Altered expression of activator proteins that control follicle reserve after ovarian tissue cryopreservation/transplanta
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FERTILITY PRESERVATION
Altered expression of activator proteins that control follicle reserve after ovarian tissue cryopreservation/transplantation and primordial follicle loss prevention by rapamycin Soner Celik 1 & Sinan Ozkavukcu 2,3 & Ciler Celik-Ozenci 1 Received: 27 August 2019 / Accepted: 29 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose We investigated whether expression of activator proteins that control follicle reserve and growth change after ovarian tissue vitrification and re-transplantation. Moreover, we assessed whether inhibition of mTOR signaling pathway by rapamycin would protect primordial follicle reserve after ovarian tissue freezing/thawing and re-transplantation. Methods Fresh control, frozen/thawed, fresh-transplanted, frozen/thawed and transplanted, rapamycin/control, rapamycin freshtransplanted, and rapamycin frozen-thawed and transplanted groups were established in rats. After freezing and thawing process, two ovaries were transplanted into the back muscle of the same rat. After 2 weeks, grafts were harvested, fixed, and embedded into paraffin block. Normal and atretic primordial/growing follicle count was performed in all groups. Ovarian tissues were evaluated for the dynamic expressions of Gdf-9, Bmp-15, KitL, Lif, Fgf-2, and p-s6K using immunohistochemistry, and H-score analyses were done. Results Primordial follicle reserve reduced almost 50% after ovarian tissue re-transplantation. Expression of Gdf-9 and Lif increased significantly in primordial and growing follicles in frozen-thawed, fresh-transplanted, and frozen/thawed and transplanted groups, whereas expression of Bmp-15, KitL, and Fgf-2 decreased in primordial follicles. Freezing and thawing of ovarian tissue solely significantly increased p-s6K expression in primordial follicles, and on the other hand, suppression of mTORC1 pathway using rapamycin preserved the primordial follicle pool. Conclusion Altered expressions of activator proteins that regulate primordial follicle reserve and growth may lead to primordial follicle loss and rapamycin treatment can protect ovarian reserve after ovarian tissue cryopreservation/transplantation. Keywords Ovarian tissue cryopreservation . Transplantation . mTOR . Rapamycin . Primordial follicle reserve . Fertility preservation
Introduction Destructive cancer treatments negatively affect ovarian physiology, resulting in decreased ovarian reserve, early menopause, and infertility in women. For prepubertal girls,
* Ciler Celik-Ozenci [email protected] 1
Department of Histology and Embryology, Akdeniz University School of Medicine, 07070 Antalya, Turkey
2
Department of Histology and Embryology, Ankara University School of Medicine, 06230 Ankara, Turkey
3
Centre for Assisted Reproduction, Department of Obstetrics and Gynecology, Ankara University School of Medicine, 06620 Ankara, Turkey
especially those scheduled for bone marrow transplantation, ovarian tissue cryopreservation (OTC) is the gold standard since it is not possible t
