Long-Term Impact of Intrauterine Neuroinflammation and Treatment with Magnesium Sulphate and Betamethasone: Sex-Specific Differences in a Preterm Labor Murine Model

Abstract : Objective: To examine the long-term effects of perinatal neuroinflammation and the benefits of prenatal MgSO4/betamethasone treatments between males and females. Methods: Eighty-eight CD1 timed-pregnant mice were randomized to receive an intrauterine injection of 50 g of lipopolysaccharide (LPS) or an equivalent volume of phosphate buffered saline (PBS) on E17.5. A subset of animals was allocated to receive MgSO4 and betamethasone 30 minutes post-injection. The neurodevelopment of surviving juvenile offspring was assessed via negative geotaxis testing. On post-natal day 60, adult brains were collected and processed for histologic and expression analysis of key neural markers. Results/Conclusion: Male but not female offspring exposed to intrauterine inflammation demonstrated impaired performance in neurodevelopmental testing in early life while those exposed to injury plus treatment fared better. Histologic analysis of adult male brains identified a significant reduction in hippocampal neural density in the injured group compared to controls. Evaluation of key neural markers via qRT-PCR demonstrated more profound differences in gene expression in adult males exposed to injury and treatment compared to female offspring.