title: Overexpression of Oct4 in porcine ovarian stem/stromal cells enhances differentiation of oocyte-like cells in vitro and ovarian follicular formation in vivo.
abstract: BACKGROUND
  Recent findings have revealed that the female gonad may have regenerative activity with having germ line stem cells in juveniles and adults. Application of these germ line stem cells could be an alternative therapy for reproductive disorders in regenerative medicine.
  
  
  METHODS
  To enhance the potency of differentiation into oocyte-like cells (OLCs) and folliculogenesis, we overexpressed Oct4 in ovarian stem/stromal cell (OvSCs) and examined the cellular properties related to stemness and self-renewal ability and finally demonstrated the ability of in vitro differentiation and folliculogenesis.
  
  
  RESULTS
  Ovarian cortex included putative stem cells in terms of AP activity, cell cycle status, cell proliferation, expression of mesenchymal lineage surface markers and pluripotent transcriptional markers. Further, Oct4 transfected OvSCs (Oct4-OvSCs) were enhanced their AP activity and cell proliferation compared to OvSCs. The potential on in vitro differentiation into OLCs and in vivo folliculogenesis was also evaluated in OvSCs and Oct4-OvSCs, respectively. Oct4-OvSCs possessed higher oogenesis potential in vitro than OvSCs, in terms of expression of germ cell markers by RT-PCR and the number of OLCs. When OvSCs and Oct4-OvSCs were xeno-transplanted into infertile mice ovaries, the OvSCs transplantation induced new primary follicle formation and hormonal levels of estradiol and FSH remained similar to that of normal mice. However, Oct4-OvSCs possessed higher ability for folliculogenesis based on inducing developing follicles with thecal layer and granulosa cells and more similar estradiol level to normal mice.
  
  
  CONCLUSIONS
  These findings demonstrated that putative stem cells were present in ovarian cortex and exhibited differentiation ability into OLCs and folliculogenesis in vivo, and Oct4-overexpression enhanced these ability, suggesting their cellular models based on gene therapy in understanding the mechanisms of oogenesis and folliculogenesis, and finally in view of reproductive cell therapy.
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 501, Jinju-daero, Jinju, 660-701, Republic of Korea.
authors.forename: Yeon-Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 501, Jinju-daero, Jinju, 660-701, Republic of Korea.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 501, Jinju-daero, Jinju, 660-701, Republic of Korea.
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 501, Jinju-daero, Jinju, 660-701, Republic of Korea.
authors.forename: Won-Jae
authors.initials: WJ
authors.lastname: Lee
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 501, Jinju-daero, Jinju, 660-701, Republic of Korea.
authors.forename: Ryoung-Hoon
authors.initials: RH
authors.lastname: Jeon
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 501, Jinju-daero, Jinju, 660-701, Republic of Korea.
authors.forename: Si-Jung
authors.initials: SJ
authors.lastname: Jang
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, 441-706, Republic of Korea.
authors.forename: Sun-A
authors.initials: SA
authors.lastname: Ock
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 501, Jinju-daero, Jinju, 660-701, Republic of Korea.
authors.forename: Sung-Lim
authors.initials: SL
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju, 660-702, Republic of Korea.
authors.forename: Bong-Wook
authors.initials: BW
authors.lastname: Park
authors.affiliation: Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, 501, Jinju-daero, Jinju, 660-701, Republic of Korea. jinrho@gnu.ac.kr.|Research Institute of Life Sciences, Gyeongsang National University, 501, Jinju-daero, Jinju, 660-701, Republic of Korea. jinrho@gnu.ac.kr.
authors.forename: Gyu-Jin
authors.initials: GJ
authors.lastname: Rho
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015870:Gene Expression; D007247:Infertility, Female / Q000097:blood / Q000628:therapy; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D006080:Ovarian Follicle / Q000473:pathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D034421:Sus scrofa
chemical_list: D015415:Biomarkers; D050814:Octamer Transcription Factor-3; D004958:Estradiol; D005640:Follicle Stimulating Hormone
keywords: Estradiol; FSH; Folliculogenesis; Oct4-overexpression; Oocyte-like cells; Porcine