Effect of mir-152 on proliferation of myocardial fibroblasts in diabetic cardiomyopathy / 中国药理学通报

Aim To explore the effect of miR-152 on proliferation of cardiac fibroblasts ( CFS) in diabetic cardiomyopathy. Methods Diabetic cardiomyopathy model was established in SD rats by STZ injection, and CFS proliferation model was established by high glucose (33. 3 mmol • L ~1). HE and Masson staining were performed in paraformaldehyde fixed myocardium of rats. Western blot determined a-SMA and collagen I protein expression. qPCK detected gene expression of miR-152. MTT assay analyzed the proliferation of cells. Results HE and Masson staining showed the higher level of myocardial collagen in diabetic cardiomyopathy model. Furthermore, the myocardial myo-cytes lined up in disorder. Western blot showed that the expressions of a-SMA and collagen I were up-regulated in the diabetes mellitus ( DM ) group, while the expression of miR-152 was down-regulated. The result of the in vitro experiment showed that a-SMA and collagen I expressions were down-regulated after trans-fected miR-152 mimics. The proliferation of CFS was also down-regulated after transfected miR-152 mimics. Conclusions miR-152 plays an important role in the proliferation of CFS and may ameliorate diabetic cardiomyopathy.

Expressions of survivin, PI3K and AKT in keratinocytes in skin lesions and their pathogenic role in psoriasis vulgaris / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the role of survivin and PI3K/AKT pathway in the pathogenesis of psoriasis vulgaris (PV).</p><p><b>METHODS</b>Plaque-like lesions collected from 22 patients with PV in progressive stage and 18 normal control skin specimens were examined using immunohistochemical staining, Western blotting and real-time quantitative PCR for expressions of survivin, PI3K and AKT in the keratinocytes, and their correlation was analyzed. A small interfering RNA (siRNA) was used to knock down AKT in cultured HaCaT cells, and Western blotting was used to detect the changes in the expression of survivin. RESULTS Compared with normal skin, PV lesions showed obviously up-regulated expressions of survivin, PI3K and AKT in the keratinocytes. Survivin expression was positively correlated with PI3K (r=0.4510, P=0.0351) and AKT (r=0.4423, P=0.0393) in the keratinocytes in PV lesions. In cultured HaCaT cells, siRNA-mediated knockdown of AKT caused down-regulation of survivin expression.</p><p><b>CONCLUSION</b>Survivin and PI3K/AKT signaling pathway may participate in the occurrence and progression of PV.</p>

Regulatory effect of Skp2 on the expression and transactivation of the androgen receptor in the progression of castration-resistant prostate cancer / 中华男科学杂志

<p><b>OBJECTIVE</b>To determine the expression of Skp2 in different prostate cancer (PCa) cell lines and tissues, and explore its influence on the androgen receptor (AR) signaling pathway and development of castration-resistant prostate cancer (CRPC).</p><p><b>METHODS</b>The expression levels of Skp2 and AR in different PCa cell lines were detected by Western blot. After knockdown of Skp2 in the C4-2 and 22RV1 cells transfected with shRNA, the expressions of AR and P27 were determined and the activity of ARR3-Luc measured by dual-luciferase reporter gene assay following treatment with dihydrotestosterone (DHT). The expressions of AR and Skp2 in human naïve PCa or CRPC specimens were detected by immunohistochemical staining followed by analysis of their differences and correlation.</p><p><b>RESULTS</b>The Skp2 protein expression level was significantly higher in the C4-2 or 22RV1 cells than in the LNCaP cells. DHT treatment increased the expression of Skp2 in the C4-2 cells, but knock-down of Skp2 significantly up-regulated the expression of the well-known downstream protein P27 and down-regulated that of AR. Consistently, DHT treatment increased the activity of ARR3-Luc, while knockdown of Skp2 remarkably decreased it in the C4-2 and 22RV1 cells (P < 0.05). In addition, significantly higher expressions of Skp2 and AR were observed in the CRPC than in the naïve specimens (P < 0.05), with a positive correlation between the two proteins (r = 0.658 1, P < 0.05).</p><p><b>CONCLUSION</b>Skp2 can enhance the expression and transcription activity of the AR protein in CRPC cells or tissues and is promising to be a critical molecular therapeutic target.</p>

