title: Human amniotic epithelial cells inhibit granulosa cell apoptosis induced by chemotherapy and restore the fertility.
abstract: BACKGROUND
  Premature ovarian failure and insufficiency are significant long-term side-effects of chemotherapy for female cancer patients. Recently, stem cell transplantation has been identified as a promising treatment for premature ovarian failure and insufficiency. We have previously demonstrated that human amniotic epithelial cells (hAECs) migrate into injured tissue and promote the recovery of ovarian function in chemoablated mice. However, the molecular mechanism guiding this process remains unclear.
  
  
  METHODS
  To further investigate the effect of hAECs on chemotherapy-induced apoptosis, cultured primary hAECs were injected intravenously into mice treated with cyclophosphamide and busulphan. Apoptosis of granulosa cells was observed by TUNEL staining, and apoptosis-related gene expression was performed on ovarian tissue by real-time PCR and Western blot 7 days after hAEC transplantation. Additionally, the ovarian function and fertility of mice were assessed via counts of follicles and mating experiments at 4 weeks after hAEC transplantation.
  
  
  RESULTS
  hAECs significantly inhibited tumor necrosis factor-alpha-mediated granulosa cell apoptosis induced by chemotherapeutics and reduced the inflammatory reaction in ovaries at 7 days after transplantation. In addition, 4 weeks after transplantation, hAECs promoted the development of follicles and increased the number of cumulus oocyte complexes in chemoablated mice. Furthermore, hAECs improved ovarian mass and increased the number of follicles compared to those of the chemoablated group, and hAEC transplantation partially rescued the fertility of chemoablated mice.
  
  
  CONCLUSIONS
  hAEC transplantation promotes ovarian function by inhibiting tumor necrosis factor-alpha-mediated cell apoptosis and reducing inflammation in chemotherapy-induced premature ovarian failure. These results suggest a potential molecular mechanism for the effective therapy of hAEC transplantation in chemotherapy-induced premature ovarian failure and insufficiency.
authors: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 145, Guang-Yuan Road, Shanghai, 200030, People's Republic of China. 10111010022@fudan.edu.cn.|Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China. 10111010022@fudan.edu.cn.
authors: Qiuwan
authors: Q
authors: Zhang
authors: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 145, Guang-Yuan Road, Shanghai, 200030, People's Republic of China. xmh900505@hotmail.com.|Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China. xmh900505@hotmail.com.
authors: Minhua
authors: M
authors: Xu
authors: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 145, Guang-Yuan Road, Shanghai, 200030, People's Republic of China. yaoxf89@126.com.|Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China. yaoxf89@126.com.
authors: Xiaofen
authors: X
authors: Yao
authors: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 145, Guang-Yuan Road, Shanghai, 200030, People's Republic of China. liting-0002@163.com.|Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China. liting-0002@163.com.
authors: Ting
authors: T
authors: Li
authors: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 145, Guang-Yuan Road, Shanghai, 200030, People's Republic of China. paulia@163.com.|Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China. paulia@163.com.
authors: Qian
authors: Q
authors: Wang
authors: International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 145, Guang-Yuan Road, Shanghai, 200030, People's Republic of China. laidongmei@hotmail.com.|Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People's Republic of China. laidongmei@hotmail.com.
authors: Dongmei
authors: D
authors: Lai
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D005298:Fertility / Q000187:drug effects / Q000502:physiology*; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction