Author ORCID Identifier

https://orcid.org/0000-0002-7123-3886

Date Available

11-22-2021

Year of Publication

2021

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Arts and Sciences

Department/School/Program

Biology

First Advisor

Dr. Jeffrey L. Osborn

Abstract

Hypertensive pregnancy disorders are a major contribution to maternal and neonatal mortality worldwide. Two of these disorders, preeclampsia and chronic hypertension in pregnancy, affect up to 10% of all pregnancies. These hypertensive disorders of pregnancy are associated with long-term, postnatal risk factors for both mother and offspring. Despite numerous recent advances in preeclampsia research, the underlying mechanisms are still not understood. This could be due to lack of a spontaneous animal model. This dissertation presents the African Green Monkey (AGM; Chlorocebus aethiops sabaeus) as the first known spontaneous animal model of preeclampsia and a highly translational model of chronic hypertension in pregnancy. The AGM diverged from the human lineage approximately 29 million years ago and shares close genetic homology to humans. Thus, the AGM is similar to humans regarding gene structure, upright posture, circadian rhythm, organ physiology, and complex familial systems. Chapter 2 characterizes preeclamptic (PE) and normotensive (NT) pregnancies in the AGM, showing that PE animals have higher systolic and diastolic arterial pressure concomitant with elevated proteinuria compared to NT animals. PE animals also had a more rapid first trimester weight gain associated with reduced plasma osmolality. Offspring born to PE mothers have lower birth weight and a higher rate of stillbirth as compared to NT pregnancies. Because low birth weight is associated with increased disease susceptibility in later life, chapter 3 characterizes blood pressure, metabolic function, and renal sufficiency in offspring from NT, PE, and chronic hypertensive (CHT) pregnancies. Overall, this chapter shows that offspring born to PE, but not CHT, pregnancies have reduced glucose tolerance, proteinuria, and kaliuresis with no effect on systolic arterial pressure in early adolescence compared to those from NT pregnancies. Together, these data support the AGM as a novel and highly translational animal model for studying the etiology of preeclampsia and transgenerational disease transmission.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2021.156

Funding Information

This study was supported in part by the American Heart Association Predoctoral Fellowship (17PRE33670127) from 2017-2019.

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