학술논문
Preeclampsia may influence offspring neuroanatomy and cognitive function: a role for placental growth factor
Document Type
Report
Source
Biology of Reproduction. August 2019, Vol. 101 Issue 2, p271, 13 p.
Subject
Language
English
ISSN
0006-3363
Abstract
Introduction Preeclampsia (PE) is a common pregnancy complication affecting 3-5% of pregnancies [1, 2]. Diagnosed after 20 weeks of gestation, the maternal syndrome of PE consists of new-onset hypertension and [...]
Preeclampsia (PE) is a common pregnancy complication affecting 3-5% of women. Preeclampsia is diagnosed clinically as new-onset hypertension with associated end organ damage after 20 weeks of gestation. Despite being diagnosed as a maternal syndrome, fetal experience of PE is a developmental insult with lifelong cognitive consequences. These cognitive alterations are associated with distorted neuroanatomy and cerebrovasculature, including a higher risk of stroke. The pathophysiology of a PE pregnancy is complex, with many factors potentially able to affect fetal development. Deficient pro-angiogenic factor expression is one aspect that may impair fetal vascularization, alter brain structure, and affect future cognition. Of the pro-angiogenic growth factors, placental growth factor (PGF) is strongly linked to PE. Concentrations of PGF are inappropriately low in maternal blood both before and during a PE gestation. Fetal concentrations of PGF appear to mirror maternal circulating concentrations. Using [Pgf.sup.-/-] mice that may model effects of PE on offspring, we demonstrated altered central nervous system vascularization, neuroanatomy, and behavior. Overall, we propose that development of the fetal brain is impaired in PE, making the offspring of preeclamptic pregnancies a unique cohort with greater risk of altered cognition and cerebrovasculature. These individuals may benefit from early interventions, either pharmacological or environmental. The early neonatal period may be a promising window for intervention while the developing brain retains plasticity. Summary Sentence Offspring of preeclamptic pregnancies have unique brains with evidence from an angiokine-deficient mouse model suggesting a role for PGF. Key words: behavior, brain, cerebrovasculature, Developmental Origins of Health and Disease, preeclampsia.
Preeclampsia (PE) is a common pregnancy complication affecting 3-5% of women. Preeclampsia is diagnosed clinically as new-onset hypertension with associated end organ damage after 20 weeks of gestation. Despite being diagnosed as a maternal syndrome, fetal experience of PE is a developmental insult with lifelong cognitive consequences. These cognitive alterations are associated with distorted neuroanatomy and cerebrovasculature, including a higher risk of stroke. The pathophysiology of a PE pregnancy is complex, with many factors potentially able to affect fetal development. Deficient pro-angiogenic factor expression is one aspect that may impair fetal vascularization, alter brain structure, and affect future cognition. Of the pro-angiogenic growth factors, placental growth factor (PGF) is strongly linked to PE. Concentrations of PGF are inappropriately low in maternal blood both before and during a PE gestation. Fetal concentrations of PGF appear to mirror maternal circulating concentrations. Using [Pgf.sup.-/-] mice that may model effects of PE on offspring, we demonstrated altered central nervous system vascularization, neuroanatomy, and behavior. Overall, we propose that development of the fetal brain is impaired in PE, making the offspring of preeclamptic pregnancies a unique cohort with greater risk of altered cognition and cerebrovasculature. These individuals may benefit from early interventions, either pharmacological or environmental. The early neonatal period may be a promising window for intervention while the developing brain retains plasticity. Summary Sentence Offspring of preeclamptic pregnancies have unique brains with evidence from an angiokine-deficient mouse model suggesting a role for PGF. Key words: behavior, brain, cerebrovasculature, Developmental Origins of Health and Disease, preeclampsia.