Penn Center for Study of Epigenetics in Reproduction

The Penn Center for the Study of Epigenetics in Reproduction (PennCSER) will elucidate epigenetic mechanisms that govern male and female reproduction, contribute to male infertility and impact development of mouse and human concepti conceived through Assisted Reproductive Technologies (ART). The PennCSER centerpiece is 4 integrated, innovative research projects, spearheaded by experienced leaders in the areas of epigenetics and reproduction. The Center also features an Outreach program that has been in place for more than 10 years; the Penn Academy of Reproductive Sciences uses hands on laboratory experiences and interactive lectures to educate high school students, largely from the Philadelphia area schools, in the reproductive sciences. The clinical project (Project 1, Senapati, Mainigi, Coutifaris, and Ghosh) will assess the impact of oocyte vitrification, including advanced maternal age, on DNA methylation and gene expression in embryonic (cord blood) and placenta tissues in IVF pregnancies. Additionally, the association between ART interventions, an altered placental or cord blood epigenome, perinatal outcomes and childhood metabolic health will be investigated. Project 2 (Bartolomei) will closely parallel Project 1 by using a validated mouse model to study the effect of ART laboratory manipulations on epigenetic gene regulation and physiological outcomes in conceptuses and adults. Project 2 will address the question of whether oocyte vitrification impacts epigenetic gene regulation and placental morphology and will also determine if altered oxygen concentration underlies adverse ART outcomes. Project 3 (Mainigi and Huh) will utilize a novel in vitro organ-on-a-chip system and iPSC-derived trophoblasts to study mechanisms underlying placental sexual dimorphism and, specifically, how sex chromosomes and sex steroids impact human trophoblast differentiation and invasion. The project will also explore how specific interventions associated with ART lead to sexually dimorphic effects in trophoblast behavior, the epigenome and the transcriptome. Project 4 (Wang) will examine the TEX15 protein, which is required for meiosis and male fertility, and is a novel epigenetic regulator essential for retrotransposon silencing. This project will determine the epigenetic state associated with retrotransposon activation in Tex15-deficient germ cells and also examine the novel function of TEX15 and its interacting partner, TASOR2, in spermiogenesis. Finally, the project will model human male infertility using a unique Tex15 revertant mosaic mouse model. PennCSER will not only provide training to clinicians, physician scientists, and basic research fellows in the area of epigenetics but also provide PennCSER’s expertise to the NCTRI and associated program members.