Effect of prenatal steroid treatment on the developing immune system
- 626 Downloads
Prenatal steroids have an undisputed positive effect of decreasing neonatal morbidity and mortality by improving fetal lung maturation. Some concerns have been raised on long-term consequences on the hypothalamic–pituitary–adrenal axis and cognition, but there are no studies addressing effects on the immune system. The thymus is an essential organ for the development and selection of T cells, and thymocytes are extremely sensitive to steroids. Using a mouse model for prenatal steroid administration, we show here that betamethasone treatment to the mother has a profound effect on the thymus of the offspring. We find the thymus volume reduced, affecting mostly the developing CD4+ CD8+ double-positive thymocytes and a compensatory accelerated transition of the earlier stages to replenish the depleted compartment. This effect lasts for at least 3 days, which correspond to a very relevant period for the selection of the T cell repertoire. Moreover, we show that low doses of betamethasone have similar effects on human thymocytes in vitro. Therefore, further studies are needed to analyze possible long-term consequences of this treatment on the immune system of the offspring.
Betamethasone administered to the mother before birth reaches the fetal thymus.
Prenatal betamethasone results in massive loss of developing thymocytes.
The effects of betamethasone on thymus development are visible for several days.
Human thymocytes are also sensitive to low doses of betamethasone.
Altered thymocyte development around birth may have an effect on the immune system.
KeywordsPrenatal steroids Pregnancy Betamethasone Thymus Apoptosis Thymocyte development
We would like to thank the Flow Cytometry Core Facility at the UKE, Tobias Mummert, Thomas Andreas, and Corinna Kulicke for excellent technical help. This project is supported by the Excellence Initiative of the Hamburg Research Foundation (LEXI).
Conflict of interest
The authors reported no potential conflicts of interest.
- 14.Roberts D, Dalziel S (2006) Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database System Rev: CD004454Google Scholar
- 16.Sugden MC, Langdown ML, Munns MJ, Holness MJ (2001) Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring. Eur J Endocrinol 145:529–539PubMedCrossRefGoogle Scholar
- 20.Nyirenda MJ, Lindsay RS, Kenyon CJ, Burchell A, Seckl JR (1998) Glucocorticoid exposure in late gestation permanently programs rat hepatic phosphoenolpyruvate carboxykinase and glucocorticoid receptor expression and causes glucose intolerance in adult offspring. J Clin Invest 101:2174–2181PubMedCrossRefGoogle Scholar
- 21.Kavelaars A, van der Pompe G, Bakker JM, van Hasselt PM, Cats B, Visser GH, Heijnen CJ (1999) Altered immune function in human newborns after prenatal administration of betamethasone: enhanced natural killer cell activity and decreased T cell proliferation in cord blood. Pediatr Res 45:306–312PubMedCrossRefGoogle Scholar
- 27.Fletcher AL, Lowen TE, Sakkal S, Reiseger JJ, Hammett MV, Seach N, Scott HS, Boyd RL, Chidgey AP (2009) Ablation and regeneration of tolerance-inducing medullary thymic epithelial cells after cyclosporine, cyclophosphamide, and dexamethasone treatment. J Immunol 183:823–831PubMedCrossRefGoogle Scholar