Adipocyte-Derived Exosomal NOX4-Mediated Oxidative Damage Induces Premature Placental Senescence in Obese Pregnancy

作者全名："Tao, Yuelan; Chen, Wei; Xu, Hongbing; Xu, Jiacheng; Yang, Huan; Luo, Xin; Chen, Miaomiao; He, Jie; Bai, Yuxiang; Qi, Hongbo"

作者地址："[Tao, Yuelan; Xu, Hongbing; Xu, Jiacheng; Luo, Xin; He, Jie; Bai, Yuxiang; Qi, Hongbo] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet, Chongqing 400016, Peoples R China; [Tao, Yuelan; Xu, Jiacheng; He, Jie; Qi, Hongbo] Chongqing Med Univ, Chongqing Key Lab Maternal & Fetal Med, Chongqing 400016, Peoples R China; [Chen, Wei] Chongqing Med Univ, Affiliated Hosp 1, Dept Emergency & Intens Care Units, Chongqing, Peoples R China; [Yang, Huan] Chongqing Univ, Gorges Hosp 3, Dept Obstet, Chongqing 404100, Peoples R China; [Chen, Miaomiao] Maternal & Child Hlth Hosp Hubei Prov, Wuhan 430070, Hubei, Peoples R China; [Qi, Hongbo] Chongqing Med Univ, Women & Childrens Hosp, Chongqing 401147, Peoples R China"

通信作者："Bai, YX; Qi, HB (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet, Chongqing 400016, Peoples R China.; Qi, HB (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Maternal & Fetal Med, Chongqing 400016, Peoples R China."

来源：INTERNATIONAL JOURNAL OF NANOMEDICINE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001052263500001

JCR分区：Q1

影响因子：6.6

年份：2023

卷号：18

期号：　

开始页：4705

结束页：4726

文献类型：Article

关键词：maternal obesity; placental premature senescence; adipose tissue; exosome; NADPH oxidase 4; oxidative damage

摘要："Background: A recent study has reported that maternal obesity is linked to placental oxidative damage and premature senescence. NADPH oxidase 4 (NOX4) is massively expressed in adipose tissue, and its induced reactive oxygen species have been found to contribute to cellular senescence. While, whether, in obese pregnancy, adipose tissue-derived NOX4 is the considerable cause of placental senescence remained elusive.Methods: This study collected term placentas from obese and normal pregnancies and obese pregnant mouse model was constructed by a high fat diet to explore placental senescence. Furthermore, adipocyte-derived exosomes were isolated from primary adipocyte medium of obese and normal pregnancies to examine their effect on placenta functions in vivo and vitro.Results: The placenta from the obese group showed a significant increase in placental oxidative damage and senescence. Exosomes from obese adipocytes contained copies of NOX4, and when cocultured with HTR8/SVneo cells, they induced severe oxidative damage, cellular senescence, and suppressed proliferation and invasion functions when compared with the control group. In vivo, adipocyte-derived NOX4-containing exosomes could induce placental oxidative damage and senescence, ultimately leading to adverse pregnancy outcomes.Conclusion: In obesity, adipose tissue can secrete exosomes containing NOX4 which can be delivered to trophoblast resulting in severe DNA oxidative damage and premature placental senescence, ultimately leading to adverse pregnancy outcomes."

基金机构：National Natural Science Foundation of China [81901506]; General Program of the National Natural Science Foundation of China [82171662]; Chongqing Science amp; Technology Bureau [cstc2019jscx-msxmX0087]

基金资助正文："This study was supported by the National Natural Science Foundation of China (No. 81901506), the General Program of the National Natural Science Foundation of China (No. 82171662), and Chongqing Science & amp; Technology Bureau (cstc2019jscx-msxmX0087)."