1.Effect of "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture on reproductive function in mice with asthenozoospermia based on mitochondrial apoptosis.
Jianheng HAO ; Boya CHANG ; Jia REN ; Zhen GAO ; Yanlin ZHANG ; Haijun WANG ; Laixi JI
Chinese Acupuncture & Moxibustion 2025;45(1):71-81
OBJECTIVE:
To observe the effects of the "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture on key regulatory factors during mitochondrial apoptosis of testicular tissue in asthenozoospermia mice, and explore the potential mechanism of the protective effect of acupuncture on reproductive function.
METHODS:
Thirty C57BL/6 male mice were randomly divided into a blank group, a model group and an acupuncture group, 10 mice in each group. In the model and the acupuncture groups, the intraperitoneal injection of cyclophosphamide (30 mg•kg-1•d-1) was delivered for 7 days to prepare the asthenozoospermia model. After the success of modeling, the modeled mice in the acupuncture group were intervened with "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture, once daily and the needles were retained for 20 min. The duration of the intervention was 2 weeks. The general condition of each mouse was observed, and the body mass was recorded before modeling, after modeling and after intervention completion. After intervention, the testicular mass was recorded and the weight coefficient was calculated, and the mouse sperm quality was examined; the serum contents of testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were detected using ELISA, the morphology of testicular tissue was observed using HE, the mitochondrial ultra-microstructure of testicular tissue was observed under transmission electrone microscopy, the mitochondrial membrane potential level of testicular tissue was detected using JC-1 staining, the positive rate of apoptosis cell of testicular tissue was observed using TUNEL; and the mRNA and protein expression of b-cell lymphocytoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome c (Cyt C), apoptotic protease-activating factor1 (Apaf-1), Caspase-9 and Caspase-3 of testicular tissue was detected using real-time quantitative fluorescence PCR and Western blot methods separately; and the positive expression of Cleaved Caspase-3 of the testicular tissue was detected using immunohistochemistry.
RESULTS:
Compared with the blank group, the mice were in listless spirits, had shaggy hairs, the reduced appetite and movement, and weight loss in the model group (P<0.01); the testicular mass and the weight coefficient decreased (P<0.01); the total number of sperms, sperm motility, and sperm viability were declined (P<0.01); while the levels of serum T, FSH, and LH were dropped (P<0.01). The morphology of seminiferous tubules in testicular tissue was abnormal, the number of spermatogenic cells and the number of mitochondria decreased, the inner mitochondrial crest was fractured and lost, and vacuoles appeared. The level of mitochondrial membrane potential was reduced (P<0.01); and the positive rate of apoptosis cell in testicular tissue increased (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was elevated (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 was dropped (P<0.01), and the average absorbance value of Cleaved Caspase-3 increased (P<0.01). When compared with the model group, in the acupuncture group, the general condition of mice was improved, the testicular mass and the weight coefficient elevated (P<0.01); the total number of sperms, sperm motility, and sperm viability increased (P<0.01); while the levels of serum T, FSH, and LH rose (P<0.01). The pathological morphology of testicular tissue and the inner mitochondrial ultra-microstructure were ameliorated, the level of mitochondrial membrane potential was elevated (P<0.01); the positive rate of apoptosis cell was reduced (P<0.01). The mRNA and protein expression of Bax, Cyt C, Apaf-1, Caspase-9 and Caspase-3 was dropped (P<0.01, P<0.05), the mRNA and protein expression of Bcl-2 elevated (P<0.05), and the average absorbance value of Cleaved Caspase-3 declined (P<0.01).
CONCLUSION
"Zhibian" (BL54)-toward- "Shuidao" (ST28) acupuncture may ameliorate mouse reproductive function by inhibiting mitochondrial apoptosis pathway, alleviating testicular tissue damage in the asthenospermia mice induced by cyclophosphamide.
Animals
;
Male
;
Mice
;
Apoptosis
;
Acupuncture Therapy
;
Mitochondria/metabolism*
;
Asthenozoospermia/genetics*
;
Humans
;
Testis/metabolism*
;
Mice, Inbred C57BL
;
Spermatozoa/metabolism*
;
Acupuncture Points
;
Sperm Motility
;
Testosterone/blood*
;
Proto-Oncogene Proteins c-bcl-2/genetics*
;
Caspase 3/genetics*
;
Follicle Stimulating Hormone/blood*
;
Reproduction
;
Cytochromes c/genetics*
;
bcl-2-Associated X Protein/genetics*
;
Apoptotic Protease-Activating Factor 1/genetics*
2.Mechanism research of "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique for improving reproductive function in mice with asthenospermia based on the ferroptosis pathway.
