OBJECTIVETo explore the influence of the DNA repair gene ERCC2 single nucleotide polymorphisms (SNPs) rs13181, rs1618536, and rs1799793 on male idiopathic infertility in Ningxia, China.

METHODSUsing MassArray, we conducted a case-control study and genotyped three ERCC2 SNPs rs13181, rs1618536, and rs1799793 for 351 males (aged 31.0 +/- 4.2 years) with idiopathic infertility and another 327 normal fertile men (aged 33.0 +/- 5.9 years) as controls.

RESULTSThe ERCC2 AnyG-anyA-anyA genotypes were significantly associated with an increased risk of idiopathic infertility (OR 0.414, 95% CI 0.176 - 0.970), while the three single ERCC2 SNPs rs13181, rs1618536, and rs1799793 showed no significant differences between the cases and controls (P > 0.05).

CONCLUSIONThe ERCC2 SNPs rs13181, rs1618536, and rs1799793 play a role of interaction in male idiopathic infertility in Ningxia, contributing to the risk of the disease.

Adult ; Case-Control Studies ; China ; DNA Repair ; Genotype ; Humans ; Infertility, Male ; genetics ; Male ; Polymorphism, Single Nucleotide ; Xeroderma Pigmentosum Group D Protein ; genetics

Acute Disease ; Animals ; Astrocytes ; metabolism ; pathology ; Cats ; Dimethoate ; analogs & derivatives ; poisoning ; Female ; Glial Fibrillary Acidic Protein ; metabolism ; Male ; Poisoning ; metabolism ; pathology

AIMTo evaluate the key lesions in spermatogenesis suppressed partially by testosterone undecanoate (TU) treatment.

METHODSAdult male SD rats were treated with vehicle or TU (19 mg/kg) injection (i.m.) every 15 days for 130 days. The numbers of all types of cells (nuclei) in the seminiferous tubules and the interstitial tissue were estimated using a contemporary stereological tool, the optical disector.

RESULTSIn response to TU treatment, the numbers of non-type B spermatogonia, type B spermatogonia and late elongated spermatids per testis were reduced to 51 %, 66 % and 14 % of the controls, respectively. The conversion ratios from type B spermatogonia to early spermatocytes and pachytene spermatocytes were not significantly affected and the ratios to the later germ cell types fell to 51 % - 65 % of the controls. Less than 1.0 % of immature round spermatids were seen sloughing into the tubule lumen, 4.0 % of elongated spermatids retained in the seminiferous epithelium, and about half of the elongated spermatid nuclei appreciably malformed. Leydig cells were atrophied but their number and the peritubular myoid cell number per testis were unchanged.

CONCLUSIONDouble inhibition of spermatogenesis (i.e. inhibition at spermiation and spermatogonial conversion to type B spermatogonia), a scenario seen in the monkey and human following gonadotrophin withdrawal, was not sufficiently effective for a complete spermatogenic suppression in the rat after TU treatment, probably due to ineffective inhibition of the Leydig cell population and therefore the intra-testicular testosterone levels.

Animals ; Cell Nucleus ; drug effects ; ultrastructure ; Depression, Chemical ; Leydig Cells ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sertoli Cells ; drug effects ; Sperm Count ; Spermatids ; drug effects ; Spermatogenesis ; drug effects ; Testosterone ; analogs & derivatives ; blood ; pharmacology

It has become more and more urgent to develop a safe, effective, recoverable and acceptable contraceptive for males. Decades of studies have made much progress on male hormonal contraception, one of the promising contraceptive methods. The principle is based on the suppression of pituitary gonadotropin and intratesticular testosterone, then the suppression of spermatogenesis, and the supplement of androgen to maintain the male characteristics and sexual function. There are many male hormonal contraceptive methods being studied include androgen, androgen combined with progesterone, GnRH antagonists combined with androgen, as well as immunological methods. To develop a safe and convenient androgen preparation with longer action and fewer side effects is also one of the key items of present research in this field.
Androgens ; Animals ; Contraception ; methods ; Contraceptive Agents, Male ; Contraceptives, Oral, Hormonal ; Humans ; Male ; Mice ; Progestins ; Rats ; Sheep

AIMObserve the effects of er-long-zuo-ci-wan (EIZCW, a compound of Chinese Traditional Medicine) on the spontaneous discharge of external cortex of inferior colliculus (ICx) and secondary auditory cortex (AII) of chronic tinnitus model rats induced by salicylate acid, to explore the neural mechanisms underlying ELZCW preventing tinnitus.

METHODS30 adult SD rats were involved and divided into three groups, normal control group, chronic tinnitus model group and ELZCW prevention group. Extracellular recording techniques and stereotaxic method were used. The spontaneous spikes were recorded and analyzed from ICx and all in different group rats. The average rate of spontaneous discharge and the interspike interval histogram of spontaneous activities were used as indexes.

