Quantitative Studies of Testicular Atrophy Following Portacaval Shunt in Rats

Abstract

To evaluate the differential effects of portacaval shunting (PCS) on the morphological changes that occur in humans with portal-systemic encephalopathy, male rats underwent either PCS (13) or sham operations (10). Normal adult rats (6) were used as controls. All animals were killed 5 to 7 weeks after the surgery. The wet weight of the testes was obtained. Hematoxylin-eosin (HE)-stained sections at 5-m thickness were used for stereological analysis using an image analysis system. Apoptosis was assessed quantitatively in HE and in in situ end-labeling (ISEL)-stained slides, while mitotic activity and mast cell numbers were assessed in 20 high-power fields. There was a significant reduction in the testicular mass (664 mg) in PCS rats in comparison with sham (2,199 mg) and control (1,937 mg) rats (P F .00001). The thickness of germinal epithelium was significantly reduced in PCS rats (64 m) compared with sham (126 m) and control groups (108 m). The number of tubules per square millimeter and the mean curvature were significantly increased in PCS rats (P F .00001). There was a 112-fold increase in apoptosis in PCS rats (112) in comparison with the control and shamoperation groups (1.2 and 0.7, respectively). Mitosis was significantly reduced in the PCS group (P ‫؍‬ .0089), but mast cells were unchanged. The results suggest that PCS in the absence of liver dysfunction produces testicular atrophy by reduction in mitosis, maturation arrest, and increased apoptosis of the germinal epithelium. PCS may therefore be responsible for gonadal atrophy that occurs with advanced liver disease in humans. (HEPATOLOGY 1998;28:1461-1466.)The creation of a portacaval shunt (PCS) is often accompanied by hepatic encephalopathy that should be referred to as portal-systemic encephalopathy. The pathogenesis is still obscure, although the condition is probably multifactorial in origin. 1 We 2 and others 3 have studied the physiological and histological changes in the small intestine in this animal model. We found that the decrease in jejunal permeability in the PCS rats was probably related to reduction in mucosal area and villi of the small intestine.It is well known that patients with advanced liver disease show testicular atrophy. The morphological and morphometric changes of testicular atrophy in alcoholic and nonalcoholic liver disease in humans have been described by several authors. 4-8 A rat model for alcohol-induced gonadal atrophy has also been reported. 9 Van Thiel et al. 10 studied the effect of portasystemic shunting and portal hypertension in rats. They found that the weight of the testes was only 42% of the control value in rats with PCS and suggested that portasystemic shunting is principally responsible for the gonadal injury. A small decrease was also observed in rats with portal hypertension from partial portal vein ligation.In this study, we report the changes occurring in the testes in PCS, sham-operated, and normal control rats. We have used a quantitative approach to study the changes in the volume of the testes and i...

Quantitative Studies of Liver Atrophy After Portacaval Shunt in the Rat

“…In a previous study [4], we have shown that testicular atrophy in PCS-operated rats resulted in a reduction in cell production, mainly by apoptosis. The liver differs from the testes because hepatocytes are in the Go phase of the cell cycle (resting or post G1 phase), unlike the germinal epithelium of the testis that is constantly within an active cell cycle phase.…”

“…We [2] and others [3] have studied the physiological and histological changes in the small intestine of the port caval shunted rat and found that a decrease in jejunal permeability was probably related to reduction in mucosal area and villi of the small intestine. In a recent study, we [4] found that PCS, in the absence of liver dysfunction, produces testicular atrophy by reductions in mitosis, maturation arrest, and increased apoptosis of the germinal epithelium of the semineferous tubules. Several authors [5][6][7][8][9][10] have studied the morphological changes of the liver in PCS operated rats.…”

Comb Atrophy after Bile Duct Ligation in Chickens

“…Prepubertal male rats that underwent BDL showed a reduction in testis size (Van Thiel et al, 1985), and portocaval shunts in rats reportedly caused testicular atrophy. This atrophy, manifested histologically by the loss of germinal epithelium, was due to decreased mitosis and increased apoptosis, loss of spermatogonia and spermatozoa in the lumen of the seminiferous tubules, and eventual atrophy of the seminiferous tubules, leaving them lined only with Sertoli cells (Zaitoun et al, 1998). Administration of insulin-like growth factor-I (IGF-I) reverses testicular atrophy and improves testicular function in a carbon tetrachloride model of liver cirrhosis in the rat (Castilla-Cortazar et al, 2000).…”

Liver transduction with a simian virus 40 vector encoding insulin-like growth factor I reduces hepatic damage and the development of liver cirrhosis

“…9 It has been shown that porto-systemic shunting may cause hypogonadism as a result of estrogens bypassing the liver. 32 Although portacaval shunting was not directly analyzed, it seems possible that lower shunting and improved liver SV40 expressing IGF-I reduces liver cirrhosis M Vera et al metabolism of estrogens in these animals may contribute to the correction of the hypogonadism.…”