Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring

Cuffe, James; Burgess, D. J.; O’Sullivan, Lee; Singh, Reetu R.

doi:10.14814/phy2.12754

Cited by 24 publications

(25 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Maternal exposure to dexamethasone in rats results in sexually dimorphic behavior in offspring, associated with structural changes to neuronal populations [43, 44]. In mice, the cardiovascular and renal renin-angiotensin-aldosterone systems also respond to elevated prenatal corticosterone in a sexually-dimorphic manner, potentially through altering adrenal function [45– 47]. Epigenetic factors may also play a key role in the glucocorticoid-driven effects of fetal programming, including altered methylation status of GR following neonatal dexamethasone exposure [48].…”

Section: Glucocorticoids Regulate the Function Of Organs In The Repromentioning

confidence: 99%

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Whirledge

Cidlowski

2017

Trends in Endocrinology & Metabolism

139

103

View full text Add to dashboard Cite

Glucocorticoids are steroid hormones that regulate diverse cellular functions and are essential to facilitate normal physiology. Yet, stress-induced levels of glucocorticoids result in several pathologies including profound reproductive dysfunction. Compelling new evidence indicates glucocorticoids are crucial to the establishment and maintenance of reproductive function. The fertility promoting or inhibiting activity of glucocorticoids depends on timing, dose, and glucocorticoid-responsiveness within a given tissue, which is mediated by the glucocorticoid receptor. The glucocorticoid receptor gene and protein are subject to cellular processing, contributing to signaling diversity and providing a mechanism by which both physiological and stress-induced levels of glucocorticoids function in a cell-specific function. Understanding how glucocorticoids regulate fertility and infertility may lead to novel approaches to the regulation of reproductive function.

show abstract

Section: Glucocorticoids Regulate the Function Of Organs In The Repromentioning

confidence: 99%

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Whirledge

Cidlowski

2017

Trends in Endocrinology & Metabolism

139

103

View full text Add to dashboard Cite

show abstract

“…Betamethasone administered to pregnant ewes caused hypertension in the 0.5-month-old male offspring that has been related to decreased expression of angiotensin 1–7 Mas receptor in the dorsal medulla and increased angiotensin-converting enzyme in the cerebrospinal fluid [85, 86]. Steroids given to pregnant mice cause dysregulation of the RAAS in 6- and 12-month-old male but not female offspring [87]. Short-term administration of corticosteroids to pregnant mice decreases nephron number in female and male offspring [87].…”

Section: Pathogenesis Of Primary Pediatric Hypertensionmentioning

confidence: 99%

“…Steroids given to pregnant mice cause dysregulation of the RAAS in 6- and 12-month-old male but not female offspring [87]. Short-term administration of corticosteroids to pregnant mice decreases nephron number in female and male offspring [87]. At 6 months of age, male but not female offspring had increased plasma aldosterone, renal expression of angiotensin II, and Na + ,K + /ATPase alpha1 subunit and sodium ion channels; blood measure was not measured [87].…”

Section: Pathogenesis Of Primary Pediatric Hypertensionmentioning

confidence: 99%

“…Short-term administration of corticosteroids to pregnant mice decreases nephron number in female and male offspring [87]. At 6 months of age, male but not female offspring had increased plasma aldosterone, renal expression of angiotensin II, and Na + ,K + /ATPase alpha1 subunit and sodium ion channels; blood measure was not measured [87]. However, at 12 months of age, the male but not female mice had decreased BP [88].…”

