4.4 Article

Postpubertal spermatogonial stem cell transplantation restores functional sperm production in rhesus monkeys irradiated before and after puberty

期刊

ANDROLOGY
卷 9, 期 5, 页码 1603-1616

出版社

WILEY
DOI: 10.1111/andr.13033

关键词

GnRH-antagonist; intracytoplasmic sperm injection; radiation; spermatogenesis; transplantation

资金

  1. Center for Strategic Scientific Initiatives, National Cancer Institute [P30 CA016672]
  2. National Institute of Child Health and Human Development [P01 HD075795, R01 HD100197]
  3. National Institutes of Health [P51 OD011092]

向作者/读者索取更多资源

The study successfully restored sperm production in non-human primates who had undergone gonadotoxic treatment before and after puberty by transplanting cryopreserved testicular cells into the seminiferous tubules. In some monkeys, functional sperm derived from the donor were produced after transplantation, with pretreatment not significantly affecting the ability to recover donor-derived sperm production.
Background Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). In macaques, spermatogenesis could be regenerated by intratesticular transplantation of SSCs, but no studies have involved cytotoxic treatment before puberty and transplantation after puberty, which would be the most likely clinical scenario. Objectives To evaluate donor-derived functional sperm production after SSC transplantation to adult monkeys that had received testicular irradiation during the prepubertal period. Materials and methods We obtained prepubertal testis tissue by unilaterally castrating six prepubertal monkeys and 2 weeks later irradiated the remaining testes with 6.9 Gy. However, because spermatogenic recovery was observed, we irradiated them again 14 months later with 7 Gy. Three of the monkeys were treated with GnRH-antagonist (GnRH-ant) for 8 weeks. The cryopreserved testis cells from the castrated testes were then allogeneically transplanted into the intact testes of all monkeys. Tissues were harvested 10 months later for analyses. Results In three of the six monkeys, 61%, 38%, and 11% of the epididymal sperm DNA were of the donor genotype. The ability to recover donor-derived sperm production was not enhanced by the GnRH-ant pretreatment. However, the extent of filling seminiferous tubules during the transplantation procedure was correlated with the eventual production of donor spermatozoa. The donor epididymal spermatozoa from the recipient with 61% donor contribution were capable of fertilizing rhesus eggs and forming embryos. Although the transplantation was done into the rete testis, two GnRH-ant-treated monkeys, which did not produce donor-derived epididymal spermatozoa, displayed irregular tubular cords in the interstitium containing testicular spermatozoa derived from the transplanted donor cells. Discussion and Conclusion The results further support that sperm production can be restored in non-human primates from tissues cryopreserved prior to prepubertal and post-pubertal gonadotoxic treatment by transplantation of these testicular cells after puberty into seminiferous tubules.

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