Synthesis and biological evaluation of novel pleuromutilin derivatives with nitrogen-containing heterocycles as antibacterial agents / 药学学报

A series of new pleuromutilins derivatives were designed and synthesized through coupling 2-aminothiazole ring of WL001 with different nitrogen-containing substituted heterocycles in the side chain. Their biological activities were evaluated against both Gram-positive and Gram-negative clinical bacteria in vitro Most new compounds displayed specificity to certain strain of bacteria. Particularly, compounds with saturated nitrogen-containing heterocycles exhibited significant antibacterial activities (0.062 5-8 µg · mL(-1)) superior or similar to those of amoxicillin, tiamulin and levofloxcin. Furthermore, treatment with 15a and 15b having piperidine or morpholine residues also could effectively inhibit Gram-negative bacteria. Therefore, our novel findings may provide a new insight into the design of novel pleuromutilin derivatives and lay the basis for further studies on the treatment of drug-resistance of pathogenic bacteria.

Treatment of lumbar intervertebral disc herniation with coblation combined with ozone nucleus pulposus ablation / 中国骨伤

<p><b>OBJECTIVE</b>To compare the clinical effects between coblation combined with ozone nucleus pulposus ablation and single radiofrequency ablation of nucleus pulposus in treating a simple segment inclusive lumbar intervertebral disc herniation.</p><p><b>METHODS</b>From June 2009 to June 2011,33 patients with lumbar intervertebral disc herniation were treated with coblation combined with ozone nucleus pulposus ablation (group A),including 19 males and 14 females,ranging in age from 20 to 60 years old with an average of (40.4+/-8.8) years old,in the course of disease from 12 to 38 months with an average of (19.9+/-5.8) months;31 patients were treated with single radiofrequency ablation of nucleus pulposus(group B),ineluding 18 males and 13 females,ranging in age from 20 to 60 years old with an average of (39.8+/-7.3) years old,in the course of disease from 12 to 48 months with an average of (19.2+/-8.1) months. Visual analogue score(VAS) and JOA score system was respectively used to evaluate pain and function after operation.</p><p><b>RESULTS</b>All patients were followed up more than 1 year. No injuries of nerve root and cauda equina nerve,infection were found. There was no significant difference in VAS score between two groups at 1 month after operation (P>0.05),but at 12 months after operation,VAS score of group A was better than that of group B (P<0.05). There was no significant difference in JOA score between two groups at 12 months after operation (P>0.05). According to the functional improvement rate to evaluate the clinical effects,in group A,9 cases got excellent results, 21 good,3 fair;and in group B,6 excellent,18 good,7 fair. Clinical effects of group A was better than that of group B (P<0.05).</p><p><b>CONCLUSION</b>Clinical effects of coblation combined with ozone nucleus pulposus ablation is better in treating a simple segment inclusive lumbar intervertebral disc herniation.</p>

Changes of intracellular cholesterol metabolism in neuroendocrine differentiation of prostate cancer and their significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the roles of intracellular cholesterol metabolism in neuroendocrine (NE) differentiation of prostate cancer based on an androgen-independent prostate cancer NE cell model induced by androgen deprivation.</p><p><b>METHODS</b>LNCaP cells were cultured in androgen-depleted medium, and NE phenotypes were identified by observing the changes in cell morphology, molecular markers (SgIII, NSE and CgA) and cell proliferation. The expression and distribution of cholesterol and Sg III were determined by immunofluorescence staining. The expressions of the key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake were detected by semi-quantitative RT-PCR.</p><p><b>RESULTS</b>The LNCaP cells showed shrinking bodies and extending axons after androgen deprivation, and all the molecular markers, such as Sg III, NSE and CgA, significantly increased in a time-dependent manner, while the cell proliferation was obviously inhibited (P < 0.05). The cholesterol distribution in the LNCaP cells after NE differentiation presented remarkable aggregation at the axon terminals. However, there were no significant differences in the expression of cholesterol between the two types of cells, nor in the changes of the expressions of key genes LDL-R, SREBP-1 and SREBP-2 involved in cholesterol synthesis and uptake (P > 0.05).</p><p><b>CONCLUSION</b>Transient androgen depletion could successfully induce NE differentiation of LNCaP cells, and the intracellular cholesterol could re-distribute into axon terminals to enhance the formation of neurosecretory granules.</p>