RESULTS(1) Compared with normal control group, the average rate of spontaneous discharge recorded from the ICx in the chronic tinnitus model group increased significantly (4.57 +/- 0.54 Hz vs. 3.14 +/- 0.40 Hz, P < 0.05). Furthermore analysis showed that the discharge rate of short spike interval from the ICx in the chronic tinnitus model group increased than that of the normal group (0-40 ms: 58% vs. 40%; 0-4 ms: 9% vs. 5%). And there was an increasing tendency of the average rate of spontaneous discharge recorded from the AII in the chronic tinnitus model group compared with that in the normal group. (2) Compared with the chronic tinnitus model group, the average rate of spontaneous discharge recorded from the ICx and AII in the ELZCW prevention group significantly decreased than that in the chronic tinnitus model group (ICx: 2.41 +/- 0.21 Hz vs. 4.57 +/- 0.54 Hz, P < 0.01. AII: 2.24 +/- 0.24 Hz vs. 4.57 +/- 0.54 Hz , P < 0.01). And the discharge rate of short spike interval from the ICx and AII in the chronic tinnitus model group decreased than that in the normal control group (ICx: 0-40 ms 50% vs. 58%, 0-4 ms 4% vs. 9%. All: 0-22 ms: 24% vs. 31%, 0-8 ms 19% vs. 16%).

CONCLUSIONIf the increasing of the spontaneous activities of ICx and AII in chronic tinnitus rats means tinnitus, the use of ELZCW could decrease this kind of changes.

Animals ; Auditory Cortex ; physiopathology ; Auditory Pathways ; drug effects ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Salicylic Acid ; Tinnitus ; chemically induced ; drug therapy ; physiopathology

OBJECTIVEThis study aimed to investigate the effect of trichloroethylene (TCE) intake via drinking water on Th17 cells in mice.

METHODSForty eight six weeks old female BALB/c mice were divided into blank control, vehicle control, 2.5 mg/ml TCE and 5.0 mg/ml TCE groups by random number table (12 mice each group), and exposed to TCE by drinking water. On the 14(th), 28(th), 56(th), 84(th) days, blood were collected and assayed for IL-17, IL-6, and TGF-β concentration in serum through ELISA. Animals were killed and spleen biopsies were taken sterility. The proportion of Th17 cells among CD4(+) T cells and RORγt mRNA expression level in spleen were measured by FCM and real-time PCR.

RESULTSIn 2.5 mg/ml TCE and 5.0 mg/ml TCE group mice, Th17 cells/CD4(+) T cells in spleen were (3.46 ± 0.32)% and (5.45 ± 0.45)% on day 14, (3.47 ± 0.33)% and (4.10 ± 0.39)% on day 84, which were significantly higher than those for solvent control group at the same time point ((2.15 ± 0.20)%, (2.16 ± 0.35)%, respectively) (P < 0.01). RORγt mRNA expression levels were (1.870 ± 0.084) and (1.965 ± 0.060) on 14 day, (1.998 ± 0.079) and (2.028 ± 0.073) on day 56, which were also significantly higher than those for solvent control group at the same time point (1.77 ± 0.04 and 1.75 ± 0.09, respectively) (P < 0.05). IL-17 concentrations in serum were (32.28 ± 5.38) and (34.47 ± 5.02) pg/ml on day 14, and (34.87 ± 5.48) and (41.94 ± 6.19) pg/ml on day 28, which were significantly higher than those for solvent control group at the same time point((21.57 ± 5.23), (22.11 ± 5.11) pg/ml). IL-6 concentration in serum were (43.07 ± 6.71) and (47.86 ± 8.52) pg/ml on day14, (41.32 ± 7.04) and (46.74 ± 9.33) pg/ml on day 56, which were significantly higher than solvent control group at the same time point ((7.56 ± 7.71) and (28.26 ± 7.22) pg/ml). TGF-β concentration were (17.48 ± 3.06) and (18.93 ± 3.12) pg/ml on day 14, which did not show significant difference from solvent control group ((15.25 ± 2.95) pg/ml). Correlation analysis showed that IL-6 in serum were significantly positively correlated with the proportion of Th17 cells among CD4(+) T cells and RORγt expression level in spleen (r = 0.741, 0.765, P < 0.01).

CONCLUSIONTCE might promote the differentiation of Th17 cells and increase IL-17 secretion by inducing IL-6 and up-regulating RORγt expression together with TGF-β.

