Single-cell RNA sequencing reveals transcriptomic landscape and potential targets for human testicular ageing.

STUDY QUESTION: What is the molecular landscape underlying the functional decline of human testicular ageing? SUMMARY ANSWER: The present study provides a comprehensive single-cell transcriptomic atlas of testes from young and old humans and offers insights into the molecular mechanisms and potential targets for human testicular ageing. WHAT IS KNOWN ALREADY: Testicular ageing is known to cause male age-related fertility decline and hypogonadism. Dysfunction of testicular cells has been considered as a key factor for testicular ageing. STUDY DESIGN, SIZE, DURATION: Human testicular biopsies were collected from three young individuals and three old individuals to perform single-cell RNA sequencing (scRNA-seq). The key results were validated in a larger cohort containing human testicular samples from 10 young donors and 10 old donors. PARTICIPANTS/MATERIALS, SETTING, METHODS: scRNA-seq was used to identify gene expression signatures for human testicular cells during ageing. Ageing-associated changes of gene expression in spermatogonial stem cells (SSCs) and Leydig cells (LCs) were analysed by gene set enrichment analysis and validated by immunofluorescent and functional assays. Cell-cell communication analysis was performed using CellChat. MAIN RESULTS AND THE ROLE OF CHANCE: The single-cell transcriptomic landscape of testes from young and old men was surveyed, revealing age-related changes in germline and somatic niche cells. In-depth evaluation of the gene expression dynamics in germ cells revealed that the disruption of the base-excision repair pathway is a prominent characteristic of old SSCs, suggesting that defective DNA repair in SSCs may serve as a potential driver for increased de novo germline mutations with age. Further analysis of ageing-associated transcriptional changes demonstrated that stress-related changes and cytokine pathways accumulate in old somatic cells. Age-related impairment of redox homeostasis in old LCs was identified and pharmacological treatment with antioxidants alleviated this cellular dysfunction of LCs and promoted testosterone production. Lastly, our results revealed that decreased pleiotrophin signalling was a contributing factor for impaired spermatogenesis in testicular ageing. LARGE SCALE DATA: The scRNA-seq sequencing and processed data reported in this paper were deposited at the Genome Sequence Archive (https://ngdc.cncb.ac.cn/), under the accession number HRA002349. LIMITATIONS, REASONS FOR CAUTION: Owing to the difficulty in collecting human testis tissue, the sample size was limited. Further in-depth functional and mechanistic studies are warranted in future. WIDER IMPLICATIONS OF THE FINDINGS: These findings provide a comprehensive understanding of the cell type-specific mechanisms underlying human testicular ageing at a single-cell resolution, and suggest potential therapeutic targets that may be leveraged to address age-related male fertility decline and hypogonadism. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research and Development Program of China (2022YFA1104100), the National Natural Science Foundation of China (32130046, 82171564, 82101669, 82371611, 82371609, 82301796), the Natural Science Foundation of Guangdong Province, China (2022A1515010371), the Major Project of Medical Science and Technology Development Research Center of National Health Planning Commission, China (HDSL202001000), the Open Project of NHC Key Laboratory of Male Reproduction and Genetics (KF202001), the Guangdong Province Regional Joint Fund-Youth Fund Project (2021A1515110921, 2022A1515111201), and the China Postdoctoral Science Foundation (2021M703736). The authors declare no conflict of interest.

[Impact of lipopolysaccharide-induced inflammation on sperm quality in male rats and its possible mechanisms].

