title: The effect of secondary cholestasis on the CD68-positive and CD163-positive macrophage population, cellular proliferation, and apoptosis in rat testis.
abstract: The pathogenesis of hypogonadism in male patients with cirrhosis is complex and not well explained. Systemic infection and inflammation can inhibit testicular functions of endocrine and spermatogenesis. The acute inflammation induced by lipopolysaccharide can cause testicular acute inflammation. Both clinical and animal experimental data indicate that the developing process of cholestasis/cirrhosis can lead to endotoxemia. Little is known about the long-term effects of cholestasis on the intratesticular macrophage population, cellular proliferation and apoptosis. A rat model of secondary cholestasis caused by common bile duct ligation (CBDL) was used to evaluate the impact of cholestasis on them, and the influence of biliary decompression (choledochoduodenostomy). Endotoxemia occurred in animals at 20 days CBDL (20dCBDL) and 30 days CBDL (30dCBDL), but disappeared after 30 days biliary decompression in rats with CBDL. There was a considerable increase in the numbers of intratesticular CD68(+) and CD163(+) macrophages following CBDL. After biliary decompression, CD68(+) macrophage numbers decreased, but remained higher than that of controls; meanwhile, CD163(+) remained elevated only in rats with 30dCBDL. After CBDL, there was a progressive decrease in the expression of Bcl-2 protein and in proliferating cell nuclear antigen (PCNA(+)) cells, and a dramatic increase in the expression of Bax, active caspase-3 and apoptotic cells. These data suggest that secondary cholestasis expands the population of CD68(+) and CD163(+) macrophages in the testicular interstitium, decreases testicular proliferative activity, and promotes testicular apoptosis, which may be one of the mechanisms of biliary cirrhosis-related hypogonadism.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Shi
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Xie
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: You-Fa
authors.initials: YF
authors.lastname: Zhu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, China. Electronic address: sms3391@hotmail.com.
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Zheng
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D049109:Cell Proliferation; D002779:Cholestasis / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000276:immunology*; D013737:Testis / Q000276:immunology*; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C539355:CD68 protein, rat; D000097382:CD68 Molecule
keywords: Apoptosis; Endotoxemia; Macrophage; Proliferating cell nuclear antigen; Secondary cholestasis; Testis