Animals ; Drinking Water ; chemistry ; Female ; Interleukin-17 ; immunology ; Interleukin-6 ; immunology ; Mice ; Mice, Inbred BALB C ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; immunology ; Th17 Cells ; drug effects ; immunology ; Transforming Growth Factor beta ; immunology ; Trichloroethylene ; toxicity

More and more study on the epididymal function and sperm maturation has shown that epididymis will be one of the best target organs of male contraception, although at present there is not a male contraceptive medicine based on epididymis for clinical practice. The promoting research aspects in epididymal contraception in animal included affecting directly epididymis (such as Sulpasalazine), interfering energy metabolism and sperm mobility (such as Chlorinated Glycerol), altering the internal environment of epididymis (such as copper particles and TW19). The epididymal specific proteins could bring out some new target antigens for immunological contraception, to produce contraceptive vaccine. Some special genes, which expressed distinctively in epididymis such as SC342, bin1, have been cloned and studied on their function. These works would be helpful not only for clinical diagnosis and treatment of epididymitis and male infertility, but also for male contraceptive research and progress.
Contraception ; Contraceptive Agents, Male ; pharmacology ; Energy Metabolism ; drug effects ; Epididymis ; drug effects ; physiology ; Humans ; Male ; Sperm Maturation ; drug effects ; Sperm Motility ; drug effects

Adolescent ; Adult ; Aged ; Ankle Joint ; pathology ; physiopathology ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Tuberculosis, Osteoarticular ; drug therapy ; pathology ; physiopathology ; surgery ; Young Adult

To investigate the role and mechanism of ceramide (Cer) regulation in alcohol-induced neuronal proliferation and the newborn neurons formation, we used sphingomyelin synthase 2 (predominant enzyme of Cer metabolism) knockout (SMS2(-/-)) and wild type (WT) female mice to establish the model of prenatal alcohol exposure. In 24 h after being given birth (postnatal day 0, P0), the offspring of model mice received blood sphingomyelin (SM) measurement with enzymatic method. On P0, P7, P14 and P30, the proliferation of granule cells in the dentate gyrus and newborn neurons were investigated with immunofluorescent labeling. The expression of protein kinase Cα (PKCα) in the hippocampus was tested with Western blot analysis. The results showed that the SM level of blood in SMS2(-/-) pups was significantly lower than that in WT pups. No matter in SMS2(-/-) or WT mice, the prenatal alcohol exposure down-regulated the SM levels in pups with dose-dependency. In both SMS2(-/-) and WT pups, the number of proliferative neurons and newborn neurons in the dentate gyrus gradually decreased with the growing age. Compared with the WT pups, SMS2(-/-) pups showed significantly more proliferative neurons and newborn neurons in the dentate gyrus. Notably, prenatal alcohol exposure dose-dependently increased proliferative neurons and newborn neurons in the dentate gyrus in both WT and SMS2(-/-) pups. The hippocampal expression of PKCα protein in SMS2(-/-) mice was lower than that in WT mice, and prenatal alcohol exposure could up-regulate the PKCα protein expression in both WT and SMS2(-/-) mice with dose dependency. These results suggest that alcohol exposure during pregnancy can induce the compensatory neural cell proliferation and the production of newborn neurons in offspring, and the Cer-ceramide-1-phosphate (C1P) pathway is involved in alcohol-induced neural cell proliferation. The activation of PKCα may be a key step to start the Cer-C1P pathway and up-regulate the alcohol-induced neural cell proliferation and the newborn neurons formation.
Animals ; Animals, Newborn ; Cell Proliferation ; drug effects ; Cells, Cultured ; Ceramides ; metabolism ; Dentate Gyrus ; cytology ; Ethanol ; toxicity ; Female ; Mice ; Mice, Knockout ; Neurons ; cytology ; Pregnancy ; Prenatal Exposure Delayed Effects ; physiopathology ; Protein Kinase C-alpha ; metabolism ; Signal Transduction ; Transferases (Other Substituted Phosphate Groups) ; genetics

OBJECTIVETo study the protective effect of Shenxiong injection on the cerebral ischemia-reperfusion injury of senile rats.

METHODTotally 108 Sprague-Dawley (SD) rats were randomly divided into the sham operation group, the model group, the Ni-modipine group and Shenxiong injection groups (low, middle, and high doses). The rat brain ischemia-reperfusion model was established by the middle cerebral artery occlusion (MCAO) method in rats, in order to observe the effect of Shenxiong injection on neurological score and brain infarct volume of rats with cerebral ischemia-reperfusion injury, and determine the contents of NOS, NO, SOD, MDA and LDH in brain tissues. The contents of TNF-alpha and IL-1beta levels in brain tissues were measured by enzyme-linked immunosorbent assay (ELISA) method.

RESULTShenxiong injection could significantly decrease neurological score, injury degree of brain tissues and brain infarct volume of rats with cerebral ischemia-reperfusion injury, increase the vigor of SOD, decrease the levels of MDA, NO, NOS and LDH, and inhibit IL-1beta and TNF-alpha expressions.

CONCLUSIONShenxiong injection has the obvious protective effect on the brain ischemia-reperfusion injury in rats. Its mechanism may be related to the improvement of neurological function, the reduction of free radical injury, and the inhibition of inflammation factor expression.

Animals ; Brain ; blood supply ; drug effects ; metabolism ; Brain Ischemia ; complications ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Injections ; L-Lactate Dehydrogenase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; complications ; drug therapy ; enzymology ; metabolism ; Superoxide Dismutase ; metabolism