Transcriptomic changes in fetal brain and placenta associated with advanced paternal age behavioral abnormalities

• Autorzy: Sampino S. , Stankiewicz A.M. , Goscik J. , Swiergiel A.H. , Loi P. , Modlinski J.A. , Ptak G.E.
• Języki publikacji: PL

Abstrakty

EN

BACKGROUND AND AIMS: Advanced Paternal Age (APA) has been shown to be a significant risk factor for neurodevelopmental psychiatric disorders, such as autism. We have recently shown that mice conceived by old fathers display behavioral abnormalities which resemble key diagnostic symptoms of human autism, including social deficits, communicative defects and repetitive behaviors. The aim of the present study was to evaluate the transcriptomic profiles of brains and placentas collected from fetuses conceived by young (CTR) or old (APA) fathers, in order to reveal molecular mechanisms acting early in life leading to postnatal autistic behaviors. METHODS: Tissues were subjected to genome-wide mRNA expression analysis using Agilent microarray technology and subsequently to Real time qPCR validation. RESULTS: Comparison of fetal brains transcriptomic profiles of CTR and APA offspring revealed that paternal age affected the expression of 1060 genes in males and 857 genes in females. Comparisons of placentas revealed alteration of 3383 genes in males and 711 genes in females. Gene set enrichment analysis performed using i.e. the KEGG pathway database, identified significant functional clusters involved in axonal growth, extracellular matrix receptors, neuroactive ligand receptors and cytokine receptors, in fetal brains. Intriguingly, placental group of deregulated genes represented functional networks involved in neuronal and metabolic pathways. qPCR confirmed that expression of genes involved in axonal growth (Neurod2, Neurod6, Epha5) were deregulated in brains of male fetuses, and that neuronal-related genes (Nrxn3, Hif3a) were expressed by the placenta and deregulated in APA mice. CONCLUSIONS: Overall, these results indicate that early events of brain development could be altered in fetuses conceived by old males, consistent with an indirect influences of the placenta on early neurodevelopment programming, which could underlie the subsequent onset of behavioral alterations.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S65

Twórcy

autor

Sampino S.

• Institute of Genetics and Animal Breeding, Jastrzebiec, Poland

autor

Stankiewicz A.M.

• Institute of Genetics and Animal Breeding, Jastrzebiec, Poland

autor

Goscik J.

• Medical University of Bialystok, Bialystok, Poland

autor

Swiergiel A.H.

• University of Gdansk, Gdansk, Poland

autor

Loi P.

• University of Teramo, Teramo, Italy

autor

Modlinski J.A.

• University of Gdansk, Gdansk, Poland

autor

Ptak G.E.

• Institute of Genetics and Animal Breeding, Jastrzebiec, Poland