ArticleClinical epigenetics2023
Sperm DNA methylation is predominantly stable in mice offspring born after transplantation of long-term cultured spermatogonial stem cells.
Article in Clinical epigenetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Views of male childhood cancer survivors on fertility preservation and restoration.Reproduction & fertility · 2025Article
- Is the time right for transplanting immature testicular tissue or cells to restore male fertility? Expert perspectives on clinical implementation of autotransplantation of cryopreserved testicular tissue or cells for fertility restoration.Best practice & research. Clinical obstetrics & gynaecology · 2025Review
- The use of deidentified organ donor testes for research.Andrology · 2025Review
- The impact, mechanisms and prevention strategies of environmental endocrine disruptors on male reproductive health.Frontiers in endocrinology · 2025Review
- Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship.Biomedicines · 2024Review
- The Organotypic Culture of Mouse Seminiferous Tubules as a Reliable Methodology for the Study of Meiosis In Vitro.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Cryopreservation of Ovarian and Testicular Tissue and the Influence on Epigenetic Pattern.International journal of molecular sciences · 2023Review
- Effects of clinical medications on male fertility and prospects for stem cell therapy.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSpermatogonial stem cell transplantation (SSCT) is proposed as a fertility therapy for childhood cancer survivors. SSCT starts with cryopreserving a testicular biopsy prior to gonadotoxic treatments such as cancer treatments. When the childhood cancer survivor reaches adulthood and desires biological children, the biopsy is thawed and SSCs are propagated in vitro and subsequently auto-transplanted back into their testis. However, culturing stress during long-term propagation can result in epigenetic changes in the SSCs, such as DNA methylation alterations, and might be inherited by future generations born after SSCT. Therefore, SSCT requires a detailed preclinical epigenetic assessment of the derived offspring before this novel cell therapy is clinically implemented. With this aim, the DNA methylation status of sperm from SSCT-derived offspring, with in vitro propagated SSCs, was investigated in a multi-generational mouse model using reduced-representation bisulfite sequencing.
resultsAlthough there were some methylation differences, they represent less than 0.5% of the total CpGs and methylated regions, in all generations. Unsupervised clustering of all samples showed no distinct grouping based on their pattern of methylation differences. After selecting the few single genes that are significantly altered in multiple generations of SSCT offspring compared to control, we validated the results with quantitative Bisulfite Sanger sequencing and RT-qPCRin various organs. Differential methylation was confirmed only for Tal2, being hypomethylated in sperm of SSCT offspring and presenting higher gene expression in ovaries of SSCT F1 offspring compared to control F1.
conclusionsWe found no major differences in DNA methylation between SSCT-derived offspring and control, both in F1 and F2 sperm. The reassuring outcomes from our study are a prerequisite for promising translation of SSCT to the human situation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.