Maternal Glucocorticoid Elevation and Associated Fetal Thymocyte Apoptosis are Involved in Immune Disorders of Prenatal Caffeine Exposed Offspring Mice

Abstract

Our previous study showed that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) and glucocorticoid elevation in the fetus. Researchers suggested that IUGR is a risk factor for T helper cell (Th)1/Th2 deviation. However, whether PCE can induce these immune disorders and the underlying mechanisms of that induction remain unknown. This study aimed to observe the effects of PCE on the Th1/Th2 balance in offspring and further explore the developmental origin mechanisms from the perspective of glucocorticoid overexposure-induced thymocyte apoptosis. An IUGR model was established by caffeine administration from gestational day (GD) 9 to GD 18, and the offspring were immunized on postnatal day (PND) 42. The results show that maternal glucocorticoid overexposure increased fetal thymocyte apoptosis by activating both the Fas-mediated and the Bim-regulated apoptotic pathways. After birth, accelerated thymocyte apoptosis and Th1 suppression were also found in the PCE offspring at PND 14 and PND 49. Moreover, the PCE offspring showed immune disorders after immunization, manifesting as increased IgG1/IgG2a ratio and IL-4 production in the serum. In conclusion, PCE could induce fetal overexposure to maternal glucocorticoids and increase thymocyte apoptosis, which could persist into postnatal life and be implicated in Th1 inhibition and further immune disorders.

Caffeine regulates both osteoclast and osteoblast differentiation via the AKT, NF-κB, and MAPK pathways

“…Caffeine (1,3,7-trimethylxanthine) is the most widely used and studied pharmacologically active substance in the world. It is found in foods, beverages, and medicinal preparations, such as coffee, tea, soft drinks, cocoa or chocolate, and various medications and dietary supplements ( Liu et al, 2017 ). Current evidence suggests that approximately 90% of adults regularly consume caffeine-containing foods and beverages throughout their lives ( Reuter et al, 2021a ).…”