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.

BackgroundFetal growth restriction (FGR) is an important but poorly understood condition of pregnancy, which results in significant fetal, neonatal and long-term morbidity and mortality. Novel research has suggested that altered miRNA expression in the plasma and placenta is associated with adverse pregnancy. We hypothesized that aberrant expression of microRNA-141 (miR-141) in the placenta is associated with FGR. Additionally, expression levels of predicted target genes of miR-141 were also analyzed in placental tissues of FGR and normal controls.Methodology/Principal FindingsUsing quantitative real time PCR, we analyzed the expression level of miR-141 and its target genes in placentas of FGR pregnancies (n = 21) and normal controls (n = 34). Western blot was used to detect the protein expression level of the target genes of miR-141. MiR-141 showed significant up regulation in FGR and significant down regulation of its targets, i.e. E2F transcription factor 3 (E2F3) protein, pleiomorphic adenoma gene 1 (PLAG1) mRNA and protein. Moreover, a positive correlation was found between PLAG1 and insulin-like growth factor 2 (IGF2) expression levels (Spearman r = 0.56, p<0.0001). MiR-141 yields an AUC of 0.83 with 88.5% sensitivity and 71.7% specificity for separating FGR from normal controls. This study indicates that miR-141 may be diagnostically important in FGR.Conclusions/SignificanceOur results indicate that aberrant high expression level of miR-141 might play important roles in the pathogenesis of FGR by suppressing E2F3 and PLAG1. We propose that miR-141 may participate in a miR-141-PLAG1-IGF2 network relating to FGR development. These findings may provide new targets via miR-141 in diagnosis and therapy of FGR in the future.

We used a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach to obtain the metabolic profiling of unexplained male infertility (UMI), and identified seminal plasma biomarkers associated with UMI by a two-stage population study. A robust OPLS-DA model based on these identified metabolites was able to distinguish 82% of the UMI patients from health controls with a specificity of 92%. In this model, 44 metabolites were found differentially expressed in UMI subjects compared with health controls. By pathway enrichment analysis, we identified several major changed metabolic pathways related to UMI. Our findings provide new perspective for the diagnosis of UMI.

Published data on the association between the GST genes polymorphisms and male infertility risk are inconclusive. We investigated GST genes polymorphisms in a large sample size case-control study, and conducted a literature-based meta-analysis of 6934 individuals. Our case-control study showed the GSTM1 null genotype was significantly associated with idiopathic oligozoospermia, while the null genotype of GSTT1 was significantly associated with normozoospermia and azoospermia. Additionally, significantly elevated GSTT1 expression levels were observed in present genotype compared with null genotype. In the meta-analysis, the null genotype of GSTM1 was associated with a significantly increased risk of male infertility. Furthermore, a stratification analysis showed that the risk of GSTM1 polymorphism was associated with male infertility in both Asian and Caucasian groups. Further studies of GSTM1 and GSTT1 with their biological functions are needed to understand the role of these genes in the development of male infertility.I nfertility is a worldwide reproductive health problem which affects 10%-15% of couples and about half of the cases are due to male factors 1 . Although several causes have been identified for impaired male fertility 2 , the aetiology remains unknown in nearly half of all cases. It is currently accepted that genetics contributes to spermatogenetic failure for about 30% of idiopathic infertility in males 3 .Sperms are susceptible to oxidative damage and excessive reactive oxygen species (ROS) generation may lead to subfertility or infertility 4 . Glutathione S-transferases (GSTs) represent an important superfamily of phase II metabolic enzymes that catalyze the conjugation of reduced glutathione with electrophilic groups of a wide variety of environmental compounds. GSTs are responsible for detoxification of many xenobiotics and endogenous ROS by catalyzing the conjugation of reduced glutathione to the substrate or sequestering toxic compounds, and play a key role in protecting cells against oxidative stress 5 . Human GSTs are divided into eight distinct classes as alpha, kappa, mu, omega, pi, sigma, theta, and zeta based on the similarity of amino acid sequence and antibody cross-reactivity 6,7 . The GSTM1 and GSTT1 gene have been located on chromosome 1p13.3 and 22q11, respectively. Homozygotes for the null alleles (deletion) of GSTM1 and GSTT1 lack activity of the respective enzymes 8 . As a result, GSTs decrease the reactivity of electrophilic substrates, which can affect spermatogenesis and spermatozoa function with cellular macromolecules, such as nucleonic acid, lipid and protein.The enzymatic deficiency in isoforms of GSTs is correlated with increased risk to develop certain diseases associated with oxidative damage. In this case an association between the genotypes of GSTM1, GSTT1 and risk of idiopathic infertility is possible.Recently, a number of molecular epidemiological studies have been conducted to examine the association between GSTM1 and GSTT1 null polymorphisms and male infertil...

