Uncoupling transcription and translation through miRNA-dependent poly(A) length control in haploid male germ cells.

As one of the post-transcriptional regulatory mechanisms, uncoupling of transcription and translation plays an essential role in development and adulthood physiology. However, it remains elusive how thousands of mRNAs get translationally silenced while stability is maintained for hours or even days before translation. In addition to oocytes and neurons, developing spermatids display significant uncoupling of transcription and translation for delayed translation. Therefore, spermiogenesis represents an excellent in vivo model for investigating the mechanism underlying uncoupled transcription and translation. Through full-length poly(A) deep sequencing, we discovered dynamic changes in poly(A) length through deadenylation and re-polyadenylation. Deadenylation appeared to be mediated by microRNAs (miRNAs), and transcripts with shorter poly(A) tails tend to be sequestered into ribonucleoprotein (RNP) granules for translational repression and stabilization. In contrast, re-polyadenylation might allow for translocation of the translationally repressed transcripts from RNP granules to polysomes. Overall, our data suggest that miRNA-dependent poly(A) length control represents a previously unreported mechanism underlying uncoupled translation and transcription in haploid male mouse germ cells.

Improving the RNA velocity approach with single-cell RNA lifecycle (nascent, mature and degrading RNAs) sequencing technologies.

We presented an experimental method called FLOUR-seq, which combines BD Rhapsody and nanopore sequencing to detect the RNA lifecycle (including nascent, mature, and degrading RNAs) in cells. Additionally, we updated our HIT-scISOseq V2 to discover a more accurate RNA lifecycle using 10x Chromium and Pacbio sequencing. Most importantly, to explore how single-cell full-length RNA sequencing technologies could help improve the RNA velocity approach, we introduced a new algorithm called 'Region Velocity' to more accurately configure cellular RNA velocity. We applied this algorithm to study spermiogenesis and compared the performance of FLOUR-seq with Pacbio-based HIT-scISOseq V2. Our findings demonstrated that 'Region Velocity' is more suitable for analyzing single-cell full-length RNA data than traditional RNA velocity approaches. These novel methods could be useful for researchers looking to discover full-length RNAs in single cells and comprehensively monitor RNA lifecycle in cells.

Circular RNA circWNK1 inhibits the progression of gastric cancer via regulating the miR-21-3p/SMAD7 axis.

Gastric cancer (GC) is a highly aggressive malignancy with limited treatment options for advanced-stage patients. Recent studies have highlighted the role of circular RNA (circRNA) as a novel regulator of cancer progression in various malignancies. However, the underlying mechanisms by which circRNA contributes to the development and progression of GC remain poorly understood. In this study, we utilized microarrays and real-time quantitative polymerase chain reaction (qRT-PCR) to identify and validate a downregulated circRNA, hsa_circ_0003251 (referred to as circWNK1), in paired GC and normal tissues. Through a series of in vitro and in vivo gain-of-function and loss-of-function assays, we demonstrated that circWNK1 exerts inhibitory effects on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of GC cells. Additionally, we discovered that circWNK1 acts as a competitive endogenous RNA (ceRNA) for SMAD7 by sequestering miR-21-3p. Our findings were supported by comprehensive biological information analysis, as well as RNA pull-down, luciferase reporter gene, and western blot assays. Notably, the downregulation of circWNK1 in GC cells resulted in reduced SMAD7 expression, subsequently activating the TGF-ß signaling pathway. Collectively, our study reveals that circWNK1 functions as a tumor suppressor in GC by regulating the miR-21-3p/SMAD7-mediated TGF-ß signaling pathway. Furthermore, circWNK1 holds promise as a potential biomarker for the diagnosis and treatment of GC.

Direct Determination of Absolute Radical Quantum Yields in Hydroxyl and Sulfate Radical-Based Treatment Processes.

