Deleterious variant in FAM71D cause male infertility with asthenoteratospermia.

Asthenoteratospermia is a significant cause of male infertility. FAM71D (Family with sequence similarity 71, member D), as a novel protein exclusively expressed in the testis, has been found to be associated with sperm motility. However, the association of FAM71D mutation with male infertility has yet to be examined. Here, we conducted whole-exome sequencing and identified a homozygous missense mutation c.440G > A (p. Arg147Gln) of FAM71D in an asthenoteratospermia-affected man from a consanguineous family. The FAM71D variant is extremely rare in human population genome databases and predicted to be deleterious by multiple bioinformatics tools. Semen analysis indicated decreased sperm motility and obvious morphological abnormalities in sperm cells from the FAM71D-deficient man. Immunofluorescence assays revealed that the identified FAM71D mutation had an important influence on the assembly of sperm structure-related proteins. Furthermore, intra-cytoplasmic sperm injection (ICSI) treatment performed on the infertile man with FAM71D variant achieved a satisfactory outcome. Overall, our study identified FAM71D as a novel causative gene for male infertility with asthenoteratospermia, for which ICSI treatment may be suggested to acquire good prognosis. All these findings will provide effective guidance for genetic counselling and assisted reproduction treatments of asthenoteratospermia-affected subjects.

Large-area, size-controlled and transferable graphene oxide-metal films for humidity sensor.

The lack of low-cost methods to synthesize large-area graphene-based materials is still an important factor that limits the practical application of graphene devices. Herein, we present a facile method for producing large-area graphene oxide-metal (GO-M) films, which are size controllable and transferable. The sensor constructed using the GO-M film exhibited humidity sensitivity while being unaffected by pressure. The relationship between the sensor's resistance and relative humidity followed an exponential trend. The GO-Mg sensor was the most sensitive among all the tested sensors. The facile synthesis of GO-M films will accelerate the widespread utilization of graphene-based materials.

Function of proprotein convertase subtilisin/kexin type 9 and its role in central nervous system diseases: An update on clinical evidence.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL-C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice.

A Novel 10-Base Pair Deletion in the First Exon of GmHY2a Promotes Hypocotyl Elongation, Induces Early Maturation, and Impairs Photosynthetic Performance in Soybean.

Plants photoreceptors perceive changes in light quality and intensity and thereby regulate plant vegetative growth and reproductive development. By screening a γ irradiation-induced mutant library of the soybean (Glycine max) cultivar "Dongsheng 7", we identified Gmeny, a mutant with elongated nodes, yellowed leaves, decreased chlorophyll contents, altered photosynthetic performance, and early maturation. An analysis of bulked DNA and RNA data sampled from a population segregating for Gmeny, using the BVF-IGV pipeline established in our laboratory, identified a 10 bp deletion in the first exon of the candidate gene Glyma.02G304700. The causative mutation was verified by a variation analysis of over 500 genes in the candidate gene region and an association analysis, performed using two populations segregating for Gmeny. Glyma.02G304700 (GmHY2a) is a homolog of AtHY2a in Arabidopsis thaliana, which encodes a PΦB synthase involved in the biosynthesis of phytochrome. A transcriptome analysis of Gmeny using the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed changes in multiple functional pathways, including photosynthesis, gibberellic acid (GA) signaling, and flowering time, which may explain the observed mutant phenotypes. Further studies on the function of GmHY2a and its homologs will help us to understand its profound regulatory effects on photosynthesis, photomorphogenesis, and flowering time.

Disruption of CHORISMATE SYNTHASE1 leads to yellow-green variegation in soybean leaves.

Yellow-green variegation leaf phenotype adds more value to ornamental plants, but it is regarded as an undesirable trait in crop plants, affecting their yields. Until recently, the underlying mechanism regulating the yellow-green variegation phenotype has remained largely unexplored in soybean. In the present study, we indentified four Glycine max leaf yellow/green variegation mutants, Gmvar1, Gmvar2, Gmvar3, and Gmvar4, from artificial mutagenesis populations. Map-based cloning, together with the allelic identification test and CRISPR-based gene knockout, proved that mutated GmCS1 controls yellow-green variegation phenotype of the Gmvar mutants. GmCS1 encodes a chorismate synthase in soybean. The content of Phe, Tyr, and Trp were dramatically decreased in Gmcs1 mutants. Exogenous supply of three aromatic amino acid mixtures, or only Phe to Gmvar mutants, leads to recovery of the mutant phenotype. The various biological processes and signalling pathways related to metabolism and biosynthesis were altered in Gmvar mutants. Collectively, our findings provide new insights about the molecular regulatory network of yellow-green variegation leaf phenotype in soybean.

