Experimentally Induced Cryptorchidism Increases Apoptosis in Rat Testis1

Abstract

Although surgical induction of cryptorchidism in the rat is known to cause infertility due to disruption of spermatogenesis, the exact cellular mechanism responsible for the degenerative changes in cryptorchid testes is unclear. Using a sensitive autoradiographic method for the detection of apoptotic DNA fragmentation, we have investigated the effect of experimentally induced cryptorchidism on apoptotic cell death in testes of immature rats. Bilateral or unilateral cryptorchidism decreased the weight of affected testes within 4 days; these decreases (24-27%) became significant (P < 0.05) at 7 days after the operation. Testes of sham-operated animals contained predominantly high molecular weight DNA (> 15 kb), whereas DNA cleavage into low molecular weight ladders characteristic of apoptosis was increased by induction of bilateral 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 cryptorchidism of the contralateral testes increased DNA cleavage into low molecular 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 after the operation indicated that germ cells, mainly primary spermatocytes were affected and that the percentage of seminiferous tubules containing labeled cells increased in the operated testis as compared to the contralateral control in the same animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of apoptosis through Bax expression in cryptorchid testis: an experimental study

“…11,12 The affected testis in experimental unilateral cryptorchidism has been shown to decrease in weight. 2 In the study of Tomomasa et al 13 on TS inbred rats (congenitally cryptorchid rat), 70% of which have cryptorchidism at birth, the weight of the affected testis was decreased significantly at the 4 th , 6 th and 8 th weeks, and spermatogenesis was decreased as well. In their experimental study, Ogi et al 14 showed that testicular weight was decreased to 23% and 31% on the 4 th and 7 th days, respectively.…”

“…1 Elevated temperature in undescended testis is another cause of germ cell loss. 2 Heatinduced apoptosis is reported to involve both the mito-…”

“…6 Cryptorchidism has proved to cause apoptosis in germ cells. 2 Zini et al 7 showed in their experimental study that cryptorchidism results in apoptosis, and orchidopexy reduces the level of apoptosis in undescended testis.…”

Clinical aspects of male germ cell apoptosis during testis development and spermatogenesis

“…Furthermore, surgically induced cryptorchidism in the immature rat testis is followed by a time-dependent, 2 ± 4 fold increase in DNA cleavage into the low molecular weight fragments characteristic of apoptosis. The cell type affected by induced cryptorchidism appears to be the primary spermatocyte (Shikone et al, 1994).…”

Apoptosis in reproductive biology

“…Morphological and quantitative studies indicate that germ cell demise is most commonly found in differentiating spermatogonia throughout testis development and that only 25% of the theoretically possible number of preleptotene spermatocytes is produced from the original population of spermatogonia (Huckins, 1978). Recent biochemical evidence links testicular cell death to increased internucleosomal apoptotic DNA fragmentation and shows that under pathological or experimental conditions, besides spermatogonia, spermatocytes and spermatides can also undergo apoptosis (Tapanienen et al, 1993;Shikone et al, 1994;Billing et al, 1995;Sinha Hikim et al, 1995;Callard et al, 1995). At least three cell death genes are expressed in the testes: bcl-2, bax and p53 (for references see the review of Dunkel and Erkkila È in this issue); However, the exact role of these genes has not been established.…”