Effect of Previous Alkylating Agent Exposure on Follicle Numbers in Cryopreserved Prepubertal and Young Adult Ovarian Tissue after Long-Term Xenografting

Mirja Nurmio; Babak Asadi-Azarbaijani; Mi Hou; Ronja Kiviö; Jorma Toppari; Helena Tinkanen; Tiina Laine; Irma C. Oskam; Kirsi Jahnukainen

doi:10.3390/cancers14020399

Effect of Previous Alkylating Agent Exposure on Follicle Numbers in Cryopreserved Prepubertal and Young Adult Ovarian Tissue after Long-Term Xenografting

Mirja Nurmio, Babak Asadi-Azarbaijani, Mi Hou, Ronja Kiviö, Jorma Toppari, Helena Tinkanen, Tiina Laine, Irma C. Oskam, Kirsi Jahnukainen

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Abstract

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.

Original language	English
Article number	399
Number of pages	13
Journal	Cancers
Volume	14
Issue number	2
DOIs	https://doi.org/10.3390/cancers14020399
Publication status	Published - Jan 2022
Publication type	A1 Journal article-refereed

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 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: 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.

Keywords

Alkylating agents
Children and young adults
Fertility preservation
Ovarian follicles
Xenografting

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

@article{a3a240e98e9c4c24b895bab6abc9f0fc,

title = "Effect of Previous Alkylating Agent Exposure on Follicle Numbers in Cryopreserved Prepubertal and Young Adult Ovarian Tissue after Long-Term Xenografting",

abstract = "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.",

keywords = "Alkylating agents, Children and young adults, Fertility preservation, Ovarian follicles, Xenografting",

author = "Mirja Nurmio and Babak Asadi-Azarbaijani and Mi Hou and Ronja Kivi{\"o} and Jorma Toppari and Helena Tinkanen and Tiina Laine and Oskam, {Irma C.} and Kirsi Jahnukainen",

note = "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{\textquoteright}s Health, Oslo University Hospital, Norway, the Swedish Childhood Cancer Foundation (PR2015-0073, TJ2015-0046; PR2017-0073; KP2020-0012), Sigrid Jus{\'e}lius Foundation, Turku University Hospital, the Finnish Cancer Society, the Finnish Pediatric Research Foundation, the Paulo Foundation, the V{\"a}re Foundation for Pediatric Cancer Research, the Birgitta and Carl-Axel Rydbeck{\textquoteright}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: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = jan,

doi = "10.3390/cancers14020399",

language = "English",

volume = "14",

number = "2",

}

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 -

Effect of Previous Alkylating Agent Exposure on Follicle Numbers in Cryopreserved Prepubertal and Young Adult Ovarian Tissue after Long-Term Xenografting

Abstract

Funding

Keywords

Publication forum classification

ASJC Scopus subject areas

UN SDGs

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