Establishment of an animal model of prostate cancer metastasis to the lung traced by AsRed2 / 中华男科学杂志

<p><b>OBJECTIVE</b>To establish an animal model of prostate cancer (PCa) metastasis to the lung using PCa PR7 (PCa PC-3 cells stably expressing red fluorescent protein AsRed2) cell lines that can be monitored by in vivo fluorescence imaging technology.</p><p><b>METHODS</b>MTT and Transwell assay were used to compare the abilities of proliferation, migration and invasion of PC-3 and PR7 cells. Twenty BALB/c nude mice were equally randomized to 4 groups to receive tail vein injection of PR7 cell suspension at the concentration of 1 x 107/ml (group A), 2.5 x 107/ml (group B), 5 x 107/ml (group C) and 2.5 x 107/ml followed by the same dose 1 week later (group D). PCa metastasis to the lung was then monitored by in vivo fluorescence imaging technology at the end of 2, 4, 6 and 8 weeks.</p><p><b>RESULTS</b>There were no statistically significant differences between PC-3 and PR7 cells in their abilities of proliferation, migration and invasion (P > 0.05). At the end of 4 weeks, lung metastasis was observed in 40% of the mice in group D, and at the end of 8 weeks, it was detected in 20% in group A, 60% in group B, 100% in group C, and 100% in group D, all confirmed by pathological examination.</p><p><b>CONCLUSION</b>The animal model of PCa metastasis to the lung that can be monitored by in vivo fluorescence imaging technology was established successfully by tail vein injection of PR7 cells carrying red fluorescent protein.</p>

GLI-1 is involved in EGF-regulated enhancement of the invasiveness of prostate cancer ARCaP(E) cells in vitro / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the role of the hedgehog (HH) signaling pathway transcription factor glioma-associated oncogene hoinolog 1 (GLI-1) in EGF-regulated enhancement of the invasiveness of the prostate cancer ARCaP(E) cell line in vitro.</p><p><b>METHODS</b>The expressions of EGFR and GLI-1 in prostate cancer ARCaP(E) cells were analyzed by immunofluorescence staining. ARCaP(E) cells were treated with EGF at 100 ng/ml, followed by detection of the changes in cell morphology and invasiveness, as well as in the expressions of p-ERK, ERK and GLI-1. Migration transwell assay was used to determine the effects of 100 ng/ml EGF and GLI-1 antagonist GANT61 on the invasiveness of the ARCaP(E) cells.</p><p><b>RESULTS</b>Both EGFR and GLI-1 were expressed in the ARCaP(E) cells. EGF induced morphological transition of epithelial-like ARCaP(E) cells to mesenchymal-like cells, increased their in vitro invasiveness, and significantly upregulated the expressions of p-ERK and GLI-1 in the ARCaP(E) cells (P<0.05). GANT61 significantly inhibited the in vitro invasiveness of the ARCaP(E) cells and reduced the enhancing effect of EGF on their invasiveness (P<0.05).</p><p><b>CONCLUSION</b>The results from ARCaP(E) cells shed light on the cross-talk of the HH pathway with the EGF/ERK signaling pathway. GLI-1 might be responsible for EGF-regulated enhancement of the invasiveness of ARCaP(E) cells in vitro.</p>

Epithelial-mesenchymal transition and human fetal prostate development / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the role and significance of epithelial-mesenchymal transition (EMT) and its transcriptional regulator Twist1 in the development of the human fetal prostate.</p><p><b>METHODS</b>Twenty-five human fetal prostate specimens at various developmental stages (16-39 weeks) were included in this study. EMT markers, such as E-Cadherin, N-Cadherin and Vimentin, and EMT transcriptional regulator Twist1 were determined by immunohistochemistry, and their relationship with the development of the human fetal prostate was analyzed.</p><p><b>RESULTS</b>E-Cadherin was expressed in the fetal prostate epithelium only, while Vimentin, N-Cadherin and Twist1 in both the epithelium and the stroma. The expression of E-Cadherin gradually increased, but those of Vimentin, N-Cadherin and Twist1 gradually decreased with the gestation stages. No significant changes were observed in the staining patterns of Vimentin, N-Cadherin and Twist1 in the stroma during the whole developmental process.</p><p><b>CONCLUSION</b>EMT is involved in the development of the human fetal prostate, which may promote epithelial cell motility to form prostatic bud tubules in early gestation stages and boost the differentiation of prostate epithelia in later stages.</p>

