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

Research output: Contribution to journalArticleScientificpeer-review

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 languageEnglish
Article number399
Number of pages13
JournalCancers
Volume14
Issue number2
DOIs
Publication statusPublished - Jan 2022
Publication typeA1 Journal article-refereed

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

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