Abnormal germline DNA methylation in males has been proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. Previous studies have been focused on imprinted genes with DNA methylation in poor quality human sperms. However, recent but limited data have revealed that sperm methylation abnormalities may involve large numbers of genes or shown that genes that are not imprinted are also affected. Using the methylation-specific polymerase chain reaction and bisulfite sequencing method, we examined methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene (NG_013351: 1538–1719) in sperm DNA obtained from 94 idiopathic infertile men and 54 normal fertile controls. Subjects with idiopathic infertility were further divided into groups of normozoospermia and oligozoospermia. Overall, 45% (41/94) of idiopathic infertile males had MTHFR hypermethylation (both hemimethylation and full methylation), compared with 15% of fertile controls (P<0.05). Subjects with higher methylation level of MTHFR were more likely to have idiopathic male infertility (P-value for trend = 0.0007). Comparing the two groups of idiopathic infertile subjects with different sperm concentrations, a higher methylation pattern was found in the group with oligozoospermia. Hypermethylation of the promoter of MTHFR gene in sperms is associated with idiopathic male infertility. The functional relevance of hypermathylation of MTHFR to male fertility warrants further investigation.

MicroRNAs (miRNAs) are small non-coding RNAs (18–25 nt), playing important regulatory roles via interaction with cellular messenger RNAs. The altered expression of miRNAs in specific tissues has been associated with diseases such as cancer and diabetes. We examined the presence of two selected miRNAs (miR-19b and let-7a) in human seminal plasma from fertile men and idiopathic infertile patients with oligozoospermia and non-obstructive azoospermia (NOA) using quantitative real-time PCR. We detected miRNAs in the seminal plasma of humans. The levels of miRNAs in the seminal plasma were reproducible in repeat samples from the same individuals. In addition, we examined the expression patterns of two selected miRNAs in 96 idiopathic infertile males (48 oligozoospermia and 48 NOA) and 48 fertile controls. Another 48 individuals of each group were used for verification. Our data showed that the expression levels of these two miRNAs in the seminal plasma significantly increased in idiopathic infertile males with NOA compared with fertile controls, whereas the expression levels were similar between idiopathic infertile males with oligozoospermia and fertile controls. In conclusion our results indicate that the expression of miR-19b and let-7a in the seminal plasma are reproducible and stable. Aberrant over-expression levels of miR-19b and let-7a may be an indicator of spermatogenic failure.

What is the profile of miRNAs in seminal plasma of patients with non-obstructive azoospermia (NOA)? miR-141, miR-429 and miR-7-1-3p are significantly increased in seminal plasma of patients with NOA compared with fertile controls. There is currently an urgent need to develop a noninvasive diagnostic test for NOA. Altered microRNA (miRNA) profiles have been proposed as potential biomarkers for the diagnosis of disease states. A total of 200 subjects (n = 100 for NOA, n = 100 for fertile control) were recruited to participate in this study. Recruitment took place from May 2008 to June 2010. We employed a strategy consisting of initial screening by TaqMan Low Density Array then further validation with a TaqMan quantitative RT–PCR assay. Validation of the profiling results was conducted in two independent phases. In addition, the expression of the three validated seminal plasma miRNAs (sp-miRNAs) was examined in testicular tissues of patients with NOA and of fertile controls. Methylation status and functional analyses were also performed for the identified sp-miRNAs. miR-141, miR-429 and miR-7-1-3p were significantly increased in seminal plasma of patients with NOA compared with fertile controls. As sensitive and specific biomarkers, the profiling of these three identified sp-miRNAs provides a novel noninvasive, semen-based test for NOA diagnosis. The methylation status of these sp-miRNAs was inversely associated with their expression patterns. Additionally, we found that Cbl and Tgfβ2 were down-regulated by miR-141, while Rb1 and Pik3r3 were down-regulated by miR-7-1-3p. miRNA expression profile was investigated in seminal plasma samples from only a small number of NOA patients. In future investigations, a larger sample size should be adopted and the functional role of the three sp-miRNAs should be further characterized in animal models. Given that sp-miRNAs show reproducible and stable expression levels, they are potentially novel noninvasive biomarkers for the diagnosis of NOA. We propose that the three sp-miRNAs described above may participate in a methylation-miRNA-gene network related to NOA development. This work provides a foundation for interpretation of miRNA changes associated with pathogenesis of NOA and extends the current understanding of human NOA pathogenesis. This work was supported by the following grants: Key Project of National Natural Science Foundation of China (No. 30930079), National Basic Research Program of China (973 Program) (No. 2009CB941703, 2011CB944304), National Natural Science Foundation of China (No. 81072328 and 30901232); Science and Technology Development Fund Key Project of Nanjing Medical University (No. 2012NJMU002) and Priority Academic Program Development of Jiangsu Higher Education Institutions. The funding organizations played no role in the design and conduct of the study, in collection, management, analysis and interpretation of the data, or in the presentation, review or approval of the manuscript. There are no conflicts of interest to be declared.

Team-based learning (TBL) has been adopted as a new medical pedagogical approach in China. However, there are no studies or reviews summarizing the effectiveness of TBL on medical education. This study aims to obtain an overall estimation of the effectiveness of TBL on outcomes of theoretical teaching of medical education in China. We retrieved the studies from inception through December, 2015. Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Wanfang Database, Chinese Scientific Journal Database, PubMed, EMBASE and Cochrane Database were searched. The quality of included studies was assessed by the Newcastle-Ottawa scale. Standardized mean difference (SMD) was applied for the estimation of the pooled effects. Heterogeneity assumption was detected by I2 statistics, and was further explored by meta-regression analysis. A total of 13 articles including 1545 participants eventually entered into the meta-analysis. The quality scores of these studies ranged from 6 to 10. Altogether, TBL significantly increased students’ theoretical examination scores when compared with lecture-based learning (LBL) (SMD = 2.46, 95% CI: 1.53–3.40). Additionally, TBL significantly increased students’ learning attitude (SMD = 3.23, 95% CI: 2.27–4.20), and learning skill (SMD = 2.70, 95% CI: 1.33–4.07). The meta-regression results showed that randomization, education classification and gender diversity were the factors that caused heterogeneity. TBL in theoretical teaching of medical education seems to be more effective than LBL in improving the knowledge, attitude and skill of students in China, providing evidence for the implement of TBL in medical education in China. The medical schools should implement TBL with the consideration on the practical teaching situations such as students’ education level.

The development of male infertility increased rapidly worldwide, which coinciding with the epidemic of obesity. However, the impact of weight abnormalities on sperm quality is still contestable. To assess the correlation between BMI and sperm parameters, we searched relevant articles in PubMed, Embase, Web of science, and Wanfang database published until June 2015 without language restriction. Otherwise, we also recruited some participants who attended fertility clinic as well as some general populations in this report. We performed a systematic review and meta-analysis about BMI and sperm parameters containing total sperm count, concentration, semen volume and sperm motility (overall and progressive). Metabolomic analysis of seminal plasma was performed to explore the mechanism from a new perspective. This study found standardized weighted mean differences (SMD) in sperm parameters (total sperm count, sperm concentration, and semen volume) of abnormal weight groups decreased to different degree compared to normal weight. Dose-response analysis found SMD of sperm count, sperm concentration and semen volume respectively fell 2.4%, 1.3% and 2.0% compared with normal weight for every 5-unit increase in BMI. Metabolomic analysis of seminal plasma showed that spermidine and spermine were likely to play a vital role in the spermatogenesis progress. This systematic review with meta-analysis has confirmed there was a relationship between BMI and sperm quality, suggesting obesity may be a detrimental factor of male infertility.