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Cellular Dynamics and Regulatory Networks Controlling Endometrial Remodelling during the Window of Implantation (360G-Wellcome-212233_Z_18_Z)

The endometrium undergoes iterative cycles of menstrual shedding, regeneration, rapid growth, and differentiation in response to ovarian hormones. During the mid-luteal phase, the endometrium becomes transiently receptive to implantation, heralding the start of a process of intense tissue remodelling, characterized by secretory transformation of glandular epithelium, angiogenesis, differentiation of stromal cells into secretory decidual cells, and activation of specialized immune cells. Several reproductive disorders, including recurrent pregnancy loss, are linked to defects in tissue remodelling at implantation. However, the cellular complexity and dynamic nature of the endometrium have so far precluded precise characterization of the underlying pathological mechanisms and drivers. We will employ high-throughput single-nucleus sequencing to map the dynamic changes in gene expression and chromatin accessibility (cis-regulatory regions) in all endometrial cell types across the luteal phase in defined patient groups. The data will be back-mapped to a future successful pregnancy or miscarriage. This analysis will yield unparalleled insight into the sequence of endometrial events (i.e. changes in cell populations, cellular states, gene expression and transcriptional regulation) leading to a successful or failed pregnancy. Further, 3D organoid cultures, consisting of glands and stroma, will be used to investigate putative drivers of endometrial dysfunction and to evaluate new treatment targets.

£1,281,629

17 Jul 2018

Grant details
Amount Awarded 1281629
Applicant Surname Brosens
Approval Committee Science Interview Panel
Award Date 2018-07-17T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Investigator Award in Science
Internal ID 212233/Z/18/Z
Lead Applicant Prof Jan Brosens
Other Applicant(s) Dr Sascha Ott
Planned Dates: End Date 2023-11-01T00:00:00+00:00
Planned Dates: Start Date 2018-11-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region West Midlands
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