Haemoglobin in pelvic fluid rescues Fallopian tube epithelial cells from reactive oxygen species stress and apoptosis.
Fallopian tube fimbrial epithelium is considered to be the major site of origin of ovarian high-grade serous carcinoma, with p53 loss being the earliest and universal change. We previously reported that reactive oxygen species (ROS) in the ovulatory follicular fluids (FFs) are mutagenic and cytotoxic to fimbrial epithelial cells, which are bathed in the peritoneal fluid mixed with FFs. Here, we observed that ferryl haemoglobin (Hb), which was abundantly present in ovulatory FFs and pelvic peritoneal fluids, could rescue p53-deficient immortalized fimbrial epithelial (FE25) cells and oviduct epithelial cells from Trp53-null mice from lethal ovulatory ROS stress. Ferryl Hb and FF containing high Hb levels protected FE25 cells from apoptosis, mainly by consuming extracellular ROS and reducing NADPH oxidase-mediated cell death. The remaining extracellular ROS could still induce DNA double-strand breaks in the fimbrial epithelial cells. Our study revealed that ferryl Hb in peritoneal fluid rescued ROS-stressed, DNA-damaged fimbrial epithelial cells from death, and suggested that peritoneal blood from various sources may contribute to the ovulation-induced transformation of Fallopian tube epithelium. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cervical Cancer Prevention Centre, Department of Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.
Hsuan-Shun
HS
Huang
Cervical Cancer Prevention Centre, Department of Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.
Che-Fang
CF
Hsu
Department of Haematology and Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.
Sung-Chao
SC
Chu
Department of Obstetrics and Gynaecology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.
Pao-Chu
PC
Chen
Department of Obstetrics and Gynaecology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.
Dah-Ching
DC
Ding
Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, ROC.
Meng-Ya
MY
Chang
Cervical Cancer Prevention Centre, Department of Research, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.|Department of Obstetrics and Gynaecology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC.|Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan, ROC.
Tang-Yuan
TY
Chu
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001202:Ascitic Fluid / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D004847:Epithelial Cells / Q000166:cytology; D005187:Fallopian Tubes / Q000166:cytology*; D005260:Female; D006454:Hemoglobins / Q000032:analysis / Q000502:physiology*; D006801:Humans; D008598:Menstruation / Q000502:physiology; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000502:physiology; D010060:Ovulation / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism*
D006454:Hemoglobins; D017382:Reactive Oxygen Species; C517773:ferrylhemoglobin; D019255:NADPH Oxidases
DNA double-strand break; Fallopian tube; follicular fluid; haemoglobin; high-grade serous carcinoma