Genetic analysis of three cases of acephalic spermatozoa syndrome caused by SUN5 mutation and the outcome of assisted reproductive technology / 北京大学学报(医学版)

To explore the genetic causes of 3 male infertility patients with acephalospermia and the outcome of assisted reproductive technology. Clinical diagnosis, sperm morphology examination, sperm transmission electron microscopy examination were performed on 3 patients, and the whole exome sequencing technology was used for screening, Sanger sequencing verification, mutation pathogenicity analysis, and protein sequence homology comparison. Assisted reproductive technology was implemented to assist pregnancy treatment. The 3 patients were all sporadic infertile men, aged 25, 42 and 26 years, and there was no obvious abnormality in the general physical examination. Male external genitalia developed normally, bilateral testicles were normal in volume, and bilateral epididymis and spermatic vein were palpated without nodules, cysts, and tenderness. Repeated semen analysis showed that a large number of immature sperm could be seen, and they had the ability to move. The SUN5 gene of the 3 male infertile patients was a case of homozygous missense mutation c.7C>T (p.Arg3Trp), a case of compound heterozygous missense mutation c.1067G>A (p.Arg356His) and nonsense mutation c.216G>A (p.Trp72*) and a case of homozygous missense mutation c.1043A>T (p.Asn348Ile), of which c.7C>T (p.Arg3Trp) and c.1067G>A (p.Arg356His) were new variants that had not been reported. SIFT, Mutation Taster and PolyPhen-2 software function prediction results were all harmful, the nonsense mutation c.216G>A (p.Trp72*) led to the premature termination of peptide chain synthesis which might have a greater impact on protein function. The homology regions in the protein sequence homology alignment were all highly conserved.The 3 male patients and their spouses obtained 4 biological offspring through intracytoplasmic sperm injection, all of which were boys, and one of them was a twin.Three male infertile patients might be caused by SUN5 gene mutations. Such patients could obtain their biological offspring through assisted reproductive technology. It was still necessary to pay attention to the genetic risk of ASS, it was recommended that both men and women conduct genetic counseling and screening at the same time. In clinical diagnosis, whole exome sequencing technology could be used to perform auxiliary examinations to determine the treatment plan and assisted reproductive methods as soon as possible to reduce the burden on the family and society. The newly discovered mutation sites of SUN5 gene provided clues and directions for elucidating the pathogenic mechanism, and at the same time expanded the pathogenic mutation spectrum of ASS.

Effects of Yishen Shengjing Capsules on semen quality and gonadal hormone levels in rats with dibutyl phthalate-induced reproductive function injury / 中华男科学杂志

<p><b>Objective</b>To study the possible pathogenesis of infertility caused by dibutyl phthalate (DBP) and investigate the effects of Yishen Shengjing Capsules (YSC, kidney-tonifying and essence-producing capsules) on DBP-induced reproductive function injury and its possible action mechanisms in male Wistar rats.</p><p><b>METHODS</b>Models of DBP-induced reproductive function injury were made in 80 male Wistar rats and another 20 were used as blank controls. After modeling, the model rats were randomly divided into a model control, a high-dose YSC, a medium-dose YSC, and a low-dose YSC group. Four weeks after intervention, all the animals were sacrified for observation of the histomorphologic changes in the testis under the light microscope, measurement of sperm concentration, motility and abnormality, and determination of the levels of serum testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by radioimmunoassay.</p><p><b>RESULTS</b>Compared with the blank controls, the model rats showed obvious pathological changes in testicular histomorphology, significantly decreased sperm concentration and motility, increased sperm abnormality, reduced contents of serum T and LH, and elevated the level of serum FSH (P<0.01). After 4 weeks of medication, the animals of the high-, medium-, and low-dose YSC groups, in comparison with the model controls, exhibited different degrees of recovery from testicular histomorphological damage, remarkably increased sperm concentration and motility, decreased sperm abnormality, elevated levels of serum T and LH, and reduced content of serum FSH (P<0.01). There were statistically significant differences in all the parameters above between the high-dose YSC and medium- and low-dose YSC groups (P<0.01).</p><p><b>CONCLUSIONS</b>DBP reduces sperm motility and concentration, increases sperm abnormality, causes damage to the morphological structure of the rat testis, decreases the contents of serum T and LH, and elevates the level of the serum FSH. Yishen Shengjing Capsules can improve DBP-induced productive function injury, increase sperm motility and concentration, decrease sperm abnormality, elevate the level of serum T and LH, reduce the content of serum FSH, improve the morphological structure of the testis, and thus promote the reproductive function of the male rat.</p>