OBJECTIVE: To investigate the influence of lipopolysaccharide (LPS)-induced inflammation on sperm quality in male rats and its possible mechanisms. METHODS: Thirty-six male SD rats were randomly divided into groups A (control), B (12 h LPS), C (24 h LPS) and D (72 h LPS), the former group injected intraperitoneally with sterile saline, and the latter three with LPS at 5 mg/kg and sacrificed at 12, 24 and 72 hours respectively after treatment. Then the left epididymides of the rats were harvested for detection of the sperm count and motility in the cauda epididymis, measurement of the relative sperm count value, examined the content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in the epididymal plasma, and determined the apoptosis rate of spermatogenic cells by flow cytometry (FCM). RESULTS: Compared with the parameters in group A, sperm motility in the cauda epididymis was decreased in groups B (ï¼»68.01 ± 1.80ï¼½% vs ï¼»62.28 ± 4.06ï¼½%, P < 0.05), C (ï¼»68.01 ± 1.80ï¼½% vs ï¼»45.35 ± 3.39ï¼½%, P < 0.05) and D (ï¼»68.01 ± 1.80ï¼½% vs ï¼»34.85 ± 4.42ï¼½%, P < 0.01), and so was the sperm count in the cauda epididymis (ï¼»38.94 ± 4.08ï¼½ vs ï¼»37.15 ± 2.54ï¼½ ×106/ 100 mg, P > 0.05; ï¼»38.94 ± 4.08ï¼½ vs ï¼»31.97 ± 2.81ï¼½ ×106/ 100 mg, P < 0.05; ï¼»38.94 ± 4.08ï¼½ vs ï¼»28.60 ± 4.03ï¼½ ×106/ 100 mg, P < 0.01), while the content of MDA in the epididymal plasma significantly increased (ï¼»4.66 ± 1.49ï¼½ vs ï¼»15.95 ± 3.26ï¼½ nmol/mg prot, P < 0.01; ï¼»4.66 ± 1.49ï¼½ vs ï¼»12.93 ± 2.54ï¼½ nmol/mg prot, P < 0.01; ï¼»4.66 ± 1.49ï¼½ vs ï¼»9.67 ± 1.68ï¼½ nmol/mg prot, P < 0.05), the activity of SOD reduced (ï¼»879.335 ± 105.089ï¼½ vs ï¼»729.265 ± 93.783ï¼½ U/mg prot, P > 0.05; ï¼»879.335 ± 105.089ï¼½ vs ï¼»694.126 ± 58.530ï¼½ U/mg prot, P < 0.05; ï¼»879.335 ± 105.089ï¼½ vs ï¼»655.352 ± 115.215ï¼½ U/mg prot, P < 0.05), and the apoptosis rate of spermatogenic cells dramatically elevated (ï¼»4.21 ± 1.67ï¼½% vs ï¼»11.01 ± 3.30ï¼½%, P < 0.05; ï¼»4.21 ± 1.67ï¼½% vs ï¼»23.88 ± 4.58ï¼½%, P < 0.01; ï¼»4.21 ± 1.67ï¼½% vs ï¼»41.28 ± 2.28ï¼½%, P < 0.01). CONCLUSION: LPS-induced inflammation damages spermatogenic cells and the quality of epididymal sperm in male rats in a time-dependent manner, which is associated with oxidative stress injury and cell apoptosis in the reproductive system.

[Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows for premature ejaculation: A prospective single-center randomized controlled study].

OBJECTIVE: To investigate the efficacy and safety of Compound Chamomile and Lidocaine Hydrochloride Gel (CCLH) (Kamistad) applied at different time-windows on premature ejaculation (PE). METHODS: This prospective study included 72 PE patients treated by application of CCLH to the glans and penile body in our hospital from February to October 2021. According to the time of drug administration before insertion into the vagina, we randomly divided the patients into a 5-minute group (n = 39) and a 15-minute group (n = 33). Before and after 1 and 2 weeks of treatment, we compared the intravaginal ejaculation latency time (IELT), PE diagnostic tool (PEDT) score, quality of life, and adverse reactions between the two groups of patients. RESULTS: Totally 62 of the patients completed the follow-up, 35 in the 5-minute group and 27 in the 15-minute group, and all showed significant improvement in IELT (P < 0.01) and PEDT score (P < 0.05) after treatment compared with the baseline. No allergic reactions, such as redness and swelling, developed at the application site in any of the patients, and no adverse significant effect was observed on the erectile hardness in 61 of the cases. Six cases showed increased erectile hardness instead. Fifty-seven of the patients experienced no obvious penile numbness or reduced sexual satisfaction, and all could complete their sexual activities. CONCLUSION: Compound Chamomile and Lidocaine Hydrochloride Gel applied at different time-windows is effective on PE, with a 5-minute rapid onset of action before intercourse, and no obvious adverse effects.

[Transcutaneous electrical acupoint stimulation improves pregnancy outcomes of in vitro fertilization- embryo transfer : A meta-analysis of randomized controlled trials].

OBJECTIVE: To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on the pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) based on the available clinical evidence. METHODS: We searched PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, VIP, CBM and Wanfang Database up to February 2021 for published randomized controlled trials (RCT) relevant to TEAS for the improvement of the pregnancy outcomes of IVF-ET. We performed literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria, followed by a meta-analysis with the RevMan 5.3 software. RESULTS: A total of 2 206 cases of IVF-ET from 9 RCTs were included, 1 018 in the TEAS group and 1 188 in the control. The clinical pregnancy rate was significantly higher in the TEAS than in the mock TEAS and non-TEAS control groups (RR = 1.85, 95% CI: 1.42－2.42, P < 0.001; RR = 1.23, 95% CI: 1.10－1.39, P = 0.0004), and so was it before and after oocyte retrieval (RR = 1.50, 95% CI: 1.03－2.17, P = 0.03; RR = 1.47, 95% CI: 1.12－1.92, P = 0.005). The TEAS group also showed dramatically improved embryo implantation rate (RR = 1.49, 95% CI: 1.24－1.79, P < 0.0001) and live birth rate (RR = 1.44, 95% CI: 1.04－1.98, P = 0.03) compared with the control. CONCLUSIONS: As a safe and non-invasive treatment, TEAS can significantly improve the pregnancy outcomes of IVF-ET, with definite effectiveness. /.

Comparative efficacy and safety of drug treatment for premature ejaculation: A systemic review and Bayesian network meta-analysis.

