Positive Effects of the Nutraceutical Association of Lycopene and Selenium in Experimental Varicocele.

Many natural substances commonly found in healthy diets have been studied for their potential to reduce male infertility associated with varicocele. A positive role of selenium (Se) or lycopene alone was demonstrated in experimental varicocele, while no data are available on their association. One group of male Sprague-Dawley rats was sham operated and daily treated with Se (3 mg/kg, i.p.), lycopene (1 mg/kg, i.p.), or their association. A second group underwent surgery to induce varicocele. Sham and half of the varicocele animals were sacrificed after twenty-eight days, while the residual animals were treated for one more month and then sacrificed. In varicocele animals, testosterone levels and testes weight were reduced, Hypoxia Inducible Factor-1α (HIF-1α) expression was absent in the tubules and increased in Leydig cells, caspare-3 was increased, seminiferous epithelium showed evident structural changes, and many apoptotic germ cells were demonstrated with TUNEL assay. The treatment with lycopene or Se alone significantly increased testis weight and testosterone levels, reduced apoptosis and caspase-3 expression, improved the tubular organization, decreased HIF-1α positivity of Leydig cells, and restored its tubular positivity. Lycopene or Se association showed a better influence on all biochemical and morphological parameters. Therefore, the nutraceutical association of lycopene plus Se might be considered a possible therapeutic tool, together with surgery, in the treatment of male infertility. However, long-term experimental and clinical studies are necessary to evaluate sperm quantity and quality.

Zishen Yutai Pill improves sperm quality and reduces testicular inflammation in experimental varicocele rats.

Objective: Zishen Yutai Pill (ZYP), containing 15 Chinese traditional medicine, is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction. The current study was designed to investigate the therapeutic effects of ZYP on sperm quality and testis in varicocele (VC) rats. Materials and methods: Male Wistar rats were randomly divided into four groups (n = 6), i.e., a sham group, a VC group, and VC groups treated with different dose of ZYP (1575 and 3150 mg/kg/d, respectively). The experimental VC model was established by partial ligation of left renal vein. Six weeks after model establishment, ZYP was orally administered once a day for the next 6 weeks. Parameters relating to testis and sperm quality were assessed. Hematoxylin-eosin staining was used to showed testicular tissue damage in experimental VC rats. Expressions of proteins relating to NLRP3 inflammasome pathways were determined using Western blot (WB). The mRNA expressions of relating genes were determined using quantitative real-time PCR (qRT-PCR) analysis. Results: ZYP could significantly improve sperm motility and decrease sperm DNA fragmentation index in VC rats (P < 0.05). Hematoxylin-eosin (HE) staining showed that ZYP could alleviate testicular tissue damage caused by experimental varicocele in rats. Compared to the VC model, expressions of NLRP3, ASC, and caspase-1 in rats treated with ZYP were significantly down-regulated, as validated by both qRT-PCR and WB analysis (P < 0.05). Conclusions: In brief, ZYP could improve sperm DNA integrity by inhibiting the NLRP3 inflammasome pathway and alleviating the chronic inflammation of testicular tissue induced by experimental varicocele in rats.

[Observation of effect of Wu Yun Liu Qi on reproductive hormones in varicocele patients].

Objective： To observe roproductive hormone levels in varicocele patients during a cycle (6 years) of Wu Yun Liu Qi, and explore whether the cycle had effect on the roproductive hormone levels. Methods： Data of roproductive hormone levels in varicocele patients from 2015 to 2020 were analyzed retrospectively. FSH、LH、T、PRL、E2 levels and T/E2 ratio were compared among the six years. According to Chinese sexagenary cycle heavenly stems and earthly branches of each year from 2015 to 2020 its yunqi characteristics were determined. Results: Totally data of 848 cases of varicocele patients were collected from 2015 to 2020. Among which, in 2015 (Yiwei year) there were 57 cases, in 2016 (Bingshen year) 83 cases, in 2017 (Dingyou year ) 133 cases, in 2018(Wuxu year) 156 cases, in 2019(Sihai year) 274 cases, and in 2020(Gengzi year) 145 cases. The levels of FSH、LH、PRL、T were not diferrent statistically from the six years except individual year. However, the level of E2 in 2016 when the Yunqi was Shao Yang Xiang Huo Si Tian and Jue Yin Feng Mu Zai Quan obviously higher than other years excpet 2018( All P< 0.05). And T/E2 ratio was lower in 2016 than other years except 2018 and 2020( All P< 0.05). Conclusions: Shi Xiang factors of Wu Yun Liu Qi had effect on roproductive hormone levels in varicocele patients, showing by higher E2 level in Yinshen year when the Shi Xiang factors may have bad effect on human fertility.