The absolute radical quantum yield (Φ) is a critical parameter to evaluate the efficiency of radical-based processes in engineered water treatment. However, measuring Φ is fraught with challenges, as current quantification methods lack selectivity, specificity, and anti-interference capabilities, resulting in significant error propagation. Herein, we report a direct and reliable time-resolved technique to determine Φ at pH 7.0 for commonly used radical precursors in advanced oxidation processes. For H2O2 and peroxydisulfate (PDS), the values of Φ•OH and ΦSO4•- at 266 nm were measured to be 1.10 ± 0.01 and 1.46 ± 0.05, respectively. For peroxymonosulfate (PMS), we developed a new approach to determine Φ•OHPMS with terephthalic acid as a trap-and-trigger probe in the nonsteady state system. For the first time, the Φ•OHPMS value was measured to be 0.56 by the direct method, which is stoichiometrically equal to ΦSO4•-PMS (0.57 ± 0.02). Additionally, radical formation mechanisms were elucidated by density functional theory (DFT) calculations. The theoretical results showed that the highest occupied molecular orbitals of the radical precursors are O-O antibonding orbitals, facilitating the destabilization of the peroxy bond for radical formation. Electronic structures of these precursors were compared, aiming to rationalize the tendency of the Φ values we observed. Overall, this time-resolved technique with specific probes can be used as a reliable tool to determine Φ, serving as a scientific basis for the accurate performance evaluation of diverse radical-based treatment processes.

Rasmussen's encephalitis is characterized by relatively lower production of IFN-ß and activated cytotoxic T cell upon herpes viruses infection.

BACKGROUND: The etiology of Rasmussen's encephalitis (RE), a rare chronic neurological disorder characterized by CD8+ T cell infiltration and unihemispheric brain atrophy, is still unknown. Various human herpes viruses (HHVs) have been detected in RE brain, but their contribution to RE pathogenesis is unclear. METHODS: HHVs infection and relevant immune response were compared among brain tissues from RE, temporal lobe epilepsy (TLE) and traumatic brain injury (TBI) patients. Viral antigen or genome, CD8+ T cells, microglia and innate immunity molecules were analyzed by immunohistochemical staining, DNA dot blot assay or immunofluorescence double staining. Cytokines were measured by multiplex flow cytometry. Cell apoptosis was visualized by TUNEL staining. Viral infection, immune response and the severity of unihemispheric atrophy were subjected to correlation analysis. RESULTS: Antigens of various HHVs were prevalent in RE and TLE brains, and the cumulative viral score of HHVs positively correlated with the unihemispheric atrophy in RE patients. CD8+ T cells infiltration were observed in both RE and TLE brains and showed co-localization with HHV antigens, but their activation, as revealed by Granzyme B (GZMB) release and apoptosis, was found only in RE. In comparison to TLE, RE brain tissues contained higher level of inflammatory cytokines, but the interferon-ß level, which was negatively correlated with cumulative viral score, was relatively lower. In line with this, the DNA sensor STING and IFI16, rather than other innate immunity signaling molecules, were insufficiently activated in RE. CONCLUSIONS: Compared with TBI, both RE and TLE had prevalently HHV infection and immune response in brain tissues. However, in comparison to TLE, RE showed insufficient activation of antiviral innate immunity but overactivation of cytotoxic T cells. Our results show the relatively lower level of antiviral innate immunity and overactivation of cytotoxic T cells in RE cases upon HHV infection, the overactivated T cells might be a compensate to the innate immunity but the causative evidence is lack in our study and need more investigation in the future.

Ultra-efficient multiple cross displacement amplification-lateral flow biosensor (MCDA-LFB) for serogroup identification of prevalent Neisseria meningitidis.

Meningococcal disease caused by Neisseria meningitidis remains a major global public health concern. Serogroup A, B, C and W135 were the major disease-causing serogroups. It is vital to timely and efficiently detect and differentiate these four serogroups. Herein, we developed multiple cross displacement amplification-lateral flow biosensor (MCDA-LFB) assays targeting ctrA, sacB, siaD, siaD and synG gene respectively for detection and subtyping of four N. meningitidis serogroups. This assay utilizes LFB to detect FITC and biotin-labeled target amplicons produced by MCDA through double antibody sandwich principle, to allow sensitive and specific detection under a constant temperature. The detection limit was as low as 10 fg or 100 fg genomic DNA in pure cultures and 5.5 CFUs or 36 CFUs in spiked cerebrospinal fluid (CSF) specimens, which were overall 100 to 1000-fold more sensitive than conventional PCR. High specificity of these assays was also validated through type strains and clinical isolates, with no cross-reactions. MCDA-LFB testing procedure can be finished within 1 h. In conclusion, the N. meningitidis- and serogroup-MCDA-LFB assays established in this study are simple, rapid and efficient, providing valuable molecular methods for diagnosis and surveillance of meningococcal disease, especially in resource-limited regions and when specimen culture fails.

Infralow-frequency transcranial magnetic stimulation as a therapy for generalized anxiety disorder: A randomized clinical trial.

