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dc.contributor.authorSones, Jennyen_US
dc.date.accessioned2015-04-06T20:13:56Z
dc.date.available2020-01-27T07:00:41Z
dc.date.issued2015-01-26en_US
dc.identifier.otherbibid: 9154445
dc.identifier.urihttps://hdl.handle.net/1813/39356
dc.description.abstractPreeclampsia (PE) is a devastating disorder of pregnancy that affects 10% of pregnancies worldwide. While it is a leading cause of perinatal morbidity and mortality, the cause of PE is unknown. To date the only definitive treatment is delivery of the placenta and the baby, which is often preterm and/or growth restricted. The origins of PE are generally regarded to be early in pregnancy at the time of placenta formation as placental developmental abnormalities often characterize PE pregnancies. In these thesis studies, early pregnancy events required for proper placentation, implantation and decidualization, were investigated in the BPH/5 spontaneous mouse model of PE. We discovered profound developmental defects in implantation, decidualization, and placentation in BPH/5 mice. Along with evidence of decidual hypoxia, these defects were associated with a distinct molecular signature of aberrant embryo-uterine interactions. We identified significant dysregulation in the periimplantation period, particularly in the overexpression of cyclooxygenase 2 (Cox2) in the maternal uterine environment. Using pharmacological intervention at early pregnancy with a selective Cox2 inhibitor, we confirmed that defects in Cox2 signaling during the periimplantation period have "ripple effects" impacting downstream adverse pregnancy outcomes at mid and late gestation in BPH/5 mice, including fetal growth restriction and demise. Finally, investigations in the periimplantation period lead us to discover deficiencies in immunoregulatory pathways crucial for placental development at the maternal-fetal interface in BPH/5 mice. We showed dramatic loss of decidual Natural Killer (dNK) cells and this was associated with overexpression of IL-15 in BPH/5 implantation sites. Furthermore, we linked Cox2 inhibition with a reduction in IL-15. Altogether, this points towards inflammation in the maternal uterine environment during early pregnancy having a central role in the poor fetoplacental and pregnancy outcomes associated with this model and highlights Cox2 inhibitors as potential therapeutics to prevent fetal morbidity/mortality associated with PE. Importantly, our data supports the "ripple effect" hypothesis that defects in early pregnancy events are the source of downstream adverse pregnancy outcomes using the BPH/5 mouse model of PE.en_US
dc.language.isoen_USen_US
dc.subjectpreeclampsiaen_US
dc.subjectpregnancyen_US
dc.subjectplacentaen_US
dc.titleDefects In Periimplantation Signaling Contribute To Adverse Pregnancy Outcomes In The Bph/5 Mouse Model Of Preeclampsiaen_US
dc.typedissertation or thesisen_US
thesis.degree.disciplinePhysiology
thesis.degree.grantorCornell Universityen_US
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Physiology
dc.contributor.chairDavisson, Robin Len_US
dc.contributor.committeeMemberCohen, Paulaen_US
dc.contributor.committeeMemberRoberson, Mark Stephenen_US
dc.contributor.committeeMemberQuirk, Susan Maryen_US


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