Inhibitory effect of Qiangjing Tablets on the Fas/FasL pathway of cell apoptosis in male SD rats with infertility / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the effects of Qiangjing Tablets (QJT) on the semen quality and Fas/FasL signaling pathway in male SD rats with infertility.</p><p><b>METHODS</b>Models of infertility were made in 50 male SD rats by intragastric administration of Tripterygium (GTW) for 3 weeks, and another 20 rats were taken as blank controls. Then 40 successfully established rat models were randomly divided into four groups, model control, low-dose QJT, medium-dose QJT, and high-dose QJT, the latter three groups treated intragastrically with QJT at 58 mg, 105 mg, and 233 mg per kg of the body weight per day, respectively. After 4 weeks of medication, the rats were killed for examination of semen quality and determination of the expression of the apoptosis factor FasL in the testis tissue.</p><p><b>RESULTS</b>Compared with the blank controls, the model rats showed significant decreases in sperm concentration ([71.99 ± 9.72] vs [10.94 ± 3.58] x 10⁶/ml, P < 0.01), motility ([48.95 ± 4.10] vs [9.31 ± 5.79]%, P < 0.01), and viability ( [82.06 ± 6.16] vs [24.03 ± 6.93]%, P < 0.01). In comparison with the model controls, the rats in the QJT groups exhibited remarkably increased sperm concentration, motility, and viability, more significantly in the high-dose group ([59.66 ± 4.53] x 10⁶/ml, [35.45 ± 5.21] %, and [61.97 ± 9.75]%) and medium-dose group ([40.89 ± 4.90] x 10⁶/ml, [24.41 ± 4.79]%, and [60.06 ± 10.62]%) (P < 0.05 or P < 0.01). The expression of FasL was markedly reduced in the low-, medium-, and high-dose QJT groups (0.5215 ± 0.0189, 0.5371 ± 0.0364, and 0.4556 ± 0.0215) as compared with that of the model controls (0.5989 ± 0.0448 ) (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>By upregulating the Fas/FasL signaling pathway, Tripterygium glycosides may induce the apoptosis of spermatogenic cells and reduce sperm concentration, motility and viability, resulting in infertility. The Chinese medicine Qiangjing Tablets can improve the reproductive function of male rats by decreasing the expression of the apoptosis factor FasL in the testis.</p>

Correlation study between the polymorphism of repetitive sequence in gene CAG of androgen receptor and the occurrence and progression of prostate cancer

OBJECTIVE@#To explore the relation between the polymorphism of repetitive sequence in gene CAG of androgen receptor (AR) and the susceptibility and clinical stages as well as pathological grading of prostate cancer among Han population.@*METHOD@#Sixty-eight cases with prostate cancer hospitalized in Urinary Surgery Department from Feb. 2010 to Feb. 2012 and 60 healthy cases were chosen as research subjects. Methods of PCR and direct sequencing were adopted to detect DNA sequence of AR gene and the length of repetitive sequence in CAG.@*RESULTS@#The lengths of repetitive sequence in CAG of patients with prostate cancer and healthy people were (22.3±4.6) and (23.0±4.9), respectively showing no statistical significance. Comparing length (repetitive sequence of CAG)>22, those with that 0.05); the proportion of patients with length <22 at clinical stage C-D was much larger than that of patients at clinical stage B (P<0.05), and as the aggravation of pathological grading, the proportion of patients with the length <22 was also remarkably increased and there was significant difference between patients with highly differentiated prostate cancer and those with poorly differentiated prostate cancer (P<0.05).@*CONCLUSIONS@#There is correlation between the occurrence and development of prostate cancer in Han population and the polymorphism of repetitive sequence in gene CAG of androgen receptor. The less the number of repetitive sequence in CAG is, the higher the risk of prostate cancer will be and the more severe the clinical stage and pathological grading will be.