BACKGROUND: Generalized anxiety disorder (GAD) is a common chronic mental disorder, and it also can cause depressive symptoms and cognitive impairment. The primary aim of this study was to determine whether inflow-frequency transcranial magnetic stimulation (ILF-TMS) improves anxiety symptoms in patients with GAD. METHODS: Sixty-two patients with GAD were randomly divided into 2 groups. Thirty-one patients in the active ILF-TMS group and 31 patients in the sham ILF-TMS group. All participants were assessed at baseline, week 2, week 4 and week 12. The intention-to-treat methodology was used for the analysis. RESULTS: The response rate was higher in the active group than in the sham group, with a significant difference at week 12 (response rate: 80.6% vs. 54.8%, respectively; P = 0.03). Although the remission rate was higher in the active group at week 12, there was no statistically significant difference between the groups (remission rate: 71.0% vs. 48.4%; P > 0.05). No statistically significant differences on the Hamilton Depression Rating Scale, Clinical Global Impression scale, and neurocognitive test between groups were observed (overall P > 0.05). Adverse events that occurred in the active group were similar to those in the sham group, with no significant differences (P > 0.05). CONCLUSION: The response rate was higher in the active group at the end of the trial, which indicated that ILF-TMS may be an effective and safe adjunctive tool to improve anxiety symptoms in patients with GAD.

Motile cilia of the male reproductive system require miR-34/miR-449 for development and function to generate luminal turbulence.

Cilia are cell-surface, microtubule-based organelles that project into extracellular space. Motile cilia are conserved throughout eukaryotes, and their beat induces the flow of fluid, relative to cell surfaces. In mammals, the coordinated beat of motile cilia provides highly specialized functions associated with the movement of luminal contents, as seen with metachronal waves transporting mucus in the respiratory tract. Motile cilia are also present in the male and female reproductive tracts. In the female, wave-like motions of oviductal cilia transport oocytes and embryos toward the uterus. A similar function has been assumed for motile cilia in efferent ductules of the male-i.e., to transport immotile sperm from rete testis into the epididymis. However, we report here that efferent ductal cilia in the male do not display a uniform wave-like beat to transport sperm solely in one direction, but rather exert a centripetal force on luminal fluids through whip-like beating with continual changes in direction, generating turbulence, which maintains immotile spermatozoa in suspension within the lumen. Genetic ablation of two miRNA clusters (miR-34b/c and -449a/b/c) led to failure in multiciliogenesis in murine efferent ductules due to dysregulation of numerous genes, and this mouse model allowed us to demonstrate that loss of efferent duct motile cilia causes sperm aggregation and agglutination, luminal obstruction, and sperm granulomas, which, in turn, induce back-pressure atrophy of the testis and ultimately male infertility.

AASRA: an anchor alignment-based small RNA annotation pipeline†.

Small noncoding RNAs deep sequencing (sncRNA-Seq) has become a routine for sncRNA detection and quantification. However, the software packages currently available for sncRNA annotation can neither recognize sncRNA variants in the sequencing reads, nor annotate all known sncRNA simultaneously. Here, we report a novel anchor alignment-based small RNA annotation (AASRA) software package (https://github.com/biogramming/AASRA). AASRA represents an all-in-one sncRNA annotation pipeline, which allows for high-speed, simultaneous annotation of all known sncRNA species with the capability to distinguish mature from precursor microRNAs, and to identify novel sncRNA variants in the sncRNA-Seq sequencing reads.

Dnmt2-null sperm block maternal transmission of a paramutant phenotype†.

Previous studies have shown that Dnmt2-null sperm block the paternal transmission (through sperm) of certain acquired traits, e.g., high-fat diet-induced metabolic disorders or white tails due to a Kit paramutation. Here, we report that DNMT2 is also required for the transmission of a Kit paramutant phenotype (white tail tip) through the female germline (i.e., oocytes). Specifically, ablation of Dnmt2 led to aberrant profiles of tRNA-derived small RNAs (tsRNAs) and other small noncoding RNAs (sncRNAs) in sperm, which correlate with altered mRNA transcriptomes in pronuclear zygotes derived from wild-type oocytes carrying the Kit paramutation and a complete blockage of transmission of the paramutant phenotype through oocytes. Together, the present study suggests that both paternal and maternal transmissions of epigenetic phenotypes require intact DNMT2 functions in the male germline.

Regulation of TWIK-related K+ channel 1 in the anterior hippocampus of patients with temporal lobe epilepsy with comorbid depression.

