Chestnut polysaccharides benefit spermatogenesis through improvement in the expression of important genes.

Recently there has been a continuing worldwide decrease in the quality of human spermatozoa, especially in spermatozoa motility and concentration. Many factors are involved in this decline, and great efforts have been made to rescue spermatogenesis; however, there has been little progress in the improvement of sperm quality. Chestnuts are used in traditional Chinese medicine; their major active components are chestnut polysaccharides (CPs). CPs have many biological activities but their effects on spermatogenesis are unknown. The current investigation was designed to explore the impact of CPs on spermatogenesis and the underlying mechanisms. We demonstrated that CPs significantly increased sperm motility and concentration (4-fold and 12-fold, respectively), and improved seminiferous tubule development by increasing the number of germ cells after busulfan treatment. CPs dramatically rescued the expression of important genes and proteins (STRA8, DAZL, SYCP1, SYCP3, TNP1 etc.) in spermatogenesis. Furthermore, CPs increased the levels of hormone synthesis proteins such as CYP17A1 and HSD17ß1. All the data suggested that CPs improved the testicular microenvironment to rescue spermatogenesis. With CPs being natural products, they may be an attractive alternative for treating infertile patients in the future. At the same time, the deep underlying mechanisms of their action need to be explored.

Alginate oligosaccharides improve germ cell development and testicular microenvironment to rescue busulfan disrupted spermatogenesis.

Rationale: Busulfan is currently an indispensable anti-cancer drug, particularly for children, but the side effects on male reproduction are so serious that critical drug management is needed to minimize any negative impact. Meanwhile, alginate oligosaccharides (AOS) are natural products with many consequent advantages, that have attracted a great deal of pharmaceutical attention. In the current investigation, we performed single-cell RNA sequencing on murine testes treated with busulfan and/or AOS to define the mitigating effects of AOS on spermatogenesis at the single cell level. Methods: Testicular cells (in vivo) were examined by single cell RNA sequencing analysis, histopathological analysis, immunofluorescence staining, and Western blotting. Testes samples (ex vivo) underwent RNA sequencing analysis. Blood and testicular metabolomes were determined by liquid chromatography-mass spectrometry (LC/MS). Results: We found that AOS increased murine sperm concentration and motility, and rescued busulfan disrupted spermatogenesis through improving (i) the proportion of germ cells, (ii) gene expression important for spermatogenesis, and (iii) transcriptional factors in vivo. Furthermore, AOS promoted the ex vivo expression of genes important for spermatogenesis. Finally, our results showed that AOS improved blood and testis metabolomes as well as the gut microbiota to support the recovery of spermatogenesis. Conclusions: AOS could be used to improve fertility in patients undergoing chemotherapy and to combat other factors that induce infertility in humans.

[Huanshao Capsules for oligoasthenospermia: A multicentered clinical trial].

Objective: To investigate the clinical efficacy and safety of Huanshao Capsules (HSC) in the treatment of oligoasthenospermia with spleen and kidney asthenia. METHODS: This randomized, open, multicentered, positive drug controlled clinical trial included 200 cases of oligoasthenospermia with spleen and kidney asthenia, which were assigned to a trial and a control group of equal number to be treated with HSC at the dose of 3 capsules tid and Wuziyanzong Pills at 6 g bid, respectively, both for 12 weeks. We compared the semen volume, sperm concentration, sperm count, sperm motility and percentage of progressively motile sperm (PMS) as the main therapeutic indicators as well as the pregnancy rate as the secondary therapeutic indicator between the two groups of patients before and at 4, 8 and 12 weeks after medication. RESULTS: Totally, 190 of the patients completed the clinical observation, 96 in the trial and 94 in the control group. Compared with the baseline, the patients of the trial group showed significant time-dependent increases at 4, 8 and 12 weeks after medication in the mean sperm concentration (14.78 vs 15.33, 20.98 and 28.78 ×106/ml, P < 0.05), percentage of grade a sperm (12.17% vs 15.05%, 21.17% and 26.97%, P < 0.05), PMS (24.78% vs 28.97%, 37.23% and 47.67%, P < 0.05), and sperm viability (38.64% vs 44.18%, 51.67% and 60.45%, P < 0.05). The pregnancy rate was significantly higher in the trial than in the control group 29.17% vs 18.09%, P < 0.05). CONCLUSIONS: Huanshao Capsules can improve the semen quality and pregnancy rate in the treatment of oligoasthenospermia patients with spleen and kidney asthenia, and therefore deserves a wide clinical application.

[Gujing Maisiha Tablets combined with natural vitamin E for the treatment of idiopathic asthenospermia].

