In the U.S., about 12% of women have impaired fecundity and 7% of couples have infertility. In women, the leading causes are increasing age, ovulatory disorders, endometriosis, and tubal factor, and in couples, about 1/3 of infertility is due to female factors, 1/3 to male factors, and 1/3 to both. As mechanisms underlying the causes of infertility are largely wanting, treatments are mostly empiric. Infertile women who conceive spontaneously or with fertility therapies are at increased risk of adverse pregnancy outcomes due mainly to implantation and placenta disorders, with life-long effects on the health of children and adults born from these pregnancies. Thus, understanding mechanisms underlying reproductive success and compromise at the genomic, molecular, and cellular levels is critical to fertility and the health and well-being of this and future generations. Moreover, building a sustainable pipeline of junior investigators in this field and engaging investigators from multiple disciplines with diverse expertise are essential components to unravel the complexities of successful reproduction with translation to improving reproductive health more broadly. These are core principles of our NIH National Center for Translational Research in Reproduction and Infertility (NCTRI) at the University of California San Francisco (UCSF), funded since 2007 and for which this renewal proposal is submitted.
The Specific Aims of our renewal application (overall) are: 1. to advance research in reproductive science and medicine through transdisciplinary collaboration and scientific and technologic innovation with the goal of improving human reproductive health and fertility 2. to serve as a national resource to inspire, mentor and train students, fellows, and junior scientists in reproduction and infertility research and to nurture their career development long-term 3. to communicate and be a national resource regarding the importance of reproductive research and its relevance to reproductive health and fertility for the public, health care professionals, and patients Our NCTRI Center for Research, Innovation and Training in Reproduction and Infertility at UCSF has 4 projects led by an experienced team of investigators/mentors and brings together expertise in clinical medicine, basic and translational science, precision medicine, genomics/eipgenomics, and advanced technologies focused on reproductive biology, oocyte aging, implantation, and placental development. Moreover, it provides a rich environment for trainees and outreach to the community about innovations in reproductive science and medicine. Our projects use advanced technologies and ?omics? approaches, animal models and human tissues and cells, and integrate well-annotated, relevant human phenotypic and clinical data to inform our studies. Our immediate goals are to determine epigenetic regulation of processes resulting in successful reproduction or infertility. Our long-term goals are to develop diagnostics and targeted therapies to alleviate infertility and poor reproductive outcomes and enhance the well-being of those with infertility and reproductive compromise.

Public Health Relevance

About 12% of reproductive aged women of all marital statuses in the US have impaired fecundity - with increasing age, ovulatory disorders, endometriosis, and tubal factor as leading causes. Those who conceive spontaneously or with fertility therapies are at increased risk of adverse pregnancy outcomes due mainly to implantation and placenta disorders. Our Center for Research, Innovation and Training in Reproduction and Infertility at UCSF brings together expertise in clinical medicine, basic and translational science, precision medicine, and advanced technologies focused on reproductive biology, oocyte aging, implantation, and placental development and provides a rich environment for trainees and outreach to the community about innovations in reproductive science and medicine.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center (P50)
Project #
5P50HD055764-13
Application #
9908127
Study Section
Special Emphasis Panel (ZHD1)
Program Officer
Moss, Stuart B
Project Start
2007-04-01
Project End
2023-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
13
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Barnhart, Kurt; Giudice, Linda; Young, Steve et al. (2018) Evaluation, validation and refinement of noninvasive diagnostic biomarkers for endometriosis (ENDOmarker): A protocol to phenotype bio-specimens for discovery and validation. Contemp Clin Trials 68:1-6
Conti, Marco; Franciosi, Federica (2018) Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events. Hum Reprod Update 24:245-266
Martin, Jeremy W; Chen, Joseph C; Neidleman, Jason et al. (2018) Potent and rapid activation of tropomyosin-receptor kinase A in endometrial stromal fibroblasts by seminal plasma. Biol Reprod 99:336-348
Logan, Philip C; Yango, Pamela; Tran, Nam D (2018) Endometrial Stromal and Epithelial Cells Exhibit Unique Aberrant Molecular Defects in Patients With Endometriosis. Reprod Sci 25:140-159
Aghajanova, Lusine; Houshdaran, Sahar; Balayan, Shaina et al. (2018) In vitro evidence that platelet-rich plasma stimulates cellular processes involved in endometrial regeneration. J Assist Reprod Genet 35:757-770
Freimer, Jacob W; Krishnakumar, Raga; Cook, Matthew S et al. (2018) Expression of Alternative Ago2 Isoform Associated with Loss of microRNA-Driven Translational Repression in Mouse Oocytes. Curr Biol 28:296-302.e3
Paikari, Alireza; D Belair, Cassandra; Saw, Daniel et al. (2017) The eutheria-specific miR-290 cluster modulates placental growth and maternal-fetal transport. Development 144:3731-3743
Aghajanova, Lusine; Houshdaran, Sahar; Irwin, Juan C et al. (2017) Effects of noncavity-distorting fibroids on endometrial gene expression and function. Biol Reprod 97:564-576
Garrido-Gomez, Tamara; Dominguez, Francisco; Quiñonero, Alicia et al. (2017) Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology. Proc Natl Acad Sci U S A 114:E8468-E8477
Altmäe, Signe; Koel, Mariann; Võsa, Urmo et al. (2017) Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers. Sci Rep 7:10077

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