A novel 7-base pair deletion at a splice site in MS-2 impairs male fertility via premature tapetum degradation in common bean (Phaseolis vulgaris L.).

KEY MESSAGE: A novel splice-site mutation in the P. vulgarisgene for TETRAKETIDE α-PYRONE REDUCTASE 2 impairs male fertility, and parthenocarpic pod development can be improved by external application of IAA. Snap bean (Phaseolus vulgaris L.) is an important vegetable crop in many parts of the world, and the main edible part is the fresh pod. Here, we report the characterization of the genic male sterility (ms-2) mutant in common bean. Loss of function of MS-2 accelerates degradation of the tapetum, resulting in a complete male sterility. Through fine-mapping, co-segregation, and re-sequencing analysis, we identified Phvul.003G032100, which encodes the TETRAKETIDE α-PYRONE REDUCTASE 2 (PvTKPR2) protein in common bean, as the causal gene for MS-2. PvTKPR2 is predominantly expressed at the early stages of flower development. A novel 7-bp (+ 6028 bp to + 6034 bp) deletion mutation spans the splice site between the fourth intron and fifth exon, leading to a 9-bp deletion in transcribed mRNA and a 3-amino acid (G210M211V212) deletion in the protein coding sequence of the PvTKPR2ms-2 gene. The 3-D structural changes in the protein due to the mutation may impair the activities of NAD-dependent epimerase/dehydratase and the NAD(P)-binding domains of PvTKPR2ms-2 protein. The ms-2 mutant plants produce many small parthenocarpic pods, and the size of the pods can be doubled by external application of 2 mM indole-3-acetic acid (IAA). Our results demonstrate that a novel mutation in PvTKPR2 impairs male fertility through premature degradation of the tapetum.

Near-infrared (NIR) imaging with indocyanine green (ICG) may assist in intraoperative decision making and improving surgical margin in bone and soft tissue tumor surgery.

BACKGROUND AND OBJECTIVES: Negative surgical margins are significant in improving patient outcomes. However, surgeons can only rely on visual and tactile information to identify tumor margins intraoperatively. We hypothesized that intraoperative fluorescence imaging with indocyanine green (ICG) could serve as an assistive technology to evaluate surgical margins and guide surgery in bone and soft tissue tumor surgery. METHODS: Seventy patients with bone and soft tissue tumors were enrolled in this prospective, non-randomized, single-arm feasibility study. All patients received intravenous indocyanine green (0.5 mg/kg) before surgery. Near-infrared (NIR) imaging was performed on in situ tumors, wounds, and ex vivo specimens. RESULTS: 60/70 tumors were fluorescent at NIR imaging. The final surgical margins were positive in 2/55 cases, including 1/40 of the sarcomas. Surgical decisions were changed in 19 cases by NIR imaging, and in 7/19 cases final pathology demonstrated margins were improved. Fluorescence analysis showed that the tumor-to-background ratio (TBR) of primary malignant tumors was higher than that of benign, borderline, metastatic, and tumors ≥5 cm in size had higher TBR than those <5 cm. CONCLUSIONS: ICG fluorescence imaging may be a beneficial technique to assist in surgical decision making and improving surgical margins in bone and soft tissue tumor surgery.

Dysfunction of an Anaphase-Promoting Complex Subunit 8 Homolog Leads to Super-Short Petioles and Enlarged Petiole Angles in Soybean.

