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 (A und ) spermatogonia and even fewer type A 1 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 KITreceptor, demonstrating that the failure of differentiation was not a result of the absence of the KIT system. Hormone suppression resulted in an increase in A und spermatogonia within 3 days, a gradual increase in KIT-positive spermatogonia, and differentiation mainly to A 3 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 A 3 stage within 1 week, Leydig cell factors were not necessary for spermatogonial differentiation.

Effects of gamma rays on rat testis tissue according to the morphological parameters and immunohistochemistry: radioprotective role of silymarin

“…This process occurs in response to cytotoxic agents through spermatogenesis, making a balance between healthy and dead germ cells ( 17 ). Apoptosis in testis tissue usually occurs in A2, A3 and A4 stages of spermatogonia; however, apoptosis rarely occurs in the spermatocytes of the stages 1 and 2 as well as spermatids; unless specific environmental and chemical factors induce this process ( 18 ). Testis tissue is highly active with poor cell renewal system and antioxidant defense, which can be an easy target for the induction of radiation through the production of the free radicals that cause indirect and reversible damages ( 19 ).…”

Effect of hormone modulations on donor‐derived spermatogenesis or colonization after syngeneic and xenotransplantation in mice

“…Several reports suggest that GDNF is positively regulated by FSH in Sertoli cells (Tadokoro et al ., ; Ding et al ., ) and by testosterone in peritubular myoid cells (Chen et al ., ), but others find no effect of FSH (Kanatsu‐Shinohara et al ., ; Tanaka et al ., ). However, in irradiated rats, we observed an increase in Sertoli cell GDNF protein after suppression of testosterone and FSH (Albuquerque et al ., ). WNT proteins also increase numbers of undifferentiated type A spermatogonia by enhancing proliferation (Yeh et al ., ).…”

Radioprotective Agents and Enhancers Factors. Preventive and Therapeutic Strategies for Oxidative Induced Radiotherapy Damages in Hematological Malignancies

“…Abdominal irradiation during RT may cause the accrual of harmful radiation concentrations in the testes. Previous studies demonstrated that IR can alter physiologic spermatogenic metabolism, growth, and differentiation, provoking low sperm counts, sterility, and sexual alterations [ 84 , 85 , 86 ].…”