Overexpression of Oct4 in porcine ovarian stem/stromal cells enhances differentiation of oocyte-like cells in vitro and ovarian follicular formation in vivo

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. To enhance the potency of differ...

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Veröffentlicht in:Journal of ovarian research 2016-04, Vol.9 (24), p.24-24, Article 24
Hauptverfasser: Lee, Yeon-Mi, Kim, Tae-Ho, Lee, Jeong-Hyeon, Lee, Won-Jae, Jeon, Ryoung-Hoon, Jang, Si-Jung, Ock, Sun-A, Lee, Sung-Lim, Park, Bong-Wook, Rho, Gyu-Jin
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container_end_page 24
container_issue 24
container_start_page 24
container_title Journal of ovarian research
container_volume 9
creator Lee, Yeon-Mi
Kim, Tae-Ho
Lee, Jeong-Hyeon
Lee, Won-Jae
Jeon, Ryoung-Hoon
Jang, Si-Jung
Ock, Sun-A
Lee, Sung-Lim
Park, Bong-Wook
Rho, Gyu-Jin
description 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. 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. 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. 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.
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Application of these germ line stem cells could be an alternative therapy for reproductive disorders in regenerative medicine. 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. 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. 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Application of these germ line stem cells could be an alternative therapy for reproductive disorders in regenerative medicine. 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. 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. 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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27067537</pmid><doi>10.1186/s13048-016-0233-z</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects Analysis
Animals
Biomarkers - metabolism
Cell Differentiation
Cell Proliferation
Cell Shape
Cells, Cultured
Estradiol
Estradiol - blood
Female
Follicle Stimulating Hormone - blood
Gene Expression
Infertility, Female - blood
Infertility, Female - therapy
Mice, Inbred BALB C
Mice, Nude
Octamer Transcription Factor-3 - genetics
Octamer Transcription Factor-3 - metabolism
Oocytes - physiology
Ovarian Follicle - pathology
Physiological aspects
Stem Cell Transplantation
Stem cells
Stem Cells - physiology
Sus scrofa
Transplantation
title Overexpression of Oct4 in porcine ovarian stem/stromal cells enhances differentiation of oocyte-like cells in vitro and ovarian follicular formation in vivo
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