[The application of acupuncture in varicocele infertility based on " Visceral Collateral " theory].

The occurrence of varicocele infertility can be attributed to the small and flexural spermatic plexus which constitutes the main structure of spermatic cord.Obstruction of blood circulation, stagnation of qi and blood, ultimately leading to infertility. The spermatic plexus ' physiological and pathological symptoms are consistent with the theory of visceral collateral. Based on the theory of visceral collaterals, the varicocele infertility caused by stagnation of liver collateral and deficiency of kidney collateral. And the acupuncture is used to directly act on the relevant points on the meridians, so as to dredge the meridians, strengthen the healthy and expel the evil, and harmonize the yin and yang of visceral, which is more in line with the therapeutic principle of " unblocking the meridians " for collateral diseases. For varicocele infertility caused by liver meridian stasis, it can regulate the liver meridian Chong Ren, eliminate blood stasis and promote stagnation, and be combined with LR3, LI4, GB34, SP6, CV3. For varicocele infertility caused by kidney deficiency and meridian syndrome, it can tonify the kidney meridian Du Yang, warm and disperse the essence, and mainly focus on GV4, CV4, KI3, BL23 and BL43.

Add-on effects of oral tocopherol supplementation to surgical varicocelectomy on the outcome of assisted reproductive technology: a single-center pilot study report.

Introduction: Varicocelectomy is well known to improve the pregnancy outcome of patients with clinical varicoceles in assisted reproductive technologies as well as spontaneous conception. Therefore, this study aimed to evaluate the additional effects of oral antioxidant therapy after varicocelectomy on the pregnancy outcome in the assisted reproductive technology setting. Methods: This study was a retrospective cohort study. The subjects were couples among whom the male partner had undergone varicocelectomy and was scheduled for subsequent assisted reproductive technology. Pregnancy outcomes were followed retrospectively in 62 couples with male partners who received tocopherol (antioxidant group) and 37 couples who did not (control group). The tocopherol and control groups were assigned dependent on the decision of the physician in charge and the patient's request. The clinical pregnancy rates per couple and embryo transfer, time to pregnancy, and the number of cycles during transfer to pregnancy were evaluated. Results: No significant differences were observed in the pregnancy rate per couple (antioxidant group 70.9% vs. control group 64.9%, P = 0.55) and per embryo transfer (50.4% vs. 39.6%, P = 0.22). Regarding the time to event analyzed by adjusted restricted mean survival time, the mean time to pregnancy was significantly shorter in the antioxidant (tocopherol) group (14.2 vs. 17.4 months, P = 0.025). No significant difference was observed in the embryo transfer cycle to pregnancy (mean embryo transfer cycles: 2.6 vs. 3.0, P = 0.238). Conclusions: Additional oral tocopherol nicotinate as antioxidant therapy after varicocelectomy was shown to shorten the time to pregnancy. It is recommended that add-on effects be tested in more well-designed randomized controlled trials to examine whether it improves assisted reproductive outcomes.

Effects of alpha-lipoic acid on sperm quality in patients with varicocele-related male infertility: study protocol for a randomized controlled clinical trial.