Tamoxifen combined with coenzyme Q10 for idiopathic oligoasthenospermia / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of tamoxifen (TMX) combined with coenzyme Q10 (CoQ10) on idiopathic oligoasthenospermia.</p><p><b>METHODS</b>A total of 183 patients with idiopathic oligoasthenospermia were randomly divided into a TMX + CoQ10 group (n = 63), a TMX group (n = 61) and a CoQ10 group (n = 59). At the end of 3 and 6 months of treatment, semen analyses and hormone tests were performed, and the results were compared with those obtained before the treatment.</p><p><b>RESULTS</b>Compared with the pre-treatment results, the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) and sperm concentration were significantly elevated in the TMX + CoQ10 and TMX groups (P < 0.05), but showed no significant difference in the CoQ10 group (P > 0.05); sperm motility and morphologically normal sperm were increased significantly in the TMX + CoQ10 and CoQ10 groups (P < 0.05), and slightly in the TMX group but with no statistically significant difference (P > 0.05).</p><p><b>CONCLUSION</b>Tamoxifen combined with CoQ10 can significantly improve sperm concentration, motility and morphology in patients with idiopathic oligoasthenospermia.</p>

Comparison of transcription factors repressing epithelial phenotype in two different prostate cancer EMT models and its significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To screen and compare the specific transcription factors that repress the epithelial phenotype in epithelial-mesenchymal transition (EMT) in two different human prostate cancer models LNCaP/HIF1alpha and ARCaP.</p><p><b>METHODS</b>We established two different prostate cancer EMT models, LNCaP/HIF1alpha and ARCaP, cultured LNCaP, LNCaP/HIF1alpha, IF11 and IA8 cells in vitro, and detected the five transcription factors Snail, Slug, ZEB1, SIP1 and Twist1 in these cells by RT-PCR.</p><p><b>RESULTS</b>Different levels of Snail, Slug, ZEB1, SIP1 and Twist1 were detected in both LNCaP and LNCaP/HIF1alpha cells, with significant differences only in the expressions of Slug and Twist1 between the two cells. The expression of Slug was increased, but that of Twist1 decreased in the LNCaP/HIF1alpha cells. All the five transcription factors but Twist1 were expressed in both the IF11 and IA8 cells, but only the express- sions of ZEB1 and Slug were increased significantly in the IA8 cells.</p><p><b>CONCLUSION</b>There are different mechanisms underlying transcriptional regulation in different prostate cancer EMT models. Slug may be one of the key transcription factors involved in the HIF1alpha-induced EMT of LNCaP cells, while ZEB1 and Slug may play an important role in repressing the epithelial phenotype of the ARCaP model.</p>

Proteomic study of retinoid acid resistant NB4R1 cells apoptosis induced by realgar / 中华血液学杂志

<p><b>OBJECTIVE</b>To obtain and identify the differential proteome of apoptosis induced by realgar (tetra-arsenic tetra-sulfide, As(4)S(4)) in retinoid acid (RA) resistant human acute promyelocytic leukemia (APL) cell line NB4-R1 cells.</p><p><b>METHODS</b>The comparative proteomic expressive profiles of NB4-R1 cells treated with and without As(4)S(4) were obtained with the high-resolution two-dimensional electrophoresis system. After the analysis of ImageMaster(TM) 2D Platinum software combining artificial comparison. The differential expression proteins were screened and performed in-gel digestion and extraction of peptides, applied mass spectrometry MALDI-TOF-MS, MALDI-TOF/TOF, UPLC-MS/MS and bioinformatics to identify differential expressive proteins.</p><p><b>RESULTS</b>Twenty-two spots with more than 2-fold (≥ 2 or ≤ 0.5) expression changes were identified and 21 known proteins obtained, including 5 down-regulated (SET/I2PP2A, RPP2, PCBP1, EIF4H-1 and ANP32A/I1PP2A) after exposed to As(4)S(4), 2 up-regulated (HSP27 and HMGB1) after exposed for 24 h, and 14 up-regulated (PHB, ERP29, DNAJC8, PSMB4, ACTB, RPP0, RhoGDI2, alpha-tubulin, transcription factor, RBM15/OTT1, eIF5A1 and H2B1M et al.) after exposed for 48 h.</p><p><b>CONCLUSION</b>It is the first time to successfully obtain and identify the global proteome of apoptosis induced by As(4)S(4) in RA-resistant cells. Among them, expressional and functional regulation of target proteins SET, RPP2 and PHB might be the potential novel therapeutic target for RA-resistant APL.</p>

