Spermatogonial stem cell transplantation into nonablated mouse recipient testes.

Hiroko Morimoto,Takashi Shinohara,Shogo Matoba,Atsuo Ogura,Mito Kanatsu-Shinohara,Narumi Ogonuki

doi:10.1016/j.stemcr.2021.05.013

Abstract

SummarySpermatogonial transplantation has been used as a standard assay for spermatogonial stem cells (SSCs). After transplantation into the seminiferous tubules, SSCs transmigrate through the blood-testis barrier (BTB) between Sertoli cells and settle in a niche. Unlike in the repair of other self-renewing systems, SSC transplantation is generally performed after complete destruction of endogenous spermatogenesis. Here, we examined the impacts of recipient conditioning on SSC homing. Germ cell ablation downregulated the expression of glial cell line-derived neurotrophic factor, which has been shown to attract SSCs to niches, implying that nonablated niches would attract SSCs more efficiently. As expected, SSCs colonized nonablated testes when transplanted into recipients with the same genetic background. Moreover, although spermatogenesis was arrested at the spermatocyte stage in Cldn11-deficient mice without a BTB, transplantation not only enhanced donor colonization but also restored normal spermatogenesis. The results show promise for the development of a new transplantation strategy to overcome male infertility.

Highlights

A spermatogonial transplantation technique was developed in 1994
Evaluation of spermatogenesis recovery after busulfan treatment We first evaluated the regeneration of spermatogenesis in 4-week-old wild-type mice after busulfan treatment
No significant difference was observed on day 3 after busulfan treatment, but the difference was significant on day 10 after treatment

Summary

Introduction

A spermatogonial transplantation technique was developed in 1994 With this technique, donor spermatogonial stem cells (SSCs) were observed to migrate into niches in recipient mice (Brinster and Zimmermann, 1994). With the transplantation of a sufficient number of SSCs, offspring can be born from the donor cells by mating the recipient males with wild-type females (Brinster and Avarbock, 1994). Because the BTB divides each seminiferous tubule into the adluminal and basal compartments, transplanted SSCs must migrate through the BTB from the adluminal compartment into the basal compartment before reaching the niche on the basement membrane. Because SSCs are the only cell type that can produce this result, spermatogonial transplantation has been used as a standard functional assay of SSCs, and it is expected that the technique will be used for the treatment of male infertility (Kubota and Brinster, 2018)

Results

Discussion

Conclusion