OBJECTIVE: To investigate the therapeutic efficacy and safety of Gujing Maisiha Tablets combined with natural vitamin E in the treatment of idiopathic asthenospermia. METHODS: This study included 135 outpatients with idiopathic asthenospermia received in our hospital from February 2015 to January 2016. We randomly divided them into a treatment group (n = 65, aged 22－44 ï¼»mean 32.8ï¼½ yr) and a control group (n = 55, aged 21－43 ï¼»mean 33.7ï¼½ yr) to be treated with Gujing Maisiha Tablets combined with natural vitamin E or natural vitamin E only, both for 90 days. We obtained total sperm motility and the percentage of progressively motile sperm (PMS) from the patients before and after medication and evaluated the clinical effects by comparing the collected parameters and pregnancy rates between the two groups. RESULTS: The baseline total sperm motility and PMS were (25.23 ± 5.57)% and (17.53 ± 5.78)% in the treatment group, with no statistically significant differences from (26.05 ± 6.77)% and (15.11 ± 6.55)% in the control (P >0.05). After 90 days of medication, both the treatment and the control groups showed remarkable increases in total sperm motility (ï¼»48.73 ± 8.66ï¼½% and ï¼»36.54 ± 8.09ï¼½%, P <0.05) and PMS (ï¼»32.77 ± 6.04ï¼½% and ï¼»26.99 ± 6.87ï¼½%, P <0.05). However, both total sperm motility and PMS were significantly higher in the treatment than in the control group after medication (P <0.05), and so was the total rate of clinical effectiveness (73.85% vs 54.55%, P <0.05). No adverse reactions were observed in either of the two groups during the treatment. CONCLUSIONS: Gujing Maisiha Tablets combined with natural vitamin E is safe and effective for the treatment of idiopathic asthenospermia.

Identification of demethylincisterol A3 as a selective inhibitor of protein tyrosine phosphatase Shp2.

Shp2 is a classical non-receptor protein tyrosine phosphatase (PTP) involved in many human diseases such as Noonan syndrome and tumors, and identified as a potential therapeutic target. In order to find a potent and selective Shp2 inhibitor, we screened a diverse collection of the secondary metabolites from endophyte fungi using an in vitro enzyme assay, and finally identified a potent Shp2 inhibitor, HLP46 (demethylincisterol A3) from Pestalotiopsis sp. HLP46 was reported to have anti-tumor and anti-inflammation activity previously. We provide the first evidence that HLP46 is an inhibitor of the Shp2. HLP46 shows high selective inhibition of Shp2 over Shp1, PTP1B, Lyp, STEP, PTPRA and Cdc25b. Enzymatic kinetic analyses showed that HLP46 is a non-competitive inhibitor of Shp2. HLP46 interrupts Gab1-Shp2 association and blocked Shp2-dependent activation of the Ras/ERK signal pathway induced by EGF. Furthermore, HLP46 decreased Src activation and inhibit tumor cell migration and invasion. As expected, HLP46 has no effect on the Shp2-independent activation of ERK induced by PMA or on the activation of the PI3K/Akt pathway. We testified therapeutic efficacy targeting both Shp2 and PI3K in MCF7 cells. HLP46 does not show any synergistic inhibition with PI3K inhibitor in suppressing cell growth. Collectively, these results suggest that HLP46 is a selective Shp2 inhibitor and could inhibit Shp2-dependent cell signaling in human cells.

[Compound amino acid combined with vitamin E for idiopathic asthenospermia].

Objective: To study the therapeutic efficacy of compound amino acid combined with vitamin E in the treatment of idiopathic asthenospermia. Methods: This study included 120 cases of idiopathic asthenospermia treated in the Outpatient Department of our hospital between February 2014 and January 2015. We randomized the patients into a treatment group( n = 70,aged23- 43 [mean 32. 5] years) and a control group( n = 50,aged 23- 44 [mean 31. 7] years),the former treated with compound amino acid plus vitamin E while the latter with vitamin E only. After 90 days of medication, we evaluated the therapeutic effects by comparing the total sperm motility( progressive motility + non-progressive motility, PR + NP),the percentage of progressively motile sperm( PR),and the pregnancy rate between the two groups. Results: Before treatment, PR + NP and PR were(26. 24 ± 6. 56) %and(24. 65 ± 6. 43) % in the treatment group and(15. 13 ± 5. 68) % and(14. 73 ± 6. 16) in the control, with no statistically significant differences between the two groups( P > 0. 05). After 90 days of medication, PR + NP and PR were( 49. 63 ± 9. 78) % and(33. 33 ± 5. 64)% in the former and(37. 67 ± 7. 98)% and(27. 23 ± 6. 46)% in the latter, remarkably increased in both groups as compared with the baseline( P < 0. 05),but significantly more in the treatment than in the control group( P < 0. 05). Four pregnancies(5. 71%) were achieved in the former group but only 1(2. 00%) in the latter. The total rate of effectiveness was markedly higher in the treatment group than in the control(74. 28% vs 44. 00%,P < 0. 05). No adverse reactions were observed in either group. Conclusion: Compound amino acid combined with vitamin E can safely and effectively improve sperm motility in idiopathic asthenospermia patients.