To assess the comparative efficacy and safety of drug treatments for premature ejaculation. A systemic review and Bayesian network meta-analysis were executed on randomised controlled trials of drug interventions for premature ejaculation. Intravaginal ejaculation latency time and related adverse effects were outcome measures. A total of 44 RCTs with 11,008 patients were included in our NMA. In therapy <8 weeks, the ranking of drug efficacy was topical creams >selective serotonin reuptake inhibitor (SSRI)+ phosphodiesterase 5 inhibitor (PDE5i) > PDE5i > sertraline > clomipramine > paroxetine > dapoxetine 60 milligram (mg) > dapoxetine 30 mg > fluoxetine>citalopram > duloxetine>placebo. In therapy ≥ 8 weeks, the ranking of drug efficacy was SSRI + PDE5i > topical creams > paroxetine > tramadol > PDE5i > fluoxetine > dapoxetine 60 mg > dapoxetine 30 mg > clomipramine>citalopram > placebo. For total adverse events, clomipramine, dapoxetine 30 mg, dapoxetine 60 mg, paroxetine, PDE5i, SSRI + PDE5i and tramadol had a higher risk than placebo. In conclusion, in ≥8 weeks of therapy, the drug combination of SSRI + PDE5i was the most effective PE therapy. In <8 weeks of therapy, the efficacy of local anaesthetics was best. All drug treatments were ranked better than placebo. In general, drugs with better effects had more obvious side effects.

CFTR variants and renal abnormalities in males with congenital unilateral absence of the vas deferens (CUAVD): a systematic review and meta-analysis of observational studies.

PURPOSE: CFTR variant is the main genetic contributor to congenital (unilateral/bilateral) absence of the vas deferens (CAVD/CUAVD/CBAVD). We performed a systematic review to elucidate the genetic link between CFTR variants, CUAVD, and the associated risk of renal abnormality (RA). METHODS: We searched relevant databases for eligible articles reporting CFTR variants in CUAVD. The frequency of CFTR variants and RA, and the odds ratios (ORs) for common alleles and RA risk, were pooled under random-/fixed-effect models. Subgroup analyses and heterogeneity tests were performed. RESULTS: Twenty-three studies were included. Among CUAVD patients, 46% had at least one CFTR variant, with 27% having one and 5% having two. The allele frequency in CUAVD was 4% for F508del and 9% for 5T. The summary OR for 5T risk in CUAVD was 5.79 compared with normal controls and 2.82 compared with non-CAVD infertile males. The overall incidence of RA was 22% in CUAVD. The pooled OR for RA risk among CUAVD patients was 4.85 compared with CBAVD patients. CONCLUSION: CFTR variants are common in CUAVD, and the 5T allele may be associated with increased CUAVD risk. CUAVD patients bear a higher RA risk than CBAVD patients, but this is not associated with CFTR variants.

[Effect of saw palmetto extract on the reproductive function of male rats with chronic prostatitis].

OBJECTIVE: To investigate the effect of saw palmetto extract (SPE) on the reproductive function of rats with chronic prostatitis (CP). METHODS: Forty male SD rats were equally randomized into groups A (blank control), B (blank control + SPE, C (CP model control) and D (CP model + SPE), and the CP model was made by injection of 1% λ-carrageenan solution into the prostate. The animals in groups A and C were gavaged with normal saline while those in groups B and D with SPE at 0.10 g/kg/d, all for 30 successive days. After drug withdrawal, the rats were mated with female ones in the ratio of 1∶1) and sacrificed 7 days later, their bilateral epididymides collected for detection of sperm count and motility. The numbers of pregnancies and fetuses were recorded and compared among different groups. RESULTS: Compared with the rats in group A, those in group C showed a marked decrease in epididymal sperm motility (ï¼»68.01 ± 1.80ï¼½% vs ï¼»62.59 ± 4.82ï¼½%, P < 0.05), but those in groups B and D exhibited no statistically significant difference (ï¼»67.69 ± 4.06ï¼½% and ï¼»67.93 ± 3.39ï¼½%, P > 0.05). There were no statistically significant differences in the count of epididymal sperm, rate of pregnancy and number of fetuses between group A and the other groups (P > 0.05). CONCLUSIONS: SPE can improve the semen parameters of CP rats, and has no adverse effect on the rate of pregnancy and number of fetuses.

[Efficacy and safety of low-intensity extracorporeal shock wave therapy in the treatment of ED: A meta-analysis of randomized controlled trials].

