title: Human amniotic epithelial cells can differentiate into granulosa cells and restore folliculogenesis in a mouse model of chemotherapy-induced premature ovarian failure.
abstract: BACKGROUND
  Ovarian dysfunction frequently occurs in female cancer patients after chemotherapy, but human amniotic epithelial cells (hAECs) that can differentiate into cell types that arise from all three germ layers may offer promise for restoration of such dysfunction. Previous studies confirmed that hAECs could differentiate into cells that express germ cell-specific markers, but at this time hAECs have not been shown to restore ovarian function.
  
  
  METHODS
  To model premature ovarian failure, hAECs infected with lenti-virus carrying green fluorescent protein were injected into the tail vein of mice sterilized with cyclophosphamide and busulphan. hAECs migrated to the mouse ovaries and overall ovarian function was measured using immunohistochemical techniques.
  
  
  RESULTS
  Seven days to two months after hAECs transplantation, ovarian cells were morphologically restored in sterilized mice. Hemotoxylin and eosin staining revealed that restored ovarian cells developed follicles at all stages. No follicles were observed in control mice at the same time period. Immunostaining with anti-human antigen antibodies and pre-transplantation labeling with green fluorescent protein (GFP) revealed that the grafted hAECs survived and migrated to mouse ovary, differentiating into granulosa cells. Furthermore, the ovarian function marker, anti-Müllerian hormone, was evident in treated mouse ovaries after hAEC transplantation.
  
  
  CONCLUSIONS
  Intravenously injected hAECs reached the ovaries of chemotherapy-treated mice and restored folliculogenesis, data which suggest promise for hAECs for promoting reproductive health and improving the quality of life for female cancer survivors.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Yao
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lai
authors.forename: Lihe
authors.initials: L
authors.lastname: Guo
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D054304:Anti-Mullerian Hormone / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology* / Q000637:transplantation; D005260:Female; D006107:Granulosa Cells / Q000166:cytology* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D006080:Ovarian Follicle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000601:surgery*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D054304:Anti-Mullerian Hormone