Epilepsy with comorbid depression has recently attracted increasing attention. Temporal lobe epilepsy (TLE) may represent an increased risk of developing depression, especially if the seizures do not generalize. The two-pore domain potassium channel-TWIK-related K+ channel (TREK-1) plays important roles in both epilepsy and depression. However, the changes in its expression in patients with epilepsy with comorbid depression remain unclear. In the present study, we analyzed depressive symptoms using neuropsychiatric scales in forty-two patients with drug-resistant TLE, who also underwent EEG in waking and sleeping states, as well as 3.0 T brain MRI. We tested for TREK-1 positive neurons and microglial cells in the anterior hippocampi of patients with drug-resistant TLE with and without comorbid depression (n=5/group). Approximately 31% of patients with TLE had comorbid depression (13/42). Meanwhile, the patients who had hippocampal sclerosis had much higher scores on the depression rating scale. The results indicated the contribution of hippocampal sclerosis to the development of depression. Immunostaining of TREK-1 channels was observed in neurons and glia in the anterior hippocampus. Increased immunoreactivity of TREK-1 neurons was observed in the hippocampi of patients with TLE with comorbid depression compared with nondepressed patients with TLE. TREK-1 was expressed in almost all microglia. Curiously, more activated TREK-1-positive microglia were observed in patients with TLE with depression than in those without depression. The results suggested that a change in TREK-1 immunoreactivity was involved, at least partly, in the development of depression as a comorbidity of TLE. Imbalance of the TREK-1 channel may be a potential target for the treatment of patients with epilepsy with comorbid depression.

ALKBH5-dependent m6A demethylation controls splicing and stability of long 3'-UTR mRNAs in male germ cells.

N6-methyladenosine (m6A) represents one of the most common RNA modifications in eukaryotes. Specific m6A writer, eraser, and reader proteins have been identified. As an m6A eraser, ALKBH5 specifically removes m6A from target mRNAs and inactivation of Alkbh5 leads to male infertility in mice. However, the underlying molecular mechanism remains unknown. Here, we report that ALKBH5-mediated m6A erasure in the nuclei of spermatocytes and round spermatids is essential for correct splicing and the production of longer 3'-UTR mRNAs, and failure to do so leads to aberrant splicing and production of shorter transcripts with elevated levels of m6A that are rapidly degraded. Our study identified reversible m6A modification as a critical mechanism of posttranscriptional control of mRNA fate in late meiotic and haploid spermatogenic cells.

Efficacy of orchard terrace measures to minimize water erosion caused by extreme rainfall in the hilly region of China: Long-term continuous in situ observations.

Terracing and rainfall characteristics notably influence the water erosion processes. However, an extensive long term in situ quantitative evaluation of the approaches to control the water erosion in different orchard terraces has not yet been performed, especially considering the increasing frequency and severity of extreme rainfall events due to the global climate change. In this study, six types of orchard terraces, including slope land as the control (SLck), level terrace with bare (LTb) and vegetation taluses (LTv), outward (OTv) and inward terrace (ITv) with vegetation taluses and level terrace having front mounds and back ditches with vegetation taluses (MDLTv), were used to analyze the effects of extreme and ordinary rainfall events on the surface runoff and soil erosion. According to the measured data for twelve consecutive years, 356 natural rainfall events were divided into extreme and ordinary rainfall, based on the World Meteorological Organization standard. The results indicated that more severe surface runoff and sediment loss occurred under extreme rainfall: the runoff coefficient and soil loss under extreme rainfall were 2.6 and 11.5 times those under ordinary rainfall, respectively. The sediment yield (contribution rate, 42.9%) exhibited a higher sensitivity to extreme rainfall events compared to that of the surface runoff generation (contribution rate, 16.4%). Moreover, the reduction in the surface runoff and sediment in the extreme rainfall case differed for different orchard terraces. The average surface runoff coefficient and soil loss amount decreased in the following order: SLck>LTb>OTv>LTv>ITv>MDLTv. Nevertheless, the highest and lowest contributions of the extreme rainfall to the sediment yield occurred in the LTb (64.8%) and MDLTv (21.7%) plots, respectively. Therefore, severe talus erosion caused by extreme rainfall should be monitored, and a combination of vegetation taluses and front mounds and back ditches on the platforms is recommended as a sustainable strategy to prevent extreme water erosion when transforming slope land into orchard terraces.

Decolorization of azo dyes in a heterogeneous persulfate system using FeS as the activator.