OBJECTIVE: To evaluate the clinical efficacy and safety of low-intensity extracorporeal shock wave therapy (LI-ESWT) in the treatment of ED based on the available clinical evidence. METHODS: We searched PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, VIP, CBM and Wanfang Database up to June 2018 for published randomized controlled trials on the treatment of ED by LI-ESWT. We performed literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria, and conducted a meta-analysis of the data obtained using the RevMan 5.3 software. RESULTS: A total of 595 ED cases in 8 double-blind randomized controlled trials (RCT) were included in this study, 362 in the LI-ESWT and 233 in the control group. Compared with the controls, the patients treated by LI-ESWT showed significantly improved IIEF (WMD = 1.70, 95% CI: 0.44－2.96, P = 0.008) and erection hardness score (EHS) (RR = 11.72, 95% CI: 5.13－26.80, P < 0.01). The IIEF scores of the patients were markedly increased at 4 and 24 weeks after LI-ESWT (WMD = 1.43, 95% CI: 0.10－2.75, P = 0.03; WMD = 3.09, 95% CI: 1.49－4.68, P = 0.0002), as well as after the 10th to 12th treatment (WMD = 1.81, 95% CI: 0.31－3.31, P = 0.02) though not after the 5th to 6th (WMD = 1.88, 95% CI: －2.10 to 5.86, P = 0.35). LI-ESWT also significantly increased the IIEF scores in the patients with the baseline IIEF ≥12 (WMD = 2.13, 95% CI: 0.51－3.75, P = 0.01) but not in those with the baseline IIEF ≤11 (WMD = 1.04, 95% CI: －0.96 to 3.03, P = 0.31). No significant adverse events were reported in the 8 RCTs. CONCLUSIONS: As a non-invasive treatment, LI-ESWT is safe and effective and can significantly improve IIEF and EHS in ED patients.

Prostaglandin E2 involvement in mammalian female fertility: ovulation, fertilization, embryo development and early implantation.

BACKGROUND: Infertility in mammalian females has been a challenge in reproductive medicine. The causes of female infertility include anovulation, ovulated oocyte defects, abnormal fertilization, and insufficient luteal support for embryo development, as well as early implantation. Ovulation induction, in vitro fertilization and luteal support regimens have been performed for decades to increase fertility rates. The identification of proteins and biochemical factors involved in female reproduction is essential to further increase female fertility rates. Evidence has shown that prostaglandins (PGs) might be involved in the female reproductive process, mainly ovulation, fertilization, and implantation. However, only a few studies on individual PGs in female reproduction have been done so far. This review aimed to identify the pivotal role of prostaglandin E2 (PGE2), a predominant PG, in female reproduction to improve fertility, specifically ovulation, fertilization, embryo development and early implantation. RESULTS: Prostaglandin E2 (PGE2) was shown to play a relevant role in the ovulatory cascade, including meiotic maturation, cumulus expansion and follicle rupture, through inducing ovulatory genes, such as Areg, Ereg, Has2 and Tnfaip6, as well as increasing intracellular cAMP levels. PGE2 reduces extracellular matrix viscosity and thereby optimizes the conditions for sperm penetration. PGE2 reduces the phagocytic activity of polymorphonuclear neutrophils (PMNs) against sperm. In the presence of PGE2, sperm function and binding capacity to oocytes are enhanced. PGE2 maintains luteal function for embryo development and early implantation. In addition, it induces chemokine expression for trophoblast apposition and adhesion to the decidua for implantation. CONCLUSION: It has been shown that PGE2 positively affects different stages of female fertility. Therefore, PGE2 should be taken into consideration when optimizing reproduction in infertile females. We suggest that in clinical practice, the administration of non-steroidal anti-inflammatory drugs, which are PGE2 synthesis inhibitors, should be reasonable and limited in infertile women. Additionally, assessments of PGE2 protein and receptor expression levels should be taken into consideration.

Open versus closed vitrification system of human oocytes and embryos: a systematic review and meta-analysis of embryologic and clinical outcomes.

BACKGROUND: The objective of this study was to carry out a systematic review and meta-analysis of embryologic and clinical outcomes following open versus closed vitrification of human oocytes and embryos. METHODS: An electronic literature search was conducted in main electronic databases up to June 30, 2018 using the following key terms: 'oocyte', 'embryo', 'blastocyst', 'vitrification', 'cryopreservation', 'device', 'survival rate', 'pregnancy rate', etc. A meta-analysis was performed using a random effect model to estimate the value of risk ratios (RRs) and 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were carried out to further confirm the results. RESULTS: Twelve (Eight prospective and four retrospective) studies comparing open versus closed vitrification of human oocytes or embryos were included. For prospective studies on oocytes, no evidence for a significant difference in cryosurvival rate (RR = 0.91, 95% CI: 0.80-1.03, P = 0.14; n = 2048) or clinical pregnancy rate (RR = 1.29, 95% CI: 0.80-2.06, P = 0.30; n = 150) was observed. Additionally, there were no significant differences between the two methods concerning secondary endpoints included positive ßHCG rate, implantation rate, miscarriage rate, ongoing pregnancy rate, live birth rate, cancellation rate, babies born per transferred blastocysts, or multiple birth rate (P > 0.05). The results of the retrospective studies were similar as the prospective studies. CONCLUSIONS: It is still impossible to conclude that closed vitrification system could be a substitution for open system in human oocyte and embryo cryopreservation based on current evidence. Therefore, more well-designed prospective studies addressing these issues are still warranted.

[Fosfomycin tromethamine inhibits the expressions of TNF-α, IL-8 and IL-6 in the prostate tissue of rats with chronic bacterial prostatitis].

