Effects of High Altitude on AMPK Activation

Study Overview
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Brief Summary
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Pregnancy elicits adaptive changes in uteroplacental blood flow, which are altered at high altitude and may contribute to the observed 3-fold increase in intrauterine growth restriction (IUGR) and preeclampsia (PreE). The investigators propose to collect myometrial, cord blood, and placental tissue samples from women at high altitude (Summit County) and low altitude (Denver) in Colorado in order to determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries (MA). If altered MA vasoreactivity is found, further studies may be able to link these changes to the increased rates of PreE and IUGR at altitude and contribute to the understanding of these two disorders.

Detailed Description
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The Investigators will determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries. This will be novel information regarding pregnancy at altitude and of significance not just for women and families in Colorado, but also at high-altitude locations throughout the world. If altered MA vasoreactivity is found, further studies may be able to link these changes to the increased rates of PreE and IUGR at altitude and contribute to the understanding of these two disorders. The Investigators will also determine whether the chronic hypoxia of high altitude alters DNA methylation patterns and expression of key genes involved in metabolic homeostasis in maternal, placental and fetal cells and, in turn, the relationship of these changes to fetal growth and maternal well-being.

Official Title
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Effects of High Altitude on 5' Adenosine Monophosphate-activated Protein Kinase (AMPK) Activation and Peroxisome Proliferator-activated Receptor Gamma (PPARγ) Regulation

Conditions
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Pregnancy, IUGR, Preeclampsia

Intervention / Treatment
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* Procedure: Collection of myometrial, cord blood, and placental tissue samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women scheduled for cesarean delivery at University of Colorado Hospital (Denver, 1600 m) and St. Anthony's Summit Medical Center (Summit County, 3000 m) Cesarean delivery at a prescheduled time without any labor, typically at 39 weeks gestation Exclusion Criteria: Women will be excluded if there are co-existing medical diagnoses that are known to affect vascular parameters (i.e., diabetes mellitus, gestational diabetes, any hypertensive disorder of pregnancy, or a current smoker). Women with multiple gestations and preterm deliveries will also be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| High Altitude (3000 m)<br>Collection of myometrial, cord blood, and placental tissue samples from women at high altitude (Summit County) and low altitude (Denver) in Colorado in order to determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries (MA). | Procedure: Collection of myometrial, cord blood, and placental tissue samples<br>* We propose to collect myometrial, cord blood, and placental tissue samples from women at high altitude (Summit County) and low altitude (Denver) in Colorado in order to determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries (MA).<br>|
| Low Altitude (1600 m)<br>Collection of myometrial, cord blood, and placental tissue samples from women at high altitude (Summit County) and low altitude (Denver) in Colorado in order to determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries (MA). | Procedure: Collection of myometrial, cord blood, and placental tissue samples<br>* We propose to collect myometrial, cord blood, and placental tissue samples from women at high altitude (Summit County) and low altitude (Denver) in Colorado in order to determine if residence at altitude during pregnancy changes the vasoreactivity of myometrial arteries (MA).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Myometrial artery dimensions | Myometrial artery dimensions as quantified by immunohistochemistry or other staining techniques, and results of studies of isolated myometrial artery studies in which vasoconstrictor and vasodilator responses to pharmacological agonists are measured using absolute values and the percent maximal contraction to potassium chloride. | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pregnancy, High altitude, vasoreactivity, myometrial arteries