Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain
2022
Authors:
Manojlović-Stojanoski, MilicaLavrnja, Irena
Stevanović, Ivana
Trifunović, Svetlana
Ristić, Nataša
Nestorović, Nataša
Sévigny, Jean
Nedeljković, Nadežda
Laketa, Danijela
Document Type:
Article (Published version)
,
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Show full item recordAbstract:
Dexamethasone (DEX) is frequently used to treat women at risk of preterm delivery, but although indispensable for the completion of organ maturation in the fetus, antenatal DEX treatment may exert adverse sex-dimorphic neurodevelopmental effects. Literature findings implicated oxidative stress in adverse effects of DEX treatment. Purinergic signaling is involved in neurodevelopment and controlled by ectonucleotidases, among which in the brain the most abundant are ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) and ecto-5ʹ-nucleotidase (e5ʹNT/CD73), which jointly dephosphorylate ATP to adenosine. They are also involved in cell adhesion and migration, processes integral to brain development. Upregulation of CD39 and CD73 after DEX treatment was reported in adult rat hippocampus. We investigated the effects of maternal DEX treatment on CD39 and CD73 expression and enzymatic activity in the rat fetal brain of both sexes, in the context of oxidative status of the brain tissue. Fetuses were obtained at embryonic day (ED) 21, from Wistar rat dams treated with 0.5 mg DEX/kg/day, at ED 16, 17, and 18, and brains were processed and used for further analysis. Sex-specific increase in CD39 and CD73 expression and in the corresponding enzyme activities was induced in the brain of antenatally DEX-treated fetuses, more prominently in males. The oxidative stress induction after antenatal DEX treatment was confirmed in both sexes, although showing a slight bias in males. Due to the involvement of purinergic system in crucial neurodevelopmental processes, future investigations are needed to determine the role of these observed changes in the adverse effects of antenatal DEX treatment.
Keywords:
Antioxidant system; Ectonucleotidases; Glucocorticoids; Neurodevelopment; Oxidative stress; Purinergic signalingSource:
Cellular and Molecular Neurobiology, 2022, 42, 1965-1981Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200007 (University of Belgrade, Institute for Biological Research 'Siniša Stanković') (RS-MESTD-inst-2020-200007)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
- University of Defense (grant number MFVMA/04/19–21)
- Natural Sciences and Engineering Research Council of Canada (NSERC; RGPIN-2016–05867)
DOI: 10.1007/s10571-021-01081-8
ISSN: 0272-4340
PubMed: 33761054