OBJECTIVE: To investigate the effects of fosfomycin tromethamine (FT) on the expressions of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) in the prostate tissue of the rats with chronic bacterial prostatitis (CBP). METHODS: We randomly divided 70 male SD rats into 7 groups of equal number: blank control, CBP model control, positive control, 14 d low-dose FT, 7 d low-dose FT, 14 d high-dose FT, and 7 d high-dose FT. The CBP model rats in the latter five groups were treated intragastrically with levofloxacin at 100 mg/kg/d for 30 days and FT at 200 mg/kg/d for 14 and 7 days and at 300 mg/kg/d for 14 and 7 days, respectively. Then we collected the prostate tissue from the animals for determination of the levels of TNF-α, IL-8 and IL-6 by ELISA. RESULTS: Compared with the blank controls, the CBP model rats showed significantly increased levels of TNF-α (ï¼»19.83 ± 6.1ï¼½ vs ï¼»32.93 ± 6.21ï¼½ ng/g prot, P <0.01), IL-8 (ï¼»8.26 ± 0.52ï¼½ vs ï¼»16.2 ± 2.84ï¼½ ng/g prot, P <0.01) and IL-6 (ï¼»1.55 ± 0.11ï¼½ vs ï¼»2.51 ± 1.06ï¼½ ng/g prot, P <0.05) in the prostate tissue. In comparison with the CBP model controls, the levels of TNF-α and IL-8 were remarkably decreased in the groups of positive control (ï¼»20.54 ± 5.78ï¼½ ng/g prot, P <0.01; ï¼»12.43 ± 4.02ï¼½ ng/g prot, P <0.05), 14 d low-dose FT (ï¼»21.95 ± 6.48ï¼½ ng/g prot, P <0.01; ï¼»11.11 ± 2.86ï¼½ ng/g prot, P <0.01), 7 d low-dose FT (ï¼»23.8 ± 6.93ï¼½ ng/g prot, P <0.05; ï¼»12.43 ± 4.02ï¼½ ng/g prot, P <0.05), 14 d high-dose FT (ï¼»19.97 ± 2.58ï¼½ ng/g prot, P <0.01; ï¼»8.83 ± 1.32ï¼½ ng/g prot, P <0.01), and 7 d high-dose FT (ï¼»21.97 ± 3.38ï¼½ ng/g prot, P <0.01; ï¼»12.68±1.97ï¼½ ng/g prot, P <0.05). No statistically significant differences were observed between the positive control and FT groups in the contents of TNF-α, IL-8 or IL-6 (P >0.05). The expression of IL-6 was markedly reduced in the 14 d high-dose FT group as compared with the model controls (ï¼»1.76 ± 0.46ï¼½ vs ï¼»2.51 ± 1.06ï¼½ ng/g prot, P<0.05) but exhibited no significant difference between the CBP model control and the other groups (P >0.05). CONCLUSIONS: Fosfomycin tromethamine inhibits the expressions of TNF-α, IL-8 and IL-6 in the prostate tissue, suppresses its inflammatory reaction, promotes the repair of damaged prostatic structure, and thus contributes to the treatment of chronic bacterial prostatitis in rats.

[Ningmitai Capsule for the treatment of andrological diseases: Advances in studies].

Ningmitai Capsule is a classical patent medicine prepared from multiple effective ingredients of Chinese herbal medicine, with a wide range of biological activities and a significant efficacy in the treatment of urogenital diseases. Ningmitai Capsule has been widely applied in the management of urological and andrological diseases, with a particularly ideal effect on chronic prostatitis, since its first introduction nearly 20 years ago. With no obvious adverse effect on the male reproductive system, it has also been gaining a gradual application in the treatment of such diseases as urinary tract infections, diabetes, non-gonococcal urethritis, seminal vesiculitis, acute epididymitis, overactive bladder, hematuria, and semen non-liquefaction. However, the definite efficacy of Ningmitai Capsule needs to be further verified with more large-scale multi-centered randomized controlled trials, and its pharmacological mechanism remains to be further explored via more biomolecular experiments. The present article focuses on the recent advances in the application and studies of Ningmitai Capsule in the treatment of urological and andrological diseases.

[Protective effect of astaxanthin against epididymal oxidative damagein rats with ornidazole-induced oligoasthenozoospermia].

