Spermatogonial survival after grafting human testicular tissue to immunodeficient mice

Mieke Geens1, Gert De Block, Ellen Goossens

  • 1Centre for Reproductive Medicine and Research Centre for Reproduction and Genetics, University Hospital and Medical School, Vrije Universiteit Brussel, Laarbeeklaan 101, B-1090 Brussels, Belgium.

Abstract

Insights

Xenografting pre-pubertal human testicular tissue to mice shows promise for fertility restoration in childhood cancer survivors. While adult human grafts showed sclerosis, immature tissue is key for external germline storage.

Area of Science:

  • Reproductive biology
  • Cancer survivorship
  • Transplantation immunology

Background:

  • Xenografting testicular tissue offers a theoretical fertility restoration strategy for childhood cancer patients.
  • This approach circumvents the risk of malignant recurrence associated with cancer treatments.
  • Comparing pre-pubertal and adult murine, and adult human testicular tissue xenografting is crucial.

Purpose of the Study:

  • To compare the survival and development of pre-pubertal and adult murine testicular tissue xenografts.
  • To evaluate the survival and development of adult human testicular tissue xenografts.
  • To assess the efficacy of two immunodeficient mouse models (Swiss Nude and SCID-NOD) as recipients.

Main Methods:

  • Subcutaneous grafting of pre-pubertal and adult murine, and adult human testicular tissue into immunodeficient mice.
  • Evaluation of graft survival and histological assessment for developmental stages and tissue integrity.
  • Comparison of outcomes between Swiss Nude and SCID-NOD mouse recipients.

Main Results:

  • Meiotic cells were observed in 69.1% of pre-pubertal testicular tissue grafts, with complete spermatogenesis in 30.9%.
  • Adult murine and 59.5% of adult human testicular grafts exhibited sclerosis; however, spermatogonia persisted in 21.6% of adult human grafts.
  • No significant differences in graft outcomes were noted between the Swiss Nude and SCID-NOD mouse models.

Conclusions:

  • Spermatogonia were maintained for over 195 days in xenografted adult human testicular tissue.
  • Immature testicular tissue is essential for successful external germline storage via xenografting.
  • Both the developmental stage of the tissue and the seminiferous epithelium's structure influence xenograft outcomes.

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