Document text
Principal Investigator: Shanmugasundaram Nallasamy
Organization: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
Fiscal Year: 2024
Award: $436,511
Funding agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development
Project Summary
Early pregnancy loss is the most prevalent early pregnancy complication, and its incidence is estimated to be
~75%. Thus, delineating the mechanisms of peri and post-implantation processes will help reduce this adverse
pregnancy outcome. Decidualization, a process of stromal cell proliferation and differentiation for the formation
of decidua, supports embryonic growth and survival from post-implantation through pre-placentation period.
Extracellular matrix (ECM) remodeling and angiogenesis are underlying events that occur in parallel to the
decidualization. Fibrillar collagens are predominant ECM group of proteins which are abundant in the decidua,
endothelial cells, and vascular wall. However, their role in the endometrial decidualization, embryo invasion and
angiogenesis are not known. Our preliminary data suggests that the fibrillar collagen undergoes dramatic
remodeling within the decidua compared to non-decidualized pre-implantation endometrium. Utilizing a novel
mouse model, we provide compelling evidence that the fibrillar collagen is playing an indispensable role in
endometrial decidualization and angiogenesis. Conditional deletion of Col5a1 (collagen type V alpha 1 chain)
resulted in complete pregnancy failure due to severe intrauterine hemorrhage and total embryo resorption. Based
on these strong preliminary data, we propose to characterize the defects in endometrial decidualization and
embryo invasion which lead to total embryo resorption in the uterus lacking Col5a1(aim 1), characterize the
Col5a1-mediated fibrillar collagen remodeling that determines progression of decidualization and embryonic
growth (aim 2), and identify impaired angiogenesis and disrupted vascular remodeling as predominant underlying
mechanisms that cause intrauterine hemorrhage in Col5a1 conditional knockout mice (aim 3). We will utilize a
physiologically relevant and novel in vivo model – uterine specific Col5a1 conditional knockout mice – to
interrogate the function of fibrillar collagen in endometrial decidualization and angiogenesis. We will also utilize
a unique combination of approaches including imaging techniques and in vitro cell derived matrices. The
outcomes of this study will enhance our understanding on the function of fibrillar collagen during endometrial
decidualization and angiogenesis.
Terms: <1st trimester><Architecture><Assay><Bioassay><Biological Assay><Blastocyst Implantation><Bleeding><Blood Vessels><Body Tissues><Brachydanio rerio><Cell Body><Cell Differentiation><Cell Differentiation process><Cell Growth in Number><Cell Multiplication><Cell Proliferation><Cell-Extracellular Matrix><Cells><Cells Placenta-Tissue><Cellular Mechanotransduction><Cellular Proliferation><Collagen><Collagen Fiber><Collagen Type V><Cutis Elastica><Cytotoxic cell><Danio rerio><Data><Decidua><Decidua Graviditas><Decidual Cell Reactions><Defect><Development><Dissection><Dysfunction><ECM><Early Placental Phase><Ehlers-Danlos Disease><Ehlers-Danlos Syndrome><Electron Microscopy><Electrons><Elements><Embryo><Embryo Implantation><Embryo Resorption><Embryonic><Endometrial><Endometrial Stromal Cell><Endometrium><Endothelial Cells><Engineering / Architecture><Epithelium><Event><Exhibits><Extracellular Matrix><Extracellular Matrix Proteins><Failure><Fibrillar Collagen><First Pregnancy Trimester><First Trimester><Functional disorder><Generalized Growth><Generations><Genetic Alteration><Genetic Change><Genetic defect><Gestation><Goals><Growth><Hemorrhage><Human><Hypoxia><Hypoxic><Imaging Procedures><Imaging Technics><Imaging Techniques><Impairment><In Vitro><Incidence><Invaded><K lymphocyte><KO mice><Knock-out Mice><Knockout Mice><Link><Literature><Maternal-Fetal Exchange><Mechanical Signal Transduction><Mechanosensory Transduction><Mediating><Mice><Mice Mammals><Modern Man><Morphology><Murine><Mus><Mutation><NK Cells><Natural Killer Cells><Negative Beta Particle><Negatrons><Nidation><Normal Placentoma><Null Mouse><Outcome><Outcome Study><Ovum Implantation><Oxygen Deficiency><Physiologic><Physiological><Physiopathology><Placenta><Placenta Embryonic Tissue><Placental Development><Placentation><Placentome><Play><Pregnancy><Pregnancy Complications><Prevention><Process><Proliferating><Proteins><Publishing><Reporting><Role><SHG imaging><Signal Pathway><Stromal Cells><Structure><Tissue Growth><Tissues><Transplacental Exposure><Uterine Bleeding><Uterine hemorrhage><Uterine lining><Uterus><VEGF><VEGFs><Vascular Endothelial Growth Factors><Vascular Permeabilities><Vascular remodeling><Woman><Zebra Danio><Zebra Fish><Zebrafish><adverse pregnancy outcome><angiogenesis><blood loss><cellular differentiation><clinical significance><clinically significant><complications during pregnancy><conditional knock-out><conditional knockout><confocal imaging><cutis hyperelastica><decidualization><design><designing><developmental><early pregnancy><early pregnancy loss><elastic skin><embryo attachment><failed pregnancy><failure Implantation><genome mutation><implantation><improved><in vivo><in vivo Model><maternal-fetal interface><mechanosensing><mechanotransduction><microscope imaging><microscopic imaging><microscopy imaging><mortality><mouse model><murine model><natural Blastocyst Implantation><novel><ontogeny><pathophysiology><pre-implantation><pregnancy failure><pregnancy-related complications><preimplantation><public health relevance><response><second harmonic><second harmonic generation imaging><social role><success><tool><trophoblast><uterus bleeding><vascular><womb>