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.

Public Health Relevance

PennCSER will provide cutting edge expertise in this emerging field of research that will rapidly translate to treatment of human infertility;bring further expertise to a number of the existing SCCPIR Focus groups;train the next generation reproductive biologists including physician scientists and basic research scientists;and educate the lay public and high school students about the reproductive sciences.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZHD1-DSR-L (32))
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De Paolo, Louis V
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University of Pennsylvania
Anatomy/Cell Biology
Schools of Medicine
United States
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Mainigi, Monica A; Olalere, Devvora; Burd, Irina et al. (2014) Peri-implantation hormonal milieu: elucidating mechanisms of abnormal placentation and fetal growth. Biol Reprod 90:26
Ihara, Motomasa; Meyer-Ficca, Mirella L; Leu, N Adrian et al. (2014) Paternal poly (ADP-ribose) metabolism modulates retention of inheritable sperm histones and early embryonic gene expression. PLoS Genet 10:e1004317
Butts, Samantha F; Owen, Carter; Mainigi, Monica et al. (2014) Assisted hatching and intracytoplasmic sperm injection are not associated with improved outcomes in assisted reproduction cycles for diminished ovarian reserve: an analysis of cycles in the United States from 2004 to 2011. Fertil Steril 102:1041-1047.e1
Butts, Samantha F; Guo, Wensheng; Cary, Mark S et al. (2013) Predicting the decline in human chorionic gonadotropin in a resolving pregnancy of unknown location. Obstet Gynecol 122:337-43
Bryant, Jessica M; Meyer-Ficca, Mirella L; Dang, Vanessa M et al. (2013) Separation of spermatogenic cell types using STA-PUT velocity sedimentation. J Vis Exp :
Meyer-Ficca, Mirella L; Lonchar, Julia D; Ihara, Motomasa et al. (2013) Alteration of poly(ADP-ribose) metabolism affects murine sperm nuclear architecture by impairing pericentric heterochromatin condensation. Chromosoma 122:319-35
de Waal, Eric; Yamazaki, Yukiko; Ingale, Puraskar et al. (2012) Primary epimutations introduced during intracytoplasmic sperm injection (ICSI) are corrected by germline-specific epigenetic reprogramming. Proc Natl Acad Sci U S A 109:4163-8
Abramowitz, Lara K; Bartolomei, Marisa S (2012) Genomic imprinting: recognition and marking of imprinted loci. Curr Opin Genet Dev 22:72-8