BACKGROUND: Varicocele is a high incidence and is considered to be the most common and correctable cause of male infertility. Oxidative stress (OS) plays a central role in the pathogenesis of varicocele-related male infertility. In addition to varicocelectomy, antioxidant supplementation seems to be an effective scheme for the treatment of varicocele-related male infertility, but it is still controversial. The purpose of this study is to determine the effects of alpha-lipoic acid (ALA) supplementation on sperm quality in patients with varicocele-related male infertility. METHODS: In this randomized controlled clinical trial, we will randomize 80 patients with varicocele-related male infertility from Guilin People's Hospital. The non-surgical observation group (n = 20) will receive ALA, the non-surgical control group (n = 20) will receive vitamin E, the surgical observation group (n = 20) will receive ALA after the operation, and the surgical control group (n = 20) will receive vitamin E after the operation. The course of treatment will be 3 months. The results will compare the changes in semen parameters, sex hormones, testicular volume, sperm DNA fragment index (DFI), seminal plasma malondialdehyde (MDA), and total antioxidant capacity (TAC) between the groups at baseline and after 3 months of antioxidant supplementation. DISCUSSION: Whether it is necessary to use antioxidants in varicocele-related male infertility, how potent antioxidants should be used, postoperative application or non-surgical independent application still needs to be explored. This study attempts to compare the effects of two antioxidants (ALA and vitamin E) on sperm quality in patients with varicocele-related male infertility (surgical or non-surgical) and attempted to answer the above questions. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100054958. Registered on 29 December 2021.

Varicocele, Functional Foods and Nutraceuticals: From Mechanisms of Action in Animal Models to Therapeutic Application.

Varicocele is one of the main causes of infertility in men, thus representing an important clinical problem worldwide. Inflammation contributes mainly to its pathogenesis, even if the exact pathophysiological mechanisms that correlate varicocele and infertility are still unknown. In addition, oxidative stress, apoptosis, hypoxia, and scrotal hyperthermia seem to play important roles. So far, the treatment of varicocele and the care of the fertility-associated problems still represent an area of interest for researchers, although many advances have occurred over the past few years. Recent experimental animal studies, as well as the current epidemiological evidence in humans, demonstrated that many functional foods of natural origin and nutraceuticals that are particularly abundant in the Mediterranean diet showed anti-inflammatory effects in varicocele. The aim of the present narrative review is to mainly evaluate recent experimental animal studies regarding the molecular mechanisms of varicocele and the state of the art about possible therapeutic approaches. As the current literature demonstrates convincing associations between diet, food components and fertility, the rational intake of nutraceuticals, which are particularly abundant in foods typical of plant-based eating patterns, may be a reliable therapeutic supportive care against varicocele and, consequently, could be very useful in the cure of fertility-associated problems in patients.

The Role and Place of Antioxidants in the Treatment of Male Infertility Caused by Varicocele.

The inability to become pregnant for at least 1 year despite regular unprotected intercourse may indicate infertility of one or both partners. This problem affects approximately 10-20% of couples worldwide, regardless of race, with male infertility reported to account for 25-60% of cases. Among the most common pathological causes of male infertility is the presence of varicocele and chronic infections of the male reproductive system. This study was performed using data collected at the Genesis Infertility Treatment Clinic, Bydgoszcz, Poland, between 1 January 2015 and 30 June 2017. A total of 163 men meeting the inclusion criteria were selected and divided into the idiopathic infertility group (78 men) and varicocele-related infertility group (85 men). All patients received treatment with a male fertility supplement containing a combination of 1725 mg of L-carnitine fumarate, 500 mg of acetyl-L-carnitine, 90 mg of vitamin C, 20 mg of coenzyme Q10, 10 mg of zinc, 200 µg of folic acid, 50 µg of selenium, and 1.5 µg of vitamin B12 (Proxeed® Plus, Sigma-Tau, Italy) twice a day for a period of 6 months from the time of the diagnosis of infertility. The treatment resulted in significant improvements in general semen parameters, particularly sperm count, sperm concentration, total motility, and progressive motility. This antioxidant therapy produced a particularly marked therapeutic benefit in patients with Grade III varicocele, with a greater improvement in progressive motility than in men with less severe or no varicocele. The use of the antioxidant preparation examined here seems reasonable in men with idiopathic infertility and as an adjuvant in those with varicocele-related infertility in whom surgical treatment has resulted in no improvement. Its use should be considered particularly in patients with Grade III varicocele who do not wish to undergo surgical treatment or in whom such a treatment is not possible for various reasons.

Exploring the mechanisms of Gui Zhi Fu Ling Wan on varicocele via network pharmacology and molecular docking.

