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Related Experiment Video

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Germ Cell Transplantation and Testis Tissue Xenografting in Mice
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DAZL Knockout Pigs as Recipients for Spermatogonial Stem Cell Transplantation.

Nathalia L M Lara1, Taylor Goldsmith2, Paula Rodriguez-Villamil2

  • 1Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N4N1, Canada.

Cells
|November 10, 2023
PubMed
Summary

Gene-edited pigs lacking DAZL support spermatogonial stem cell (SSC) transplantation, enabling donor sperm production. However, low sperm concentration limits their use for breeding.

Keywords:
DAZLDAZL knockoutgenetically modified pigsspermatogonial stem cell transplantation

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Area of Science:

  • Reproductive Biology
  • Developmental Biology
  • Genetics

Background:

  • Spermatogonial stem cell (SSC) transplantation is crucial for propagating gene-edited large animal models.
  • DAZL (Deleted in AZoospermia Like) is essential for germ cell (GC) development, and its absence causes GC defects.

Purpose of the Study:

  • To characterize DAZL knockout (KO) pigs as recipients for SSC transplantation.
  • To evaluate the efficiency of donor-derived spermatogenesis in DAZL-KO pigs.

Main Methods:

  • DAZL-KO pigs were generated and assessed for germ cell depletion.
  • Donor GCs were transplanted into 10-13 week old DAZL-KO recipients.
  • Testes and semen were analyzed at sexual maturity for transplantation success and spermatogenesis.

Main Results:

  • Complete germ cell depletion occurred by 10 weeks in DAZL-KO pigs.
  • Approximately 22% of seminiferous tubules in recipients contained donor GCs, including elongated spermatids.
  • Sperm of donor origin was found in 89% of recipient ejaculates, though at lower concentrations than wild-type.
  • Testicular and hormonal profiles were comparable to wild-type, with increased intratesticular testosterone and Leydig cell volume in KO recipients.

Conclusions:

  • DAZL-KO pigs can support donor-derived spermatogenesis after SSC transplantation.
  • Current limitations in spermatogenic efficiency hinder the use of DAZL-KO pigs for offspring production.