E. A. Malolina (1), A. Yu. Kulibin (2)
1 -Federal State Budgetary Institution «Research Institute of Virology named after D.I. Ivanovsky» of the Ministry of Health Care and Social Development
2 -Federal State Budgetary Institution of Science «Koltzov Institute of Developmental Biology» of the Russian Academy of Sciences

Sertoli cells are the primary cells that support developing spermatogenic cells in the seminiferous tubules. Heat treatment induces a reversible change in the Sertoli cells (SC) from the mature differentiated state to an immature-like dedifferentiated state. We suggested that under experimental bilateral cryptorchidism (type of heat treatment) SC in adult mice differ from neonatal dedifferentiated SC according to high regeneration capacity. To confirm this suggestion we transplanted testis cells from adult cryptorchid transgenic mice line ROSA26-B6 into testes of infertile mice with damaged endogenous SCs. We demonstrated that after transplantation SC from cryptorchid mice not only generate new seminiferous tubules and reestablish Sertoli cells on the basement membrane of host seminiferous tubules, but also can support spermatogenesis; the total number of new structures after the testis cell injection into seminiferous tubules and the interstitium is 16.1 and 8.0 structures per histological section, respectively. Testis cells from adult wild-type mice were transplanted as a control; the total number of new structures was significantly less than after cryptorchid testis cell injection (1.3 and 0 after transplantation into seminiferous tubules and the interstitium respectively). Furthermore specificity of heat treatment was confirmed by transplantation testis cells from busulfan-treated mice. Busulfan treatment destroys germ cells and alters transcriptomes of SC like cryptorchidism. However SC from busulfan-treated mice have low regeneration capacity like adult wild-type donor cells (the total number of new structures is 2.4 and 0.4 after injection into seminiferous tubules and the interstitium, respectively). Also we found that a marker of immature SC – cytokeratin 18 re-expressed in the cells of the adult mice cryptorchid testes. It is an additional evidence for relation between heat-induced high regeneration capacity of Sertoli cells and their dedifferentiation.
Sertoli cell, regeneration capacity, heat treatment, cryptorchidism, restoration of spermatogenesis, cytokeratin 18