Varicocele (VC) is a common urogenital disease that leads to a high risk of testicular pain or male infertility. The purpose of this research was to explore the molecular mechanism of the Gui Zhi Fu Ling Wan (GFW) in the treatment of VC. The main active ingredients and targets information of GFW were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and the targets related to VC were determined by GeneCards, Online Mendelian Inheritance in Man (OMIM), and Disease Gene Network (DisGeNET) databases. The intersection of active ingredient targets and disease targets was selected to construct a protein-protein interaction (PPI) network through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Based on the use of CytoNCA plug-in to find the main targets, a 'component-target-disease' network was constructed by Cytoscape 3.8.2. Metascape was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of drug and disease targets. Molecular docking was employed to investigate the binding interaction between the main active components and core targets. A total of 76 active components of GFW were screened out. The main targets of the active components on VC were tumour protein p53 (TP53), tumour necrosis factor (TNF), hypoxia inducible factor 1 subunit alpha (HIF1A), interleukin-6 (IL-6), caspase 3 (CASP3), catalase (CAT), prostaglandin-endoperoxide synthase 2 (PTGS2), vascular endothelial growth factor A (VEGFA). The PI3K-Akt signalling pathway, HIF-1 signalling pathway, and apoptosis signalling pathway were mainly involved in the regulation of VC. The results of molecular docking showed that the binding potential and activity of the main active components and the core targets of GFW were good. We found that GFW could alleviate apoptosis, participate in venous vessel morphogenesis, and reduce oxidative stress in the treatment of VC. This study can provide a reference for subsequent clinical and scientific research experiments, which can be used to design new drugs and develop new therapeutic instructions to treat VC.

The efficacy and mechanism of acupuncture in the treatment of male infertility: A literature review.

Fertility, a social, cultural, and medical issue, has aroused public attention because of its potential to predict future health. In recent years, the incidence of male infertility has increased significantly, and various risk factors, such as congenital factors, acquired factors, and idiopathic factors, have led to this situation. Male infertility causes substantial psychological and social distress in patients. With the implementation of the two-child policy, male infertility has brought enormous psychological and social pressure and huge economic burden to patients and the healthcare system. This has attracted the attention of not only men of childbearing age but also many male experts. The conventional therapeutic approaches for treating male infertility, including drugs, varicocele surgery, intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection, can restore fertility to a certain extent, but their efficacy is far from satisfactory, not to mention some adverse events. Therefore, acupuncture has been chosen by many men to treat their infertility and produced significant effects. In the present paper, the efficacy and mechanism of acupuncture in the treatment of male infertility were analyzed from different perspectives such as regulating hormone secretion, reducing inflammation, and improving semen parameters. The existing literature shows that acupuncture can effectively treat male infertility.

Improvement in sperm quality by oral antioxidant supplementation in infertile men with varicocele who have not undergone surgical repair: Systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess whether oral antioxidant supplementation improves sperm quality in men with infertility and varicocele (VCL) who have not undergone surgical repair. In men with infertility and VCL who had not undergone surgical repair oral antioxidant supplementation significantly increased sperm concentration (WMD +5.86 × 106 /ml 95% CI: +1.47 to +10.24, p < 0.01; random effects model, six studies, 213 patients), total motility (WMD + 3.76%, 95% CI: +0.18 to +7.34, p = 0.04; random effects model, three studies, 93 patients), progressive motility (WMD + 6.38%, 95% CI: +3.04 to +9.71, p < 0.01; random effects model, three studies, 84 patients) and seminal volume (WMD +0.55 ml, 95%CI: +0.06 to +1.04, p = 0.03; random effects model, four studies, 120 patients). On the other hand, no significance difference was observed in sperm morphology (WMD +3.89%, 95% CI: -0.14 to +7.92, p = 0.06; random effects model, five studies, 187 patients). In conclusion, limited evidence suggests that the use of oral antioxidants in men with infertility and VCL, who have not undergone surgical repair improves their seminal volume, sperm concentration, total and progressive motility.

Melatonin epigenetic potential on testicular functions and fertility profile in varicocele rat model is mediated by silent information regulator 1.

