Abstract

Adverse environments during pregnancy can increase susceptibility to chronic diseases in adult offspring. The occurrence and development of fetal-originated diseases were associated with adrenal developmental programming and homeostasis alteration in offspring. Dexamethasone is widely used for preterm delivery-related pregnancy diseases, but the intrauterine programming alteration and its occurrence mechanism of prenatal dexamethasone exposure (PDE) on adrenal development in offspring have not been clarified. In this study, prenatal dexamethasone therapy could inhibit neonatal development and cause a low exposure of maternally derived glucocorticoid in clinic. Then, we established a rat model of PDE and observed a similar phenomenon. Further, the adrenal steroidogenic function was continuously inhibited in the PDE male offspring rats, accompanied by the decreased H3K27ac level of adrenal insulin-like growth factor 1 (IGF1) and its expression. Moreover, chronic stress in PDE adult offspring rats could reverse the changes of the above indicators through the high level of glucocorticoid. In combination with in vivo, in vitro and a series of interference experiments, we confirmed that the low level of endogenous glucocorticoids inhibited the adrenal IGF1 expression and steroidogenic function through the GRα/miR-370-3p/Sirt3 pathway. In summary, PDE could continuously inhibit the adrenal steroidogenic function in the male offspring, which is associated with the maternally derived low glucocorticoid-mediated the adrenal developmental programming alteration in offspring. This study provides a theoretical and experimental basis for explaining the adrenal development origin of PDE-induced adult chronic diseases.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.