Plant height, petiole length, and the angle of the leaf petiole and branch angles are crucial traits determining plant architecture and yield in soybean (Glycine max L.). Here, we characterized a soybean mutant with super-short petioles (SSP) and enlarged petiole angles (named Gmssp) through phenotypic observation, anatomical structure analysis, and bulk sequencing analysis. To identify the gene responsible for the Gmssp mutant phenotype, we established a pipeline involving bulk sequencing, variant calling, functional annotation by SnpEFF (v4.0e) software, and Integrative Genomics Viewer analysis, and we initially identified Glyma.11G026400, encoding a homolog of Anaphase-promoting complex subunit 8 (APC8). Another mutant, t7, with a large deletion of many genes including Glyma.11G026400, has super-short petioles and an enlarged petiole angle, similar to the Gmssp phenotype. Characterization of the t7 mutant together with quantitative trait locus mapping and allelic variation analysis confirmed Glyma.11G026400 as the gene involved in the Gmssp phenotype. In Gmssp, a 4 bp deletion in Glyma.11G026400 leads to a 380 aa truncated protein due to a premature stop codon. The dysfunction or absence of Glyma.11G026400 caused severe defects in morphology, anatomical structure, and physiological traits. Transcriptome analysis and weighted gene co-expression network analysis revealed multiple pathways likely involved in these phenotypes, including ubiquitin-mediated proteolysis and gibberellin-mediated pathways. Our results demonstrate that dysfunction of Glyma.11G026400 leads to diverse functional consequences in different tissues, indicating that this APC8 homolog plays key roles in cell differentiation and elongation in a tissue-specific manner. Deciphering the molecular control of petiole length and angle enriches our knowledge of the molecular network regulating plant architecture in soybean and should facilitate the breeding of high-yielding soybean cultivars with compact plant architecture.

Electrochemical Sulfoxidation of Thiols and Alkyl Halides.

Sulfoxides are actively engaged as versatile synthetic building blocks, chiral ligands, bioactive molecules, and function materials. However, their oxidative syntheses from thioethers are inevitably impeded by overoxidation, excess oxidants, and the tedious preparation of thioethers. To address these shortcomings, we report herein a highly selective electrochemical sulfoxidation reaction featuring the use of simple starting materials, i.e., thiols and alkyl halides, in a single operation.

Evaluation of formic acid sandwich (FA-sandwich): A pretreatment method for filamentous fungi, for the identification of clinically relevant filamentous fungi by two MALDI-TOF MS systems.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been successfully applied to identify microorganisms. However, unlike bacteria and yeast where identification results can be obtained rapidly and accurately by using a simple direct-coating pretreatment method, the traditional pretreatment methods for filamentous fungi are more complex, involving ethanol, formic acid, acetonitrile, and a protein extraction process by centrifugation, i.e., the EtOH-FA full extraction. This cumbersome pretreatment for filamentous fungi is a major reason for the lack of widespread use of MALDI-TOF MS for the identification of filamentous fungi in clinical settings. The present study describes an alternative method, the FA-sandwich, and demonstrates that the approach is efficient and effective. 148 clinical filamentous fungal isolates collected from three large general hospitals in Hubei Province, China, were processed by the FA-sandwich method and identified by two MALDI-TOF MS platforms, Autof ms and Vitek MS. The FA-sandwich allowed a 93.9% species-level identification with Autof ms, and 97.3% species-level identification rates were found for Vitek MS when the IVD, the RUO and in-house databases are used in combination. Further comparison of the ease of FA-sandwich with the EtOH-FA full extraction showed that the FA-sandwich is a more convenient, time- and reagent-saving, and sensitive pretreatment method. These findings indicate that the FA-sandwich method is suitable for pretreating filamentous fungi followed by MALDI-TOF MS identification in clinical microbiology laboratories. LAY SUMMARY: The FA-sandwich method improves the efficiency of identification of filamentous fungi using MALDI-TOF MS while ensuring identification accuracy. The method is easy to perform and very suitable for detecting mold in the microbiology laboratory with the goal of promoting timely and accurate therapies.

Contactless treatment for scoliosis by electromagnetically controlled shape-memory alloy rods: a preliminary study in rabbits.