OBJECTIVE: To investigate the improving effect of astaxanthin (AST) on the sperm quality of rats with ornidazole (ORN)-induced oligoasthenozoospermiaand its action mechanism. METHODS: Forty adult male SD rats were equally randomized into groups A (solvent control), B (low-dose ORN ï¼»400 mg/（kg·d）］), C (high-dose ORN ï¼»800 mg/（kg·d）］), D (low-dose ORN ï¼»400 mg/（kg·d）］ + AST ï¼»20 mg/（kg·d）］), and E (high-dose ORN ï¼»800 mg/（kg·d）］ + AST ï¼»20 mg/（kg·d）］), all treated intragastrically for3 weeks.After treatment, the epididymal tails ononeside was taken for determination of sperm concentration and activity, and the epididymideson the other side harvested for measurement of the activities of GSH-Px, GR, CAT and SOD and the MDA contentin the homogenate. RESULTS: Compared with group A, sperm motilityin the epididymal tail andGSH-Px and SOD activities in theepididymiswere markedly decreased while the MDAcontent significantlyincreased in group B (P<0.05), spermmotility and concentrationin the epididymal tail, testisindex, and the activities of GSH-Px, GR, CAT and SOD in the epididymis were remarkably reduced while theMDA contentsignificantly increased in group C(P<0.05). In comparison with group B, group D showed markedly increased sperm motility (ï¼»45.3±8.7ï¼½% vs ï¼»66.3±8.9ï¼½%, P<0.05) in the epididymal tail and SOD activity in the epididymis (ï¼»116.7±25.3ï¼½ U/mg prot vs ï¼»146.1±23.8ï¼½ U/mg prot, P<0.05), decreased MDA content(ï¼»1.68±0.45ï¼½ nmol/mg prot vs ï¼»1.19±0.42ï¼½ nmol/mg prot, P<0.05).Compared with group C, group Eexhibited significant increases in the weight gained (ï¼»89.0±9.5ï¼½ vs ï¼»99.9±4.1ï¼½ %, P<0.05) and sperm motility (ï¼»17.9±3.5ï¼½% vs ï¼»27.3±5.3ï¼½ %, P<0.05) but a decrease in the content of MDA (ï¼»2.03±0.30ï¼½ nmol/mg prot vs ï¼»1.52±0.41ï¼½ nmol/mg prot, P<0.05). CONCLUSIONS: AST can improve spermquality in rats with ORN-inducedoligoasthenozoospermia, which may be associated with its enhancing effect on the antioxidant capacity of the epididymis.

[Effects of Xialiqi Capsules on the expressions of PCNA and caspase-3 in rats withbenign prostatic hyperplasia].

OBJECTIVE: To explore the effects of Xialiqi Capsules(XLQ) on the expressions of the proliferating cell nuclear antigen (PCNA) and caspase-3 in the prostate tissue of the BPH rat model. METHODS: Fifty male SD ratswereequally randomized into groups A (sham operation control), B (BPH model control), C (high-dose XLQ), D (low-dose XLQ), and E (finasteridecontrol) andthe BPH modelswere established by subcutaneous injection of testosterone propionate at 0.5 mg per kilogram of the body weight per day for 30 days after castration. After modeling, the animals in groups A and B were treated intragastricallywith normal saline, while those in C, D, and E with XLQ at 1.20 and 0.61 g per kilogram of the body weight per day or finasterideat 0.8 mg per kilogram of the body weight per day, respectively, all for 30 days. Then,the bilateral prostates were harvestedfrom the rats for calculation of the prostatic index (prostate wet weight/ body weight) and determination of the expressions of PCNA and caspase-3 in the prostate tissue by immunohistochemistry and immunofluorescence staining, respectively. RESULTS: The prostate wet weight and prostate index were significantly increased in group B as compared with group A, (ï¼»1326±60ï¼½ vsï¼»471±17ï¼½ g, P<0.01; ï¼»2.89±0.18ï¼½ vs ï¼»1.06±0.06ï¼½ mg/g, P<0.01), but decreased in groups C (ï¼»914±36ï¼½ g;ï¼»2.02±0.08ï¼½ mg/g), D (ï¼»1 099±46ï¼½g;ï¼»2.39±0.11ï¼½ mg/g), and E (ï¼»817±53ï¼½ g;ï¼»1.83±0.10ï¼½ mg/g)in comparison with B (P<0.01), with statistically significant differences among groups C, D, and E(P<0.01) and most significantly in E.The PCNA level in the prostate tissue wasremarkably higher in group B than in A, but lower in groups C, D and E than in B. The expression of caspase-3 was down-regulatedin group B as compared with A, but up-regulated in groups C, D and E in comparison with B, most significantly in E. CONCLUSIONS: Xialiqi Capsules can effectively reduce the prostate wet weight and prostatic index of in rats with BPH by inhibiting the level of PCNA and promoting the expression of caspase-3.

[Ubiquitin-proteasome system and sperm DNA repair: An update].

The ubiquitin-proteasome system (UPS) is a proteasome system widely present in the human body, which is composed of ubiquitin (Ub), ubiquitin activating enzymes (E1), ubiquitin conjugating enzymes (E2), ubiquitin protein ligases (E3), 26S proteasome, and deubiquitinating enzymes (DUBs) and involved in cell cycle regulation, immune response, signal transduction, DNA repair as well as protein degradation. Sperm DNA is vulnerable to interference or damage in the progression of chromosome association and homologous recombination. Recent studies show that UPS participates in DNA repair in spermatogenesis by modulating DNA repair enzymes via ubiquitination, assisting in the identification of DNA damage sites, raising damage repair-related proteins, initiating the DNA repair pathway, maintaining chromosome stability, and ensuring the normal process of spermatogenesis.

