[F31] Pinopode formation in endometrial receptivity and fertility
Ente: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Scadenza: 2029-06-30
Importo max: 44.340 EUR
Paese: US
Descrizione
PROJECT SUMMARY/ABSTRACT
Human fertility is remarkably inefficient, with a large proportion of conceptions ending in early pregnancy
loss. A major contributor to this inefficiency, impacting both natural and assisted pregnancies, is failure of
blastocyst implantation. Successful implantation requires a receptive endometrial environment during a narrow
“window of implantation,” yet the molecular and cellular mechanisms governing endometrial receptivity remain
poorly understood. This knowledge gap limits the development of effective therapies to improve pregnancy
outcomes. The Caron Lab investigates pinopodes - large, spherical protrusions on the endometrial luminal
epithelium - as a morphological marker of uterine receptivity. Pinopode presence correlates with the implantation
window in both mice and humans and is repeatedly implicated with improved outcomes following utilization of
assisted reproduction tehnologies such as in vitro fertilization. Adrenomedullin (AM) is a key endocrine factor at
the maternal-fetal interface enhancing implantation success, embryo spacing and live birth rates in mice. AM
has also been shown to promote pinopode number, size and endometrial luminal epitehlial coverage. However,
the downstream cellular mechanisms by which AM promotes pinopode development remain unknown. We
employed gentically-tagged animal systems to isolate and identify epitheilum specific RNAs that change with AM
stimulation. Based on this data, we have developed a series of novel hypotheses that explore how downstream
cellular effectors of AM signlaing can transform the uterine epithelial surface for enhanced pinopode numbers,
and ultimatley improve blastocyst attachment. This proposal harnesses the power of uterine organoids and
genetic in vivo models to pave the way towards therapeutic approaches to improve blastocyst implantaion and
reproductive outcomes. In parallel, this project will provide rigorous training in reproductive biology, molecular
techniques, and data analysis, as well as other tangible skills needed to support development as an independent
and innovative scientist aligned with the NIH mission.
Istituzione: UNIV OF NORTH CAROLINA CHAPEL HILL
PI: Anna Beeson
Progetto: 1F31HD122384-01
Settori: Eunice Kennedy Shriver National Institute of Child Health and Human Development
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