Identification of small noncoding RNAs as sperm quality biomarkers for in vitro fertilization
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE110190 | GEO | 2019/02/21
REPOSITORIES: GEO
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2023-04-02 | GSE203494 | GEO
Project description:Small non-coding RNAs (sncRNAs) are key molecules regulating gene expression. High-throughput RNA-seq greatly advanced sncRNA discovery; however, traditional cDNA library construction protocols generate biased sequencing results, in part due to RNA modifications that interfere with adapter ligation and reverse transcription processes, preventing the detection of sncRNAs bearing these modifications. Here, we present PANDORA-seq (Panoramic RNA Display by Overcoming RNA modification Aborted Sequencing), employing a combination of enzymatic treatments to remove key RNA modifications that block adapter ligation and reverse transcription during cDNA library construction. PANDORA-Seq enables the discovery of thousands of modified sncRNAs previously undetected, mostly tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), which are tissue/cell-specifically detected across mouse brain, liver, spleen, sperm, mouse and human embryonic stem cells, and HeLa cells. Moreover, PANDORA-Seq reveals dynamic changes of tsRNAs and rsRNAs during reprogramming of induced pluripotent stem cells (iPSCs), pointing to future investigations on their potential regulatory functions.
2021-02-16 | GSE144666 | GEO
Project description:Sperm-derived tsRNAs could act as acquired epigenetic factors and contribute to offspring phenotypes. However, the roles of specific tsRNAs in early embryo development remain to be elucidated. Here, by using pigs as a research model, we probed the tsRNA dynamics during spermatogenesis and sperm maturation, and demonstrated the delivery of tsRNAs from semen-derived exosomes to spermatozoa. By microinjection of the antisense sequence into in vitro fertilized oocytes and subsequent single-cell RNA-sequencing of embryos, we identified a specific functional tsRNA group (Gln-TTGs) that participate in the early cleavage of porcine preimplantation embryos, probably by regulating cell cycle-associated genes. Thus, specific tsRNAs present in mature spermatozoa play significant roles during preimplantation embryo development.
2020-07-13 | PXD019054 | Pride
Project description:Excessive accumulation of manganese in brain can cause Parkinsonian-like symptoms, known as Manganism. Methylcyclopentadienyl Manganese Tricarbonyl (MMT), a gasoline antiknock additive, is one of environmental exposures of manganese, which can lead to manganism in Rats. Though some researches showed that small non-coding RNAs (sncRNAs) were differently expressed in Parkinson’s disease (PD) patients, it was still unclear whether and how sncRNAs dysfunction appeared in Manganism. Unfartunately, transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs) are highly modified, including 3’ terminal modification such as 3’-phosphate and 2’,3’-cyclic phosphate that block the adapter ligation process, and RNA methylations such as m1A, m3C, m1G and m22G that interfere with reverse transcription. Thus, sncRNAs could escape from traditional small RNA-seq. Here, we present the differential expression of sncRNAs in MMT-induced unrepaired striatum in rats compared with control group, using PANDORA-seq, which could discover the highly modified sncRNAs. By removing sncRNAs modification, we found that 599 sncRNAs were differently expressed in Striatum of MMT-treated rats compared with control group, and 1155 sncRNAs in Mn-treated vs control. Further function analysis for predicted targets of these DE-sncRNAs shown that dysregulation of sncRNAs was implicated Manganism in rats.
2023-03-18 | GSE227299 | GEO
Project description:Increasing evidences indicate diet-induced metabolic disorder could be paternally inherited, but the exact sperm epigenetic carrier remains unclear. Here, in a paternal high-fat diet (HFD) mouse model, we revealed that a highly enriched subset of sperm small RNAs (30-34 nt) that derived from the 5â halves of tRNAs (tsRNAs), exhibit changes in both expression profiles and RNA modifications. Injection of sperm tsRNAs from HFD male but not synthetic tsRNAs lacking RNA modifications, into normal zygotes generated metabolic disorders in the F1 offspring. Injection of HFD sperm tsRNAs derails gene expression in both early embryos and islets of F1 offspring, enriched in metabolic pathways, but unrelated to DNA methylation at CpG-enriched region. Collectively, we uncover sperm tsRNAs as a type of âepigenetic carrierâ that mediate intergenerational inheritance of acquired traits. Mature sperm small-RNA profiles between High-fat-diet (HFD) and Normal-diet (ND) males; Transcriptional profiles of 8-cell embryos and balstocysts that developed from zygotes that injected with sperm RNAs from HFD vs ND males. Transcriptional profiles and RRBS profiles of islets of F1 offsrping that generated from zygotes that injected with sperm RNAs from HFD vs ND males.