Jianheng HAO ; Boya CHANG ; Qingkai JIN ; Jia REN ; Haijun WANG ; Laixi JI
Chinese Acupuncture & Moxibustion 2025;45(3):351-360
OBJECTIVE:
To investigate the underlying mechanism of "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique for improving reproductive function in mice with asthenospermia by regulating ferroptosis pathway.
METHODS:
Sixty male C57BL/6 mice were randomly divided into a blank group, a model group, an acupuncture group and a Fer-1 group, 15 mice in each one. Except the blank group, the intraperitoneal injection with cyclophosphamide (50·kg-1·d-1) was administered to establish the asthenospermia model in the mice of the rest 3 groups for 5 consecutive days. In the acupuncture group, "Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique was operated in the mice, for 20 min each time; and in the Fer-1 group, Fer-1 solution (1 mg/kg) was injected intraperitoneally. The interventions of these two groups were delivered once daily and for 2 consecutive weeks. The testicular wet weight was measured and the testicular coefficient was calculated. Using sperm quality detection system, the sperm quality was detected. With ELISA used, the contents of testosterone (T), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum were detected. With HE staining, testicular and epididymal morphology was observed. Immunofluorescence was used to detect the expression of reactive oxygen species (ROS) in the testes. Biochemical assay was conducted to determine the contents of malondialdehyde (MDA), reduced glutathione (GSH), and total iron ion (TFe) in the testicular tissue. Transmission electron microscopy was used to examine mitochondrial structure of the testis, while JC-1 staining was used to assess mitochondrial membrane potential in the testicular tissue. Fluorescence quantitative PCR and Western blot analyses were employed to measure the mRNA and protein expression of solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and acyl-CoA synthetase long-chain family member 4 (ACSL4) in the testicular tissue.
RESULTS:
Compared with the blank group, in the model group, the testicular wet weight and testicular coefficient decreased (P<0.01); the sperm concentration and sperm motility reduced (P<0.01), and the contents of T, FSH, and LH decreased in the serum (P<0.01); and the seminiferous tubules in the testis showed loose structure and deformed lumen, sperm cells were disorganized and the sperm numbers reduced; the tubular walls became thinner, and sperm numbers in the lumen less; the expression of ROS in testicular tissue, as well as the contents of MDA and TFe increased (P<0.01), and the content of GSH decreased (P<0.01); and the numbers of mitochondria reduced, the structure of cristae was serious damaged, and mitochondrial membrane potential level declined (P<0.01); the mRNA and protein expression of SLC7A11, GPX4, and FTH1 decreased (P<0.01), while the mRNA and protein expression of ACSL4 increased (P<0.01). In comparison with the model group, the acupuncture and Fer-1 groups showed the increase of testicular wet weight and coefficient (P<0.01), sperm concentration and motility (P<0.01), and the serum contents of T, FSH, and LH (P<0.01); and the improvements in testicular and epididymal histopathology; ROS expression and the contents of MDA and TFe decreased (P<0.01), and the content of GSH elevated (P<0.05); the mitochondrial structure and numbers were ameliorated and mitochondrial membrane potential rose (P<0.01). Besides, in comparison with the model group, the mRNA expression of SLC7A11 was higher (P<0.05, P<0.01), the mRNA and protein expression of GPX4 and FTH1 increased (P<0.01, P<0.05), and the mRNA and protein expression of ACSL4 decreased (P<0.01) in the acupuncture and the Fer-1 groups; and the protein expression of SLC7A11 was higher in the Fer-1 group (P<0.05).
CONCLUSION
"Zhibian" (BL54)-toward-"Shuidao" (ST28) acupuncture technique may improve the reproductive capacity in the mice with asthenospermia by alleviating ferroptosis-induced cellular damage and ameliorating testicular function.
