Autologous transplantation of spermatogonial stem cells restores fertility in congenitally infertile mice

Significance Stem cell transplantation is widely used to rescue defects in stem cell-derived cells. However, it is generally impossible to rescue tissue dysfunction caused by defective microenvironment. In this study, we report that autologous spermatogonial stem cell (SSC) transplantation rescues congenital male infertility caused by Cldn11 deficiency. Cldn11 -deficient mice lack spermatogenesis due to defects in the blood–testis barrier. However, WT or Cldn11 -deficient SSC transplantation allowed development of fertile sperm from the donor cells in chemically castrated Cldn11 -deficient mice. Because in vivo depletion of Cldn3 or Cldn5 restored endogenous spermatogenesis, complete spermatogenesis may be inhibited by the imbalance of claudin expression caused by Cldn11 deficiency. Our result suggests that some forms of male infertility can be rescued by autologous SSC transplantation.