Article (Scientific journals)
The mTOR Inhibitor Rapamycin Counteracts Follicle Activation Induced by Ovarian Cryopreservation in Murine Transplantation Models
Bindels, Jules; Squatrito, Marlyne; Bernet, Laëtitia et al.
2023In Medicina, 59 (8), p. 1474
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Keywords :
ovarian cryopreservation; follicle activation; fertility preservation; heterotopic transplantation; animal models
Abstract :
[en] Background and Objectives: Ovarian tissue cryopreservation followed by autotransplantation (OTCTP) is currently the only fertility preservation option for prepubertal patients. Once in remission, the autotransplantation of frozen/thawed tissue is performed when patients want to conceive. A major issue of the procedure is follicular loss directly after grafting mainly due to follicle activation. To improve follicular survival during the OTCTP procedure, we inhibited the mTOR pathway involved in follicle activation using rapamycin, an mTOR inhibitor. Next, we compared two different in vivo models of transplantation: the recently described non-invasive heterotopic transplantation model between the skin layers of the ears, and the more conventional and invasive transplantation under the kidney capsule. Materials and Methods: To study the effects of adding rapamycin during cryopreservation, 4-week-old C57BL/6 mouse ovaries, either fresh, slow-frozen, or slow-frozen with rapamycin, were autotransplanted under the kidney capsule of mice and recovered three weeks later for immunohistochemical (IHC) analysis. To compare the ear with the kidney capsule transplantation model, fresh 4-week-old C57BL/6 mouse ovaries were autotransplanted to either site, followed by an injection of either LY294002, a PI3K inhibitor, vehicle control, or neither, and these were recovered three weeks later for IHC analysis. Results: Rapamycin counteracts cryopreservation-induced follicle proliferation, as well as AKT and mTOR pathway activation, in ovaries autotransplanted for three weeks under the kidney capsule of mice. Analyses of follicle proliferation, mTOR activation, and the effects of LY294002 treatment were similar in transplanted ovaries using either the ear or kidney capsule transplantation model. Conclusions: By adding rapamycin during the OTCTP procedure, we were able to transiently maintain primordial follicles in a quiescent state. This is a promising method for improving the longevity of the ovarian graft. Furthermore, both the ear and kidney capsule transplantation models were suitable for investigating follicle activation and proliferation and pharmacological strategies.
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
Bindels, Jules ;  Université de Liège - ULiège > GIGA > GIGA Cancer - Tumours and development biology
Squatrito, Marlyne ;  Université de Liège - ULiège > GIGA
Bernet, Laëtitia  ;  Université de Liège - ULiège > GIGA
Nisolle, Michelle ;  Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Henry, Laurie  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique (CHR)
Munaut, Carine  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Language :
Title :
The mTOR Inhibitor Rapamycin Counteracts Follicle Activation Induced by Ovarian Cryopreservation in Murine Transplantation Models
Publication date :
16 August 2023
Journal title :
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Volume :
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Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Leon Fredericq Foundation [BE]
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