Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor

Sun, Yan; Wan, Xiaoyan; Ouyang, Jian; Xie, Renfeng; Wang, Xueping; Chen, Peisong

doi:10.1155/2016/9409452

Cited by 13 publications

(10 citation statements)

References 28 publications

(34 reference statements)

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“…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]. It is important to recognize the timing of exposure when considering the correlation between animal models and human fetuses.…”

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

135

103

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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.

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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

135

103

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“…Obviously, prenatal exposure to glucocorticoids can alter the epigenome of the offspring, affecting multiple organs and pathways ( 75 ). Therefore, in addition to the observed effects on TCR repertoire, we cannot discard epigenetic effects on glucose metabolism or pancreatic beta cell development as disease modifiers ( 76 ), and research on this topic is ongoing. Moreover, changes in the microbiome are likely to influence immune system development in the offspring ( 77 ).…”

Section: Discussionmentioning

confidence: 99%

Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity

et al. 2017

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Prenatal glucocorticoids are routinely administered to pregnant women at risk of preterm delivery in order to improve survival of the newborn. However, in half of the cases, birth occurs outside the beneficial period for lung development. Glucocorticoids are potent immune modulators and cause apoptotic death of immature T cells, and we have previously shown that prenatal betamethasone treatment at doses eliciting lung maturation induce profound thymocyte apoptosis in the offspring. Here, we asked if there are long-term consequences on the offspring’s immunity after this treatment. In the non-obese diabetic mouse model, prenatal betamethasone clearly decreased the frequency of pathogenic T cells and the incidence of type 1 diabetes (T1D). In contrast, in the lupus-prone MRL/lpr strain, prenatal glucocorticoids induced changes in the T cell repertoire that resulted in more autoreactive cells. Even though glucocorticoids transiently enhanced regulatory T cell (Treg) development, these cells did not have a protective effect in a model for multiple sclerosis which relies on a limited repertoire of pathogenic T cells for disease induction that were not affected by prenatal betamethasone. We conclude that prenatal steroid treatment, by inducing changes in the T cell receptor repertoire, has unforeseeable consequences on development of autoimmune disease. Our data should encourage further research to fully understand the consequences of this widely used treatment.

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“…Similarly, a study performed in rats demonstrated that prenatal dexamethasone, another glucocorticoid, exposure increases the susceptibility to autoimmunity, namely, experimental autoimmune encephalomyelitis (EAE) and adjuvant‐induced arthritis (AIA) in offspring (Sun et al, ). The study found that epigenetic programing of the glucocorticoid receptor in peripheral blood mononuclear cells was associated with susceptibility to AIA and EAE (Sun et al, ).…”

Section: Autoimmunitymentioning

confidence: 99%

Environmental exposures during pregnancy: Mechanistic effects on immunity

Rychlik

Sillé

2019

Birth Defects Research

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In human studies, it is well established that exposures during embryonic and fetal development periods can influence immune health. Coupled with genetic predisposition, these exposures can alter lifetime chronic and infectious disease trajectory, and, ultimately, life expectancy. Fortunately, as research advances, mechanisms governing long‐term effects of prenatal exposures are coming to light and providing the opportunity for intervention and risk reduction. For instance, human association studies have provided a foundation for the association of prenatal exposure to particulate matter with early immunosuppression and later allergic disease in the offspring. Only recently, the mechanisms mediating this response have been revealed and there is much we have yet to discover. Although cellular immune response is understood for many exposure scenarios, molecular pathways are still unidentified. This review will provide commentary and synthesis of the current literature regarding environmental exposures during pregnancy and mechanisms determining immune outcomes. Shared mechanistic features and current gaps in the state of the science are identified and discussed. To such purpose, we address exposures by their immune effect type: immunosuppression, autoimmunity, inflammation and tissue damage, hypersensitivity, and general immunomodulation.

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Prenatal Dexamethasone Exposure Increases the Susceptibility to Autoimmunity in Offspring Rats by Epigenetic Programing of Glucocorticoid Receptor

Cited by 13 publications

References 28 publications

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Glucocorticoids and Reproduction: Traffic Control on the Road to Reproduction

Prenatal Administration of Betamethasone Causes Changes in the T Cell Receptor Repertoire Influencing Development of Autoimmunity

Environmental exposures during pregnancy: Mechanistic effects on immunity

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