TY - JOUR
T1 - Long-term impact of intrauterine neuroinflammation and treatment with magnesium sulphate and betamethasone
T2 - Sex-specific differences in a preterm labor murine model
AU - Thagard, Andrew S.
AU - Slack, Jessica L.
AU - Estrada, Sarah M.
AU - Kazanjian, Avedis A.
AU - Chan, Sem
AU - Burd, Irina
AU - Napolitano, Peter G.
AU - Ieronimakis, Nicholas
N1 - Funding Information:
The authors wish to acknowledge Ms. M.J. DeHart, Ms. Deborah Tinnemore, Ms. Amber Lane, Ms. Joanna Dandeneau, Ms. Shelley Spahnbridges, Ms. Karen Gibeault, Dr. Shannon Marko, Dr. Mariano Mesngon, Dr. Sarah Bro, and Dr. Monica Lutgendorf. The research was funded by Madigan Army Medical Center and a United States Air Force SG5 award.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Preterm infants are at significantly increased risk for lifelong neurodevelopmental disability with male offspring disproportionately affected. Corticosteroids (such as betamethasone) and magnesium sulphate (MgSO4) are administered to women in preterm labor to reduce neurologic morbidity. Despite widespread use of MgSO4 in clinical practice, its effects on adult offspring are not well known nor have sex-specific differences in therapeutic response been explored. The objective of our study was to examine the long-term effects of perinatal neuroinflammation and the effectiveness of prenatal MgSO4/betamethasone treatments between males and females in a murine model via histologic and expression analyses. Our results demonstrate that male but not female offspring exposed to intrauterine inflammation demonstrated impaired performance in neurodevelopmental testing in early life assessed via negative geotaxis, 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, which largely showed resistance to injury. Prenatal treatment with MgSO4/betamethasone confers long-term benefits beyond cerebral palsy prevention with sex-specific differences in response.
AB - Preterm infants are at significantly increased risk for lifelong neurodevelopmental disability with male offspring disproportionately affected. Corticosteroids (such as betamethasone) and magnesium sulphate (MgSO4) are administered to women in preterm labor to reduce neurologic morbidity. Despite widespread use of MgSO4 in clinical practice, its effects on adult offspring are not well known nor have sex-specific differences in therapeutic response been explored. The objective of our study was to examine the long-term effects of perinatal neuroinflammation and the effectiveness of prenatal MgSO4/betamethasone treatments between males and females in a murine model via histologic and expression analyses. Our results demonstrate that male but not female offspring exposed to intrauterine inflammation demonstrated impaired performance in neurodevelopmental testing in early life assessed via negative geotaxis, 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, which largely showed resistance to injury. Prenatal treatment with MgSO4/betamethasone confers long-term benefits beyond cerebral palsy prevention with sex-specific differences in response.
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U2 - 10.1038/s41598-017-18197-x
DO - 10.1038/s41598-017-18197-x
M3 - Article
C2 - 29263436
AN - SCOPUS:85038809473
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 17883
ER -