Epigenetic Mechanisms Mediating the Inheritance of Reproductive Behavior

母婴互动的自然变化对后代的发育有着深远的影响 和行为。特别是，有证据表明产后护理对产妇的影响 行为本身，这样，低水平的母亲照顾表现出的女性谁收到较少 照顾婴儿。这种母性行为从母亲到女儿的传播， 先前与下丘脑雌激素受体（ER）α的表观遗传调节有关 大脑区域。该项目的目的是探讨这些表观遗传效应在 生殖行为的背景下，并制定收敛的证据来源， 母亲照顾的跨代影响。为了实现这一目标， 将在啮齿动物模型中探索社会、性和母性行为。这将提供一个 实验设计，用于确定生殖策略的潜在变化，以应对早期 环境经验。这些母体效应的可逆性将通过以下方式进行探讨： ERα基因启动子区域内DNA甲基化的药理学操作。 DNA甲基化在环境经历世代传递中的作用， 产后期间发生的，也将被调查，以应对妊娠应激 和青少年接触不同水平的社会互动。最后，生态有效 将发展的范例，其中跨代的影响，生殖行为可以 在小鼠模型中测定。这些范例将涉及1）社区与社区的比较。 非社区饲养的后代和孙子女，2）哺乳期热量食物限制 （3）比较无经验或有经验的母亲所生的后代。总体而言， 该项目将为遗传研究和遗传的作用提供一种创新的方法。 表观遗传机制在维持环境影响内和跨代。 此外，它将提供一个实验设计，阐明生殖的发生， 在哺乳动物中的权衡。

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.