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There is increasing concern that early-life exposure to endocrine disruptors affects male offspring reproduction. However, whether di-n-butyl phthalate (DBP), a widely used endocrine disruptor, has transgenerational effects and, if so, the exact underlying molecular mechanisms involved remain unknown. In our study, 5 of time-mated pregnant SD rats were exposed to 0 and 500 mg/kg DBP with corn oil as the vehicle via oral gavage from embryonic days (E8-E14). Epigenetic and metabolomic of testis were analyzed after post-natal 60 days. Sperm and testicular cell functions were examined to confirm the transgenerational effects. DBP exposure significantly decreased the sperm counts in F1 through F3 generation. We found distinct metabolic changes in the testis of both F1 and F3 generation offspring, specifically, a significantly increased level of betaine, which is an important methyl donor. In contrast, the expression of betaine homocysteine S-methyltransferase (BHMT), which catalyzes the transfer of methyl moiety from betaine to homocysteine, significantly decreased. There was accompanying global DNA hypomethylation, along with a reduction in follistatin-like 3 (Fstl3) promoter hypomethylation, which is a known modulator of Sertoli cell number and spermatogenesis. In summary, we conclude that metabolomic and epigenetic changes induced by the aberrant expression of BHMT represent a novel mechanism linking in utero DBP exposure to transgenerational spermatogenesis failure.

Several studies have investigated the association between polymorphisms in the Deleted in AZoospermia-Like (DAZL) gene and male infertility risk, but with inconsistent results. We aimed to derive a more precise estimation of the relationship, therefore a meta-analysis was performed. A total of 13 case-control studies, including 2556 cases and 1997 controls, were selected. Two polymorphisms in DAZL were investigated, namely T12A (Thr12 → Ala) and T54A (Thr54 → Ala). Our meta-analysis showed that A > G is a risk factor for male infertility (P = 0.047, OR = 1.262, 95%CI = 1.003–1.587). However, when using trial sequential analysis (TSA) to confirm, we found that A > G risk effect turned out to be false positive. In addition, significant association was found between the T54A polymorphism and male infertility under co-dominant model (AG vs. AA: OR = 4.364, 95%CI = 2.207–8.630, P < 0.001) and dominant model (OR = 4.584, 95%CI = 2.320–9.058, P < 0.001). Stratified analysis showed that significantly strong association between T54A polymorphism and male infertility was present only in Asians, but not in Caucasians. Further studies of T12A and T54A with their biological functions are needed to understand the role of these polymorphisms in the development of male infertility.

Macrosomia is one of the most common perinatal complications of pregnancy and has life-long health implications for the infant. microRNAs (miRNAs) have been identified to regulate placental development, yet the role of miRNAs in macrosomia remains poorly understood. Here we investigated the role of miR-17-92 cluster in macrosomia. The expression levels of five miRNAs in miR-17-92 cluster were significantly elevated in placentas of macrosomia, which may due to the up-regulation of miRNA-processing enzyme Drosha and Dicer. Cell cycle pathway was identified to be the most relevant pathways regulated by miR-17-92 cluster miRNAs. Importantly, miR-17-92 cluster increased proliferation, attenuated cell apoptosis and accelerated cells entering S phase by targeting SMAD4 and RB1 in HTR8/SVneo cells. Furthermore, we found that expression of miR-17-92 cluster in serum had a high diagnostic sensitivity and specificity for macrosomia (AUC: 80.53%; sensitivity: 82.61%; specificity: 69.57%). Our results suggested that miR-17-92 cluster contribute to macrosomia development by targeting regulators of cell cycle pathway. Our findings not only provide a novel insight into the molecular mechanisms of macrosomia, but also the clinical value of miR-17-92 cluster as a predictive biomarker for macrosomia.