PURPOSE: To evaluate the safety and efficacy of a system aiming to correct scoliosis called "electromagnetically controlled shape-memory alloy rods" (EC-SMAR) used in a rabbit model. METHODS: We heat-treated shape-memory alloy (SMA) rods to achieve a transition temperature between 34 and 47 °C and a C-shape austenite phase. We then developed a water-cooled generator capable of generating an alternating magnetic field (100 kHz) for induction heating. We next studied the efficacy of this system in vitro and determined some parameters prior to proceeding with animal experiments. We then employed a rabbit model, in which we fixed a straight rod along the spinous processes intraoperatively, and conducted induction heating postoperatively every 4 days for 1 month, while performing periodic X-ray assessments. RESULTS: Significant kyphotic deformations with Cobb angles of about 45° (p < 0.01) were created in five rabbits, and no complications occurred throughout the experiment. The rabbits are still very much alive and do not show any signs of discomfort. CONCLUSIONS: This is the first system that can modulate spinal deformation in a gradual, contactless, noninvasive manner through electromagnetic induction heating applied to SMA alloy rods. Although this study dealt with healthy spines, it provides promising evidence that this device also has the capacity to correct human kyphosis and even scoliosis in the future. These slides can be retrieved under Electronic Supplementary Material.

Icariin promotes osteogenic differentiation of bone marrow stromal cells and prevents bone loss in OVX mice via activating autophagy.

Osteoporosis (OP) results from the impaired function of endogenous bone marrow mesenchymal stem cells (BMSCs). Icariin (ICA) has shown potential osteoprotective effects. However, the molecular mechanism for the anabolic action of ICA remains largely unknown. The objective of the present study is to investigate whether ICA prevents bone loss by acting on BMSCs via affecting the level of autophagy after ovariectomy (OVX). The BMSCs were extracted from BALB/c mice treated with ICA, chloroquine (CQ, an autophagy inhibitor) or ICA + CQ. The OVX mice were injected with ICA, CQ, or ICA + CQ for 1 month. We performed Alizarin Red staining and alkaline phosphatase staining to detect osteogenic differentiation of BMSCs. Micro-CT, hematoxylin and eosin staining, Oil Red O staining, and tartrate-resistant acid phosphatase staining were used to assess the bone mass, lipid droplets and osteoclasts in femurs. Autophagy activity in BMSCs from different groups was evaluated by Western blot analysis. The osteogenic differentiation of BMSCs from OVX-induced OP mice was decreased. Treatment with ICA reduced bone loss and formation of osteoclasts and increased osteogenic differentiation of BMSCs in vitro and vivo. In addition, autophagy was enhanced in BMSCs of OVX mice treated with ICA. Our results indicate that ICA prevents OVX-induced bone loss possibly by strengthening the osteogenic differentiation of BMSCs via increasing autophagic activity.

Endometrium cytokine profiles are altered following ovarian stimulation but almost not in subsequent hormone replacement cycles.

PURPOSE: To investigate the impact of ovarian stimulation and hormone replacement treatment on key regulatory cytokines in endometrial secretion during endometrium implantation window. METHODS: Fifty-six patients undergoing ovarian stimulation (OS) with gonadotropin releasing hormone antagonist and frozen embryo transfer with hormone replacement treatment (HRT) were recruited. Endometrial secretion aspiration was performed repeatedly during implantation window in natural, OS and HRT cycles of every patient. The concentrations of 17 mediators, known to be involved in human embryo implantation, were assessed by multiplex immunoassay. RESULTS: Compared with natural cycle (NC), the concentration of IFN-γ, G-CSF and IL-8 within endometrium were almost the same following OS and HRT. Furthermore, increased MCP-1 levels were observed following HRT and OS. In addition, an increase in IL-1b, IL-7, IL-17, IL-6, TNF-a, IL-12, IL-4, IL-13, IL-10, IL-5, VEGF and MIP-1b concentrations were found in OS cycle only. The level of GM-CSF was lower in HRT cycle and higher in OS cycle, when compared with NC. Among all 17 cytokines, no correlation was found between cytokine concentrations and serum estradiol and progesterone, while only IL-7 concentration has a low correlation with serum LH level. CONCLUSION: Compared to natural and hormone replacement cycle, patients' endometrium cytokine profiles present an increased inflammatory response following ovarian stimulation.

Suspect and Nontarget Screening of Per- and Polyfluoroalkyl Substances in Wastewater from a Fluorochemical Manufacturing Park.

