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http://hdl.handle.net/11375/12068
Title: | Fetal Origin of Chronic Immune Disease: Role of Prenatal Stress Challenge |
Authors: | Jago, Caitlin A. |
Advisor: | Arck, Petra Ashkar, Ali Khalil Karimi, Mark Larché |
Department: | Medical Sciences |
Keywords: | Fetal Programming;Progesterone;Immune Ontogeny;Regulatory T Cells;Hematopoietic Stem Cells;Allergy and Immunology;Biological Phenomena, Cell Phenomena, and Immunity;Hemic and Immune Systems;Immune System Diseases;Maternal and Child Health;Medical Immunology;Other Immunology and Infectious Disease;Allergy and Immunology |
Publication Date: | 2012 |
Abstract: | <p><strong>Introduction: </strong>Increasing incidence of chronic immune diseases are mirrored by changing disease risk factors, which include maternal stress during pregnancy. To date, no studies have investigated the impact of prenatal stress challenge (PNS) on the fetal immune system. Fetal liver and bone marrow represent major sources of hematopoietic stem cells (HSC) at mid gestation, which differentiate and mature in the thymus. Disturbance of immune development may cause immune impairment in later life. Further, progesterone is recognized as a critical part of feto-maternal interaction. This study aimed to determine if PNS interferes with normal fetal immune development in mice and the impact of progesterone supplementation on stress effects. <strong>Methods: </strong>DBA/2J-mated BALB/c dams were sorted into three groups: control, PNS (gestation days (GDs) 12.5 and 14.5) and PNS plus progesterone supplementation (DHD). Fetal tissue was collected on GDs 16.5 and 18.5. Flow cytometric analysis examined frequency and phenotype of fetal immune cell populations: HSC in fetal liver and bone marrow, and different stages of T cell maturation and regulatory T (Treg) cells in the thymus. Fetal tails were collected to determine fetal sex by PCR analysis. <strong>Results: </strong>PNS induced a decrease in organ size on GD16.5, which was not seen on GD18.5 and was reversed by DHD treatment. PNS altered the percentage and absolute number of HSC within the liver and bone marrow populations, on GD16.5 and 18.5. There was a significant lag in T cell maturation as demonstrated by the altered expression of CD3 and skewed CD3-:CD3+ ratio. There was a significant decrease in Treg cells within CD3+ thymic cells in response to PNS. PNS effects in the thymus were ameliorated by DHD treatment. There was no PNS-induced sex bias. <strong>Conclusions: </strong>These results indicate that PNS compromises the developing fetal immune system, which could account for impaired immune responses in adults with chronic immune disease, and provide evidence for a therapeutic role of progesterone supplementation.</p> |
Description: | <p>NB: I had another committee member, Dr. Mark Larché; and would like to have his name included in the document.</p> <p>Thank you.</p> |
URI: | http://hdl.handle.net/11375/12068 |
Identifier: | opendissertations/6985 7937 2728461 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Size | Format | |
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fulltext.pdf | 14.41 MB | Adobe PDF | View/Open |
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