BACKGROUND AND PURPOSE: Varicocele is a leading cause of male infertility. Melatonin is a highly pleiotropic neurohormone. We aimed to characterize the melatonin epigenetic potential in varicocele and the involved molecular mechanisms. EXPERIMENTAL APPROACH: Fifty-two male albino rats were randomly divided into four groups (13 rats each): control (I), melatonin (II), varicocele (III) and melatonin treated varicocele (IV) groups. Left varicocele was induced by partial left renal vein ligation. Reproductive hormones, epididymal sperm functional parameters, testicular 3/17 ß-hydroxysteroid dehydrogenases, antioxidant enzymes, malondialdehyde, nicotinamide adenine dinucleotide phosphate oxidase, 8-hydroxy-2'-deoxyguanosine and histopathological/Johnsen's score were evaluated. Flow cytometry and Comet were carried out to explore extent of sperm and testicular DNA damage. Testicular expression of silent information regulator 1 (SIRT1), forkhead transcription factors-class O (type1) (FOXO1), tumour suppressor gene, P53, cation channels of sperm (CatSper) and steroidogenic acute regulatory protein was evaluated by western blot technique. Testicular expression of Bcl-2 and its associated X protein and nuclear factor kappa-light-chain-enhancer of activated B cells were assayed by immunohistochemical staining. Testicular miR-34a expression was quantified by quantitative reverse transcription-polymerase chain reaction. KEY RESULTS: The varicocele induced testicular histological injury, enhanced oxidative stress, P53-mediated apoptosis, DNA damage and increased testicular miR-34a expression paralleled with down-regulated SIRT1/FOXO axis. Melatonin treatment of varicocele rats displayed antioxidant/anti-apoptotic efficacy and improved reproductive hormones axis, CatSper expression and fertility parameters. MiR-34a/SIRT1/FOXO1 epigenetic axis integrates testicular melatonin mediated intracellular transduction cascades in varicocele. CONCLUSION AND IMPLICATIONS: Melatonin can be used as an adjuvant therapy to improve varicocele and its complication.

[Danhong Tongjing Prescription versus microsurgery in the treatment of varicocele-induced infertility: A retrospective multivariate analysis of 218 cases].

OBJECTIVE: To compared the traditional Chinese medicine Danhong Tongjing Prescription (DTP) and microsurgery in the treatment of varicocele (VC)-induced infertility and investigate the factors influencing the recovery of semen parameters of the patients. METHODS: We retrospectively analyzed the clinical data on 218 cases of VC-induced infertility with qi-deficiency and blood-stasis treated with DTP (n = 86) or by microsurgery (n = 132) in our hospital from January 2017 to July 2019, and compared the semen parameters between the two groups of patients after treatment. With age, course of disease, degree of VC, change of the testis volume, estrogen/testosterone (E/T) ratio and levels of FSH and LH as independent variables, and increased semen parameters after treatment as dependent variables, we constructed a multivariate linear regression model and identified statistically significant independent variables. RESULTS: After treatment, sperm concentration and the percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS) were obviously improved in both the DTP and microsurgery groups, with statistically significant difference between the two groups in sperm concentration and MNS, but not in PMS. Linear regression analysis showed that the severity of VC was an influencing factor for the recovery of sperm concentration after treatment in the DTP group (r = －11.599, Ra2 = 0.044 9) and the course of VC infertility was a factor affecting the recovery of sperm count in the microsurgery group (r = －1.837, Ra2 = 0.035 7). CONCLUSION: DTP is comparable to microsurgery in improving sperm motility while microsurgery is more effective in increasing the percentage of MNS in the treatment of VC-induced infertility. Early surgery is recommended for the treatment of infertility induced by severe bilateral VC, and DTP can be selected for infertility caused by mild or moderate bilateral VC if the patient is unwilling to accept surgery or microsurgery is inaccessible in the hospital.

Effect of keishibukuryogan combined with tocopherol nicotinate on sperm parameters in patients with a varicocele.

