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Maternal Malnutrition, Glucocorticoids, and Fetal Programming: A Role for Placental 11β-Hydroxysteroid Dehydrogenase Type 2

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Diet, Nutrition, and Fetal Programming

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Abstract

Maternal malnutrition during pregnancy alters the growth and development of the fetus and associates with adverse adult health outcomes in the offspring. Frequently underlying these associations is overexposure of the fetus to glucocorticoids. Fetal exposure to glucocorticoids is primarily regulated by 11β-HSD2, which catalyzes the intracellular inactivation of glucocorticoids. This enzyme is abundantly expressed at the maternal-fetal interface of the placenta and within fetal tissues, thus limiting glucocorticoid passage to the fetus. This is critical as overexposure of the fetus to glucocorticoids perturbs placental and fetal growth and development. Maternal malnutrition (obesity, restriction of food intake, protein restriction) frequently results in a reduction of placental 11β-HSD2 as well as increases in maternal and fetal glucocorticoids. These have subsequent ramifications for not only fetal development but also placental development and function. This chapter highlights the critical role of placental and fetal glucocorticoid exposure in models of maternal malnutrition and developmental programming and focuses on the importance of placental 11β-HSD2 in determining these outcomes.

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Abbreviations

11β-HSD2:

11-β hydroxysteroid dehydrogenase type 2

CBG:

Corticosteroid binding globulin

DOHAD:

Developmental programming of adult health and disease

GLUT:

Glucose transporter

HPA:

Hypothalamic-pituitary-adrenal

LPD:

Low-protein diet

PPAR:

Peroxisome proliferator-activated receptor

SAME:

Syndrome of apparent mineralocorticoid excess

VEGF:

Vascular endothelial growth factor

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Chivers, E.K., Wyrwoll, C.S. (2017). Maternal Malnutrition, Glucocorticoids, and Fetal Programming: A Role for Placental 11β-Hydroxysteroid Dehydrogenase Type 2. In: Rajendram, R., Preedy, V., Patel, V. (eds) Diet, Nutrition, and Fetal Programming. Nutrition and Health. Humana Press, Cham. https://doi.org/10.1007/978-3-319-60289-9_39

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