This renewal of our NIH U54 SCCPIR Center at the University of California, San Francisco proposes a transdisciplinary, team science approach to elucidate mechanisms underlying seminal events in early development as they relate to the origins and biological consequences of human infertility. Our investigators focus on the developmental continuum from oocyte competence to embryo and placental development to implantation and promote a shared vision of excellence and innovation in reproductive research, advanced technologies, informatics data analyses, mentoring, and community engagement. We combine powerful experimental techniques, system approaches and computational analyses to address critical questions at the intersection of stem cell biology, epigenomics, and clinical reproductive medicine. To accomplish these goals, we have proposed four highly interactive projects by established investigators and one pilot project with a new investigator, which are supported by three cores. Project I (Marco Conti) focuses on mechanisms controlling oocyte developmental competence and early embryo development;Project II (Susan Fisher) will investigate a molecular analysis of the early stages of trophoblast differentiation;Project III (Robert Blelloch) focuses on post-transcriptional regulation of trophoblast differentiation;Project IV (Linda Giudice) will investigate development of human endometrium for embryonic implantation;and the Pilot Project (Nam Tran) proposes to investigate molecular mechanisms underlying the pathogenesis and pathophysiology of endometriosis, a common disorder in women associated with infertility and poor pregnancy outcomes These projects are supported by Core A for administration (Linda Giudice), Core B for computational biology research (Jun Song), and Core C for education and community outreach (Synthia Mellon). Our long-term goals are to understand mechanisms underlying normal and abnormal early development fundamentally and for developing novel strategies to diagnose, prevent and treat infertility;optimize fertility and pregnancy outcomes and minimize adverse outcomes;educate aspiring students, the public, health care professionals and patients about human development and disorders associated with abnormal development;and inspire career choice and nurture career development in this important area of reproductive health and research. These goals are consistent with the mission of the NICHD.

Public Health Relevance

There is compelling evidence that many causes of human infertility and poor pregnancy outcomes can be traced to abnormalities in early gamete maturation, fertilization, embryogenesis, placentation, and implantation. These effects on reproductive health also affect quality of life across the life span. Thus, the origins and biological consequences of abnormalities in early development, the central theme of our proposal, are highly relevant to the public health

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54HD055764-06
Application #
8286521
Study Section
Special Emphasis Panel (ZHD1-DSR-L (50))
Project Start
2012-04-01
Project End
2017-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
6
Fiscal Year
2012
Total Cost
$183,509
Indirect Cost
$64,088
Name
University of California San Francisco
Department
Type
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Bianco, Katherine; Gormley, Matthew; Farrell, Jason et al. (2016) Placental transcriptomes in the common aneuploidies reveal critical regions on the trisomic chromosomes and genome-wide effects. Prenat Diagn 36:812-22
Tran, Nam D; Kissner, Michael; Subramanyam, Deepa et al. (2016) A miR-372/let-7 Axis Regulates Human Germ Versus Somatic Cell Fates. Stem Cells 34:1985-91
Krishnakumar, Raga; Chen, Amy F; Pantovich, Marisol G et al. (2016) FOXD3 Regulates Pluripotent Stem Cell Potential by Simultaneously Initiating and Repressing Enhancer Activity. Cell Stem Cell 18:104-17
Maltepe, Emin; Fisher, Susan J (2015) Placenta: the forgotten organ. Annu Rev Cell Dev Biol 31:523-52
Parchem, Ronald J; Moore, Nicole; Fish, Jennifer L et al. (2015) miR-302 Is Required for Timing of Neural Differentiation, Neural Tube Closure, and Embryonic Viability. Cell Rep 12:760-73
Guzman-Ayala, Marcela; Sachs, Michael; Koh, Fong Ming et al. (2015) Chd1 is essential for the high transcriptional output and rapid growth of the mouse epiblast. Development 142:118-27
Piltonen, T T; Chen, J C; Khatun, M et al. (2015) Endometrial stromal fibroblasts from women with polycystic ovary syndrome have impaired progesterone-mediated decidualization, aberrant cytokine profiles and promote enhanced immune cell migration in vitro. Hum Reprod 30:1203-15
Smith-McCune, Karen; Chen, Joseph C; Greenblatt, Ruth M et al. (2015) Unexpected Inflammatory Effects of Intravaginal Gels (Universal Placebo Gel and Nonoxynol-9) on the Upper Female Reproductive Tract: A Randomized Crossover Study. PLoS One 10:e0129769
Rahmioglu, Nilufer; Fassbender, Amelie; Vitonis, Allison F et al. (2014) World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project: III. Fluid biospecimen collection, processing, and storage in endometriosis research. Fertil Steril 102:1233-43
Fassbender, Amelie; Rahmioglu, Nilufer; Vitonis, Allison F et al. (2014) World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: IV. Tissue collection, processing, and storage in endometriosis research. Fertil Steril 102:1244-53

Showing the most recent 10 out of 73 publications