OBJECTIVE: To evaluate the efficacy of keishibukuryogan, a traditional Kampo formula known to be an anti-Oketsu (impaired microcirculation and non-physiological blood congestion) drug, in combination with an anti-oxidant for the treatment of varicoceles. METHODS: We retrospectively analyzed 119 patients with palpable and subclinical varicoceles who were treated with 7.5 g/day of keishibukuryogan and 600 mg/day of tocopherol nicotinate. Their motile sperm concentrations at the start of medication and after 3 months were compared. As a subgroup analysis, a comparison test was carried out between patients with a high-grade varicocele and those with a low-grade varicocele. RESULTS: The mean age of the study patients was 35.6 years. Among them, 17, 41, 44 and 17 had subclinical, grade 1, grade 2 and grade 3 varicoceles, respectively. Overall, the differences in motile sperm concentration (millions/mL) before and after treatment were not significant (median 0.58, 95% confidence interval -0.12 to 1.56; P = 0.115). The results of the subgroup analysis showed that the motile sperm concentration in patients with a low-grade varicocele significantly increased (median 1.21, 95% confidence interval 0.45-2.47; P = 0.024); however, no significant improvements were seen in patients with a high-grade varicocele. CONCLUSIONS: The results of the present study showed that the combination of keishibukuryogan and an anti-oxidant had a limited effect on varicoceles, but they suggest that it is effective for the treatment of low-grade varicoceles.

Treatment of subclinical varicocele with acupuncture: A case report.

Varicocele is a vascular lesion characterized by abnormal dilatation and/or tortuosity of the veins of the pampiniform plexus, which sometimes manifests as chronic, dull pain in the scrotum, testicle or inguinal area. Subclinical varicocele (SCV) is as an early phase in the progression of its clinical analog. Given the lack of relevant studies on treatment strategies, no conclusive answer exists regarding how SCV should be managed. In this case report, a 40-year-old male patient visited our acupuncture outpatient clinic for left-sided scrotal pain and heaviness caused by SCV. After ten sessions of acupuncture treatments (acupuncture was performed at Zhongji (CV3), Guanyuan (CV4), qihai (CV6) and bilateral Guilai (ST29), Hegu (LI4), Taichong (LR3), Zusanli (ST36), Sanyinjiao (SP6), with electroacupuncture (EA) stimulation at Qihai (CV6) and Zhongji (CV3) as well as Guilai (ST29) on both sides), the patient was symptom-free. More unexpectedly, ultrasound reexamination showed no obvious abnormalities in bilateral spermatic veins. From this case, we conclude that acupuncture may be an effective alternative therapy for SCV treatment.

[Morinda officinalis how extract up-regulates the expression of SPAG11T and inhibits that of miR-210 in the testis tissue of varicocele rats].

OBJECTIVE: To investigate the effects of morinda officinalis how (MOH) on SPAG11T and microRNA-210 (miR-210) in the testis tissue of SD rats with varicocele (VC). METHODS: Forty SD rats were randomly divided into four groups of an equal number: blank control, VC model control, low-dose MOH and high-dose MOH. The rats in the former two groups were treated intragastrically with normal saline and those in the latter two with MOH extract at 200 and 400 mg/kg/d, respectively, all for 30 days. Then, the testis tissues of the rats were harvested for measurement of the levels of SOD, MDA and AI and determination of the expressions of vimentin, sperm-associated antigen 11T (SPAG11T) protein and RNA, and miR-210. RESULTS: There were no statistically significant differences in the testicular and epididymal weights among the four groups of rats (P > 0.05). Compared with the rats in the VC model control group, those in the MOH groups showed a remarkably increased SOD content (P < 0.05) but a decreased MDA level and AI in the testis tissue (P < 0.05). The expression of vimentin mRNA in the testis tissue was significantly reduced in the VC model control in comparison with that in the blank control group (0.18 ± 0.03 vs 1.00 ± 0.02), but dramatically up-regulated after treated with low-dose MOH (0.68 ± 0.07) and high-dose MOH (0.92 ± 0.08) (F = 432.901, P< 0.01). The level of SPAG11T mRNA was also remarkably decreased in the VC model control group compared with the blank controls (0.32 ± 0.04 vs 1.00 ± 0.05), but markedly elevated after treated with low-dose MOH (0.61 ± 0.09) and high-dose MOH (0.82 ± 0.13) (F = 117.423, P< 0.01). The level of testicular miR-210, however, was significantly increased in the VC model controls compared with the blank controls (1.39 ± 0.12 vs 1.00 ± 0.06), but decreased in both the low-dose MOH (1.17 ± 0.08) and high-dose MOH groups (1.09 ± 0.08) (F = 36.136, P< 0.01). CONCLUSIONS: MOH extract can up-regulate the expressions of vimentin and SPAG11T and inhibit that of miR-210 in the testis tissue of varicocele rats.