Animals
;
Male
;
Ferroptosis
;
Mice
;
Acupuncture Therapy
;
Mice, Inbred C57BL
;
Asthenozoospermia/metabolism*
;
Humans
;
Acupuncture Points
;
Testis/metabolism*
;
Luteinizing Hormone/metabolism*
;
Malondialdehyde/metabolism*
;
Reproduction
;
Testosterone/metabolism*
3.Efficacy and mechanism of Cistanches Herba extract in treating reproductive dysfunction in rats with kidney-Yang deficiency based on metabolomics.
Ze-Hui LI ; Pan-Yu XU ; Jia-Shan LI ; Li GUO ; Yuan LI ; Si-Qi LI ; Na LIN ; Ying XU
China Journal of Chinese Materia Medica 2025;50(7):1850-1860
This study investigates the reproductive protective effect and potential mechanism of Cistanches Herba extract(CHE) on a rat model of kidney-Yang deficiency induced by adenine. Rats were randomly divided into five groups: normal, model, low-dose CHE(0.6 g·kg~(-1)·d~(-1)), high-dose CHE(1.2 g·kg~(-1)·d~(-1)), and L-carnitine(100 mg·kg~(-1)·d~(-1)). The rats were administered adenine(200 mg·kg~(-1)·d~(-1)) by gavage for the first 14 days to induce kidney-Yang deficiency, while simultaneously receiving drug treatment. After 14 days, the modeling was discontinued, but drug treatment continued to 49 days. The content of components in CHE was analyzed by high-performance liquid chromatography. The adenine-induced kidney-Yang deficiency model was assessed through symptom characterization and measurement of testosterone(T) levels using an enzyme-linked immunosorbent assay kit. Pathological damage to the testis and epididymis was evaluated based on the wet weight and performing hematoxylin-eosin staining. Sperm density and motility were measured using computer-aided sperm analysis, and sperm viability was assessed using live/dead sperm staining kits, and sperm morphology was evaluated using eosin staining, thereby determining rat sperm quality. Metabolomics was used to analyze changes in serum metabolites, enrich related metabolic pathways, and explore the mechanism of CHE in improving reproductive function damage in rats with kidney-Yang deficiency syndrome. Compared to the normal group, the model group exhibited significant kidney-Yang deficiency symptoms, reduced T levels, decreased testicular and epididymal wet weights, and significant pathological damage to the testis and epididymis. The sperm density, motility, and viability decreased, with an increased rate of sperm abnormalities. In contrast, rats treated with CHE showed marked improvements in kidney-Yang deficiency symptoms, restored T levels, alleviated pathological damage to the testis and epididymis, and improved various sperm parameters. Metabolomics results revealed 286 differential metabolites between the normal and model groups(191 upregulated and 95 downregulated). Seventy-five differential metabolites were identified between the model and low-dose CHE groups(21 upregulated and 54 downregulated). A total of 24 common differential metabolites were identified across the three groups, with 22 of these metabolites exhibiting opposite regulation trends between the two comparison groups. These metabolites were primarily involved in linoleic acid metabolism, ether lipid metabolism, and pantothenic acid and coenzyme A biosynthesis, as well as metabolites including 13-hydroperoxylinoleic acid, lysophosphatidylcholine, and pantethine. CHE can improve kidney-Yang deficiency symptoms in rats, alleviate reproductive organ damage, and enhance sperm quality. The regulation of lipid metabolism may be a potential mechanism through which CHE improves reproductive function in rats with kidney-Yang deficiency. The potential bioactive compounds of CHE include echinacoside, verbascoside, salidroside, betaine, and cistanoside A.
Animals
;
Male
;
Rats
;
Yang Deficiency/physiopathology*
;
Metabolomics
;
Kidney/physiopathology*
;
Rats, Sprague-Dawley
;
Drugs, Chinese Herbal/administration & dosage*
;
Cistanche/chemistry*
;
Kidney Diseases/metabolism*
;
Testis/metabolism*
;
Humans
;
Reproduction/drug effects*
;
Testosterone/blood*
4.The SPARC-related modular calcium binding 1 ( Smoc1 ) regulated by androgen is required for mouse gubernaculum development and testicular descent.
