Penn Center for Study of Epigenetics in Reproduction

描述（由申请人提供）：PennCSER（宾夕法尼亚大学生殖表观遗传学研究中心）将阐明管理男性和女性生殖的表观遗传机制，导致男性不育，并影响人类和小鼠胚胎和胚外组织的发育。该中心的核心是4个综合性的创新研究项目，由经验丰富的领导者带头。一个试点项目，从一个年轻的研究员（对接）和一个项目的基础上，我们的K12/RSDP初级教师（Mainigi）与西北SCCPIR的富有成效的合作也进行了描述。一个推广计划，介绍了一种新的课堂，实验室和基于互联网的生殖模块到现有的和非常成功的生物学计划，在费城公立学校的高中生提出。最后，介绍了为其他U 54和K12项目的受训人员开展的生殖表观遗传学培训计划。核心项目：项目I（Coutifaris/Sapienza）将评估氧分压对新生儿、胚胎外组织中DNA甲基化和基因表达的影响，以及对IVF妊娠和非辅助妊娠后滋养层分化和功能的影响。在项目II（Bartolomei/Schultz）中，将使用经验证的小鼠模型研究ART程序（包括可变氧分压）对妊娠中期胚胎和足月胚胎表观遗传基因调控的影响。将评价行为、发育和生理结局。项目III（Berger）将研究小鼠精子发生过程中的组蛋白修饰，并确定其在正常人类精子中的保守性，以及在异常人类精子和表现出多聚（ADP-核糖）（PAR）代谢失调的小鼠模型中的破坏性。项目IV（Meyer）将研究PAR代谢在男性生殖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。宾夕法尼亚中心加入SCCPIR将使人们对表观遗传学在生殖中不断演变的作用有一个新的全面的理解，将扩大该联盟目前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.