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Principal Investigator: Adrian Erlebacher
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2024
Award: $1,633,501
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
In the U.S., about 12% of women have impaired fecundity and 7% of couples have infertility, with 1/3 attributable
to female factors. Underlying mechanisms remain largely unknown, however, even when more proximal
pathologies are identified, thus precluding the development of accurate diagnostics and personalized therapies.
In addition, pregnancies in subfertile women, conceived naturally or as a result of infertility treatments, have
greater risk of complications such as pre-eclampsia, preterm birth, and fetal growth restriction that have life-long
effects on the offspring. Thus, dissecting the mechanisms underlying reproductive success and compromise at
the genomic, molecular, and cellular level is crucial to the health and well-being of this and future generations.
Engaging investigators from multiple disciplines and building a sustainable pipeline of junior investigators,
including those underrepresented in science and medicine, is also essential to this effort, as is the promotion of
public literacy about reproductive health and science. 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 new proposal is submitted with a new central theme focused on
the inter-related roles of endometrial inflammation, epigenetics, and developmental processes of the peri-
implantation uterus and early conceptus as central determinants of early pregnancy success or failure. This
focus is motivated by the fact that the clinical association between pathological endometrial inflammation and
female infertility, while well-established, lacks a deep mechanistic understanding. Our proposed Center is
comprised of three inter-related Research Projects and a pilot project (to be determined), supported by an
administrative core (A), and an education/outreach core (B). Project 1 (Roan/Huddleston, co-Leads) focuses
on the phenotypes and functions of endometrial lymphocytes in the normal and inflamed human endometrium
and decidua, including determinations of T and B cell antigen specificities. Project 2 (Erlebacher) focuses on
how epigenetic processes active within endometrial and decidual stromal cells control, and are in turn controlled
by, endometrial and decidual inflammation. Lastly, Project 3 (Blelloch/Fisher, co-Leads) addresses how
primitive trophoblasts of the extra-embryonic tissues that comprise the fetal portion of maternal-fetal interface
differentiate into the subtypes that determine the polarity of the implanted conceptus with respect to the decidua.
We believe our Center will also advance reproduction and infertility research more generally by setting an
example of successful transdisciplinary collaboration built upon the shared use of rare clinical specimens
analyzed through complementary, multi-omics approaches combined with mechanistic investigations using
model systems. Our Center also is designed to attract students, fellows, and junior scientists to careers in
reproduction and infertility research, and to engage the community with regards to the importance of infertility
research.
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