Although per- and polyfluoroalkyl substances (PFASs) have always been a key issue in the global environmental field, there are still a lot of undiscovered PFASs in the environment due to new PFAS alternatives developed by manufacturers. Wastewater treatment plants (WWTPs), as one of the sources for PFASs, are an important part of the process of releasing new PFASs into the environment. In this study, suspect screening and PFAS homologue analysis with quadrupole time-of-flight tandem mass spectrometry were used to discover PFASs in wastewater from a WWTP near Yangtze River. Fifteen classes with 90 PFASs were identified, including 12 legacy PFASs (2 classes), 41 previously reported PFASs (7 classes), and 37 new PFASs (6 classes), and 18 of these PFASs were also detected in the nearby Yangtze River. Only 1 PFAS class was removed through the treatment processes (fold change < 1/6). Conversely, 4 PFAS classes increased through the treatment processes (fold change > 6), which could be the transformation products of PFAS precursors. These results implied that most discovered PFASs were not effectively removed in the WWTP. Chlorine-substituted perfluoroalkyl carboxylates (Cl-PFCAs) as the main component of wastewater were detected only in downstream, meaning that Cl-PFCAs in downstream possibly originated from the WWTP.

Identifying key factors of the seawater intrusion model of Dagu river basin, Jiaozhou Bay.

Seawater intrusion is a complex groundwater - seawater interaction process, and it is influenced by many factors from ground surface to underground, from groundwater to seawater. Generally, for seawater intrusion model, some model parameters and boundary conditions are always specified by model users' personal experiences or literature's reference value. The defective model would damage the groundwater management for controlling and preventing seawater intrusion when making decisions are based on this model. In order to improve the reliability of seawater intrusion model, the influences of model inputs on output should be identified prior at optimizing model inputs. Dagu river basin, Jiaozhou Bay is one of the most serious areas of seawater intrusion in China, and it is chosen as the study area in this study. The seawater intrusion model of Dagu river basin is built based on a general program SEAWAT4. The key influence factors of model output are analyzed by two sensitivity analysis methods, i.e., stepwise regression and mutual entropy. The results demonstrated that the most important influence factors which have largest sensitivities to groundwater Cl- concentration are the precipitation rate and groundwater pumping in agriculture area. In addition, the hydraulic conductivity of zone 1 has a non-negligible influence on seawater intrusion process. Stepwise regression analysis is capable of identifying most important influence factor, and it can't handle complicated nonlinear input-output relationship. Mutual entropy analysis is reliable for identifying the influence factors for complex seawater intrusion model.

UFBP1, a Key Component of the Ufm1 Conjugation System, Is Essential for Ufmylation-Mediated Regulation of Erythroid Development.

The Ufm1 conjugation system is an ubiquitin-like modification system that consists of Ufm1, Uba5 (E1), Ufc1 (E2), and less defined E3 ligase(s) and targets. The biological importance of this system is highlighted by its essential role in embryogenesis and erythroid development, but the underlying mechanism is poorly understood. UFBP1 (Ufm1 binding protein 1, also known as DDRGK1, Dashurin and C20orf116) is a putative Ufm1 target, yet its exact physiological function and impact of its ufmylation remain largely undefined. In this study, we report that UFBP1 is indispensable for embryonic development and hematopoiesis. While germ-line deletion of UFBP1 caused defective erythroid development and embryonic lethality, somatic ablation of UFBP1 impaired adult hematopoiesis, resulting in pancytopenia and animal death. At the cellular level, UFBP1 deficiency led to elevated ER (endoplasmic reticulum) stress and activation of unfolded protein response (UPR), and consequently cell death of hematopoietic stem/progenitor cells. In addition, loss of UFBP1 suppressed expression of erythroid transcription factors GATA-1 and KLF1 and blocked erythroid differentiation from CFU-Es (colony forming unit-erythroid) to proerythroblasts. Interestingly, depletion of Uba5, a Ufm1 E1 enzyme, also caused elevation of ER stress and under-expression of erythroid transcription factors in erythroleukemia K562 cells. By contrast, knockdown of ASC1, a newly identified Ufm1 target that functions as a transcriptional co-activator of hormone receptors, led to down-regulation of erythroid transcription factors, but did not elevate basal ER stress. Furthermore, we found that ASC1 was associated with the promoters of GATA-1 and Klf1 in a UFBP1-dependent manner. Taken together, our findings suggest that UFBP1, along with ASC1 and other ufmylation components, play pleiotropic roles in regulation of hematopoietic cell survival and differentiation via modulating ER homeostasis and erythroid lineage-specific gene expression. Modulating the activity of this novel ubiquitin-like system may represent a novel approach to treat blood-related diseases such as anemia.

