Epigenetic Mechanisms Mediating the Inheritance of Reproductive Behavior

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Natural variations in mother-infant interaction have profound effects on offspring development and behavior. In particular, there is evidence for the influence of postpartum care on maternal behavior itself, such that low levels of maternal care are exhibited by females who received less care in infancy. This transmission of maternal behavior from mother to daughter has been previously associated with epigenetic regulation of estrogen receptor (ER) α in hypothalamic brain regions. The purpose of the proposed project is to explore these epigenetic effects in the context of reproductive behavior and develop convergent sources of evidence for the transgenerational influence of maternal care. To achieve this goal, the maternal regulation of social, sexual and maternal behavior will be explored in a rodent model. This will provide an experimental design for determining potential shifts in reproductive strategy in response to early environmental experiences. The reversibility of these maternal effects will be explored through pharmacological manipulation of DNA methylation within the promoter region of the ERα gene. The role of DNA methylation in the generational transmission of environmental experiences that occur beyond the postpartum period will also be investigated in response to gestational stress and juvenile exposure to differential levels of social interaction. Finally, ecologically valid paradigms will be developed in which transgenerational effects on reproductive behavior can be determined in a mouse model. These paradigms will involve 1) comparison of communally vs. non-communally reared offspring and grand-offspring, 2) caloric food restriction during lactation and 3) comparison of offspring born to either inexperienced or experienced mothers. Overall, this project will provide an innovative approach to both the study of inheritance and the role of epigenetic mechanisms in sustaining environmental effects within and across generations. Moreover, it will provide an experimental design for elucidating the occurrence of reproductive trade-offs in mammals.