Zhi-Yi ZHAO ; Yong SIOW ; Ling-Yun LIU ; Xian LI ; Hong-Liang WANG ; Zhen-Min LEI
Asian Journal of Andrology 2025;27(1):44-51
Testicular descent occurs in two consecutive stages: the transabdominal stage and the inguinoscrotal stage. Androgens play a crucial role in the second stage by influencing the development of the gubernaculum, a structure that pulls the testis into the scrotum. However, the mechanisms of androgen actions underlying many of the processes associated with gubernaculum development have not been fully elucidated. To identify the androgen-regulated genes, we conducted large-scale gene expression analyses on the gubernaculum harvested from luteinizing hormone/choriogonadotropin receptor knockout ( Lhcgr KO) mice, an animal model of inguinoscrotal testis maldescent resulting from androgen deficiency. We found that the expression of secreted protein acidic and rich in cysteine (SPARC)-related modular calcium binding 1 ( Smoc1 ) was the most severely suppressed at both the transcript and protein levels, while its expression was the most dramatically induced by testosterone administration in the gubernacula of Lhcgr KO mice. The upregulation of Smoc1 expression by testosterone was curtailed by the addition of an androgen receptor antagonist, flutamide. In addition, in vitro studies demonstrated that SMOC1 modestly but significantly promoted the proliferation of gubernacular cells. In the cultures of myogenic differentiation medium, both testosterone and SMOC1 enhanced the expression of myogenic regulatory factors such as paired box 7 ( Pax7 ) and myogenic factor 5 ( Myf5 ). After short-interfering RNA-mediated knocking down of Smoc1 , the expression of Pax7 and Myf5 diminished, and testosterone alone did not recover, but additional SMOC1 did. These observations indicate that SMOC1 is pivotal in mediating androgen action to regulate gubernaculum development during inguinoscrotal testicular descent.
Animals
;
Male
;
Mice
;
Testis/growth & development*
;
Mice, Knockout
;
Androgens/pharmacology*
;
Testosterone/pharmacology*
;
Receptors, LH/metabolism*
;
Calcium-Binding Proteins/metabolism*
5.Regulation of testosterone synthesis by circadian clock genes and its research progress in male diseases.
Gang NING ; Bo-Nan LI ; Hui WU ; Ruo-Bing SHI ; A-Jian PENG ; Hao-Yu WANG ; Xing ZHOU
Asian Journal of Andrology 2025;27(5):564-573
The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms. Testosterone, as one of the most critical sex hormones, is essential for the development of the reproductive system, maintenance of reproductive function, and the overall health of males. The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes. Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis. We also examined the specific effects of these genes on the occurrence, development, and treatment of common male diseases, including late-onset hypogonadism, erectile dysfunction, male infertility, and prostate cancer.
Testosterone/metabolism*
;
Humans
;
Male
;
Circadian Clocks/genetics*
;
Circadian Rhythm Signaling Peptides and Proteins/metabolism*
;
Circadian Rhythm/physiology*
;
Hypogonadism/metabolism*
;
Erectile Dysfunction/metabolism*
;
Infertility, Male/metabolism*
;
Prostatic Neoplasms/metabolism*
;
Men's Health
6.Wheat-grain moxibustion at the Guanyuan point to regulate low testosterone and hypothalamic-pituitary-gonadal axis in naturally aged mice.
Meng-Fan CUI ; Bing-Zhe MA ; Zhi-Yang YIN ; Yu-Tong QIAN ; Dan-Li JIAO ; Shi-Min LIU
National Journal of Andrology 2025;31(2):157-164
OBJECTIVE:
To investigate the effects of wheat-grain moxibustion at the Guanyuan point on testosterone (T) synthesis and the hypothalamic-pituitary-gonadal (HPG) axis in naturally aged mice.
METHODS:
We fed 40 twelve-month-old SPF male C57BL/6J mice with a normal diet for 3 months, randomized them into a moxibustion and an aged group of an equal number, and selected 7 four-month-old ones as young controls. We treated the animals of the moxibustion group by wheat-grain moxibustion at the Guanyuan point, once 5 moxibustion sticks, qd, 5 times a week, and fed those of the aged group normally, all for 12 weeks. After treatment, we obtained the testicular index of the mice, observed the histomorphology of the testis tissue by HE staining, measured the contents of T in the testis, gonadotropin-releasing hormone (GnRH) in the hypothalamus and total T (tT), free T (fT), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the serum by ELISA, and determined the expressions of silence information regulator-1 (SIRT1), P53, glutathione peroxidase (GPX4) and cholesterol side-chain?cleavage enzyme (CYP11A1) in the testis by Western blot.