Textile effluents containing synthetic refractory azo dyes are one of the most important sources of water pollution. However, these kinds of refractory organic pollutants did not resist a persulfate (PS) oxidation process which was correctly activated. In this study, PS was activated by ferrous sulfide (FeS) in a heterogeneous system to break down azo dyes wastewater. The results showed that all five selected azo dyes were efficiently broken down using the PS/FeS system, except for DY 12, and more than 95% of azo dyes were decolored within 60 minutes. The decolorization efficiency of DR 81 in the PS/FeS system was comparable to PS activated with heat (60 °C) or Fe2+, and was slightly superior to Fe0 powders under the same conditions. Quenching studies indicated that both SO4-• and •OH were formed in the FeS surface and diffused into the solution to facilitate the successive transformation of DR 81, the •OH reaction with DR 81 might the crucial reaction. The coexisting chelating agents in real azo dye effluents at high concentrations had a negative influence on azo dye decolorization by PS/FeS. However, the superior factor of the PS/FeS system was the regenerability and reusability of the heterogeneous catalyst.

LncRNA ADAMTS9-AS2 suppresses the proliferation of gastric cancer cells and the tumorigenicity of cancer stem cells through regulating SPOP.

Nowadays, research on CSCs is still in an initial stage, and there are few studies reporting the successful isolation and identification of CSCs. In the present study, we attempted to isolate CSCs through cultivating the cell line MKN45 in defined serum-free medium and study the expression of stem cell markers or related proteins (Oct3/4, Sox2, Nanog and CD44) in CSCs. Moreover, immunofluorescence staining was performed to validate the stem cell markers of spheroid body-forming cells. Further experiments were used to evaluate the SPOP expression in tumorsphere cells. In addition, ADAMTS9-AS2 is a lncRNA that contributes to the genesis and development of many cancers, including gastric cancer (GC). We found ADAMTS9-AS2 functioned as an anti-oncogene and positively correlated with the expression of SPOP in GC tissues by combining bioinformatics analyses. Furthermore, we reported that ADAMTS9-AS2 regulated the expression of SPOP in GC cells and tumorsphere cells to inhibit GC progression. Together, our results demonstrated that SPOP and ADAMTS9-AS2 can be potential targets for GC treatment.

MicroRNA-92a promotes proliferation and invasiveness of gastric cancer cell by targeting FOXO1 gene.

The aim of this study is to   investigate the effect of miRNA-92a on GC cell proliferation, migration and invasiveness, and the mechanism(s) involved.  Four GC cell lines (SGC-7901, BGC-823, MKN45 and HGC-27) and normal human gastric epithelial cells (GES1) were used in this study. MicroRNA-92a mimics or inhibitor were transfected into the cells. The results of transfection were assessed using real-time quantitative polymerase chain reaction (qRT-PCR). Cell proliferation, migration, invasiveness and apoptosis were determined using cell counting kit 8 (CCK-8), scratch test, Transwell invasion assay, and flow cytometric analysis, respectively. The protein target of miRNA-92a was predicted using Bioinformatics. The expression of FOXO1 protein was measured using Western blotting. The expression of miRNA-92a was significantly upregulated in GC cells, relative to normal gastric epithelial cells (p < 0.05). Overexpression of miRNA-92a significantly promoted the proliferation, migration and invasiveness of GC cells, but significantly inhibited their apoptosis (p < 0.05). MicroRNA-92a directly targeted FOXO1 gene, and significantly reduced its protein expression. Overexpression of miRNA-92a promotes the proliferation, migration and invasiveness of GC cells, and plays a role similar to that of oncogene. It directly targets FOXO1 gene by inhibiting its protein expression.

Performance, microbial community and inhibition kinetics of long-term Cu2+ stress on an air-lift nitritation reactor with self-recirculation.

Biological nitrogen removal process could be affected due to the presence of heavy metals owing to their toxicity and accumulation in the sludge. In this study, the impact of Cu2+ shock on a long-term nitritation operation was investigated in an air-lift reactor with self-recirculation. Both the dynamics of microbial community and inhibition kinetics under Cu2+ stress were ascertained. The results showed that Cu2+ exerted severe inhibition on nitritation performance of an air-lift reactor (ALR) at 25 mg/L. The corresponding NH4+-N removal efficiency decreased to below 50%, which was mainly due to the variation of microbial community structure, especially the inhibition of nitrifiers like Nitrosomonas (the relative abundance decreased from 30% to 1% after Cu2+ inhibition). Kinetic parameters were obtained and compared after fitting the Haldane model. The long-term Cu2+ stress on the ALR aggravated the ammonium affinity and the resistance to substrate self-inhibition of the nitritation sludge, but reduced the resistance to Cu2+ inhibition. Furthermore, Cu2+ acted as uncompetitive inhibitor on nitritation process. Our results provide new insights into the nitritation characteristics under long-term Cu2+ stress.