Two mutations of the KRT6A gene in Chinese patients with pachyonychia congenita type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the gene mutation in a Chinese pedigree and one sporadic case with pachyonychia congenita type I(PC-1), as well as to explore the relationship between the genotype and phenotype.</p><p><b>METHODS</b>The whole coding region of the KRT16 and KRT6A genes were amplified by long-range polymerase chain reaction (PCR). Six patients with PC-1 were studied, five of them were from a pedigree and the other one was sporadic. One unaffected member in the pedigree and 100 unrelated healthy individuals were also studied in order to exclude polymorphism. PCR products were directly sequenced to detect the mutation.</p><p><b>RESULTS</b>No mutations in the KRT16 gene were observed. All patients harbored a mutation in the KRT6A gene. All five patients in the pedigree had a mutation at codon 465 (TAC to CAC) which substitutes tyrosine (Y) by histidine (H). In the sporadic patient, codon 171 (AAC) was mutated to GAC, which changes the asparagines (N) to aspartic acid (D). No such mutations were found in the unaffected member of the pedigree and the 100 unrelated controls. The mutation of Y465H is located at the end of 2B and N171D at the beginning of 1A domain of KRT6A, both are hotspots for pathogenic keratin mutations.</p><p><b>CONCLUSION</b>The mutations Y465H and N171D of the KRT16A gene were detected in the pedigree and the sporadic case respectively. The Y465H mutation was a novel mutation, and the N171D mutation was reported recently.</p>

Identification of Wnt/beta-catenin signal pathway in human prostate cancer cell lines and its significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To determine the Wnt/beta-catenin signal pathway in different human prostate cancer cell lines and explore its role in epithelial-mesenchymal transition (EMT) in human prostate cancer.</p><p><b>METHODS</b>We detected the expressions of beta-catenin, t-GSK3beta and p-GSK3beta in several prostate cancer cell lines (LNCaP, C4, C4-2, C4-2B, IF11, IA8, PC-3 and DU145) with different characteristics of epithelial-mesenchymal transition (EMT) by Western blotting.</p><p><b>RESULTS</b>There were remarkable differences in the expressions of beta-catenin and p-GSK3beta among the cell lines, with beta-catenin and p-GSK3beta highly expressed in LNCaP, C4, C4-2, C4-2B, IF11 and IA8, lowly expressed in PC-3 and DU145, but no difference was observed in the expressions of t-GSK3beta in all the cell lines.</p><p><b>CONCLUSION</b>There are differences in the state of the Wnt/beta-catenin signal pathway among the cell lines with different characters of EMT.</p>

Expression of Smad4 in prostate cancer LNCaP and ARCaP cell lines with different metastatic potentials and its significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the expression of Smad4, the core of TGF-beta/Smads signal transduction pathway in different prostate cancer cell lines, and explore their molecular mechanism of bone metastatic potential.</p><p><b>METHODS</b>The Millicell polycarbonate filter coated with matrigel was used to confirm the invasive potency of LNCaP and ARCaP cell lines (IF11 and IA8). The expressions of the Smad4 protein and mRNA in these prostate cancer cells with different metastatic potentials were detected by Western blotting and RT-PCR, respectively.</p><p><b>RESULTS</b>ARCaP cell lines (IF11 and IA8) exhibited a stronger potency of invasion than LNCaP (P < 0.01). The Smad4 protein and mRNA highly expressed in the LNCaP cell line that was well-known with a low metastatic potential, but not in the ARCaP (IF11 or IA8) cells with high metastatic potentials (P < 0.01).</p><p><b>CONCLUSION</b>Smad4 expresses differently in LNCaP and ARCaP cell lines with different metastatic potentials and, as a tumor suppressive gene, its deficient expression may play an important role in the invasion and metastasis of advanced prostate cancer.</p>