[ICSI with testicular or epididymal sperm for patients with obstructive azoospermia: A systematic review].

OBJECTIVE: To assess the effects of testicular sperm and epididymal sperm on the outcomes of ICSI for patients with obstructive azoospermia. METHODS: We searched PubMed, MEDLINE, EMBASE, Cochrane, CNKI, VIP, CBM, and Wanfang Database up to December 2015 for published literature relevant to ICSI with testicular or epididymal sperm for obstructive azoospermia patients. According to the inclusion and exclusion criteria, two reviewers independently conducted literature screening, data extraction and quality assessment of the included trials, followed by meta-analysis with the RevMan 5.3 software. RESULTS: A total of 14 studies were identified, involving 1 278 patients and 1 553 ICSI cycles. ICSI with epididymal sperm exhibited a significantly higher fertilization rate than that with testicular sperm (RR = 1.08, 95% CI 1.05－1.11, P<0.01). No statistically significant differences were observed between the epididymal and testicular sperm groups in the rates of cleavage (RR = 1.04, 95% CI 0.99－1.10, P = 0.13), good-quality embryo (RR = 1.01, 95% CI 0.93－1.09,P = 0.85), implantation (RR = 1.14, 95% CI 0.75－1.73, P = 0.55), clinical pregnancy (RR = 1.14, 95% CI 0.98－1.31, P = 0.08), and miscarriage (RR = 0.86, 95% CI 0.53－1.39,P = 0.54). CONCLUSIONS: ICSI with epididymal sperm yields a markedly higher fertilization rate than that with testicular sperm, but has no statistically significant differences from the latter in the rates of cleavage, good-quality embryo, implantation, clinical pregnancy, and miscarriage in the treatment of obstructive azoospermia.

[Longjintonglin Capsules for type IIIA prostatitis accompanied by abnormal semen liquefaction: A clinical observation].

OBJECTIVE: To evaluate the therapeutic effect of Longjintonglin Capsules on type IIIA prostatitis accompanied by abnormal semen liquefaction. METHODS: We selected 140 patients with type IIIA prostatitis accompanied by abnormal semen liquefaction according to the diagnostic standards of the American Institutes of Health (NIH) and treated them with Longjintonglin Capsules orally 3 capsules once tid for 12 weeks. We obtained the NIH Chronic Prostatitis Symptom Indexes (NIH-CPSI), traditional Chinese medicine (TCM) syndrome scores, leukocyte count in the expressed prostatic secretion (EPS), semen liquefaction time, and the results of semen analysis and compared these indicators before and after the treatment. RESULTS: Of the 140 cases, 132 were included in this study, excluding 8 due to their incomplete case histories. Before and after 4, 8 and 12 weeks of medication, the total NIH-CPSI scores were 24.52 ± 5.43, 21.28 ± 4.85, 18.01 ± 4.28, and 14.49 ± 3.65 (P < 0.01), the TCM syndrome scores were 35.63 ± 6.07, 26.66 ± 5.03, 17.37 ± 4.18, and 11.11 ± 3.96 (P < 0.01), and the leukocyte counts (/HP) were 27.50 ± 7.01, 22.38 ± 5.22, 16:76 ± 4.10, and 11.40 ± 4.74 (P < 0.01), respectively. After 12 weeks of treatment, 31 of the patients with type IIIA prostatitis were cured and another 72 well responded, with an overall response rate of 78.0%. Of those with abnormal semen liquefaction, 61 were cured, 39 well responded, and 32 failed to respond, with an overall effectiveness rate of 75.8%. Semen analysis showed significantly increased percentage of progressively motile sperm after 4, 8 and 12 weeks of medication as compared with the baseline (P < 0.01). No abnormal liver or renal function or other adverse reactions were observed during the treatment. CONCLUSION: Longjintonglin Capsules, with its advantages of safety, effectiveness and no obvious adverse effects, deserve to be recommended for the treatment of type IIIA prostatitis accompanied by abnormal semen liquefaction.

[Related reproductive issues on male autosomal dominant polycystic kidney disease].

Autosomal dominant polycystic kidney disease (ADPKD) is a most common inherited renal disease, about 50% with a family history, although the exact etiology not yet clear. To date, ADPKD, a multisystem disorder without effective preventive and therapeutic means, has been shown to be detrimental to human health. Recent studies show that severe oligoasthenozoospermia, necrospermia, immotile sperm, azoospermia, epididymal cyst, seminal vesicle cyst, and ejaculatory duct cyst found in male ADPKD patients may lead to male infertility, though the specific mechanisms remain unknown. Structural anomaly of spermatozoa, defect of polycystin, mutation of PKD genes, and micro-deletion of the AZF gene could be the reasons for the higher incidence of abnormal semen quality in male ADPKD patients. Assisted reproductive techniques can increase the chances of pregnancy, whereas the health of the offspring should be taken into consideration. This article presents an overview of reproductive issues concerning infertile male ADPKD patients from the perspective of the morbidity, pathophysiological mechanism, diagnosis, and management of the disease.

