title: Spermatogonial behavior in rats during radiation-induced arrest and recovery after hormone suppression.
abstract: Ionizing radiation has been shown to arrest spermatogenesis despite the presence of surviving stem spermatogonia, by blocking their differentiation. This block is a result of damage to the somatic environment and is reversed when gonadotropins and testosterone are suppressed, but the mechanisms are still unknown. We examined spermatogonial differentiation and Sertoli cell factors that regulate spermatogonia after irradiation, during hormone suppression, and after hormone suppression combined with Leydig cell elimination with ethane dimethane sulfonate. These results showed that the numbers and cytoplasmic structure of Sertoli cells are unaffected by irradiation, only a few type A undifferentiated (Aund) spermatogonia and even fewer type A1 spermatogonia remained, and immunohistochemical analysis showed that Sertoli cells still produced KIT ligand (KITLG) and glial cell line-derived neurotrophic factor (GDNF). Some of these cells expressed KIT receptor, demonstrating that the failure of differentiation was not a result of the absence of the KIT system. Hormone suppression resulted in an increase in Aund spermatogonia within 3 days, a gradual increase in KIT-positive spermatogonia, and differentiation mainly to A3 spermatogonia after 2 weeks. KITL (KITLG) protein expression did not change after hormone suppression, indicating that it is not a factor in the stimulation. However, GDNF increased steadily after hormone suppression, which was unexpected since GDNF is supposed to promote stem spermatogonial self-renewal and not differentiation. We conclude that the primary cause of the block in spermatogonial development is not due to Sertoli cell factors such (KITL\GDNF) or the KIT receptor. As elimination of Leydig cells in addition to hormone suppression resulted in differentiation to the A3 stage within 1 week, Leydig cell factors were not necessary for spermatogonial differentiation.
authors.affiliation: Laboratory of Structural Biology and Reproduction, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Avenida Antônio Carlos, 6627 - Pampulha, 31.270-901 Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Amanda V
authors.initials: AV
authors.lastname: Albuquerque
authors.forename: Fernanda R C L
authors.initials: FR
authors.lastname: Almeida
authors.forename: Connie C
authors.initials: CC
authors.lastname: Weng
authors.forename: Gunapala
authors.initials: G
authors.lastname: Shetty
authors.forename: Marvin L
authors.initials: ML
authors.lastname: Meistrich
authors.forename: Hélio
authors.initials: H
authors.lastname: Chiarini-Garcia
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000528:radiation effects; D002478:Cells, Cultured; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013091:Spermatogenesis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013093:Spermatogonia / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D019089:Stem Cell Factor / Q000378:metabolism*; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D000728:Androgens; D051100:Glial Cell Line-Derived Neurotrophic Factor; D019089:Stem Cell Factor; D013739:Testosterone