Zhonghua nan ke xue = National journal of andrology · 2025
[Hypoandrogenism and the mode of cell death in the penile cavernosum tissue of male rats].
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Zhao Xin, Li Jing, Jiang Rui
Аннотация
OBJECTIVE: To study the mode of cell death in the penile cavernosum tissue of male rats in the hypoandrogenic state.
METHODS: We equally randomized 36 10-week-old SD male rats into six groups: 4-week sham-operation (4-wk SO), 8-week sham-operation (8-wk SO), 4-week castration (4-wk C), 8-week castration (8-wk C), 4-week castration + testosterone replacement (4-wk C+T), and 8-week castration + T replacement (8-wk C+T). The rats in the SO groups received incision of the scrotal skin with preservation of the testis and epididymis, those in the C groups underwent bilateral orchiectomy and epididymectomy, and those in the C+T groups were subcutaneously injected with T propionate at 3 mg/kg qd alt. We measured the ratio of maximum intracavernous pressure to mean arterial pressure (ICPmax/MAP), the concentration of serum T and the level of nitric oxide (NO), and determined the expressions of active caspase-1 and caspase-3 in the penile cavernosum of all the animals.
RESULTS: The ICPmax/MAP ratio, serum T and NO levels and smooth muscle / collagen ratio were significantly lower in the C than in the SO and C+T groups (all P<0.05). The rats in the 4-wk C group, compared with those in the SO group, showed dramatic increases in the rates of endothelial cell pyroptosis (［15.31 ± 0.55］% vs ［0.78 ± 0.53］%, P<0.01), endothelial cell apoptosis (［16.32 ± 0.97］% vs ［0.88 ± 0.39］%, P<0.01), total cell pyroptosis (［9.67 ± 0.49］% vs ［1.53 ± 0.24］%, P<0.01) and total cell apoptosis (［11.27 ± 0.94］% vs ［1.68 ± 0.15］%, P<0.01) in the penile cavernous tissue, and so did those of the 8-wk C group in the rates of endothelial cell pyroptosis (［27.37 ± 0.65］% vs ［1.02 ± 0.65］%, P<0.01), endothelial cell apoptosis (［24.27 ± 0.54］% vs ［1.00 ± 0.63］%, P<0.01), total cell pyroptosis (［14.85 ± 0.55］% vs ［1.72 ± 0.52］%, P<0.01) and total cell apoptosis (［15.92 ± 0.53］% vs ［1.27 ± 0.31］%, P<0.01). The rats of the 8-wk C group exhibited an even more significant elevation than those of the 4-wk C group in the rates of endothelial cell pyroptosis (［27.37 ± 0.65］% vs ［15.31 ± 0.55］%, P<0.05) and endothelial cell apoptosis (［24.27 ± 0.54］% vs ［16.32 ± 0.97］%, P<0.05) .
CONCLUSION: Pyroptosis and apoptosis are the main modes of death of endothelial cells in the penile cavernosum of male rats after 4 weeks of castration and, with the progression of the disease, both increase with minimally expressed caspase-1 and caspase-3 in the smooth muscle cells. Endothelial cells and smooth muscle cells have different modes of death in different stages of hypoandrogenism.
METHODS: We equally randomized 36 10-week-old SD male rats into six groups: 4-week sham-operation (4-wk SO), 8-week sham-operation (8-wk SO), 4-week castration (4-wk C), 8-week castration (8-wk C), 4-week castration + testosterone replacement (4-wk C+T), and 8-week castration + T replacement (8-wk C+T). The rats in the SO groups received incision of the scrotal skin with preservation of the testis and epididymis, those in the C groups underwent bilateral orchiectomy and epididymectomy, and those in the C+T groups were subcutaneously injected with T propionate at 3 mg/kg qd alt. We measured the ratio of maximum intracavernous pressure to mean arterial pressure (ICPmax/MAP), the concentration of serum T and the level of nitric oxide (NO), and determined the expressions of active caspase-1 and caspase-3 in the penile cavernosum of all the animals.
RESULTS: The ICPmax/MAP ratio, serum T and NO levels and smooth muscle / collagen ratio were significantly lower in the C than in the SO and C+T groups (all P<0.05). The rats in the 4-wk C group, compared with those in the SO group, showed dramatic increases in the rates of endothelial cell pyroptosis (［15.31 ± 0.55］% vs ［0.78 ± 0.53］%, P<0.01), endothelial cell apoptosis (［16.32 ± 0.97］% vs ［0.88 ± 0.39］%, P<0.01), total cell pyroptosis (［9.67 ± 0.49］% vs ［1.53 ± 0.24］%, P<0.01) and total cell apoptosis (［11.27 ± 0.94］% vs ［1.68 ± 0.15］%, P<0.01) in the penile cavernous tissue, and so did those of the 8-wk C group in the rates of endothelial cell pyroptosis (［27.37 ± 0.65］% vs ［1.02 ± 0.65］%, P<0.01), endothelial cell apoptosis (［24.27 ± 0.54］% vs ［1.00 ± 0.63］%, P<0.01), total cell pyroptosis (［14.85 ± 0.55］% vs ［1.72 ± 0.52］%, P<0.01) and total cell apoptosis (［15.92 ± 0.53］% vs ［1.27 ± 0.31］%, P<0.01). The rats of the 8-wk C group exhibited an even more significant elevation than those of the 4-wk C group in the rates of endothelial cell pyroptosis (［27.37 ± 0.65］% vs ［15.31 ± 0.55］%, P<0.05) and endothelial cell apoptosis (［24.27 ± 0.54］% vs ［16.32 ± 0.97］%, P<0.05) .
CONCLUSION: Pyroptosis and apoptosis are the main modes of death of endothelial cells in the penile cavernosum of male rats after 4 weeks of castration and, with the progression of the disease, both increase with minimally expressed caspase-1 and caspase-3 in the smooth muscle cells. Endothelial cells and smooth muscle cells have different modes of death in different stages of hypoandrogenism.