Examination of generational impacts of adolescent chemotherapy: Ifosfamide and potential for epigenetic transgenerational inheritance

Ryan P. Thompson; Daniel Beck; Eric Nilsson; Millissia Ben Maamar; Margarett Shnorhavorian; Michael K. Skinner

doi:10.1016/j.isci.2022.105570

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Examination of generational impacts of adolescent chemotherapy: Ifosfamide and potential for epigenetic transgenerational inheritance

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Examination of generational impacts of adolescent chemotherapy: Ifosfamide and potential for epigenetic transgenerational inheritance

Ryan P. Thompson, Daniel Beck, Eric Nilsson, Millissia Ben Maamar, Margarett Shnorhavorian and Michael K. Skinner

iScience, Vol.25(12), pp.105570-105570

12/22/2022

DOI: https://doi.org/10.1016/j.isci.2022.105570

PMCID: PMC9708925

PMID: 36465105

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Abstract

Omics

Epigenetics

Developmental Genetics

The current study was designed to use a rodent model to determine if exposure to the chemotherapy drug ifosfamide during puberty can induce altered phenotypes and disease in the grand-offspring of exposed individuals through epigenetic transgenerational inheritance. Pathologies such as delayed pubertal onset, kidney disease, and multiple pathologies were observed to be significantly more frequent in the F1 generation offspring of ifosfamide lineage females. The F2 generation grand-offspring ifosfamide lineage males had transgenerational pathology phenotypes of early pubertal onset and reduced testis pathology. Reduced levels of anxiety were observed in both males and females in the transgenerational F2 generation grand-offspring. Differential DNA methylated regions (DMRs) in chemotherapy lineage sperm in the F1 and F2 generations were identified. Therefore, chemotherapy exposure impacts pathology susceptibility in subsequent generations. Observations highlight the importance that prior to chemotherapy, individuals need to consider cryopreservation of germ cells as a precautionary measure if they have children. [Display omitted] •Chemotherapy-induced sperm DNA methylation facilitates epigenetic inheritance•Chemotherapy promotes epigenetic transgenerational inheritance of pathology•Pubertal exposure to chemotherapy impacts later life sperm epigenetics and genetics•Cancer chemotherapy treatment needs to consider later life and generational impacts Developmental genetics; Epigenetics; Omics

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Title: Examination of generational impacts of adolescent chemotherapy
Creators: Ryan P. Thompson - Washington State University
Daniel Beck - Washington State University
Eric Nilsson - Washington State University
Millissia Ben Maamar - Washington State University
Margarett Shnorhavorian - ITER
Michael K. Skinner - Washington State University
Publication Details: iScience, Vol.25(12), pp.105570-105570
Academic Unit: Biological Sciences, School of
Publisher: Elsevier Inc
Identifiers: 99901080305401842
Language: English
Resource Type: Journal article