[Effect and safety of L-carnitine in the treatment of idiopathic oligoasthenozoospermia: a systemic review].

OBJECTIVE: To evaluate the effect and safety of L-carnitine in the treatment of idiopathic oligoasthenozoospermia based on current clinical evidence. METHODS: We searched the Cochrane Library, PubMed, MEDLINE, EMBASE, CNKI, VIP, CBM and Wanfang Database from the establishment to April 2014 for the published literature on the treatment of idiopathic oligoasthenozoospermia with L-carnitine. We conducted literature screening, data extraction, and assessment of the methodological quality of the included trials according to the inclusion and exclusion criteria, followed by statistical analysis with the RevMan 5. 2 software. RESULTS: Seven randomized controlled trials involving 751 patients with idiopathic oligoasthenozoospermia met the inclusion criteria, and 678 of them were included in the meta-analysis. L-carnitine treatment achieved a significantly increased rate of spontaneous pregnancy as compared with the control group (RR = 3.2, 95% CI 1.74 to 5.87, P = 0.0002). After 12-16 and 24-26 weeks of medication, total sperm motility (WMD = 5.21, 95% CI 2.78 to 7.64, P < 0.0001 and WMD = 9.29, 95% CI 1.28 to 17.29, P = 0.02) and the percentage of progressively motile sperm (WMD = 12.44, 95% CI 4.58 to 20.31, P = 0.002 and WMD = 9.76, 95% CI 3.56 to 15.97, P = 0.002) were remarkably higher than those in the control group, but no statistically significant differences were observed in sperm concentration between the two groups (WMD = 4.91, 95% CI -2.63 to 12.45, P = 0.2 and WMD = 0.93, 95% CI -3.48 to 5.34, P = 0.68). After 12-16 weeks of treatment, the percentage of morphologically abnormal sperm was markedly decreased in the L-carnitine group as compared with the control (WMD = -2.48, 95% CI -4.35 to -0.61, P = 0.009), but showed no significant difference from the latter group after 24-26 weeks (WMD = -4.38, 95% CI -9.66 to 0.89, P = 0.1). No statistically significant difference was found in the semen volume between the two groups after 12-16 or 24-26 weeks of medication (WMD = -0.13, 95% CI -0.43 to 0.18, P = 0.42 and WMD = 0.28, 95% CI -0.02 to 0.58, P = 0.07). No serious L-carnitine-related adverse events were reported in 4 of the randomniized controlled trials. CONCLUSION: The current evidence indicates that L-carnitine can improve spontaneous pregnancy and semen parameters in the treatment of idiopathic oligoasthenozoospermia, with no serious adverse reactions.

[Lipopolysaccharide affects testicular histology and reproductive endocrine function in male rats].

OBJECTIVE: To study the influence of lipopolysaccharide (LPS)-induced inflammation on the testicular histology and reproductive endocrine function in male rats and investigate the possible mechanism of inflammation affecting male fertility. METHODS: Thirty-six male SD rats were randomly divided into a control group (A) and three LPS intervention groups (B, C, and D) to receive saline and LPS (5 mg/kg i. p, once), respectively. The animals in groups B, C, and D were killed by anesthesia at 12, 24, and 72 hours after treatment. Histopathological changes in the left testis of the rats were observed by HE staining and the levels of the reproductive hormones T, FSH, and LH in the serum were determined by ELISA. RESULTS: Compared with group B, group A showed clear structure of seminiferous tubules, orderly arrangement of spermatogenic cells, a slightly decreased number of sperm in some seminiferous tubular lumens, and shed spermatogenic cells in the rat testis tissue; group C exhibited thinner seminiferous epithelia, disordered structure of seminiferous tubules, irregular arrangement of spermatogenic cells, decreased number of mature sperm and obvious shedding of spermatogenic cells in seminiferous tubular lumens; group D manifested similar findings to those of group C, with even more shed spermatogenic cells that blocked the tubular lumens. The levels of serum T, LH, and FSH were (0.490 +/- 0.028) ng/ml, (6.290 +/- 0.515) ng/L, and (1.837 +/- 0.127) IU/L in group A, (0.460 +/- 0.024) ng/ml, (5.881 +/- 0.124) ng/L, and (1.707 +/- 0.098) IU/L in group B, (0.417 +/- 0.021) ng/ml, (5.123 +/- 0.271) ng/L, and (1.620 +/- 0.115) IU/L in group C, and (0.378 +/- 0.021) ng/ml, (4.504 +/- 0.279) ng/L and (1.562 +/- 0.216) IU/L in group D, all decreased in group B as compared with A (P > 0.05). The decreases of T and LH were extremely significant (P < 0.01) and that of FSH was significant in groups C and D (P < 0.05) in comparison with A. CONCLUSION: LPS-induced inflammation affects the testicular tissue and reproductive endocrine function of male rats, resulting in decreased levels of serum T, LH, and FSH.