenesis. A considerable advantage of this tool will be the ability to image the same animal multiple times substantially reducing the number of animals required for our studies.This work is important not just in helping us to fundamentally understand how maternal care is induced but also how this process may be influenced by the maternal environment, and how we might be able to restore maternal care - work that will have wide relevance to the welfare of experimental, domestic and agricultural animals as well as human health.