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Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation

Ovarian tissue cryopreservation is the only feasible method for fertility preservation in prepubertal girls that will undergo gonadotoxic chemotherapy. To date, the only clinical use of cryopreserved tissue is by a later tissue retransplantation to the patient. Clinical challenges in fertility prese...

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Autores principales: Hao, Xia, Anastácio, Amandine, Viñals-Ribé, Laia, Santamaria Lacuesta, Ana, Diakaki, Christina, Alonso de Mena, Sara, Liu, Kui, Rodriguez-Wallberg, Kenny A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497963/
https://www.ncbi.nlm.nih.gov/pubmed/34631518
http://dx.doi.org/10.3389/fonc.2021.682470
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author Hao, Xia
Anastácio, Amandine
Viñals-Ribé, Laia
Santamaria Lacuesta, Ana
Diakaki, Christina
Alonso de Mena, Sara
Liu, Kui
Rodriguez-Wallberg, Kenny A.
author_facet Hao, Xia
Anastácio, Amandine
Viñals-Ribé, Laia
Santamaria Lacuesta, Ana
Diakaki, Christina
Alonso de Mena, Sara
Liu, Kui
Rodriguez-Wallberg, Kenny A.
author_sort Hao, Xia
collection PubMed
description Ovarian tissue cryopreservation is the only feasible method for fertility preservation in prepubertal girls that will undergo gonadotoxic chemotherapy. To date, the only clinical use of cryopreserved tissue is by a later tissue retransplantation to the patient. Clinical challenges in fertility preservation of very young patients with cancer include time constraints that do not allow to retrieve the tissue for cryopreservation before starting chemotherapy and the preclusion of future ovarian tissue transplantation due to the risk of reintroduction of malignant cells in patients with systemic diseases. To overcome these two challenges, we investigated using an experimental model the feasibility of retrieving secondary follicles from ovaries of prepubertal mice after cyclophosphamide (CPA) treatment in increasing doses of 50, 75, and 100 mg/kg. The follicles were thereafter cultured and matured in vitro. The main outcomes included the efficiency of the method in terms of obtained matured oocytes and the safety of these potentially fertility preservative procedures in terms of analyses of oocyte competence regarding normality of the spindle and chromosome configurations. Our findings demonstrated that it was feasible to isolate and culture secondary follicles and to obtain mature oocytes from prepubertal mice ovaries recently treated with CPA. The efficiency of this method was highly demonstrated in the 100 mg/kg CPA group, with near 90% follicle survival rate after 12 days’ culture, similarly to control. Around 80% of the follicles met the criteria to put into maturation, and more than 40% of them achieved metaphase II, with normal spindle and chromosome configurations observed. Suboptimal results were obtained in the 50 and 75 mg/kg CPA groups. These paradoxical findings towards CPA dose might probably reflect a more difficult selection of damaged growing follicles from ovaries recently treated with lower doses of CPA and a hampered ability to identify and discard those with reduced viability for the culture.
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spelling pubmed-84979632021-10-09 Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation Hao, Xia Anastácio, Amandine Viñals-Ribé, Laia Santamaria Lacuesta, Ana Diakaki, Christina Alonso de Mena, Sara Liu, Kui Rodriguez-Wallberg, Kenny A. Front Oncol Oncology Ovarian tissue cryopreservation is the only feasible method for fertility preservation in prepubertal girls that will undergo gonadotoxic chemotherapy. To date, the only clinical use of cryopreserved tissue is by a later tissue retransplantation to the patient. Clinical challenges in fertility preservation of very young patients with cancer include time constraints that do not allow to retrieve the tissue for cryopreservation before starting chemotherapy and the preclusion of future ovarian tissue transplantation due to the risk of reintroduction of malignant cells in patients with systemic diseases. To overcome these two challenges, we investigated using an experimental model the feasibility of retrieving secondary follicles from ovaries of prepubertal mice after cyclophosphamide (CPA) treatment in increasing doses of 50, 75, and 100 mg/kg. The follicles were thereafter cultured and matured in vitro. The main outcomes included the efficiency of the method in terms of obtained matured oocytes and the safety of these potentially fertility preservative procedures in terms of analyses of oocyte competence regarding normality of the spindle and chromosome configurations. Our findings demonstrated that it was feasible to isolate and culture secondary follicles and to obtain mature oocytes from prepubertal mice ovaries recently treated with CPA. The efficiency of this method was highly demonstrated in the 100 mg/kg CPA group, with near 90% follicle survival rate after 12 days’ culture, similarly to control. Around 80% of the follicles met the criteria to put into maturation, and more than 40% of them achieved metaphase II, with normal spindle and chromosome configurations observed. Suboptimal results were obtained in the 50 and 75 mg/kg CPA groups. These paradoxical findings towards CPA dose might probably reflect a more difficult selection of damaged growing follicles from ovaries recently treated with lower doses of CPA and a hampered ability to identify and discard those with reduced viability for the culture. Frontiers Media S.A. 2021-09-24 /pmc/articles/PMC8497963/ /pubmed/34631518 http://dx.doi.org/10.3389/fonc.2021.682470 Text en Copyright © 2021 Hao, Anastácio, Viñals-Ribé, Santamaria Lacuesta, Diakaki, Alonso de Mena, Liu and Rodriguez-Wallberg https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Hao, Xia
Anastácio, Amandine
Viñals-Ribé, Laia
Santamaria Lacuesta, Ana
Diakaki, Christina
Alonso de Mena, Sara
Liu, Kui
Rodriguez-Wallberg, Kenny A.
Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation
title Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation
title_full Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation
title_fullStr Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation
title_full_unstemmed Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation
title_short Follicle Rescue From Prepubertal Ovaries After Recent Treatment With Cyclophosphamide—An Experimental Culture System Using Mice to Achieve Mature Oocytes for Fertility Preservation
title_sort follicle rescue from prepubertal ovaries after recent treatment with cyclophosphamide—an experimental culture system using mice to achieve mature oocytes for fertility preservation
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497963/
https://www.ncbi.nlm.nih.gov/pubmed/34631518
http://dx.doi.org/10.3389/fonc.2021.682470
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