Low-frequency germline variants across 6p22.2-6p21.33 are associated with non-obstructive azoospermia in Han Chinese men.

Genome-wide association studies (GWAS) have identified several common loci contributing to non-obstructive azoospermia (NOA). However, a substantial fraction of NOA heritability remains undefined, especially those low-frequency [defined here as having a minor allele frequency (MAF) between 0.5 and 5%] and rare (MAF below 0.5%) variants. Here, we performed a 3-stage exome-wide association study in Han Chinese men to evaluate the role of low-frequency or rare germline variants in NOA development. The discovery stage included 962 NOA cases and 1348 healthy male controls genotyped by exome chips and was followed by a 2-stage replication with an additional 2168 cases and 5248 controls. We identified three low-frequency variants located at 6p22.2 (rs2298090 in HIST1H1E encoding p.Lys152Arg: OR = 0.30, P = 2.40 × 10(-16)) and 6p21.33 (rs200847762 in FKBPL encoding p.Pro137Leu: OR = 0.11, P = 3.77 × 10(-16); rs11754464 in MSH5: OR = 1.78, P = 3.71 × 10(-7)) associated with NOA risk after Bonferroni correction. In summary, we report an instance of newly identified signals for NOA risk in genes previously undetected through GWAS on 6p22.2-6p21.33 in a Chinese population and highlight the role of low-frequency variants with a large effect in the process of spermatogenesis.

Assessing the pollution risk of a groundwater source field at western Laizhou Bay under seawater intrusion.

Coastal areas have great significance for human living, economy and society development in the world. With the rapid increase of pressures from human activities and climate change, the safety of groundwater resource is under the threat of seawater intrusion in coastal areas. The area of Laizhou Bay is one of the most serious seawater intruded areas in China, since seawater intrusion phenomenon was firstly recognized in the middle of 1970s. This study assessed the pollution risk of a groundwater source filed of western Laizhou Bay area by inferring the probability distribution of groundwater Cl(-) concentration. The numerical model of seawater intrusion process is built by using SEAWAT4. The parameter uncertainty of this model is evaluated by Markov Chain Monte Carlo (MCMC) simulation, and DREAM(ZS) is used as sampling algorithm. Then, the predictive distribution of Cl(-) concentration at groundwater source field is inferred by using the samples of model parameters obtained from MCMC. After that, the pollution risk of groundwater source filed is assessed by the predictive quantiles of Cl(-) concentration. The results of model calibration and verification demonstrate that the DREAM(ZS) based MCMC is efficient and reliable to estimate model parameters under current observation. Under the condition of 95% confidence level, the groundwater source point will not be polluted by seawater intrusion in future five years (2015-2019). In addition, the 2.5% and 97.5% predictive quantiles show that the Cl(-) concentration of groundwater source field always vary between 175mg/l and 200mg/l.

Association of a TDRD1 variant with spermatogenic failure susceptibility in the Han Chinese.

PURPOSE: Piwi-interacting RNAs (piRNAs) are a broad group of noncoding small RNAs that have important biological functions in germline cells and can maintain genome integrity via silencing of retrotransposons. In this study, we aimed to explore the associations between genetic variants of important genes involved in piRNA biogenesis and male infertility with spermatogenic impairment. METHODS: To this end, five single-nucleotide polymorphisms (SNPs) in the ASZ1, PIWIL1, TDRD1, and TDRD9 genes were genotyped by TaqMan allelic discrimination assays in 342 cases of nonobstructive azoospermia (NOA) and 493 controls. RESULTS: The SNP rs77559927 in TDRD1 was associated with a reduced risk of spermatogenic impairment. The genotypes TC and TC + CC showed odds ratios and 95 % confidence intervals of 0.73 (0.55-0.98, P = 0.034) and 0.73 (0.56-0.97, P = 0.030), respectively, in patients with NOA compared with those in the controls. CONCLUSION: Thus, our results provided the first epidemiological evidence supporting the involvement of TDRD1 genetic polymorphisms in piRNA processing genes in determining the risk of spermatogenic impairment in a Han Chinese population.