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 5 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, Coutifaris, Sapienza, Mainigi and Senapati) will assess the impact of the periconceptional maternal environment on DNA methylation and gene expression in embryonic (placental vessels and endothelial cells) and extra-embryonic (trophoblasts) tissues in IVF pregnancies following fresh or frozen transfer, pregnancies resulting from unassisted conception and pregnancies following trophectoderm biopsy for pre-implantation genetic testing for aneuploidy (PGT-A). This project will also determine the stability of epigenetic signatures determined at birth into childhood and correlate them with the children?s growth phenotype. Project 2 (Bartolomei, Mainigi, Schultz) will closely parallel Project 1 using a validated mouse model to study the effect of ART laboratory manipulations on epigenetic gene regulation and physiological outcomes in term conceptuses and adults. Project 2 will address the question of whether embryo freezing and transfer to an unstimulated uterus is optimal and evaluate the safety and outcomes associated with trophectoderm biopsy. Project 2 will also test whether decreased expression of Grb10, a growth-regulatory imprinted gene overexpressed in human and mouse ART-derived conceptuses, can rescue ART-associated phenotypes in a mouse model. Project 3 (Berger) will investigate histone modifications during mouse spermatogenesis and determine their conservation in normal human sperm and disruption in abnormal human sperm, as well as in mouse models exhibiting abnormal histone retention. Project 4 (Wang and Masson) will examine the function of TEX15, a protein that is required for meiosis and male fertility, and is a novel epigenetic regulator essential for retrotransposon silencing. Project 4 will also determine whether aberrant retrotransposon activity is associated with male infertility. 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.
PennCSER will provide cutting edge expertise in the area of epigenetics of reproduction that will rapidly translate into treatment of human infertility, bring further expertise to the NCTRI program, train the next generation of reproductive biologists, including physician scientists and basic research scientists, and educate the lay public and high school students about the reproductive sciences.
|Ghosh, Jayashri; Coutifaris, Christos; Sapienza, Carmen et al. (2017) Global DNA methylation levels are altered by modifiable clinical manipulations in assisted reproductive technologies. Clin Epigenetics 9:14|
|Vrooman, Lisa A; Bartolomei, Marisa S (2017) Can assisted reproductive technologies cause adult-onset disease? Evidence from human and mouse. Reprod Toxicol 68:72-84|
|Weinerman, Rachel; Ord, Teri; Bartolomei, Marisa S et al. (2017) The superovulated environment, independent of embryo vitrification, results in low birthweight in a mouse model. Biol Reprod 97:133-142|
|Vrooman, Lisa A; Xin, Frances; Bartolomei, Marisa S (2016) Morphologic and molecular changes in the placenta: what we can learn from environmental exposures. Fertil Steril 106:930-40|
|Ghosh, Jayashri; Mainigi, Monica; Coutifaris, Christos et al. (2016) Outlier DNA methylation levels as an indicator of environmental exposure and risk of undesirable birth outcome. Hum Mol Genet 25:123-9|
|Hur, Stella K; Freschi, Andrea; Ideraabdullah, Folami et al. (2016) Humanized H19/Igf2 locus reveals diverged imprinting mechanism between mouse and human and reflects Silver-Russell syndrome phenotypes. Proc Natl Acad Sci U S A 113:10938-43|
|Smoak, Evan M; Stein, Paula; Schultz, Richard M et al. (2016) Long-Term Retention of CENP-A Nucleosomes in Mammalian Oocytes Underpins Transgenerational Inheritance of Centromere Identity. Curr Biol 26:1110-6|
|Weinerman, Rachel; Feng, Rui; Ord, Teri S et al. (2016) Morphokinetic Evaluation of Embryo Development in a Mouse Model: Functional and Molecular Correlates. Biol Reprod 94:84|
|Castle, Megan; Cleveland, Charlotte; Gordon, Diana et al. (2016) Reproductive Science for High School Students: A Shared Curriculum Model to Enhance Student Success. Biol Reprod 95:28|
|Luense, Lacey J; Wang, Xiaoshi; Schon, Samantha B et al. (2016) Comprehensive analysis of histone post-translational modifications in mouse and human male germ cells. Epigenetics Chromatin 9:24|
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