Antenatal endogenous and exogenous glucocorticoids and their impact on immune ontogeny and long-term immunity

Area of Science:

• Reproductive biology
• Immunology
• Endocrinology

Background:

• Glucocorticoids are crucial for fetal organ maturation near birth.
• The enzyme 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) in the placenta and fetus protects the fetus from excessive maternal glucocorticoids.
• Maternal stress or synthetic glucocorticoid administration can bypass this protection, leading to increased fetal exposure.

Purpose of the Study:

• To review the role of placental and fetal 11β-HSD2 in regulating fetal glucocorticoid exposure.
• To examine how fetal glucocorticoid exposure and hypothalamic-pituitary-adrenal (HPA) axis programming influence immune development.
• To identify knowledge gaps in glucocorticoid-induced immune disease programming.

Main Methods:

• Literature review and synthesis of existing evidence.
• Analysis of the interplay between 11β-HSD2 activity, fetal glucocorticoid levels, and HPA axis function.
• Hypothesizing mechanisms of immune programming based on current data.

Main Results:

• Fetal exposure to excessive glucocorticoids, particularly during critical developmental windows, is linked to altered immune system programming.
• The placental and fetal 11β-HSD2 enzyme system plays a critical protective role.
• Gaps exist in understanding the precise mechanisms of glucocorticoid-induced immune dysregulation.

Conclusions:

• Prenatal glucocorticoid exposure can program offspring for increased risk of immune diseases, including atopies, infections, and type I diabetes.
• The HPA axis and immune system development are sensitive to prenatal glucocorticoid levels.
• Further research is needed to elucidate the specific molecular pathways involved in this programming.