The link between intrauterine environmental conditions and adult cardiovascular system is well established. Independent of lifestyle factors such as poor diet and exercise habits, individuals who have been exposed to stressful conditions in utero show an increased risk of health problems such as hypertension, stroke, and type II diabetes. In support of the Fetal Origin of Adult Disease hypothesis, many labs have reported permanent anatomical and physiological changes associated with fetal stress and nutrient deficiency, with a focus on organ systems such as the kidney and heart. One key idea proposed by many of these studies is the glucocorticoid hypothesis, which suggests that fetal stress develops at least in part by fetal overexposure to stress hormones, like glucocorticoids, during gestation. However, few studies have looked at the glucocorticoid hypothesis in the context of blood vessels of the brain. In our first study (cohort 1), pregnant female Sprague-Dawley rats were exposed to 50% maternal undernutrition during the last ten days of gestation. One subgroup was also administered Metyrapone, a corticosterone synthesis inhibitor, during gestation. After delivery, the pups were allowed to grow to maturity at 8-months of age, at which time their middle cerebral arteries were harvested and examined using a combination of vessel bath myography and confocal microscopy. In our second study (cohort 2), pregnant female Sprague-Dawley rats were exposed to Metyrapone (±). On postnatal day 9-10, the rats then underwent Hypoxia-Ischemia (±) (unilateral carotid ligation combined with 1.5 hours 8% hypoxia after 24 hours). The goal of both studies was to determine whether glucocorticoids would increase ischemic vulnerability, an important marker of vascular health. Our results demonstrated that food restriction as well as perturbations to early glucocorticoid exposure are critical to the development of the cerebrovasculature, and that pharmacological glucocorticoid inhibition during gestation can alter the vulnerability to mild hypoxic-ischemic injury. Future studies are currently in progress to determine the ultimate effects of food restriction on the cerebrovasculature during the neonatal period.
","abstract_html":"<p>The link between intrauterine environmental conditions and adult cardiovascular system is well established. Independent of lifestyle factors such as poor diet and exercise habits, individuals who have been exposed to stressful conditions in utero show an increased risk of health problems such as hypertension, stroke, and type II diabetes. In support of the Fetal Origin of Adult Disease hypothesis, many labs have reported permanent anatomical and physiological changes associated with fetal stress and nutrient deficiency, with a focus on organ systems such as the kidney and heart. One key idea proposed by many of these studies is the glucocorticoid hypothesis, which suggests that fetal stress develops at least in part by fetal overexposure to stress hormones, like glucocorticoids, during gestation. However, few studies have looked at the glucocorticoid hypothesis in the context of blood vessels of the brain. In our first study (cohort 1), pregnant female Sprague-Dawley rats were exposed to 50% maternal undernutrition during the last ten days of gestation. One subgroup was also administered Metyrapone, a corticosterone synthesis inhibitor, during gestation. After delivery, the pups were allowed to grow to maturity at 8-months of age, at which time their middle cerebral arteries were harvested and examined using a combination of vessel bath myography and confocal microscopy. In our second study (cohort 2), pregnant female Sprague-Dawley rats were exposed to Metyrapone (±). On postnatal day 9-10, the rats then underwent Hypoxia-Ischemia (±) (unilateral carotid ligation combined with 1.5 hours 8% hypoxia after 24 hours). The goal of both studies was to determine whether glucocorticoids would increase ischemic vulnerability, an important marker of vascular health. Our results demonstrated that food restriction as well as perturbations to early glucocorticoid exposure are critical to the development of the cerebrovasculature, and that pharmacological glucocorticoid inhibition during gestation can alter the vulnerability to mild hypoxic-ischemic injury. Future studies are currently in progress to determine the ultimate effects of food restriction on the cerebrovasculature during the neonatal period.</p>","abstract_has_math":false,"creators":["Durrant, Lara"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Basic Sciences","degree_department":null,"school":null,"contributors":["Pearce, William J.","Buchholz, John N.","Khorram, Omid","Kirsch, Wolff M.","Mata-Greenwood, Eugenia","Zhang, Lubo"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-06-01T07:00:00Z","date_published":"2017-06-01T07:00:00Z","updated_at":"2026-07-24T02:52:45Z","subjects":["Medical Sciences","Medicine and Health Sciences","Physiological Processes","Physiology","Nutrition - In Pregnancy; Prenatal Care; Pregnancy - Physiology; Cardiovascular System - Diseases","Prenatal nutrition disorders; Fetal Origin of Adult Disease; Mytropone; Corticosterone synthesis inhibitor; Vessel bath myography; Confocal microscopy"],"languages":["English"],"rights":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarsrepository.llu.edu/etd/461","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Pearce, William J.","Buchholz, John N.","Khorram, Omid","Kirsch, Wolff M.","Mata-Greenwood, Eugenia","Zhang, Lubo"]},{"key":"dc:creator","label":"Author","values":["Durrant, Lara"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Basic Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Medical Sciences","Medicine and Health Sciences","Physiological Processes","Physiology","Nutrition - In Pregnancy; Prenatal