Low androgen status inhibits erectile function by increasing pyroptosis in rat corpus cavernosum

Abstract

Background:The mechanism of erectile dysfunction (ED) caused by low androgen status is not fully understood.Objectives: To investigate whether low androgen status inhibits erectile function of rats by inducing pyroptosis in the corpus cavernosum (CC).Materials and methods: Thirty-six eight-weeks-old healthy male Sprague-Dawley rats were equally divided into six groups: sham-operated group (4w sham, 8w sham), castration group (4w cast, 8w cast), and castration + testosterone (T) group (4w cast + T, 8w cast + T). The rats in castration + T groups were injected with testosterone propionate subcutaneously every other day. After 4 and 8 weeks, the ratio of maximum intracavernous pressure (ICPmax)/mean arterial pressure (MAP), the level of serum T, the concentration of nitric oxide (NO) and interleukin-1β (IL-1β), the expression of NOD-like receptor pyrin domain containing 3 (NLRP3), apoptosis-associated specklike protein containing a caspase activation and recruitment domain (ASC), Caspase-1 p20, gasdermin D-N (GSDMD-N), transforming growth factor β1 (TGF-β1), collagen-I, and collagen-III, the ratio of smooth muscle/collagen (SM/C), and the proportion of pyroptotic cells in the CC were analyzed. Results:The ratio of ICPmax/MAP (3/5 V) and SM/C, the level of NO and serum T was significantly decreased in castration groups when compared to other groups (p < 0.01). NLRP3, ASC, Caspase-1, and GSDMD were mainly expressed in the cytoplasm of smooth muscle cells (SMCs) and endothelial cells (ECs) in the CC. The expression of NLRP3, ASC, Caspase-1p20, GSDMD-N, IL-1β, TGF-β1, collagen-I, and collagen-III was significantly increased in castration groups when compared with other groups (p < 0.01). The proportion of pyroptotic cells in the CC was increased significantly in castration groups when compared with other groups (p < 0.05). Discussion and Conclusion: Low androgen status inhibits erectile function of rats bypromoting CC fibrosis and reducing NO synthesis through pyroptosis of SMCs and ECs in the CC. K E Y W O R D Sandrogen, pyroptosis, penile, ratSince the first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported in Wuhan, China, it has rapidly spread and affected more than 21 million people worldwide as of 17 August 2020. 1 SARS-CoV-2 uses angiotensin-converting enzyme II (ACE2) to enter host cells, similar to SARS-CoV, which emerged 18 years ago. 2 COVID-19 induces respiratory-predominant multiorgan dysfunction, including myocardial, renal, enteric and hepatic dysfunction, which coincides with the tissue expression of ACE2. 3 Meanwhile, several studies have shown that ACE2 is expressed in human testes (eg spermatogonia, Leydig cells and Sertoli cells), 4,5 suggesting that the testes may be another organ affected by COVID-19.Numerous viruses have been detected in human semen. 6 Viruses may persist in semen and last longer in seminal fluid than in other body fluids due to the immune privilege of the testes and the contribution of the blood-teste...

Low androgen level impairs erectile function of rat by regulating the Ng/CaN/AKT/eNOS pathway in penile corpus cavernosum

“…This study showed that compared to the control group and castrated+T replacement group, the level of serum testosterone and ICPmax/MAP of rat were remarkably decreased in the castrated group. This was consistent with previous study 22 . It suggested that low androgen level impaired the erectile function of rat.…”

“…The testes and epididymis were removed in the castrated rats. Rats in the castrated+T repleacement group received subcutaneous injection of testosterone propionate (3 mg/kg) every other day after surgical castration 22 . And the other groups received subcutaneous injection of the same dose of vegetable oil.…”

Effect of low androgen levels on transient receptor potential channels expression in rat penile corpus cavernosum tissue and its relationship with erectile function

“…After 3 V and 5 V electro‐stimulation, ICPmax/MAP was remarkably lower in cast group than in the control and cast + T groups. This suggested that erectile function of rats was inhibited by low androgen levels and improved with testosterone supplementation, which was consistent with the previous findings (Chen et al, 2021; Xiong et al, 2020). TRPC1, TRPC3, TRPC4 and TRPC6 are expressed on the membrane of SMCs in rat penile corpora cavernosum (Sung et al, 2014).…”

“…In accordance with our previous method (Chen et al, 2021), the penile tissues were sectioned, dehydrated, deparaffinized and blocked. The tissue sections were incubated with primary antibodies (TRPC1, TRPC3 and TRPC6, 1:100, Santa Cruz Biotech., Dallas, TX, USA; TRPC4, 1:200, Abcam, Cambridge, MA, USA) in immunohistochemistry wet boxes for 1 h at room temperature and then at 4 °C overnight.…”

Low androgen status inhibits erectile function by upregulating the expression of proteins of mitochondria‐associated membranes in rat corpus cavernosum

“…Pressure transducers were connected to monitor the MAP and ICP. The cavernous nerve, a branch of the major pelvic ganglion at the rear side of the prostate, was used as an electrical stimulation site 23 (intensity: 0, 3, and 5 V; amplitude: 5 ms; frequency: 12 Hz; duration: 35 s; and interval: 3 min). The BL420 biological signal acquisition system (Techman Technology Co., Ltd., Chengdu, Sichuan, China) was used to record the changes of the ICPmax/MAP.…”