EXPERIMENTALLY-INDUCED CRYPTORCHIDISM INCREASES APOPTOSIS IN RAT TESTIS

Although surgical induction of cryptorchidism in the rat is known to c ause infertility due to disruption of spermatogenesis, the exact cellu lar mechanism responsible for the degenerative changes in cryptorchid testes is unclear. Using a sensitive autoradiographic method for the d etection of apoptotic DNA fragmentation, we have investigated the effe ct of experimentally induced cryptorchidism on apoptotic cell death in testes of immature rats. Bilateral or unilateral cryptorchidism decre ased the weight of affected testes within 4 days; these decreases (24- 27%) became significant (p < 0.05) at 7 days after the operation. Test es of sham-operated animals contained predominantly high molecular wei ght DNA (> 15 kb), whereas DNA cleavage into low molecular weight ladd ers characteristic of apoptosis was increased by induction of bilatera l cryptorchidism in a time-dependent manner, i.e., 2.0-, 2.8-, and 4.2 -fold (P < 0.05) at 2, 4, and 7 days after operation, respectively. In unilaterally cryptorchid animals, sham-operated testes also contained predominantly high molecular weight DNA, whereas induction of cryptor chidism of the contralateral testes increased DNA cleavage into low mo lecular weight fragments 3.0-, 2.8-, and 3.9-fold (P < 0.05) at 2, 4, and 7 days after the operation, respectively. In situ analysis of DNA fragmentation in testes of unilaterally cryptorchid rats at 7 days aft er the operation indicated that germ cells, mainly primary spermatocyt es, were affected and that the percentage of seminiferous tubules cont aining labeled cells increased in the operated testis as compared to t he contralateral control in the same animal. Furthermore, according to radioligand receptor analysis, specific [I-125]-hCG binding to crypto rchid testes was not affected at 2 and 4 days after the operation but was significantly (P < 0.05) decreased (32-35%), in relation to values in sham-operated testes in both bilaterally and unilaterally cryptorc hid animals, at 7 days after surgery. In addition, testis [I-125]-hCG binding per milligram protein was not affected by the induction of bil ateral or unilateral cryptorchidism throughout the 7 days of the exper iment. Our data indicate that cryptorchidism-induced testis cell degen eration is mediated by apoptosis probably as the result of increases i n testis temperature, leading to delayed decreases in LH receptors of Leydig cells. Although apoptotic cell death induced by bilateral crypt orchidism might be affected by changes in systemic factors, the increa se of apoptosis in male germ cells after unilateral cryptorchidism is presumably regulated by local testicular factors. Experimentally induc ed cryptorchidism provides a useful model for study of the role of ele vated temperature on testis cell apoptosis.