[Antagonistic effect of modified Dahuang Zhechong Granule against the apoptosis of epididymal spermatogenic cells in varicocele rats based on Nrf2/HO-1 pathways].

OBJECTIVE: To investigate the effects of modified Dahuang Zhechong Granule (DZG) on the epididymal tissue of varicocele (VC) rats and the expressions of the nuclear factor erythroid 2 (NF-E2)-related factor (Nrf2) and heme oxygenase-1 (HO-1) protein. METHODS: Sixty SD rats were randomly divided into six groups of an equal number: sham operation, VC model control, aescuven forte (AF) and low-, medium- and high-dose DZG. The VC model was established by ligation of the left renal vein with the Turner's method, followed by intragastrical administration of normal saline to the rats in the sham operation and VC model control groups, AF Tablets at 54 mg/kg to those in the AF group, and modified DZG at 0.6, 1.2 and 2.4 g/ml to those in the low-, medium- and high-dose DZG groups respectively, all once daily for 8 weeks. Then, all the animals were sacrificed and their left epididymides harvested for examination of semen quality, observation of local ultrastructural changes, measurement of the apoptosis of spermatogenic cells by Annexin V-FITC, and determination of the expressions of Nrf2 and HO-1 in the epididymal tissue by immunohistochemistry. RESULTS: Evident pathological damage was observed in the left epididymal tissue of the VC model controls, with significantly reduced numbers of spermatogenic cells and sperm at all levels, partially destroyed cellular structure, and disappearance of some subcellular structures such as the lysosome, mitochondrion, endoplasmic reticulum, nucleus and cell membrane, which were all improved to some extent in the DZG and AF group. Sperm concentration and motility in the left epididymis were significantly higher in the medium- and high-dose DZG and AF groups than in the VC model controls (P < 0.05), even more significantly in the high-dose DZG than in the AF group (P < 0.05). The apoptosis rate of spermatogenic cells was markedly higher in the VC model control than in the sham operation group (P < 0.05), but lower in the medium- and high-dose DZG and AF groups than in the VC model controls (P < 0.05). Immunohistochemistry showed positive expressions of Nrf2 and HO-1 proteins, brown, scattered and with a low luminance of the cells, in the left epididymis tissue of the VC model control rats, but with a significantly higher cell luminance in the high-dose DZG and AF groups. CONCLUSIONS: Modified Dahuang Zhechong Granule can effectively repair pathological damage to the epididymis of varicocele rats, increase the expressions of Nrf2 and HO-1 proteins, antagonize the apoptosis of spermatogenic cells and provide a favorable condition for sperm maturation.

[Danhong Tongjing Prescription improves sperm quality in patients with bilateral varicocele after varicocelectomy].

OBJECTIVE: To investigate the effect of Danhong Tongjing Prescription (DTP) on sperm quality in patients with bilateral varicocele (VC) after microsurgical varicocelectomy. METHODS: We randomly assigned 68 patients with bilateral VC to receive microsurgical varicocelectomy (the control group, n = 34) or microsurgical varicocelectomy followed by oral administration of DTP for a course of 90 days (the DTP group, n = 34). Before and after treatment, we obtained the sperm concentration, total sperm count, total sperm motility, the percentage of progressively motile sperm (PMS), sperm acrosomal enzyme activity, inhibin B (Inh-B) level, and sperm DNA fragmentation index (DFI) from the patients and compared the parameters between the two groups. RESULTS: There were no statistically significant differences in sperm concentration, PMS, acrosomal enzyme activity or sperm DFI among the patients with different degrees of VC preoperatively. After 3 months of medication, sperm concentration, total sperm count, total sperm motility, PMS and acrosomal enzyme activity were all increased while DFI decreased in both the control and DTP groups, even more significantly in the DTP group than in the control, and the Inh-B level was also markedly elevated in the DTP group in comparison with the baseline. CONCLUSIONS: The severity of bilateral VC is not correlated with the reduction of semen quality. DTP can improve sperm quality by improving total sperm count, PMS and acrosomal enzyme activity and reducing DFI in VC patients after varicocelectomy. The underlying mechanisms of the prescription may be related to its anti-oxidative stress action and abilities of improving reproductive hypoxia, spermatogenic environment and the function of Sertoli cells, but the specific signaling pathway involved is not yet clear.