Identification of TGF-beta/Smads pathway in human prostate cancer cell lines and its significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To determine the TGF-beta/Smads signal pathway in different human prostate cancer cell lines, and to explore the role of the TGF-beta/Smads pathway in the progression and metastasis of prostate cancer and its possible mechanisms.</p><p><b>METHODS</b>We detected the expressions of the key proteins involved in the TGF-beta/Smads pathway, TbetaR II, Smad2/3, p-Smad2 and Smad4, in prostate cancer cell lines LNCaP, PC-3, DU145, IF11 and IA8 with different metastatic potentials by Western blotting.</p><p><b>RESULTS</b>TbetaR II was expressed highly in PC-3, DU145, IF11 and IA8, but extremely lowly in LNCaP. Smad2/3 was highly expressed in all the cell lines with different intensity, while p-Smad2 only in PC-3 and DU145. The expression of Smad4 was detected in LNCaP, PC-3 and DU145, but not in IF11 and IA8.</p><p><b>CONCLUSION</b>The status of the TGF-beta/Smads pathway differs in the cell lines with different metastatic potentials, only active in PC-3 and DU145. The TGF-beta/Smads pathway may be involved in the invasion and metastasis of prostate cancer through altering the expressions of the key proteins in it.</p>

High-dose estrogen inhibits prostate development by down-regulating SHH signaling in new-born SD rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of high-dose estrogen on the development of the prostate in new-born SD rats and its possible relationship with the sonic hedgehog (SHH) signaling pathway.</p><p><b>METHODS</b>One hundred new-born male SD rat pups were assigned to an experimental group, subcutaneously injected with 25 microg Estradiol + 25 microl corn oil vehicle, and a control group, given corn oil alone, on postnatal day (PD) 0, 1, 3 and 5. The animals were sacrificed by decapitation and their prostates removed on PD 1, 6, 10, 20 and 30. The morphological changes of the prostate were observed by HE staining, and SHH signaling related molecules were detected by immunohistochemistry and reverse transcription PCR.</p><p><b>RESULTS</b>High-dose estrogen significantly inhibited the organogenesis of the new-born SD rat prostate and down-regulated the expressions of SHH signaling related molecules.</p><p><b>CONCLUSION</b>High-dose estrogen may restrain the development of the prostate in new-born SD rats via inhibition of SHH signaling.</p>

