Prenatal dexamethasone exposure induces changes in nonhuman primate offspring cardiometabolic and hypothalamic-pituitary-adrenal axis function

Abstract

Prenatal stress or glucocorticoid administration has persisting "programming" effects on offspring in rodents and other model species. Multiple doses of glucocorticoids are in widespread use in obstetric practice. To examine the clinical relevance of glucocorticoid programming, we gave 50, 120, or 200 μg/kg/d of dexamethasone (dex50, dex120, or dex200) orally from mid-term to a singleton-bearing nonhuman primate, Chlorocebus aethiops (African vervet). Dexamethasone dose-dependently reduced maternal cortisol levels without effecting maternal blood pressure, glucose, electrolytes, or weight gain. Birth weight was unaffected by any dexamethasone dose, although postnatal growth was attenuated after dex120 and dex200. At 8 months of age, dex120 and dex200 offspring showed impaired glucose tolerance and hyperinsulinemia, with reduced (approximately 25%) pancreatic β cell number at 12 months. Dex120 and dex200 offspring had increased systolic and diastolic blood pressures at 12 months. Mild stress produced an exaggerated cortisol response in dex200 offspring, implying hypothalamic-pituitary-adrenal axis programming. The data are compatible with the extrapolation of the glucocorticoid programming hypothesis to primates and indicate that repeated glucocorticoid therapy and perhaps chronic stress in humans may have long-term effects.

Prenatal exposure to a natural disaster increases risk for obesity in 5½-year-old children

“…For example, preweaning maternal stress (30) did not influence offspring birth weight but was associated with greater weight, BMI, and abdominal circumference among juvenile macaques (30). Furthermore, antenatal exposure to synthetic GCs resulted in increased subcutaneous fat thickness, decreased β-cell numbers, and increased blood pressure among juvenile vervet monkeys, despite the lack of impact on birth weight (31). However, similar findings among humans are limited.…”

Le concept des origines développementales de la santé

“…En effet, ces animaux, lorsqu'ils sont devenus adultes, présentent une intolérance au glucose. Dans un modèle de primate à grossesse unique, le Chlorocebus aethiops ou singe vert, l'exposition prénatale à de faibles doses de dexaméthasone, un glucocorticoïde de synthèse, produit des troubles de l'homéostasie du glucose et de l'insuline, réduit la masse des cellules bêta pancréatiques, et augmente la pression artérielle et les niveaux de cortisol chez les descendants adolescents [34]. Ces données sont ainsi compatibles avec une extrapolation, faite sur les primates, de l'hypothèse de la programmation par les glucocorticoïdes.…”

Effect of intrauterine growth retardation on liver and long-term metabolic risk

“…41,42 The exposure to dexamethasone during fetal life results in hypothalamic-pituitary-adrenal axis (HPAA) programming in non-human primate offspring. 43 In humans, low-birth weight is associated with increased levels of plasma cortisol in both childhood and adulthood, and hyperactivity of HPAA. [44][45][46][47] HPAA activation may ultimately lead to the metabolic rearrangement.…”