Section: Pathogenesis Of Primary Pediatric Hypertensionmentioning

confidence: 99%

See 1 more Smart Citation

Primary Pediatric Hypertension: Current Understanding and Emerging Concepts

et al. 2017

View full text Add to dashboard Cite

The rising prevalence of primary pediatric hypertension and its tracking into adult hypertension point to the importance of determining its pathogenesis to gain insights into its current and emerging management. Considering that the intricate control of BP is governed by a myriad of anatomical, molecular biological, biochemical, and physiological systems, multiple genes are likely to influence an individual's BP and susceptibility to develop hypertension. The long-term regulation of BP rests on renal and non-renal mechanisms. One renal mechanism relates to sodium transport. The impaired renal sodium handling in primary hypertension and salt sensitivity may be caused by aberrant counter-regulatory natriuretic and anti-natriuretic pathways. The sympathetic nervous and renin-angiotensin-aldosterone systems are examples of antinatriuretic pathways. An important counter-regulatory natriuretic pathway is afforded by the renal autocrine/paracrine dopamine system, aberrations of which are involved in the pathogenesis of hypertension, including that associated with obesity. We present updates on the complex interactions of these two systems with dietary salt intake in relation to obesity, insulin resistance, inflammation, and oxidative stress. We review how insults during pregnancy such as maternal and paternal malnutrition, glucocorticoid exposure, infection, placental insufficiency, and treatments during the neonatal period have long-lasting effects in the regulation of renal function and BP. Moreover, these effects have sex differences. There is a need for early diagnosis, frequent monitoring, and timely management due to increasing evidence of premature target organ damage. Large controlled studies are needed to evaluate the long-term consequences of the treatment of elevated BP during childhood, especially to establish the validity of the current definition and treatment of pediatric hypertension.

show abstract

“…Importantly, these sex specific placental adaptations were associated with impaired renal (Cuffe et al . ), adrenal (Cuffe et al . ) and cardiovascular (O'Sullivan et al .…”

Section: Introductionmentioning

confidence: 99%

Maternal corticosterone in the mouse alters oxidative stress markers, antioxidant function and mitochondrial content in placentas of female fetuses

Bartho

Holland

Moritz

et al. 2019

The Journal of Physiology

Self Cite

View full text Add to dashboard Cite

Key points Maternal exposure to the stress hormone corticosterone is known to programme a range of sex specific disease outcomes in offspring. Sex differences in placental adaptations are thought to mediate these processes. Placental oxidative stress is implicated in a range of pregnancy disorders but the role of placental oxidative stress in sex specific disease outcomes following prenatal corticosterone exposure is unknown. This study demonstrates that maternal corticosterone reduced placental hydrogen peroxide and 8‐hydroxy‐2′‐deoxyguanosine concentrations but increased protein carbonyl content and advanced glycation end product concentrations in placentas of female fetuses but not male fetuses. These results highlight that placentas of female fetuses respond differently to maternal corticosterone exposure, with oxidative stress a major finding in placentas of female fetuses. Abstract Maternal exposure to glucocorticoids during pregnancy increases offspring risk of developing a range of sex specific disease phenotypes. These sex specific disease outcomes are thought to be in part mediated by different placental adaptations in males and females. The placenta is a highly metabolic organ which is vulnerable to the effects of oxidative stress. In other tissues, males and females have been shown to respond differently to the pro‐oxidant effects of glucocorticoids. This study therefore used a well characterized animal model of maternal corticosterone exposure to investigate sex specific alterations in reactive oxygen species production, antioxidant concentrations and mitochondrial properties that might contribute to sex differences in placental outcomes. C57BL/6 mice were implanted with osmotic minipumps containing corticosterone (33 μg kg−1 h−1) at embryonic day (E) 12.5 and placentas collected at E14.5 for analysis. Corticosterone exposure reduced placental hydrogen peroxide (H2O2) and 8‐hydroxy‐2′‐deoxyguanosine concentrations but increased protein carbonyl content and advanced glycation end product concentrations in placentas of female fetuses but not male fetuses. This dysregulation of different markers of oxidative stress may be due to increased placental activity of thioredoxin reductase in female but not male fetuses. Corticosterone reduced placental mitochondrial content but increased protein expression of the autophagosome cargo protein p62. This study demonstrates that placentas of female fetuses respond differently to maternal corticosterone exposure and highlights an important role of reactive oxygen species, mitochondrial adaptations and antioxidant responses in glucocorticoid induced programmed disease.

show abstract

Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring

Cited by 24 publications

References 47 publications

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Primary Pediatric Hypertension: Current Understanding and Emerging Concepts

Maternal corticosterone in the mouse alters oxidative stress markers, antioxidant function and mitochondrial content in placentas of female fetuses

Contact Info

Product

Resources

About