RESULTS:
Compared with the young controls, the mice in the aged group showed obviously losing and dull hair, energy declination, loose structure of the spermatogenic tubule with different degrees of cell loss and rupture, reduced testicular index, and evident aging phenotype. In comparison with the aged mice, the animals of the moxibustion group were fairly energetic and exhibited distinct structure of the spermatogenic tubules, orderly arranged and highly differentiated cells at all levels, significantly increased T level, up-regulated expressions of SIRT1, GPX4 and CYP11A1, and down-regulated expression of P53 in testis tissue, and elevated levels of GnRH, FSH, LH, tT and fT in the HPG axis.
CONCLUSION
Wheat-grain moxibustion at the Guanyuan point protects testosterone synthesis in the testis tissue of naturally aged mice, promotes negative feedback regulation of the HPG axis, and improves low testosterone.
Animals
;
Male
;
Moxibustion
;
Mice
;
Testosterone/metabolism*
;
Mice, Inbred C57BL
;
Testis/metabolism*
;
Hypothalamo-Hypophyseal System/metabolism*
;
Triticum
;
Gonadotropin-Releasing Hormone/metabolism*
;
Luteinizing Hormone/blood*
;
Follicle Stimulating Hormone/blood*
;
Aging
;
Hypothalamus/metabolism*
;
Acupuncture Points
;
Sirtuin 1/metabolism*
;
Hypothalamic-Pituitary-Gonadal Axis
7.Hypoandrogenism and the mode of cell death in the penile cavernosum tissue of male rats.
Xin ZHAO ; Jing LI ; Rui JIANG
National Journal of Andrology 2025;31(4):291-299
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.
Animals
;
Male
;
Penis/cytology*
;
Rats
;
Rats, Sprague-Dawley
;
Apoptosis
;
Caspase 3/metabolism*
;
Caspase 1/metabolism*
;
Testosterone/blood*
;
Cell Death
;
Orchiectomy
8.Effect of high ligation of spermatic vein on leukocytes in expressed prostate secretion of patients with chronic prostatitis and varicocele.
Ji-Yang DING ; Peng ZHANG ; Chun-Hua NIU ; Hai-Yong LI ; Wen-Zhu XU ; Ying-Chen ZHANG ; Gang MA
National Journal of Andrology 2025;31(4):319-322
OBJECTIVE:
To investigate the effect of laparoscopic high ligation of spermatic cord vein in patients with chronic prostatitis and varicocele prostatitis.
METHODS:
A total of 90 varicocele patients were selected from January 2016 to December 2020, including 33 patients with chronic prostatitis. Changes of white blood cell count, National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score and serum testosterone level in the expressed prostate secretion (EPS) were observed before and after the operation of laparoscopic high ligation of spermatic vein.
RESULTS:
All patients were followed up three months after the surgery. There was no significant difference in the white blood cell counts in EPS, NIH-CPSI score, and serum testosterone level in patients with varicocele-only who underwent high ligation surgery after the operation. However, the white blood cell count in the EPS of patients with chronic prostatitis was lower than that before 3 months of operation ( [12.39±4.23]×109/L vs [21.36±5.05]×109/L). The NIH-CPSI score was significantly lower than that before operation ( [12.71±6.21] vs [26.76±8.43]). And the serum testosterone level was higher than that before operation ([4.34±1.77]ng/ml vs [2.36±1.05]ng/ml).
CONCLUSION
Laparoscopic high ligation of the spermatic vein in patients with chronic prostatitis and varicocele could effectively reduce the number of white blood cells in the EPS, boost the level of serum testosterone and improves symptoms of chronic prostatitis.
Male
;
Humans
;
Varicocele/surgery*
;
Prostatitis/blood*
;
Ligation
;
Spermatic Cord/blood supply*
;
Testosterone/blood*
;
Chronic Disease
;
Prostate/metabolism*
;
Veins/surgery*
;
Leukocyte Count
;
Leukocytes
;
Laparoscopy
;
Adult
9.The role of endogenous testosterone in relationship with low- and intermediate-risk prostate cancer: a systematic review.
