Altered expression of activator proteins that control follicle reserve after ovarian tissue cryopreservation/transplantation and primordial follicle loss prevention by rapamycin

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...

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Published in:Journal of assisted reproduction and genetics 2020-09, Vol.37 (9), p.2119-2136
Main Authors: Celik, Soner, Ozkavukcu, Sinan, Celik-Ozenci, Ciler
Format: Article
Language:English
Subjects:
Cryopreservation
Fertility Preservation
Fibroblast growth factor 2
Follicles
Freezing
Gynecology
Human Genetics
Immunohistochemistry
Medicine
Medicine & Public Health
Ovaries
Paraffin
Proteins
Rapamycin
Reproductive Medicine
Signal transduction
Thawing
TOR protein
Transplantation
Vitrification
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Summary: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 fresh-transplanted, 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.
ISSN:1058-0468
1573-7330
DOI:10.1007/s10815-020-01875-7