Penn Center for Study of Epigenetics in Reproduction

宾夕法尼亚大学生殖表观遗传学研究中心（宾夕法尼亚大学生殖表观遗传学研究中心）将研究控制男性和女性生殖的表观遗传学机制，有助于男性不育，并影响人类和小鼠胚胎和胚胎外组织的发育。中心的核心是由经验丰富的领导领导的4个综合创新研究项目。一个试点项目，从一个年轻的研究者（Butts）和一个基于我们的K12/RSDP初级教师（Mainigi）与西北SCCPIR富有成效的合作项目也被描述。本文提出了一项扩展计划，将一种新颖的教室、实验室和基于互联网的生殖模块引入到费城公立学校现有的非常成功的高中生生物学课程中。最后，对来自其他U54和K12项目的受训者进行了生殖表观遗传学的培训。核心项目：项目一（Coutifaris/Sapienza）将评估氧张力对新生儿、胚胎外组织DNA甲基化和基因表达的影响，以及对体外受精妊娠和无辅助受孕妊娠后滋养细胞分化和功能的影响。在项目II （Bartolomei/Schultz）中，将使用一个经过验证的小鼠模型来研究ART程序（包括可变氧张力）对妊娠中期胚胎和足月表观遗传基因调控的影响。将评估行为、发育和生理结果。项目III （Berger）将研究小鼠精子发生过程中的组蛋白修饰，并确定它们在正常人类精子中的保护作用，以及在异常人类精子和小鼠模型中表现出不受调节的多磷酸核糖（PAR）代谢的破坏作用。Project IV （Meyer）将研究PAR代谢在男性种系表观遗传标记的建立、消除和维持中的作用，并确定PAR代谢缺陷是否与人类精子异常有关。宾州中心加入SCCPIR将为表观遗传学在生殖中不断发展的作用带来新的全面的理解，将扩大目前联盟的专业知识和调查领域，并将开辟新的合作、教育和培训途径。

DESCRIPTION (provided by applicant): PennCSER (Penn Center for the Study of Epigenetics in Reproduction) will elucidate epigenetic mechanisms that govern male and female reproduction, contribute to male infertility and impact development of human and mouse embryos and extra-embryonic tissues. The Center's centerpiece is 4 integrated, innovative research projects, spearheaded by experienced leaders. A pilot project from a young investigator (Butts) and a project based on a productive collaboration of our K12/RSDP junior faculty (Mainigi) with the Northwestern SCCPIR are also described. An outreach program that introduces a novel classroom, laboratory and internet-based Reproduction module into an existing and highly successful biology program for high school students in Philadelphia public schools is proposed. Finally, initiation of a training program on the epigenetics of reproduction for trainees from other U54 and K12 programs is described. Core projects: Project I (Coutifaris/Sapienza) will assess the impact of oxygen tension on DNA methylation and gene expression in newborns, extra-embryonic tissues and on trophoblast differentiation and function following IVF pregnancies and pregnancies resulting from unassisted conception. In Project II (Bartolomei/Schultz) a validated mouse model will be used to study the effect of ART procedures, including variable oxygen tensions, on epigenetic gene regulation in midgestation embryos and at term. Behavioral, developmental and physiological outcomes will be evaluated. Project III (Berger) will investigate histone modifications during mouse spermatogenesis and determine their conservation in normal human sperm and disruption in abnormal human sperm and mouse models exhibiting deregulated poly(ADP-ribose) (PAR) metabolism. Project IV (Meyer) will investigate the role of PAR metabolism in establishment, erasure and maintenance of epigenetic marks in the male germline and ascertain whether defects in PAR metabolism are associated with abnormal human sperm. Addition of the Penn Center to the SCCPIR will bring a new and comprehensive level of understanding to the evolving role of epigenetics in reproduction, will broaden the current areas of expertise and investigation of the consortium and will open new avenues of collaboration, education and training.