P668 - IMPACT OF GESTATIONAL FOOD RESTRICTION IN ADULT OFFSPRING IMMUNOLOGICAL STATUS: ASSOCIATION BETWEEN MATERNAL HYPERCORTICOSTERONEMIA AND INBORN IMPAIRED INNATE RESPONSE

P668

IMPACT OF GESTATIONAL FOOD RESTRICTION IN ADULT OFFSPRING IMMUNOLOGICAL STATUS: ASSOCIATION BETWEEN MATERNAL HYPERCORTICOSTERONEMIA AND INBORN IMPAIRED INNATE RESPONSE

N. L. Gil¹, P. H. Severo¹, G. A. Azevedo¹, S. Andreotti², R. R. Ferreira^1,2, M. E. B. Padua¹, R. G. Landgraf¹, M. A. Landgraf^3,*

¹Pharmacological Sciences, Universidade Federal de São Paulo, Diadema, ²Physiology, Universidade de São Paulo, São Paulo, ³Campus Rangel, Universidade Paulista, Santos, Brazil

Rationale: Maternal malnutrition can cause serious health issues in offspring, including a compromised immune system. Our study, investigated how maternal corticosterone hypersecretion impacts the offspring's immune system, especially the innate response to bacteria. 

Methods: Maternal 50 % global food restriction was realized throughout gestation in Wistar female rats and one group of restricted mothers was treated with metyrapone. The placenta and puppies was weighted. Adult male offspring (12 weeks old) received intranasal instillation of lipopolysaccharide, and 6 h later, the acute inflammatory response was analyzed together with the behavior of the hypothalamus-pituitary-adrenal axis.

Results: Food restriction during pregnancy resulted in low birth weight (LBW) offspring with a weakened immune response to airway lipopolysaccharide challenge. LBW animals exhibited lower airway inflammation, with fewer inflammatory cells and reduced levels of pro-inflammatory cytokines (IL-1b, IL-6, TNF-a) compared to offspring from normally nourished mothers. Food restriction also led to maternal hypercortisolism. Inhibition of corticosterone by metyrapone restored the offspring's ability to respond to bacterial antigens, but did not improve other pathological outcomes, such as LBW, alveolar wall thickening, or elevated ACTH levels. (CEUA-UNIFESP 3662220517)

Conclusion: Our results suggest that prolonged glucocorticoid exposure affects fetal physiological development, with significant alterations in HPA pathophysiology occurring before changes in immune system programming. Although the exact mechanism remains unclear, our study indicates that monitoring and managing glucocorticoid levels during pregnancy could help prevent or predict specific adult health issues.

Disclosure of Interest: None declared