TY - JOUR
T1 - Effect of Previous Alkylating Agent Exposure on Follicle Numbers in Cryopreserved Prepubertal and Young Adult Ovarian Tissue after Long-Term Xenografting
AU - Nurmio, Mirja
AU - Asadi-Azarbaijani, Babak
AU - Hou, Mi
AU - Kiviö, Ronja
AU - Toppari, Jorma
AU - Tinkanen, Helena
AU - Laine, Tiina
AU - Oskam, Irma C.
AU - Jahnukainen, Kirsi
N1 - Funding Information:
This research was funded by grants from the Norwegian National Advisory Unit on Women?s Health, Oslo University Hospital, Norway, the Swedish Childhood Cancer Foundation (PR2015-0073, TJ2015-0046; PR2017-0073; KP2020-0012), Sigrid Jus?lius Foundation, Turku University Hospital, the Finnish Cancer Society, the Finnish Pediatric Research Foundation, the Paulo Foun-dation, the V?re Foundation for Pediatric Cancer Research, the Birgitta and Carl-Axel Rydbeck?s Research Grant for Paediatric Research (2020-00335; 2021-00079)the Academy of Finland, the Swedish Research Council (2016-01296), ALF Stockholm County, and the Karolinska Institute.
Funding Information:
Funding: This research was funded by grants from the Norwegian National Advisory Unit on Women’s Health, Oslo University Hospital, Norway, the Swedish Childhood Cancer Foundation (PR2015-0073, TJ2015-0046; PR2017-0073; KP2020-0012), Sigrid Jusélius Foundation, Turku University Hospital, the Finnish Cancer Society, the Finnish Pediatric Research Foundation, the Paulo Foundation, the Väre Foundation for Pediatric Cancer Research, the Birgitta and Carl-Axel Rydbeck’s Research Grant for Paediatric Research (2020-00335; 2021-00079)the Academy of Finland, the Swedish Research Council (2016-01296), ALF Stockholm County, and the Karolinska Institute.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1
Y1 - 2022/1
N2 - Purpose and methods: To elucidate whether previous cancer treatment affects graft recovery and follicle numbers, morphology, and development in grafts, cryopreserved ovarian biopsies obtained from 18 cancer patients aged 1–24 years with and without exposure to chemotherapy were xenografted as 1 mm3 fragments to immunodeficient mice for 22 weeks with exogenous stimulation. Results: Graft recovery showed no association with chemotherapy exposure, pubertal stage, or leukemia contamination. Total follicle number per recovered graft varied between 0 and 1031 in the chemotherapy-exposed and between 0 and 502 in the non-chemotherapy-exposed group. Atretic follicles formed the largest proportion of the follicle pool in chemotherapy-exposed grafts. Increased atresia correlated with exposure to alkylating agents (mean ± SD 8866.2 ± 9316.3 mg/m2) but not with anthracyclines, pubertal stage, or leukemia contamination. Conclusion: The observation confirms the harmful effects of alkylating agents on ovarian tissue. Therapy at the median cumulative dose of 8866 mg/m2 leads to the decreased quality of cryopreserved ovarian follicles in children and young adults.
AB - Purpose and methods: To elucidate whether previous cancer treatment affects graft recovery and follicle numbers, morphology, and development in grafts, cryopreserved ovarian biopsies obtained from 18 cancer patients aged 1–24 years with and without exposure to chemotherapy were xenografted as 1 mm3 fragments to immunodeficient mice for 22 weeks with exogenous stimulation. Results: Graft recovery showed no association with chemotherapy exposure, pubertal stage, or leukemia contamination. Total follicle number per recovered graft varied between 0 and 1031 in the chemotherapy-exposed and between 0 and 502 in the non-chemotherapy-exposed group. Atretic follicles formed the largest proportion of the follicle pool in chemotherapy-exposed grafts. Increased atresia correlated with exposure to alkylating agents (mean ± SD 8866.2 ± 9316.3 mg/m2) but not with anthracyclines, pubertal stage, or leukemia contamination. Conclusion: The observation confirms the harmful effects of alkylating agents on ovarian tissue. Therapy at the median cumulative dose of 8866 mg/m2 leads to the decreased quality of cryopreserved ovarian follicles in children and young adults.
KW - Alkylating agents
KW - Children and young adults
KW - Fertility preservation
KW - Ovarian follicles
KW - Xenografting
U2 - 10.3390/cancers14020399
DO - 10.3390/cancers14020399
M3 - Article
AN - SCOPUS:85122873400
SN - 2072-6694
VL - 14
JO - Cancers
JF - Cancers
IS - 2
M1 - 399
ER -