title: Prenatal exposure to hypoxia induced Beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses.
abstract: OBJECTIVE
  Hypoxia has adverse effects on renal development. This study was the first to test hypoxia-induced renal autophagy in rat fetuses.
  
  
  METHODS
  Pregnant rats were exposed to hypoxia or normoxia during pregnancy and fetal kidneys were collected at gestation day 21.
  
  
  RESULTS
  Fetal kidney weight and ratio of kidney-body weight were reduced. Histological analysis showed enlargement in Bowman space and wider space between interstitia in the kidneys of fetus exposed to hypoxia. Fetal renal B-cell lymphoma 2 (BCL-2) was decreased accompanied with higher 2'-deoxyuridine 5'-triphosphate nick end-labeling staining and unchanged soluble FAS in the hypoxia group. Hypoxia increased autophagic structures, including autophagosomes and autolysosomes, in fetal kidneys and increased renal APG5L. There was an increase in renal LC3-II, Beclin 1, p-S6, hypoxia inducible factor 1α (HIF-1a), and ratio of LC3-II-LC3-I and a decrease in P62, protein kinase B (AKT), and phosphorylated AKT in the hypoxia group. Both renal mammalian target of rapamycin (mTOR) and Beclin 1 signaling were upregulated.
  
  
  CONCLUSIONS
  Hypoxia-affected fetal renal development was associated with renal apoptosis and Beclin 1 signaling-mediated autophagy.
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Shuixiu
authors.initials: S
authors.lastname: Xia
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Juanxiu
authors.initials: J
authors.lastname: Lv
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Ningjing
authors.initials: N
authors.lastname: Chen
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Wei
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Tao
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Caiping
authors.initials: C
authors.lastname: Mao
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China Center for Perinatal Biology, Loma Linda University, Loma Linda, CA, USA.
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China Center for Perinatal Biology, Loma Linda University, Loma Linda, CA, USA xuzhice@suda.edu.cn.
authors.forename: Zhice
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D005260:Female; D005865:Gestational Age; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D018811:Maternal Exposure / Q000009:adverse effects*; D009929:Organ Size; D010766:Phosphorylation; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D038601:Ribosomal Protein S6 / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D038601:Ribosomal Protein S6; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: autophagy; hypoxia; kidney; rat fetus