title: Age-associated up-regulation of EGR1 promotes granulosa cell apoptosis during follicle atresia in mice through the NF-κB pathway.
abstract: Follicular atresia is the main process responsible for the loss of follicles and oocytes from the ovary, and it is the root cause of ovarian aging. Apoptosis of granulosa cells (GCs) is the cellular mechanism responsible for follicular atresia in mammals. Recent advances have highlighted fundamental roles for EGR1 in age-related diseases via the induction of apoptosis. In the present study, we found that the expression of EGR1 was significantly increased in aged mouse ovaries compared with young ovaries. Immunohistochemical analysis revealed strongly positive EGR1 staining in atretic follicles, especially in apoptotic granulosa cells. We further showed that EGR1 up-regulation in mouse primary granulosa cells inhibited cell proliferation and promoted apoptosis. In addition, the promotion of apoptosis in GCs by EGR1 increases over time and with reactive oxygen species (ROS) stimulation. Our mechanistic study suggested that EGR1 regulates GC apoptosis in a mitochondria-dependent manner and that this mainly occurs through the NF-κB signaling pathway. In conclusion, our results suggested that age-related up-regulation of EGR1 promotes GC apoptosis in follicle atresia during ovarian aging.
authors.affiliation: a Department of Obstetrics and Gynecology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Suzhen
authors.initials: S
authors.lastname: Yuan
authors.affiliation: a Department of Obstetrics and Gynecology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Wen
authors.affiliation: a Department of Obstetrics and Gynecology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: a Department of Obstetrics and Gynecology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: a Department of Obstetrics and Gynecology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Su
authors.initials: S
authors.lastname: Zhou
authors.affiliation: a Department of Obstetrics and Gynecology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: a Department of Obstetrics and Gynecology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.affiliation: a Department of Obstetrics and Gynecology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Aiyue
authors.initials: A
authors.lastname: Luo
authors.affiliation: a Department of Obstetrics and Gynecology , Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , Hubei , China.
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005496:Follicular Atresia / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006107:Granulosa Cells / Q000166:cytology*; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D016328:NF-kappa B; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase
keywords: EGR1; NF-κB; apoptosis; follicular atresia; granulosa cell; ovarian aging