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Reprod Biol. 2015 Sep;15(3):131-8. doi: 10.1016/j.repbio.2015.05.001. Epub 2015 Jun 11.

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

Author information

1
Department of Obstetrics, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
2
Department of Obstetrics, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. Electronic address: taka0197@med.hokudai.ac.jp.
3
Laboratory of Host Defense, WPI Immunology Frontier Research Centre, Osaka University, Suita 565-0871, Japan.
4
Division of Developmental Genomics, Department of Maternal-Fetal Biology, National Centre for Child Health and Development, Tokyo, Japan.
5
Department of Molecular and Cellular Biology and Laboratory of Embryonic and Genetic Engineering, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
6
Division of Cell Proliferation, Tohoku University School of Medicine, Sendai 980-8575, Japan.

Abstract

Autophagy is activated by environment unfavorable for survival and requires Atg9a protein. Mice heterozygous for p57(Kip2), devoid of the imprinted paternal allele (p57(Kip2+/-)), 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 p57(Kip2+/-). The pregnant mice heterozygous for both knockout alleles of Atg9a and p57(Kip2) (Atg9a(+/-)/p57(Kip2+/-)), 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 p57(Kip2) are more susceptible to hypertensive stress than fetuses with intact autophagic machinery.

KEYWORDS:

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

PMID:
26370455
DOI:
10.1016/j.repbio.2015.05.001
[Indexed for MEDLINE]
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