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Dedifferentiation of Adult Monkey Sertoli Cells through Activation of Extracellularly Regulated Kinase 1/2 Induced by Heat Treatment

State Key Laboratory of Reproductive Biology (X.-S.Z., Z.-H.Z., X.J., P.W., X.-Q.H., M.C., C.-L.L., Z.-Y.H., Y.-X.L.), Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China; Division of Endocrinology (Y.-H.H., A.P.S.H., R.S.S., C.W.), Department of Medicine, Harbor-University of California, Los Angeles, Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90509; and Graduate School of the Chinese Academy of Sciences (X.-S.Z.), Beijing 100039, China

Address all correspondence and requests for reprints to: Yi-Xun Liu, Professor, State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 25, Bei Si Huan Xi Lu, Beijing 100080, China. E-mail: liuyx{at}ioz.ac.cn.

Sertoli cells play a key role in triggering and regulating the process of spermatogenesis. Failure of a Sertoli cell to mature functionally will presumably render it incapable of supporting germ cell survival and development that appeared after puberty. Expression of cytokeratin 18 (ck-18) intermediate filaments indicates a state of undifferentiation usually observed in Sertoli cells of prepubertal testis. In this study we demonstrated that local testicular heat treatment of adult monkey with water at 43 C for 30 min once daily for 2 consecutive days was capable of activating reexpression of ck-18 in Sertoli cells, which was coincident with activation of ERK1/2 and Akt kinases. Using primary Sertoli cell culture isolated from adult monkey testis, we further confirmed that the heat treatment of the cells at 43 C could also induce ck-18 reexpression, which was similar to the in vivo treatment. ERK MAPK was also induced by the heat treatment in a time- and protein kinase A (PKA)-dependent manner. After blocking the ERK MAPK signaling pathway, an inhibition of ck-18 expression in the cultured Sertoli cells was observed, and this inhibitory effect was also detected by blocking the PKA activation. However, ck-18 activation in Sertoli cells remained unaltered when the phosphatidylinositol 3-kinase/Akt pathway was blocked. In conclusion, the heat treatment of adult monkey Sertoli cells are capable of inducing a reversible change in the Sertoli cells from an adult differentiated state to an immature-like dedifferentiated state through PKA-ERK MAPK-dependent pathways but not via the phosphatidylinositol 3-kinase/Akt pathway.

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