International Journal of Nanomedicine (Aug 2023)
Adipocyte-Derived Exosomal NOX4-Mediated Oxidative Damage Induces Premature Placental Senescence in Obese Pregnancy
Abstract
Yuelan Tao,1,2 Wei Chen,3 Hongbing Xu,1 Jiacheng Xu,1,2 Huan Yang,4 Xin Luo,1 Miaomiao Chen,5 Jie He,1,2 Yuxiang Bai,1,* Hongbo Qi1,2,6,* 1Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Emergency & Intensive Care Units, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Obstetrics, Chongqing University Three Gorges Hospital, Chongqing, 404100, People’s Republic of China; 5Maternal and Child Health Hospital of Hubei Province, Wuhan City, Hubei Province, 430070, People’s Republic of China; 6Women and Children’s Hospital of Chongqing Medical University, Chongqing, 401147, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuxiang Bai; Hongbo Qi, Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Tel +8602389011007, Email [email protected]; [email protected]: 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.Keywords: maternal obesity, placental premature senescence, adipose tissue, exosome, NADPH oxidase 4, oxidative damage
