Adrenal steroidogenesis following prenatal dexamethasone exposure in the spiny mouse

Abstract

Antenatal stress disturbs the development of the fetal hypothalamic-pituitary-adrenal axis and adrenal steroidogenesis. We investigated the effect of brief maternal exposure to high glucocorticoids (dexamethasone (DEX)) at mid-and late-pregnancy on adrenal structure and production of steroids in spiny mouse. Pregnant spiny mice were treated for 60 h with 125 mg/kg DEX or saline s.c. by osmotic minipump at day 20 (0.5) or 30 (0.75) of gestation. Immunohistochemical expression of steroidogenic acute regulatory-protein (StAR), 3b-hydroxysteroid dehydrogenase (3bHSD), 17-hydroxylase,17-20lyase (P450C17), and cytochromeb5 (CYTB5) was determined in adrenals on postnatal (P) day 170G20. DHEA, testosterone, and cortisol were measured by RIA. Maternal DEX at 20 days significantly reduced the expression of STAR, P450C17 (CYP17A1), and CYTB5 in the adrenal zona reticularis (ZR) of adult offspring, with greater change in male vs female offspring (P!0.05). Plasma DHEA was decreased in male offspring from DEX-treated (6.84G1.24 ng/ml) vs saline-treated (13G0.06 ng/ml; PZ0.01) dams, and the DHEA:cortisol ratio was lower in males (P!0.05). Testosterone levels increased in male offspring from DEX (266.03G50.75 pg/ml) vs saline (83.47G32.3 pg/ml, P!0.05)-treated dams. DEX treatment at 0.75 gestation had no significant effect on any parameters measured. This study shows that brief exposure to excess glucocorticoid has long-term impacts on the ZR and adrenal steroidogenesis, affecting the secretion of DHEA and testosterone in male offspring, an effect produced at 0.5 but not at 0.75 gestation. DHEA is important for brain development, and its suppression in adult life might contribute to the neurobehavioral pathologies that can arise after illness and stress during pregnancy.

PKA signaling drives reticularis differentiation and sexually dimorphic adrenal cortex renewal

“…Because rats and mice lack postnatal expression of CYP17 in the adrenal, they have long been considered as nonrelevant experimental models to study adrenarche. However, the spiny mouse has been shown to express CYP17 and to produce adrenal-derived androgens from an individualized zR (47)(48)(49). This provides cues for possible usefulness of rodent models to explore underpinnings of adrenarche.…”

Adrenal, metabolic and cardio‐renal dysfunction develops after pregnancy in rats born small or stressed by physiological measurements during pregnancy

“…It is important to note that blood pressure can be regulated by multiple physiological systems, and studies have demonstrated that offspring of female rodents exposed to glucocorticoids develop alterations in adrenal outcomes (Quinn et al . ), renal function (Singh et al . ) and blood pressure regulation (O'Sullivan et al .…”

“…While it was hypothesised that stress during pregnancy would further exacerbate and increase post-pregnancy blood pressure, this was not observed when measured by tail cuff. It is important to note that blood pressure can be regulated by multiple physiological systems, and studies have demonstrated that offspring of female rodents exposed to glucocorticoids develop alterations in adrenal outcomes (Quinn et al 2014), renal function (Singh et al 2007) and blood pressure regulation (O'Sullivan et al 2013). It is therefore likely that the impairments in adrenal and renal function may contribute to the elevated blood pressure observed in growth-restricted females after pregnancy.…”

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

“…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).…”