Effects of maternal dexamethasone treatment on pancreatic β cell function in the pregnant mare and post natal foal

Valenzuela, OA; Jellyman, Juanita K.; Allen, V. L.; Holdstock, N. B.; Fowden, Abigail L.

doi:10.1111/evj.12560

Cited by 10 publications

(8 citation statements)

References 35 publications

(92 reference statements)

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“…Much of what 232:1 we know about glucocorticoid induced programming of disease is based on animal studies using synthetic glucocorticoids such as dexamethasone. Numerous studies have demonstrated that maternal exposure to dexamethasone can reduce foetal or postnatal growth and impair offspring cardiometabolic physiology (Langdown et al 2001, de Vries et al 2007, Quinn et al 2014, Valenzuela et al 2016. Importantly, this growth restriction is often associated with compensatory catch-up growth, which may further increase the risk of cardiometabolic outcomes (Ozanne 2001).…”

Section: Introductionmentioning

confidence: 99%

Prenatal corticosterone exposure programs sex-specific adrenal adaptations in mouse offspring

Cuffe

Turton

Akison

et al. 2017

Journal of Endocrinology

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Maternal stress can impair foetal development and program sex-specific disease outcomes in offspring through the actions of maternally produced glucocorticoids, predominantly corticosterone (Cort) in rodents. We have demonstrated in mice that male but not female offspring prenatally exposed to Cort (33 µg/kg/h for 60 h beginning at E12.5) develop cardiovascular/renal dysfunction at 12 months. At 6 months of age, renal function was normal but male offspring had increased plasma aldosterone concentrations, suggesting that altered adrenal function may precede disease. This study investigated the long-term impact of prenatal exposure to Cort on adrenal growth, morphology and steroidogenic capacity as well as plasma Cort concentrations in offspring at postnatal day 30 (PN30), 6 months and 12 months of age. Prenatal Cort exposure decreased adrenal volume, particularly of the zona fasciculata, in male offspring at PN30 but increased both relative and absolute adrenal weight at 6 months of age. By 12 months of age, male Cort-exposed offspring had reduced absolute adrenal weight in association with increased adrenal plaque deposition (lipogenic pigmentation). Plasma Cort concentrations were elevated in male 6-month offspring but not at other ages. mRNA expression of Mc2r (ACTH receptor) was increased in males at PN30, and Cyp11a1 expression was decreased at 6 and 12 months of age. There were no changes in the adrenals of female Cort-exposed offspring. This study demonstrates that prenatal Cort exposure induces offspring adrenal gland dysfunction in an age- and sex-specific manner, which may contribute to long-term programmed disease in male offspring after maternal stress.

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Section: Introductionmentioning

confidence: 99%

Prenatal corticosterone exposure programs sex-specific adrenal adaptations in mouse offspring

Cuffe

Turton

Akison

et al. 2017

Journal of Endocrinology

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“…[17][18][19] Similarly, dexamethasone treatment of mares during late pregnancy alters arginine-stimulated insulin secretion in their foals 12 weeks after birth relative to controls of the same BW. 20 Collectively, the experimental and epidemiological studies have led to the concept that postnatal metabolic phenotype can be programmed in utero, particularly by environmental conditions suboptimal for normal fetal development.…”

Section: Introductionmentioning

confidence: 99%

Effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics in young adult horses

Valenzuela

Jellyman

Allen

et al. 2016

J Dev Orig Health Dis

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In several species, adult metabolic phenotype is influenced by the intrauterine environment, often in a sex-linked manner. In horses, there is also a window of susceptibility to programming immediately after birth but whether adult glucose-insulin dynamics are altered by neonatal conditions remains unknown. Thus, this study investigated the effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose-insulin dynamics of young adult horses. For the first 5 days after birth, term foals were treated with saline as a control or ACTH to raise cortisol levels to those of stressed neonates. At 1 and 2 years of age, insulin secretion and sensitivity were measured by exogenous glucose administration and hyperinsulinaemic-euglycaemic clamp, respectively. Glucose-stimulated insulin secretion was less in males than females at both ages, although there were no sex-linked differences in glucose tolerance. Insulin sensitivity was greater in females than males at 1 year but not 2 years of age. Birth weight was inversely related to the area under the glucose curve and positively correlated to insulin sensitivity at 2 years but not 1 year of age. In contrast, neonatal glucocorticoid overexposure induced by adrenocorticotropic hormone (ACTH) treatment had no effect on whole body glucose tolerance, insulin secretion or insulin sensitivity at either age, although this treatment altered insulin receptor abundance in specific skeletal muscles of the 2-year-old horses. These findings show that glucose-insulin dynamics in young adult horses are sexually dimorphic and determined by a combination of genetic and environmental factors acting during early life.

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“…In the fetal sheep (Fowden 1980, Aldoretta et al 1998 and horse (Fowden et al 1980(Fowden et al , 1982(Fowden et al , 2005, and also in atricial species such as the rat (Kervran et al 1979, Kervran & Randon 1980, there are maturational changes in pancreatic function in late gestation with increasing insulin secretion in response to glucose and arginine stimulation. These changes are associated with increasing endogenous cortisol concentrations in the prepartum period (Fowden et al 2005), can be modified by exogenous stimuli such as maternal undernutrition (Oliver et al 2001), multiple conception (Rumball et al 2008, Green et al 2011 and exogenous glucocorticoid administration (Valenzuela et al 2017) and extend into postnatal life. It has also been reported that there is a wave of β-cell apoptosis in late gestation in the human (Tornehave & Larsson 1997), which may represent a change from fetal β-cells to more mature β-cells in preparation for extra-uterine life.…”

Section: How Might Preterm Birth Be Linked With Later Diabetes?mentioning

confidence: 99%

Impact of prematurity for pancreatic islet and beta-cell development

Bloomfield

2018

Journal of Endocrinology

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As increasing numbers of babies born preterm survive into adulthood, it is becoming clear that, in addition to the well-described risks of neurodevelopmental sequelae, there also are increased risks for non-communicable diseases, including diabetes. Epidemiological studies indicate that risks are increased even for birth at late preterm and early term gestations and for both type 1 and type 2 diabetes. Thus, factors related to preterm birth likely affect development of the fetal and neonatal beta-cell in addition to effects on peripheral insulin sensitivity. These factors could operate prior to preterm birth and be related to the underlying cause of preterm birth, to the event of being born preterm itself, to the postnatal care of the preterm neonate or to a combination of these exposures. Experimental evidence indicates that factors may be operating during all these critical periods to contribute to altered development of beta-cell mass in those born preterm. Greater understanding of how these factors impact upon development of the pancreas may lead to interventions or management approaches that mitigate the increased risk of later diabetes.

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Effects of maternal dexamethasone treatment on pancreatic β cell function in the pregnant mare and post natal foal

Cited by 10 publications

References 35 publications

Prenatal corticosterone exposure programs sex-specific adrenal adaptations in mouse offspring

Prenatal corticosterone exposure programs sex-specific adrenal adaptations in mouse offspring

Effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics in young adult horses

Impact of prematurity for pancreatic islet and beta-cell development

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