Differential expression and regulation of the retinoblastoma family of proteins during testicular development and spermatogenesis: roles in the control of germ cell proliferation, differentiation and apoptosis.
Normal spermatogenesis is highly dependent on well-balanced germ cell proliferation, differentiation, and apoptosis. However, the molecular mechanisms that govern these processes are largely unknown. Retinoblastoma family proteins (pRb, p107 and p130) are potentially important regulators of cell growth, differentiation and apoptosis. pRb has been shown to be expressed in the rat testis and involved in the regulation of spermatogenesis. In the present study, the expression and localization of the other two pRb family members, p107 and p130, were analysed at both mRNA and protein levels during testicular development and spermatogenesis using Northern, Western blotting, immunohistochemistry, and in situ hybridization. Furthermore, changes of levels and phosphorylation status of pRb family proteins in response to growth suppression and/or apoptosis induction were investigated using a seminiferous tubule culture system and three animal models. Our data suggest that: (1) pRb family proteins are differentially expressed in the rat testis and they function in a cell-type-specific manner during testicular development and spermatogenesis; (2) they participate in the control of germ cell cycle and act in a cell cycle-phase-specific fashion during germ cell proliferation, and (3) they are also involved in the regulation of apoptosis of germ cells and Leydig cells.
Yan
W
W
Department of Physiology, University of Turku, Kiinamyllynkatu 10, 20520, Turku, Finland.
Kero
J
J
Suominen
J
J
Toppari
J
J
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D005786:Gene Expression Regulation; D008297:Male; D008698:Mesylates / Q000494:pharmacology; D005810:Multigene Family; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D010766:Phosphorylation; D011506:Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics*; D050717:Retinoblastoma-Like Protein p130; D012671:Seminiferous Tubules / Q000166:cytology; D013090:Spermatocytes / Q000187:drug effects; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000166:cytology*
D000085:Acetates; D008698:Mesylates; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C493839:Rbl2 protein, rat; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; C002994:ethylene dimethanesulfonate; C013598:methoxyacetic acid