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Advanced paternal age affects ultrasound vocalization in adult mouse offspring

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Zietek M. , Swiergiel A. H. , Sampino S.

Acta Neurobiologiae Experimentalis

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2017

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tom 77

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nr Suppl.1

EN

INTRODUCTION: Advanced paternal age (APA) is a risk factor for conceiving children with autism spectrum disorders. Social deficits, altered communication and repetitive behaviors are key diagnostic symptoms of autism. AIM(S): In this study we used a mouse model to investigate the effects of APA on offspring communicative behaviors - ultrasound vocalization (USV). METHOD(S): 4–5 month old Swiss males conceived by fathers of 3 different ages – 12 month old (Advanced Paternal Age, APA n=32), 2 month old (Young Paternal Age, YPA-1 n=17), 5 month old (YPA-2 n=16) - and mothers aged 3 months, were subjected to the resident-intruder test to evoke USVs emission. The tested mouse, which had been previously isolated for 7 days, was habituated for 7 minutes to a soundproof chamber. An intruder (C57/CBA 2–4 month old male) was then introduced to the home-cage of the tested mouse. Ultrasound vocalizations were recorded for 180 s using an ultrasound-sensitive microphone placed 10 cm above the cage and were analysed using Avisoft SASLab software. RESULTS: There were no statistically significant differences among groups in the latency to start USV emission. The percentage of vocalizing mice in APA was 87,5%, YPA‑1 – 53% and YPA‑2 – 87,5%. APA mice displayed increased number of USVs (p=0.003), increased duration and decreased sound amplitude of USVs, compared to YPA mice (p<0.001 and p<0.0001, respectively). No significant changes were observed in minimum and maximum USV frequencies. Furthermore, USVs were classified based on their waveform pattern. Mice conceived by differently aged fathers exhibited different repertoires of vocalizations. CONCLUSIONS: Overall, paternal age affects USV patterns in adult offspring. Heritable de novo mutations and/ or epigenetic alterations transmitted by the sperm may underlie the phenotypic changes observed in offspring. FINANCIAL SUPPORT: This work was supported by the Polish National Science Center (2014/15/D/NZ4/04274) and in part by Statutory Research Fund of the Department of Animal and Human Physiology of University of Gdansk.

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Effect of advanced paternal age on ultrasound vocalization in mice

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Zacchini F. , Sampino S. , Swiergiel A. , Loi P. , Ptak G.

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nr S

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Effects of blastomere biopsy of preimplantation embryos on expression of imprinted genes and anxiety - and depression - like behaviours in mice

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Sampino S. , Zacchini F. , Swiergiel A. , Modlinski J. , Loi P. , Ptak G.

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nr S

EN

Prenatal developmental period is a critical window, where any perturbation of embryonic/fetal environment can lead to behavioural abnormalities and diseases in adult life, such as depression and stress disorders. The mechanisms underlying long term effects, induced by early perturbation, are not well described, but an epigenetic origin has been suggested. In this work we wanted to investigate whether and how blastomere biopsy on 8-cells stage embryos can have long-term effects on behaviour. Onemonth-old mice derived from the biopsed embryos were subjected to a battery of behavioural tests. The animals displayed an increased locomotor and exploration activity (p<0.05) and increased anxiety-like behaviour. Interestingly, the depressionlike behaviour in the tail suspension test was observed only in female offspring (p<0.001). In addition, to investigate the epigenetic mechanism underlying these behavioural alterations, we analyzed expression of imprinted genes Snrpn, Peg1 and Ube3a in blastocysts obtained after biopsy. These imprinted genes are highly expressed in pre-implantation embryos, where their epigenetic programming is defined, and in brain, shaping the behavioural phenotype of offspring. Real-Time PCR analysis revealed significant down-regulation of Peg1 (p<0.05), Snrpn and Ube3a (p<0.01) in blastocysts derived from the biopsed embryos, compared to controls. The results suggest that blastomere biopsy causes an altered expression of imprinted genes in preimplantation embryo. The reduction of expression of these transcripts can cause anxiety- or depression-like behaviours and alteration of locomotory activity in offspring obtained following biopsy of early embryos.

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Effects of blastomere biopsy of preimplantation embryos on expression of imprinted genes and anxiety - and depression - like behaviours in mice

75%

Sampino S. , Zacchini F. , Swiergiel A. , Modlinski J. , Loi P. , Ptak G.