A new massively parallel nanoball sequencing platform for whole exome research.

BACKGROUND: Whole exome sequencing (WES) has been widely used in human genetics research. BGISEQ-500 is a recently established next-generation sequencing platform. However, the performance of BGISEQ-500 on WES is not well studied. In this study, we evaluated the performance of BGISEQ-500 on WES by side-to-side comparison with Hiseq4000, on well-characterized human sample NA12878. RESULTS: BGISEQ demonstrated similarly high reproducibility as Hiseq for variation detection. Also, the SNVs from BGISEQ data is highly consistent with Hiseq results (concordance 96.5%~ 97%). Variation detection accuracy was subsequently evaluated with data from the genome in a bottle project as the benchmark. Both platforms showed similar sensitivity and precision in SNV detection. While in indel detection, BGISEQ showed slightly higher sensitivity and lower precision. The impact of sequence depth and read length on variation detection accuracy was further analyzed, and showed that variation detection sensitivity still increasing when the sequence depth is larger than 100x, and the impact of read length is minor when using 100x data. CONCLUSIONS: This study suggested that BGISEQ-500 is a qualified sequencing platform for WES.

Comparison of blood lipid profile/thyroid function markers between unipolar and bipolar depressed patients and in depressed patients with anhedonia or suicidal thoughts.

BACKGROUND: This study aimed to investigate the differences in the serum levels of glucose, lipid, and thyroid function markers between unipolar and bipolar depressed patients, as well as the effect of anhedonia and suicidal thoughts on the levels of these biochemical parameters. METHODS: A total of 287 unmedicated depressed patients from January 2016 to December 2017 were included in this study, including 92 bipolar depressions and 195 unipolar depressions. Anhedonia was determined using the item 32 of Symptom Checklist (SCL-90). Suicide ideation was assessed by item 15 of SCL-90. RESULTS: The bipolar group had significantly lower lipid levels (including triglycerides, cholesterol, low-density lipoprotein cholesterol [LDL], very low-density lipoprotein cholesterol [VLDL]) and insulin resistance index but higher levels of prolactin, low triiodothyronine (T3) and free T3 (FT3) as well as higher incidence of anhedonia as compared with the unipolar group. Depressed patients with anhedonia had significantly higher LDL level than those without anhedonia. Depressed patients with suicidal thoughts had cholesterol and high-density lipoprotein cholesterol (HDL) level. The above-mentioned differences were confirmed by logistic regression analysis. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve (AUC) ranged from 0.546 to 0.685. CONCLUSION: Triglycerides, cholesterol, LDL, VLDL T3, FT3 levels were significantly different between unipolar and bipolar depressed patients, which might have the potential to be the markers for differential diagnosis. Patients with anhedonia had lower LDL level, while patients with suicidal thoughts had higher levels of cholesterol and HDL as compared with the corresponding control groups.

Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development.

Although it is believed that mammalian sperm carry small noncoding RNAs (sncRNAs) into oocytes during fertilization, it remains unknown whether these sperm-borne sncRNAs truly have any function during fertilization and preimplantation embryonic development. Germline-specific Dicer and Drosha conditional knockout (cKO) mice produce gametes (i.e. sperm and oocytes) partially deficient in miRNAs and/or endo-siRNAs, thus providing a unique opportunity for testing whether normal sperm (paternal) or oocyte (maternal) miRNA and endo-siRNA contents are required for fertilization and preimplantation development. Using the outcome of intracytoplasmic sperm injection (ICSI) as a readout, we found that sperm with altered miRNA and endo-siRNA profiles could fertilize wild-type (WT) eggs, but embryos derived from these partially sncRNA-deficient sperm displayed a significant reduction in developmental potential, which could be rescued by injecting WT sperm-derived total or small RNAs into ICSI embryos. Disrupted maternal transcript turnover and failure in early zygotic gene activation appeared to associate with the aberrant miRNA profiles in Dicer and Drosha cKO spermatozoa. Overall, our data support a crucial function of paternal miRNAs and/or endo-siRNAs in the control of the transcriptomic homeostasis in fertilized eggs, zygotes and two-cell embryos. Given that supplementation of sperm RNAs enhances both the developmental potential of preimplantation embryos and the live birth rate, it might represent a novel means to improve the success rate of assisted reproductive technologies in fertility clinics.