2015-12-31 | E-GEOD-75544 | biostudies-arrayexpress
Project description:Semen samples from men after a short ejaculatory abstinence show improved sperm quality and result in increased pregnancy rates, but the underlying mechanisms remain unclear. Herein, we report that ejaculates from short (1–3 hours) compared with long (3–7 days) periods of abstinence showed increases in motile sperm count, sperm vitality, normal sperm morphology, acrosome reaction capacity, total antioxidant capacity, sperm mitochondrial membrane potential, high DNA stainability, and a decrease in the sperm DNA fragmentation index (P < 0.05). Sperm proteomic analysis showed 322 differentially expressed proteins (minimal fold change of ±1.5 or greater and P < 0.05), with 224 up-regulated and 98 down-regulated. These differentially expressed proteins are profoundly involved in specific cellular processes, such as motility and capacitation, oxidative stress, and metabolism. Interestingly, protein trimethyllysine modification was increased, and butyryllysine, propionyllysine, and malonyllysine modifications were decreased in ejaculates from a short versus long abstinence (P < 0.05). Finally, the rates of implantation, clinical pregnancy, and live births from in vitro fertilization treatments were significantly increased in semen samples after a short abstinence. Our study provides preliminary mechanistic insights into improved sperm quality and pregnancy outcomes associated with spermatozoa retrieved after a short ejaculatory abstinence
2019-02-22 | PXD010695 | Pride
Project description:<h4><strong>BACKGROUND: </strong>Semen quality is negatively correlated with male age and is mainly quantified by a routine semen analysis, which is descriptive and inconclusive. Sperm proteins or semen metabolites are used as the intermediate or end-products, reflecting changes in semen quality, and hold much promise as a new biomarker to predict fertility in advanced-aged males.</h4><h4><strong>OBJECTIVES: </strong>In this study, we sought to assess whether the semen metabolome and proteome of aged males can affect semen quality and serve as biomarkers for predicting semen quality.</h4><p><strong>MATERIALS AND METHODS: </strong>We retrospectively analyzed 12825 males that underwent semen routine analysis to understand the age-dependent changes in sperm quality. To identify the difference between aged and young adults, metabolomics (n=60) analyses of semen and proteomics (n=12) analyses of sperm were conducted. Finally, integrated machine learning of metabolomics was conducted to screen biomarkers to identify aging semen.</p><p><strong>RESULTS:</strong> We discovered that male age was positively correlated with sperm concentration as well as DNA fragmentation index(DFI), and negatively with progressive motile sperm count, total sperm count, sperm volume and progressive sperm motility. The differential metabolites were significantly enriched in various metabolic pathways, and four of these differential metabolites (Pipamperone, 2,2-Bis(hydroxymethyl)-2,2',2''-nitrilotriethanol, Arg-Pro and Triethyl phosphate) were utilized to establish a biomarker panel to identify aging semen. Proteomic analysis showed that differential proteins were significantly enriched in protein digestion and absorption and some energy-related pathways. An integrated analysis of the metabolome and proteome identified differential energy metabolism and oxidative stress-related proteins, which could explain the decreased motility and the increased DFI of aging sperm.</p><p><strong>DISCUSSION AND CONCLUSION:</strong> We provide compelling evidence that the changes in semen metabolome and sperm proteome are related to the decline of semen quality in aged males. Moreover, a biomarker panel based on four metabolites was established to identify aging semen.</p>
2024-01-16 | MTBLS5289 | MetaboLights
Project description:The discovery of RNAs (e.g. mRNAs, non-coding RNAs) in sperm has opened the possibility that sperm may function in delivering additional paternal information aside from solely providing the DNA1. Increasing evidence now suggests that sperm small non-coding RNAs (sncRNAs) can mediate intergenerational transmission of paternally acquired phenotypes, including mental stress2, 3 and metabolic disorders4-6. How sperm sncRNAs encode paternal information remains unclear, but the mechanism may involve RNA modifications. Here we show that deletion of a mouse tRNA methyltransferase, DNMT2, abolished sperm sncRNA-mediated transmission of high-fat diet (HFD)-induced metabolic disorders to offspring. Dnmt2 deletion prevented the elevation of RNA modifications (m5C, m2G) in sperm 30-40nt RNA fractions that are induced by HFD. Also, Dnmt2 deletion altered the sperm small RNA expression profile, including levels of tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNA-28S), which might be essential in composing a sperm RNA ‘coding signature’ that is needed for paternal epigenetic memory. Finally, we show that Dnmt2-mediated m5C contributes to the secondary structure and biological properties of sncRNAs, implicating sperm RNA modifications as an additional layer of paternal hereditary information.
2018-03-06 | GSE97645 | GEO
Project description:Primary objectives: To assess the impact of antiTNF agents on the male inflammatory bowel diseases patients` fertility
Primary outcomes:- semen quality and quantity, inclusive sperm chromatine structure analysis prior and during anti-TNF therapy- time to conception
| 2525194 | ecrin-mdr-crc
Project description:Purpose: Screening the sperm sncRNAs that are responsible for dairy cattle fertility is of great interest, however, exploring the fertility-associated sncRNAs in sperm and linking them with the epigenetic inheritance in bovine has not been performed yet. Here in this study, we hypothesized that some sncRNAs in bovine sperm have a great potential to be linked with direct and immediate bull fertility data and could later influence the embryo and possibly impacting the daughter fertility. Methods: 12 bovine cryopreserved semen (high bull fertility, n=3 VS low bull fertility, n=3; high daughter fertility, n=3 vs low daughter fertility, n=3) that came from a pre-filtered 100 bull list (Figure 1) had been selected to extract total sperm RNA, the somatic cell lysis buffer had been added during the RNA extraction process to avoid the somatic cell pollution. The maternal and other confounding factors had been taken into consideration during the calculation of the phenotype criteria index.After the library construction, the library size that was smaller than 200 base pairs (adapter size around 125 nt) had been cut and sent for next-generation sequencing Results: bull fertility and daughter fertility related sncRNAs had been identified. Conclusions: providing promising epigenetic biomarker for cattle fertility improvement in the future, although these small non-coding RNAs need to be validated in larger sample sizes before being used as biomarkers.
2024-02-16 | GSE225705 | GEO