Effects of prepubertal exposure to diethylstilbestrol on testicular development and function of SD rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of prepubertal exposure to diethylstilbestrol (DES) on the testicular development and function of Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>Ninety 21-day-old male SD rats were randomly and equally divided into 4 experimental groups (Da, Db, Dc and Dd), which were injected with DES dissolved in corn oil at the dose of 0.01, 0.1, 1.0 and 10.0 microg/(kg x d) from postnatal day (PND) 22 to 35, and a control group (C), which received vehicle only. The testicular development of all the rats was observed, and their testes were harvested in the stages of late puberty (PND 50), sexual maturity (PND 64) and adulthood (PND 130) respectively to determine the weight and histological features of the testis and examine the quality of the sperm in the epididymal cauda of the PND 130 rats.</p><p><b>RESULTS</b>The testis descent in the C, Da, Db, Dc and Dd groups occurred on PND 26.17 +/- 1.94, 26.83 +/- 1.47, 28.68 +/- 1.03, 33.50 +/- 1.87 and 41.50 +/- 2.74 respectively, significantly delayed in the Db, Dc and Dd groups compared with the C group (P < 0.05 or P < 0.01). On PND 50, the unilateral testis weights in the C, Da, Db, Dc and Dd groups were (1.38 +/- 0.01) g, (1.38 +/- 0.12) g, (1.30 +/- 0.14) g, (0.86 +/- 0.18) g and (0.73 +/- 0.27) g respectively, significantly less in the Dc and Dd groups than in the C group (P < 0.01). Compared with the C group, there was a slight decrease in the number of the cells in the epithelia of a few seminiferous tubules in the Db group on PND 50, maldevelopment of seminiferous tubules, reduced cell number in seminiferous epithelia, blocked spermatogenesis and aplasia of Leydig cells in the Dc and Dd groups in a dose-dependent manner. On PND 64, the unilateral testis weights in the C, Da, Db, Dc and Dd groups were (1.60 +/- 0. 06) g, (1.62 +/- 0.11) g, (1.58 +/- 0.08) g, (1.47 +/- 0.10) g and (0.99 +/- 0.37) g respectively, significantly less in the Dc and Dd groups than in the C group (P < 0.05 or P < 0.01), and the histological alteration of the testis in the Dc and Dd groups was similar to or less than that on PND 50. On PND 130, no statistic difference was observed either in unilateral testis weight or in the histological features of the testis between any experimental group and the control (P > 0.05). The sperm concentration in the epididymal cauda in the C, Da, Db, Dc and Dd groups were (73.00 +/- 16.90) x 10(6)/ml, (68.00 +/- 19.67) x 10(6)/ml, (68.67 +/- 12.15) x 10(6)/ml, (35.17 +/- 15.64) x 10(6)/ml and (19.13 +/- 5.17) x 10(6)/ml, significantly lower in the Dc and Dd groups than in the C group (P < 0.01). There was a significant decrease in sperm motility in the Dd group (P < 0.01), the percentage of grade a sperm in the Db, Dc and Dd groups (P < 0.05) and the percentage of grade b sperm in the Dd group (P < 0.01).</p><p><b>CONCLUSION</b>Prepubertal exposure to low dose of DES (0.01 microg/[kg x d] x 14 d) does not significantly affect the testicular development and function of SD rats, while high dose (1.0-10.0 microg/[kg x d] x 14 d) has significant short- (PND 50 and 64) or long-term (PND 130) toxic effect, which increases with dose and decreases with age. The mechanism of the toxic effect involves the insults to the development and function of Leydig and Sertoli cells.</p>

Genetic polymorphism of glutathione S-transferase T1 gene and susceptibility to idiopathic azoospermia or oligospermia in northwestern China / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To investigate the association of glutathione S-transferase T1 (GSTT1) gene polymorphism in patients with idiopathic azoospermia or oligospermia in the northwestern China population.</p><p><b>METHODS</b>In the case-control study, GSTT1 genotypes were identified by multiplex polymerase chain reaction (PCR) with peripheral blood DNA samples from 78 patients with idiopathic azoospermia, 103 patients with idiopathic oligospermia and 156 age-matched controls with normal sperm concentration and motility, according to the criteria adapted from World Health Organization guidelines. All of the patients and controls were from northwestern China.</p><p><b>RESULTS</b>There is a significant association between GSTT1 null genotype with idiopathic azoospermia risk (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.33-4.20, P=0.003) or idiopathic oligospermia risk (OR: 2.00, 95% CI: 1.17-3.27, P=0.010).</p><p><b>CONCLUSION</b>GSTT1 null genotype is a predisposing risk factor for sporadic idiopathic azoospermia or oligospermia in northwestern China.</p>

Genetic polymorphism of glutathione S-transferase T1 associated with idiopathic azoospermia and oligospermia / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the association of glutathioneS-transferase T (GSTT1) gene polymorphism with azoospermia and oligospermia.</p><p><b>METHODS</b>Semen samples from 34 patients with idiopathic azoospermia, 40 patients with idiopathic oligospermia and 53 healthy controls with normal sperm concentration and motility were assessed according to the standards of WHO. The GSTT1 genotypes were identified by multiplex polymerase chain reaction (PCR) with peripheral blood DNA samples.</p><p><b>RESULTS</b>The frequencies of null GSTTI genotypes in the patients with idiopathic azoospermia, idiopathic oligospermia and the healthy controls were 76.5%, 72.5% and 49.1%, respectively. There was a significant association between the null alleles of GSTT1 and idiopathic azoospermia (odds ratio 3.13, 95% CI 1.20-8.16, P = 0.020) and idiopathic oligospermia (odds radio 2.53, 95% CI 1.06-6.11, P = 0.038).</p><p><b>CONCLUSION</b>The null alleles of GSTTI are a strong predisposing risk factor for idiopathic azoospermia and oligospermia.</p>