Antonio Benito PORCARO ; Emanuele SERAFIN ; Davide BRUSA ; Sonia COSTANTINO ; Claudio BRANCELLI ; Maria Angela CERRUTO ; Alessandro ANTONELLI
Asian Journal of Andrology 2024;26(6):569-574
An enduring debate in research revolves around the association between elevated endogenous testosterone levels and prostate cancer. This systematic review is intended to assess the present understanding of the role of endogenous testosterone in the diagnosis and treatment of low- and intermediate-risk prostate cancer. Our search strategy was the following: (endogenous testosterone) AND (((low risk) OR (intermediate risk)) AND ((diagnosis) OR (treatment))) AND (prostate cancer); that was applied to PubMed, Web of Science, and Scopus databases to identify pertinent articles. Two investigators performed an independent selection following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The preliminary investigation detected 105 records, and 81 records remained after eliminating duplicates. Following the review of titles and abstracts, 71 articles were excluded. A comprehensive examination of the full text was conducted for 10 articles, excluding 3 of them. After revising the references of eligible articles, other 3 articles were included. We finally identified 10 suitable studies, including three main topics: (1) association between endogenous testosterone and European Association of Urology (EAU) risk classes; (2) association between endogenous testosterone density and the tumor load; and (3) association of endogenous testosterone with tumor upgrading and tumor upstaging. Actual literature about the impact of endogenous testosterone on low- and intermediate-risk prostate cancer is not numerous, but appears to be still conflicting. More investigations are needed to increase the consistency of the literature's results.
Humans
;
Male
;
Prostatic Neoplasms/metabolism*
;
Testosterone/metabolism*
;
Risk Factors
;
Neoplasm Grading
;
Tumor Burden
10.Mechanisms mediating the inhibitory effects of quercetin against phthalates-induced testicular oxidative damage in rats.
Lilan LIU ; Ruya DENG ; Wenjin ZHOU ; Min LIN ; Lingzi XIA ; Haitao GAO
Journal of Southern Medical University 2023;43(4):577-584
OBJECTIVE:
To explore the mechanism underlying the inhibitory effect of quercetin against testicular oxidative damage induced by a mixture of 3 commonly used phthalates (MPEs) in rats.
METHODS:
Forty male Sprague-Dawley rats were randomly divided into control group, MPEs exposure group, and MPEs with low-, median- and high-dose quercetin treatment groups. For MPEs exposure, the rats were subjected to intragastric administration of MPEs at the daily dose of 900 mg/kg for 30 consecutive days; Quercetin treatments were administered in the same manner at the daily dose of 10, 30, and 90 mg/kg. After the treatments, serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and testicular malondialdeyhde (MDA), catalase (CAT) and superoxide dismutase (SOD) were detected, and testicular pathologies of the rats were observed with HE staining. The expressions of nuclear factor-E2-related factor 2 (Nrf2), Kelch-like ECH2 associated protein 1 (Keap1) and heme oxygenase 1 (HO-1) in the testis were detected using immunofluorescence assay and Western blotting.
RESULTS:
Compared with the control group, the rats with MPEs exposure showed significant reductions of the anogenital distance, weight of the testis and epididymis, and the coefficients of the testis and epididymis with lowered serum testosterone, LH and FSH levels (P < 0.05). Testicular histological examination revealed atrophy of the seminiferous tubules, spermatogenic arrest, and hyperplasia of the Leydig cells in MPEs-exposed rats. MPEs exposure also caused significant increments of testicular Nrf2, MDA, SOD, CAT and HO-1 expressions and lowered testicular Keap1 expression (P < 0.05). Treatment with quercetin at the median and high doses significantly ameliorated the pathological changes induced by MPEs exposure (P < 0.05).
CONCLUSION
Quercetin treatment inhibits MPEs-induced oxidative testicular damage in rats possibly by direct scavenging of free radicals to lower testicular oxidative stress and restore the regulation of the Nrf2 signaling pathway.
Rats
;
Male
;
Animals
;
Testis
;
Quercetin/pharmacology*
;
Rats, Sprague-Dawley
;
NF-E2-Related Factor 2/metabolism*
;
Kelch-Like ECH-Associated Protein 1/metabolism*
;
Oxidative Stress
;
Testosterone/pharmacology*
;
Superoxide Dismutase/metabolism*
;
Follicle Stimulating Hormone
;
Luteinizing Hormone

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