Effects of Qiangjing Capsule on the oxidative and antioxidative system in the epididymis of varicocele rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the effects of Qiangjing Capsule (QC) on the oxidative amd antioxidative system in the epididymis of varicocele rats in comparison with those of Shaofuzhuyu Capsule (SC) and Wuziyanzong Capsule (WC), and to explore its possible mechanism of enhancing epididymal sperm maturation.</p><p><b>METHODS</b>Ten of 100 adolescent male SD rats were randomized to a sham-operation group, and varicocele models were successfully established in 72 of the other 90 by narrowing of the left renal vein. Then the model rats were equally assigned to 6 groups: model control, high-dose QC (0.216 g/ml), medium-dose QC (0.108 g/ml), low-dose QC (0.054 g/ml), SC (0.146 g/ml), and WC (0.130 g/ml). After 4 weeks of treatment, we determined the activity of glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in the left epididymis of different groups of rats.</p><p><b>RESULTS</b>Compared with the sham-operation group, the model group showed a significant decrease in GPx activity (P < 0.01) and a marked increase in the MDA level (P < 0.05). And the high-dose QC group exhibited a significantly hither GPx activity and lower MDA level than all the other groups (P < 0.01 and P < 0.05).</p><p><b>CONCLUSION</b>Varicocele can reduce the activity of GPx and elevate the level of MDA in the epididymis of rats, while Qiangjing Capsule can increase the former and decrease the latter, and thereby may improve epididymal microenvironment, enhance epididymal sperm maturation and promote fertility.</p>

Modified Bazhengsan for urination symptoms of chronic prostatis with damp-heat accumulated in the lower jiao / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the clinical effects of the modified formula of Bazhengsan on the urination symptoms of chronic prostatis with damp-heat accumulated in the lower jiao.</p><p><b>METHODS</b>A total of 72 chronic prostatitis patients with damp-heat accumulated in the lower jiao were equally randomized to receive the modified formula of Bazhengsan (the trial group) and the primal Bazhengsan (the control group), both for a course of 28 days. Then we observed the changes in the NIH-CPSI scores, scores on Traditional Chinese Medicine (TCM) syndrome, maximum flow rate of urine (MFR) and results of the expressed prostatic secretion test (EPS).</p><p><b>RESULTS</b>Among the 31 patients of the trial group, 6 were cured, 10 achieved excellent results, 9 got improved, and 6 failed to respond, with a total efficacy rate of 80.6%. While in the control group, 4 were cured, 10 achieved excellent results, 11 got improved, and 7 failed to respond, with a total efficacy rate of 78.1%. Significant improvement was observed in NIH-CPSI scores, TCM syndrome and EPS results in both of the groups (P < 0.05), and the trial group showed significant difference from the control in the improvement of urination symptoms (P < 0.05).</p><p><b>CONCLUSION</b>Modified Bazhengsan is effective in the treatment of chronic prostatis with damp-heat in the lower jiao. It can significantly improve its clinical symptoms, especially urination symptoms.</p>

Xiaojin Wan inhibits the expression of COX-2 in prostate tissues of prostatitis pain rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the effect of Xiaojin Wan on the expression of COX-2 in the prostate tissues of rats with prostatitis pain, and the action mechanism of the drug alleviating the prostatitis pain.</p><p><b>METHODS</b>Sixty male Wistar rats were randomized into two groups, 10 as blank controls, injected with aqua pro injection into the ventral part of prostate, and the other 50 as prostatitis pain models, given complete Freund's adjuvant (CFA). Three days later, the pain model rats were again equally divided into 5 subgroups: model control, Celecoxib Capsules, high-, median- and low-dose Xiaojin Wan, receiving intragastric administration of distilled water, Celecoxib Capsules and different doses of Xiaojin Wan respectively for 4 weeks. Then they were killed, the harvested tissues fixed with 10% paraformaldehyde and the changes of the COX-2 expression in the prostate detected with the immunohistochemical technique and graphics video analysis system.</p><p><b>RESULTS</b>The expression of COX-2 was strong in the model group, significantly lower in the high- and median-dose and the Celecoxib Capsules groups than in the model control (P < 0.01) as well as in the high-dose than in the median- and low-dose groups (P < 0.01).</p><p><b>CONCLUSION</b>Xiaojin Wan may alleviate prostatitis pain by inhibiting the expression of COX-2 in prostate tissues.</p>