Evidence map›Paper›PMID 33272271›Full record

ArticleBMC medicine2020

Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer.

Melissa D Tharmalingam, Gabriele Matilionyte, William H B Wallace, Jan-Bernd Stukenborg, Kirsi Jahnukainen, Elizabeth Oliver, Anne Goriely, Sheila Lane, Jingtao Guo, Bradley Cairns and 6 more

Open access · goldAbstract readCase Reports
In one paragraph

Article in BMC medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
11.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Platinum accumulation in chemotherapy: toxicity mechanisms, challenges, and mitigation strategies.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Review
  4. Article
  5. Antimetastatic Effects of aAntioxidants (Basel, Switzerland) · 2026
    Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. The impact ofHuman reproduction open · 2025
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. BRCA Mutations and Fertility Preservation.International journal of molecular sciences · 2023
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 11 institutions in 6 countries.

Melissa D TharmalingamMRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK.
Gabriele MatilionyteMRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK.
William H B WallaceEdinburgh Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh, EH9 1LF, Scotland, UK.
Jan-Bernd StukenborgNORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Kirsi JahnukainenNORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Elizabeth OliverNORDFERTIL Research Lab Stockholm, Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Anne GorielyRadcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX39DS, UK.
Sheila LaneDepartment of Paediatrics and Child Health, Oxford University Hospitals NHS Foundation Trust, and Nuffield Department of Womens and Reproductive Health, University of Oxford, Oxford, UK.
Jingtao GuoSection of Andrology, Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
Bradley CairnsHoward Hughes Medical Institute, Department of Oncological Sciences and Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.
Anne JorgensenDepartment of Growth and Reproduction, Copenhagen University Hospital (Rigshospitalet), Blegdamsvej 9, 2100, Copenhagen, Denmark.
Caroline M AllenBiomedical Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.
Federica LopesMRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK.
Richard A AndersonMRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK.
Norah SpearsBiomedical Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.
Rod T MitchellMRC Centre for Reproductive Health, The Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, UK. rod.mitchell@ed.ac.uk.
University of Edinburgh · GBKarolinska Institutet · SERoyal Hospital for Children · GBThe Queen's Medical Research Institute · GBCopenhagen University Hospital · DKHelsinki University Hospital · FIHoward Hughes Medical Institute · USHuntsman Cancer Institute · USMRC Centre for Reproductive Health · GBMRC Weatherall Institute of Molecular Medicine · GBUniversity of Oxford · GB

Funding

Medical Research Council G1100357Medical Research Council MR/N022556/1Medical Research Council MR/R006237/1Medical Research Council MR/S017151/1Wellcome TrustWellcome Trust 098522
6 · The paper itself

Abstract

backgroundClinical studies indicate chemotherapy agents used in childhood cancer treatment regimens may impact future fertility. However, effects of individual agents on prepubertal human testis, necessary to identify later risk, have not been determined. The study aimed to investigate the impact of cisplatin, commonly used in childhood cancer, on immature (foetal and prepubertal) human testicular tissues. Comparison was made with carboplatin, which is used as an alternative to cisplatin in order to reduce toxicity in healthy tissues.

methodsWe developed an organotypic culture system combined with xenografting to determine the effect of clinically-relevant exposure to platinum-based chemotherapeutics on human testis. Human foetal and prepubertal testicular tissues were cultured and exposed to cisplatin, carboplatin or vehicle for 24 h, followed by 24-240 h in culture or long-term xenografting. Survival, proliferation and apoptosis of prepubertal germ stem cell populations (gonocytes and spermatogonia), critical for sperm production in adulthood, were quantified.

resultsCisplatin exposure resulted in a significant reduction in the total number of germ cells (- 44%, p < 0.0001) in human foetal testis, which involved an initial loss of gonocytes followed by a significant reduction in spermatogonia. This coincided with a reduction (- 70%, p < 0.05) in germ cell proliferation. Cisplatin exposure resulted in similar effects on total germ cell number (including spermatogonial stem cells) in prepubertal human testicular tissues, demonstrating direct relevance to childhood cancer patients. Xenografting of cisplatin-exposed human foetal testicular tissue demonstrated that germ cell loss (- 42%, p < 0.01) persisted at 12 weeks. Comparison between exposures to human-relevant concentrations of cisplatin and carboplatin revealed a very similar degree of germ cell loss at 240 h post-exposure.

conclusionsThis is the first demonstration of direct effects of chemotherapy exposure on germ cell populations in human foetal and prepubertal testis, demonstrating platinum-induced loss of all germ cell populations, and similar effects of cisplatin or carboplatin. Furthermore, these experimental approaches can be used to determine the effects of established and novel cancer therapies on the developing testis that will inform fertility counselling and development of strategies to preserve fertility in children with cancer.

Indexed as

AnimalsCarboplatinChildCisplatinFertility PreservationHumansMaleMiceNeoplasmsTestisXenograft Model Antitumor AssaysCarboplatinCisplatinCisplatinFertilityFoetalGerm cellHumanPrepubertalTestisXenograft

Identifiers

PMID33272271
PMCPMC7716476
OpenAlexW3109351175

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.