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Neurodevelopmental Disorders

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

Advanced paternal age affect maternal separation-induced ultrasonic vocalization in the offspring

  • P2-356
  • 吉崎 嘉一 / Kaichi Yoshizaki:1 木村 龍一 / Ryuichi Kimura:1 小池 航平 / Kohei Koike:1 稲田 仁 / Hitoshi Inada:1 大隅 典子 / Noriko Osumi:1 
  • 1:東北大学 / Dept Dev Neursci, Grad Sch of Med, Tohoku Univ, Sendai, Japan 

Advanced paternal age induces several abnormal behaviors such as learning deficit, impaired social behavior, and hyper anxiety in the offspring of rodents through genetic and epigenetic manner inheritance. Here we examined whether advanced paternal age affects communicative behaviors in their offspring. To obtain F1 offspring, C57BL6/J (3-month-old) female mice were mated with C57BL6/J male mice at three different ages, i.e., young (3-month-old), middle-aged (6-8-month-old) and advanced aged (>12-month old). F2 offspring were obtained from crossing C57BL6/J (3-month-old) female mice with young F1 offspring (3-month-old) derived from young or advanced aged F0 father. Maternal separation-induced ultrasonic vocalization (USV) and body weight of both F1 and F2 offspring were measured at postnatal day 6. The number of USV calls in F1 offspring derived from advanced-aged fathers showed 67.3% and 62.8% decrease compared to that derived from young and middle-aged fathers, respectively. The first USV call was significantly lengthened in the offspring derived from advanced aged father. In contrast, both the number of USV calls and the latency to the first call were not different between the groups in F2 offspring, implicating that the USV phenotype would be canceled in the next generation. In contrast to the USV phenotype, body weight was decreased in both F1 and F2 offspring. To explore molecular mechanisms of epigenetic inheritance into the next generation, histone methylation at H3K4, H3K9, H3K27, H3K79 were compared between young and advanced aged spermatocytes. In advanced aged spermatocytes, global methylation at H3K9me3, H3K27me3 and H3K79me3 was increased, while that at H3K4me2 and H3K4me3 was decreased. These results suggest an intriguing possibility that aberrant epigenetic alteration during spermatogenesis by advanced paternal age might contribute to behavioral abnormalities such as maternal separation-induced USV in the offspring. We are testing whether these altered histone methylation remains in sperm and the developing brain.

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