Care; Pregnancy - Physiology; Cardiovascular System - Diseases","Prenatal nutrition disorders; Fetal Origin of Adult Disease; Mytropone; Corticosterone synthesis inhibitor; Vessel bath myography; Confocal microscopy"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarsrepository.llu.edu/etd/461"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The link between intrauterine environmental conditions and adult cardiovascular system is well established. Independent of lifestyle factors such as poor diet and exercise habits, individuals who have been exposed to stressful conditions in utero show an increased risk of health problems such as hypertension, stroke, and type II diabetes. In support of the Fetal Origin of Adult Disease hypothesis, many labs have reported permanent anatomical and physiological changes associated with fetal stress and nutrient deficiency, with a focus on organ systems such as the kidney and heart. One key idea proposed by many of these studies is the glucocorticoid hypothesis, which suggests that fetal stress develops at least in part by fetal overexposure to stress hormones, like glucocorticoids, during gestation. However, few studies have looked at the glucocorticoid hypothesis in the context of blood vessels of the brain. In our first study (cohort 1), pregnant female Sprague-Dawley rats were exposed to 50% maternal undernutrition during the last ten days of gestation. One subgroup was also administered Metyrapone, a corticosterone synthesis inhibitor, during gestation. After delivery, the pups were allowed to grow to maturity at 8-months of age, at which time their middle cerebral arteries were harvested and examined using a combination of vessel bath myography and confocal microscopy. In our second study (cohort 2), pregnant female Sprague-Dawley rats were exposed to Metyrapone (±). On postnatal day 9-10, the rats then underwent Hypoxia-Ischemia (±) (unilateral carotid ligation combined with 1.5 hours 8% hypoxia after 24 hours). The goal of both studies was to determine whether glucocorticoids would increase ischemic vulnerability, an important marker of vascular health. Our results demonstrated that food restriction as well as perturbations to early glucocorticoid exposure are critical to the development of the cerebrovasculature, and that pharmacological glucocorticoid inhibition during gestation can alter the vulnerability to mild hypoxic-ischemic injury. Future studies are currently in progress to determine the ultimate effects of food restriction on the cerebrovasculature during the neonatal period.
"]},{"key":"dc:title","label":"Title","values":["Prenatal Undernutrition, Metyrapone, and the Cerebrovasculature"]}]}],"canonical_facts":{"dc:contributor":["Pearce, William J.","Buchholz, John N.","Khorram, Omid","Kirsch, Wolff M.","Mata-Greenwood, Eugenia","Zhang, Lubo"],"dc:creator":["Durrant, Lara"],"dc:description.abstract":["The link between intrauterine environmental conditions and adult cardiovascular system is well established. Independent of lifestyle factors such as poor diet and exercise habits, individuals who have been exposed to stressful conditions in utero show an increased risk of health problems such as hypertension, stroke, and type II diabetes. In support of the Fetal Origin of Adult Disease hypothesis, many labs have reported permanent anatomical and physiological changes associated with fetal stress and nutrient deficiency, with a focus on organ systems such as the kidney and heart. One key idea proposed by many of these studies is the glucocorticoid hypothesis, which suggests that fetal stress develops at least in part by fetal overexposure to stress hormones, like glucocorticoids, during gestation. However, few studies have looked at the glucocorticoid hypothesis in the context of blood vessels of the brain. In our first study (cohort 1), pregnant female Sprague-Dawley rats were exposed to 50% maternal undernutrition during the last ten days of gestation. One subgroup was also administered Metyrapone, a corticosterone synthesis inhibitor, during gestation. After delivery, the pups were allowed to grow to maturity at 8-months of age, at which time their middle cerebral arteries were harvested and examined using a combination of vessel bath myography and confocal microscopy. In our second study (cohort 2), pregnant female Sprague-Dawley rats were exposed to Metyrapone (±). On postnatal day 9-10, the rats then underwent Hypoxia-Ischemia (±) (unilateral carotid ligation combined with 1.5 hours 8% hypoxia after 24 hours). The goal of both studies was to determine whether glucocorticoids would increase ischemic vulnerability, an important marker of vascular health. Our results demonstrated that food restriction as well as perturbations to early glucocorticoid exposure are critical to the development of the cerebrovasculature, and that pharmacological glucocorticoid inhibition during gestation can alter the vulnerability to mild hypoxic-ischemic injury. Future studies are currently in progress to determine the ultimate effects of food restriction on the cerebrovasculature during the neonatal period.
"],"dc:identifier":["https://scholarsrepository.llu.edu/etd/461"],"dc:language":["English"],"dc:rights":["This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights."],"dc:subject":["Medical Sciences","Medicine and Health Sciences","Physiological Processes","Physiology","Nutrition - In Pregnancy; Prenatal Care; Pregnancy - Physiology; Cardiovascular System - Diseases","Prenatal nutrition disorders; Fetal Origin of Adult Disease; Mytropone; Corticosterone synthesis inhibitor; Vessel bath myography; Confocal microscopy"],"dc:title":["Prenatal Undernutrition, Metyrapone, and the Cerebrovasculature"],"thesis:degree_discipline":["Basic Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T02:52:45Z"}