ObjectiveRecent information provided by genetically modified mouse model has suggested that PI3K-Akt-mTOR/PTEN signaling pathway controlled primordial follicle activation in vivo. Also, PPAR gamma agonist induced PTEN expression and inhibited Akt phosphorylation in vitro. Ovary specific PPAR gamma was predominantly expressed in ovarian tissue. The aim of this study was to investigate whether PPAR gamma modulator might induce the activation and growth of primordial follicles from 5day female mouse after birth.DesignAnimal study.Materials and MethodsOvaries were collected from 5days old B6D2F1 or ICR female mouse and cultured on six well plate and insert for 10 days in vitro. Ovaries were cultured in DMEM/F12 containing BSA, ITS-X, and ascorbic acid, with or without PPAR gamma modulator for 2 days and transferred PPAR gamma modulator free medium. To evaluate the expression of PPAR gamma, PTEN, and Akt1 on mouse ovary, we performed real-time-PCR, immunohistochemistry, and western blot. Also, end of culture, ovaries were fixed 10% neutral-buffered formalin and subjected of HE staining, immunohistochemistry against Ki-67, AMH, PTEN, Akt1 and FOXO-3a, and apoptosis assay with TUNEL. Also, western blot was performed to evaluate the changes of PTEN, Akt1.ResultsThe expression of PPAR gamma, PTEN, Akt1 and FOXO3a were evaluated in ovaries from 5, 10, 15, 20 days and 8 weeks old mouse by RT-PCR. PPAR gamma was expressed in ovaries from all the ages, it increased in ovary in 20 days explosively. PTEN and Akt1 were increased in ovary form 10 Days. In PPAR gamma antagonist treated ovaries, PTEN was decreased and Akt1 was activated. Also nuclear exclusion of FOXO3a was observed in oocytes of primordial follicles at 6hr treatment with PPAR gamma antagonist. AMH expression was observed in PPAR gamma antagonist treated ovaries, but was not in PPAR gamma agonist. After 12 days culture, increases of ovarian sizes of PPAR gamma antagonist treated groups were observed as compare to non-treated or PPAR gamma agonist treatment.ConclusionsFrom these result, PPAR gamma may participate primordial follicle activation and further development, possibly mediated in part of PI3K-PTEN signaling pathway in vitro. Generation of activated primordial follicle in cancer treatment patients, or other infertile women may allow fertility preservation. Also Production of a large number of oocytes may facilitate future derivation of embryonic stem cell for regenerative medicine. ObjectiveRecent information provided by genetically modified mouse model has suggested that PI3K-Akt-mTOR/PTEN signaling pathway controlled primordial follicle activation in vivo. Also, PPAR gamma agonist induced PTEN expression and inhibited Akt phosphorylation in vitro. Ovary specific PPAR gamma was predominantly expressed in ovarian tissue. The aim of this study was to investigate whether PPAR gamma modulator might induce the activation and growth of primordial follicles from 5day female mouse after birth. Recent information provided by genetically modified mouse model has suggested that PI3K-Akt-mTOR/PTEN signaling pathway controlled primordial follicle activation in vivo. Also, PPAR gamma agonist induced PTEN expression and inhibited Akt phosphorylation in vitro. Ovary specific PPAR gamma was predominantly expressed in ovarian tissue. The aim of this study was to investigate whether PPAR gamma modulator might induce the activation and growth of primordial follicles from 5day female mouse after birth. DesignAnimal study. Animal study. Materials and MethodsOvaries were collected from 5days old B6D2F1 or ICR female mouse and cultured on six well plate and insert for 10 days in vitro. Ovaries were cultured in DMEM/F12 containing BSA, ITS-X, and ascorbic acid, with or without PPAR gamma modulator for 2 days and transferred PPAR gamma modulator free medium. To evaluate the expression of PPAR gamma, PTEN, and Akt1 on mouse ovary, we performed real-time-PCR, immunohistochemistry, and western blot. Also, end of culture, ovaries were fixed 10% neutral-buffered formalin and subjected of HE staining, immunohistochemistry against Ki-67, AMH, PTEN, Akt1 and FOXO-3a, and apoptosis assay with TUNEL. Also, western blot was performed to evaluate the changes of PTEN, Akt1. Ovaries were collected from 5days old B6D2F1 or ICR female mouse and cultured on six well plate and insert for 10 days in vitro. Ovaries were cultured in DMEM/F12 containing BSA, ITS-X, and ascorbic acid, with or without PPAR gamma modulator for 2 days and transferred PPAR gamma modulator free medium. To evaluate the expression of PPAR gamma, PTEN, and Akt1 on mouse ovary, we performed real-time-PCR, immunohistochemistry, and western blot. Also, end of culture, ovaries were fixed 10% neutral-buffered formalin and subjected of HE staining, immunohistochemistry against Ki-67, AMH, PTEN, Akt1 and FOXO-3a, and apoptosis assay with TUNEL. Also, western blot was performed to evaluate the changes of PTEN, Akt1. ResultsThe expression of PPAR gamma, PTEN, Akt1 and FOXO3a were evaluated in ovaries from 5, 10, 15, 20 days and 8 weeks old mouse by RT-PCR. PPAR gamma was expressed in ovaries from all the ages, it increased in ovary in 20 days explosively. PTEN and Akt1 were increased in ovary form 10 Days. In PPAR gamma antagonist treated ovaries, PTEN was decreased and Akt1 was activated. Also nuclear exclusion of FOXO3a was observed in oocytes of primordial follicles at 6hr treatment with PPAR gamma antagonist. AMH expression was observed in PPAR gamma antagonist treated ovaries, but was not in PPAR gamma agonist. After 12 days culture, increases of ovarian sizes of PPAR gamma antagonist treated groups were observed as compare to non-treated or PPAR gamma agonist treatment. The expression of PPAR gamma, PTEN, Akt1 and FOXO3a were evaluated in ovaries from 5, 10, 15, 20 days and 8 weeks old mouse by RT-PCR. PPAR gamma was expressed in ovaries from all the ages, it increased in ovary in 20 days explosively. PTEN and Akt1 were increased in ovary form 10 Days. In PPAR gamma antagonist treated ovaries, PTEN was decreased and Akt1 was activated. Also nuclear exclusion of FOXO3a was observed in oocytes of primordial follicles at 6hr treatment with PPAR gamma antagonist. AMH expression was observed in PPAR gamma antagonist treated ovaries, but was not in PPAR gamma agonist. After 12 days culture, increases of ovarian sizes of PPAR gamma antagonist treated groups were observed as compare to non-treated or PPAR gamma agonist treatment. ConclusionsFrom these result, PPAR gamma may participate primordial follicle activation and further development, possibly mediated in part of PI3K-PTEN signaling pathway in vitro. Generation of activated primordial follicle in cancer treatment patients, or other infertile women may allow fertility preservation. Also Production of a large number of oocytes may facilitate future derivation of embryonic stem cell for regenerative medicine. From these result, PPAR gamma may participate primordial follicle activation and further development, possibly mediated in part of PI3K-PTEN signaling pathway in vitro. Generation of activated primordial follicle in cancer treatment patients, or other infertile women may allow fertility preservation. Also Production of a large number of oocytes may facilitate future derivation of embryonic stem cell for regenerative medicine.