lncRNA and mRNA sequencing of the left testis in experimental varicocele rats treated with Morinda officinalis polysaccharide.

Varicocele is a common disease of the male reproductive system. Morinda (M.) officinalis is a Chinese herbal medicine, whose main bioactive component M. officinalis polysaccharide (MOP) is believed to have a therapeutic effect on varicocele; however, the underlying molecular mechanisms of this effect are poorly understood. In the present study, 24 rats were randomly divided into three groups: i) Control group; ii) experimental varicocele group; and iii) 300 mg/kg MOP administration group. Analysis of mRNA and long non-coding RNA (lncRNA) expression in rat left testicular tissue was performed. The results suggested that a total of 144 mRNAs and 63 lncRNAs, 63 mRNAs and 148 lncRNAs, and 173 mRNAs and 54 lncRNAs were differentially expressed between the varicocele non-treatment and control groups, the varicocele treatment and varicocele non-treatment groups, and the varicocele treatment and control groups, respectively. Following validation by reverse transcription-quantitative PCR, the Yip1 domain family member 7 (YIPF7) gene was identified as a key mediator of varicocele pathogenesis and repair effect of MOP. Additionally, genes such as purinergic receptor P2X 4 (P2RX4), transmembrane protein 225B (TMEM255B) and Wnt family member 9B (WNT9B) were confirmed to be differentially expressed between the varicocele non-treatment and control groups. We hypothesize that TMEM255B could be a potential novel diagnostic biomarker for varicocele; WNT9B and P2RX4 likely play notable roles in the pathophysiology of the disease through the Wnt signaling pathway and regulation of transmembrane ion channels, respectively. In summary, the present study delineated the molecular mechanisms underlying varicocele pathogenesis and the therapeutic effect of MOP, identified a potential novel diagnostic marker and therapeutic target for varicocele, and provided feasible directions for further studies in the future.

Vitamins as primary or adjunctive treatment in infertile men with varicocele: A systematic review.

OBJECTIVE: To investigate the usage and the efficacy of vitamins as primary or adjuvant treatment in infertile men with varicocele. METHODS: A systematic search in PubMed, the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Cochrane Library with the terms (varicocele) AND (vitamins) was performed. We searched for studies: a) reporting the administration of vitamins (individually or as part of a complex) in men with varicocele and infertility, b) primarily or adjuvant to invasive treatment, and c) reporting the impact on semen parameters and/or pregnancy rates. Exclusion criteria were animal, adolescent and non-English studies, grey literature and trials reporting abstracts only. RESULTS: Seven studies were identified eligible for qualitative analysis. All studies were randomised except one (case series). Vitamins were administered dominantly as part of antioxidant complex and only two studies used vitamins (C and E, respectively) as sole agent. In two studies, vitamin monotherapy resulted in improvement in semen quality, but the effect on pregnancy rates is unknown. One study reported no efficacy of adjuvant multivitamin treatment after embolisation in terms of both semen quality and pregnancy rates. Finally, four studies reported a positive effect of vitamins on semen parameters after varicocelectomy, but the effect on pregnancy rates is conflicting; one study reported improved pregnancy rates with adjuvant treatment, two studies did not evaluate the pregnancy rates, and in one study the outcome was unclear due to missing data. CONCLUSIONS: Vitamins have been used mostly as part of an antioxidant panel for the management of infertile men with varicocele. Most studies have found a positive impact on semen parameters in selected men with varicocele and infertility, as primary or adjuvant treatment. However, the clinical benefit of vitamins administration on pregnancy rate is under-evaluated and should be the target of future research.