Role of the Atg9a gene in intrauterine growth and survival of fetal mice

Takashi Kojima, Takahiro Yamada, Rina Akaishi, Itsuko Furuta, Tatsuya Saitoh, Kazuhiko Nakabayashi, Keiichi I. Nakayama, Keiko Nakayama, Shizuo Akira, Hisanori Minakami

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Autophagy is activated by environment unfavorable for survival and requires Atg9a protein. Mice heterozygous for p57Kip2, devoid of the imprinted paternal allele (p57Kip2+/-), are known to develop hypertension during pregnancy. To determine whether fetal Atg9a is involved in the intrauterine survival and growth of fetal mice, this study was performed on Atg9a heterozygous (Atg9a+/-) pregnant mice with and without p57Kip2+/-. The pregnant mice heterozygous for both knockout alleles of Atg9a and p57Kip2 (Atg9a+/-/p57Kip2+/-), but not those heterozygous for Atg9a alone, developed hypertension during pregnancy. Placental expression of Atg9a mRNA was significantly decreased in the Atg9a-/- mice compared to Atg9a+/- or Atg9a+/+ mice. The Atg9a-/- fetal mice exhibited significantly retarded growth and were more likely to die in utero compared to Atg9a+/+ and Atg9a+/- fetal mice. Growth retardation was observed in the presence of maternal hypertension in Atg9a-/- fetal mice. These results suggest that Atg9a-/- fetal mice from pregnant dams heterozygous for both knockout alleles of Atg9a and p57Kip2 are more susceptible to hypertensive stress than fetuses with intact autophagic machinery.

Original languageEnglish
Pages (from-to)131-138
Number of pages8
JournalReproductive Biology
Volume15
Issue number3
DOIs
Publication statusPublished - 2015 Sep 1

Keywords

  • Autophagy
  • Fetal growth restriction
  • Hypertension
  • Hypoxia
  • Intrauterine fetal death

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Endocrinology
  • Developmental Biology

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    Kojima, T., Yamada, T., Akaishi, R., Furuta, I., Saitoh, T., Nakabayashi, K., Nakayama, K. I., Nakayama, K., Akira, S., & Minakami, H. (2015). Role of the Atg9a gene in intrauterine growth and survival of fetal mice. Reproductive Biology, 15(3), 131-138. https://doi.org/10.1016/j.repbio.2015.05.001