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nr S

EN

Prenatal developmental period is a critical window, where any perturbation of embryonic/fetal environment can lead to behavioural abnormalities and diseases in adult life, such as depression and stress disorders. The mechanisms underlying long term effects, induced by early perturbation, are not well described, but an epigenetic origin has been suggested. In this work we wanted to investigate whether and how blastomere biopsy on 8-cells stage embryos can have long-term effects on behaviour. One-month-old mice derived from the biopsed embryos were subjected to a battery of behavioural tests. The animals displayed an increased locomotor and exploration activity (p<0.05) and increased anxiety-like behaviour. Interestingly, the depression-like behaviour in the tail suspension test was observed only in female offspring (p<0.001). In addition, to investigate the epigenetic mechanism underlying these behavioural alterations, we analyzed expression of imprinted genes Snrpn, Peg1 and Ube3a in blastocysts obtained after biopsy. These imprinted genes are highly expressed in preimplantation embryos, where their epigenetic programming is defined, and in brain, shaping the behavioural phenotype of offspring. Real-Time PCR analysis revealed significant down-regulation of Peg1 (p<0.05), Snrpn and Ube3a (p<0.01) in blastocysts derived from the biopsed embryos, compared to controls. The results suggest that blastomere biopsy causes an altered expression of imprinted genes in preimplantation embryo. The reduction of expression of these transcripts can cause anxiety- or depression-like behaviours and alteration of locomotory activity in offspring obtained following biopsy of early embryos.

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

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Sampino S. , Stankiewicz A. M. , Goscik J. , Swiergiel A. H. , Loi P. , Modlinski J. A. , Ptak G. E.

Acta Neurobiologiae Experimentalis

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2015

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tom 75

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nr Supl.

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.

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Effect of advanced paternal age on ultrasound vocalization in mice

75%

Zacchini F. , Sampino S. , Swiergiel A. , Modlinski J. , Loi P. , Ptak G.

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nr S

EN

Delayed parenthood is a growing phenomenon in western countries due to modern lifestyle. In particular, delayed fatherhood has been described as a factor of risk for several mental disorders and intermediate phenotypes such as poor cognitive or social functions. In this work we want to investigate whether and how advanced paternal age can affect development of offspring. We evaluated UltraSound Vocalization (USV) activity on 4-day old mice, born from both aged and young (control) father, after removal from their nest. We found that the total number of USV in the 5 minutes of testing was significantly higher in pups from aged mice than control (p<0.002) and that the main difference was present during the first minute (p <0.0004). Also, our data showed that the number of high intensity USV was increased in pups from aged mice (p<0.002). We also evaluated the righting reflex ability of 6 and 10-days-old mice. We did not find any difference in righting reflex ability between groups. All together our data show that delayed fatherhood affect communication skills and anxiety likebehavior but no innate righting reflex ability. In conclusion, advanced paternal age affects the development of offspring and these effects are detectable already in first days of post-natal life and they could be first signs of brain diseases in adult life. Future analysis will be necessary to define the long term effect of advanced paternal age and the mechanism underlying developmental alterations in offspring.

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Apple polyphenols in human and animal health

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Yeung A. W. K. , Tzvetkov N. T. , El-Demerdash A. , Horbanczuk O. K. , Das N. , Pirgozliev V. , Lucarini M. , Durazzo A. , Souto E. B. , Santini A. , Devkota H. P. , Uddin M. S. , Echeverria J. , Wang D. , Gan R.-Y. , Brncic M. , Kalfin R. E. , Tancheva L. P. , Tewari D. , Berindan-Neagoe I. , Sampino S. , Horbanczuk J. O. , Atanasov A. G.

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2021

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tom 39

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nr 2

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Resveratrol, a popular dietary supplement for human and animal health: Quantitative research literature analysis - a review

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Wai Kan Yeunga A. , Bhushan Aggarwal B. , Erdogan Orhan I. , Horbanczuk O. K. , Barreca D. , Battino M. , Belwal T. , Bishayee A. , Daglia M. , Devkota J. P. , Echeverria J. , El-Demerdash A. , Balacheva A. , Georgieva M. , Godfrey K. , Gupta V. K. , Horbanczuk J. O. , Huminiecki L. , Jozwik A. , Strzelkowska N. , Mocan A. , Mozos I. , Nabavi S. M. , Pajpanova T. , Pittala V. , Feder-Kubis J. , Sampino S. , Sanches Silva A. , Sheridan H. , Sureda A. , Tewari D. , Wang D. , Weissig V. , Yang Y. , Zengin G. , Shanker K. , Moosavi M. A. , Shah M. A. , Kozuharova E. , Al-Rimawi F. , Durazzo A. , Lucarini M. , Soutoa E. B. , Santini A. , Malainer C. , Djilianov D. , Tancheva L. P. , Li H.-B. , Gan R.-Y. , Tzvetkov N. T. , Atanasov A. G.

Animal Science Papers and Reports

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2019

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tom 37

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nr 2