Prenatal exposure to hypoxia induced beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses

Shuixiu Xia; Juanxiu Lv; Qinqin Gao; Ngjun Li; Ningjing Chen; Xiaoguang Wei; Jianping Xiao; Jie Chen; Jianying Tao; Miao Sun; Caiping Mao; Lubo Zhang; Zhice Xu

doi:10.1177/1933719114536474

Prenatal exposure to hypoxia induced beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses

Shuixiu Xia
, Juanxiu Lv
, Qinqin Gao
, Ngjun Li
, Ningjing Chen
, Xiaoguang Wei
, Jianping Xiao
, Jie Chen
, Jianying Tao
, Miao Sun
, Caiping Mao
, Lubo Zhang
, Zhice Xu

Research output: Contribution to journal › Article › peer-review

Abstract

AIMS: 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.

CONCLUSION: Hypoxia-affected fetal renal development was associated with renal apoptosis and Beclin 1 signaling-mediated autophagy.

Original language	English
Pages (from-to)	156-164
Number of pages	9
Journal	Reproductive Sciences
Volume	22
Issue number	2
DOIs	https://doi.org/10.1177/1933719114536474
State	Published - Dec 30 2015

ASJC Scopus Subject Areas

Obstetrics and Gynecology

Keywords

Rat fetus
Hypoxia
Autophagy
Kidney
Beclin-1
Up-Regulation
Phosphorylation
Signal Transduction
Organ Size
Hypoxia/complications
Proto-Oncogene Proteins c-akt/metabolism
Gestational Age
Rats, Sprague-Dawley
Kidney/metabolism
Pregnancy
Ribosomal Protein S6/metabolism
Animals
Female
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
Apoptosis Regulatory Proteins/metabolism
Maternal Exposure/adverse effects
TOR Serine-Threonine Kinases/metabolism

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10.1177/1933719114536474

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title = "Prenatal exposure to hypoxia induced beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses",

abstract = "AIMS: 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.CONCLUSION: Hypoxia-affected fetal renal development was associated with renal apoptosis and Beclin 1 signaling-mediated autophagy.",

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author = "Shuixiu Xia and Juanxiu Lv and Qinqin Gao and Ngjun Li and Ningjing Chen and Xiaoguang Wei and Jianping Xiao and Jie Chen and Jianying Tao and Miao Sun and Caiping Mao and Lubo Zhang and Zhice Xu",

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doi = "10.1177/1933719114536474",

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T1 - Prenatal exposure to hypoxia induced beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses

AU - Xia, Shuixiu

AU - Lv, Juanxiu

AU - Gao, Qinqin

AU - Li, Ngjun

AU - Chen, Ningjing

AU - Wei, Xiaoguang

AU - Xiao, Jianping

AU - Chen, Jie

AU - Tao, Jianying

AU - Sun, Miao

AU - Mao, Caiping

AU - Zhang, Lubo

AU - Xu, Zhice

N1 - Publisher Copyright: © The Author(s) 2014.

PY - 2015/12/30

Y1 - 2015/12/30

N2 - AIMS: 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.CONCLUSION: Hypoxia-affected fetal renal development was associated with renal apoptosis and Beclin 1 signaling-mediated autophagy.

AB - AIMS: 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.CONCLUSION: Hypoxia-affected fetal renal development was associated with renal apoptosis and Beclin 1 signaling-mediated autophagy.

KW - Rat fetus

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KW - Signal Transduction

KW - Organ Size

KW - Hypoxia/complications

KW - Proto-Oncogene Proteins c-akt/metabolism

KW - Gestational Age

KW - Rats, Sprague-Dawley

KW - Kidney/metabolism

KW - Pregnancy

KW - Ribosomal Protein S6/metabolism

KW - Animals

KW - Female

KW - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism

KW - Apoptosis Regulatory Proteins/metabolism

KW - Maternal Exposure/adverse effects

KW - TOR Serine-Threonine Kinases/metabolism

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U2 - 10.1177/1933719114536474

DO - 10.1177/1933719114536474

M3 - Article

C2 - 24872334

SN - 1933-7191

VL - 22

SP - 156

EP - 164

JO - Reproductive Sciences

JF - Reproductive Sciences

IS - 2

ER -

Prenatal exposure to hypoxia induced beclin 1 signaling-mediated renal autophagy and altered renal development in rat fetuses

Abstract

ASJC Scopus Subject Areas

Keywords

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