Loss of mammalian glutaminase orthologs impairs sperm function in C. elegans
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA929928 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23285388_1.fastq.gz | Fastqsanger.gz | |||
| SRR23285388_2.fastq.gz | Fastqsanger.gz | |||
| SRR23285389_1.fastq.gz | Fastqsanger.gz | |||
| SRR23285389_2.fastq.gz | Fastqsanger.gz | |||
| SRR23285390_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:The decline in sperm function is a major cause of human male infertility. Glutaminase, a mitochondrial enzyme that catalyzes the hydrolysis of glutamine to generate glutamate, takes part in many diverse biological processes such as neurotransmission, metabolism, and cellular senescence. Here we report a role of glutaminase in regulating sperm function. By generating a triple mutant that harbors a loss-of-function allele for each of all three mammalian glutaminase orthologs, we found that glutaminase gene activity is required for optimal C. elegans sperm function. Tissue-specific gene manipulations showed that germline glutaminase activity plays an important role. Moreover, transcriptional profiling and antioxidant treatment suggested that glutaminase promotes sperm function by maintaining cellular redox homeostasis. As maintaining a low level of ROS is crucial to human sperm function, it is very likely that glutaminase plays a similar role in humans and therefore can be a potential target for treating human male infertility.
2023-02-15 | GSE224117 | GEO
Project description:Prototypical micro RNAs (miRNAs) are 21~25-base-pair RNAs that regulate differentiation, carcinogenesis and pluripotency by eliminating mRNAs or blocking their translation, processes collectively termed RNA interference (RNAi). RNAi mediated by miRNAs regulates early development in zebrafish, and mouse embryos lacking the miRNA precursor processor, Dicer, are inviable. However, the role of miRNAs during mammalian fertilization is unknown. We here show using microarrays that miRNAs are present in mouse sperm structures that enter the oocyte at fertilization. Sperm contained a broad profile of miRNAs and a subset of potential mRNA targets were expressed in fertilizable, metaphase II (mII) oocytes. Oocytes contained transcripts for the RNAinduced silencing complex (RISC) catalytic subunit, EIF2C3 (formerly AGO3). However, levels of sperm-borne miRNA (measured by quantitative PCR) were apparently low relative to those of unfertilized, mII oocytes, and fertilization did not alter the part of the mII oocyte miRNA landscape that included the most abundant sperm-borne miRNAs. Coinjection of mII oocytes with sperm heads plus anti-miRNAs - to suppress miRNA function - did not perturb pronuclear activation or preimplantation development. Contrastingly, we provide evidence that nuclear transfer by microinjection alters the miRNA profile of enucleated oocytes. These data argue that sperm-borne prototypical miRNAs play a limited role, if any, in mammalian fertilization or early preimplantation development. Keywords: miRNA profiling Seven samples were analyzed for the study.
2010-06-10 | E-GEOD-4011 | biostudies-arrayexpress
Project description:DNA methylation in sperm is among the most important factors shaping evolution of the mammalian genome. By directly altering germline mutation rates, the DNA methylation system has shaped the CpG landscape of mammalian genomes, resulting in the CpG island phenomenon. Yet little is known about how this system itself has co-evolved with its substrate during mammalian evolution. We analyzed full-genome single-CpG DNA methylation profiles in sperm from human, chimp, gorilla, rhesus, mouse, rat and dog. Our results point to an evolutionary expansion of the unmethylated portion of mammalian genomes. Within the mutually orthologous genome this trend is driven both by the birth of unmethylated regions and by widening of intervals that are unmethylated in ancestors. We find strikingly divergent global features in rodents. At the same time, we observe the evolutionary emergence of methylome features in mouse sperm bears association with similar pathways to those found in human. Together,these results revealed general principles in mammalian epigenome evolution.
2017-12-14 | GSE79566 | GEO
Project description:To find and fuse with the egg, mammalian sperm must complete an arduous voyage through the female reproductive tract. This odyssey is powered by the sperm tail, a specialized motile cilium. Mammalian sperm tails are reinforced at the molecular scale with sperm-specific microtubule inner proteins (sperm-MIPs), but the identities of these sperm-MIPs are unknown. Here, we report high-resolution cryo-electron microscopy structures of bovine sperm doublet microtubules (DMTs), allowing us to identify many sperm-MIPs. We also resolve structures of singlet MTs in the endpiece, revealing MIPs shared between singlet and doublet MTs. We demonstrate that at least two sperm-MIPs bind and stabilize MTs in vitro. Our structures shed light on ciliary diversity across cell types and provide structural frameworks for understanding molecular underpinnings of male infertility
2023-06-20 | PXD035941 | Pride
Project description:Prototypical micro RNAs (miRNAs) are 21~25-base-pair RNAs that regulate differentiation, carcinogenesis and pluripotency by eliminating mRNAs or blocking their translation, processes collectively termed RNA interference (RNAi). RNAi mediated by miRNAs regulates early development in zebrafish, and mouse embryos lacking the miRNA precursor processor, Dicer, are inviable. However, the role of miRNAs during mammalian fertilization is unknown. We here show using microarrays that miRNAs are present in mouse sperm structures that enter the oocyte at fertilization. Sperm contained a broad profile of miRNAs and a subset of potential mRNA targets were expressed in fertilizable, metaphase II (mII) oocytes. Oocytes contained transcripts for the RNAinduced silencing complex (RISC) catalytic subunit, EIF2C3 (formerly AGO3). However, levels of sperm-borne miRNA (measured by quantitative PCR) were apparently low relative to those of unfertilized, mII oocytes, and fertilization did not alter the part of the mII oocyte miRNA landscape that included the most abundant sperm-borne miRNAs. Coinjection of mII oocytes with sperm heads plus anti-miRNAs - to suppress miRNA function - did not perturb pronuclear activation or preimplantation development. Contrastingly, we provide evidence that nuclear transfer by microinjection alters the miRNA profile of enucleated oocytes. These data argue that sperm-borne prototypical miRNAs play a limited role, if any, in mammalian fertilization or early preimplantation development. Keywords: miRNA profiling
2006-09-06 | GSE4011 | GEO
Project description:The mammalian sperm genome is generally thought to be condensed and transcriptionally inert. Here we show that most promoters in mouse sperm contain elongating RNA polymerase II and are flanked by several positioned nucleosomes marked by a variety of active histone modifications. The sperm genome is bound by several transcription factors, including Nanog, Oct4, Mediator, condensin, and the pioneer factor FoxA1. These proteins are found at promoters, enhancers, and super-enhancers, many of which are active in mESCs or adult tissues. CTCF and cohesin are also present in sperm DNA, where they mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results indicate that the sperm genome is rich in epigenetic information and primed for its expression during embryonic and adult life, and suggest mechanisms by which environmental effects on the paternal germline can be transmitted trans-generationally.
2017-01-17 | GSE79227 | GEO
Project description:The mammalian sperm genome is generally thought to be condensed and transcriptionally inert. Here we show that most promoters in mouse sperm contain elongating RNA polymerase II and are flanked by several positioned nucleosomes marked by a variety of active histone modifications. The sperm genome is bound by several transcription factors, including Nanog, Oct4, Mediator, condensin, and the pioneer factor FoxA1. These proteins are found at promoters, enhancers, and super-enhancers, many of which are active in mESCs or adult tissues. CTCF and cohesin are also present in sperm DNA, where they mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results indicate that the sperm genome is rich in epigenetic information and primed for its expression during embryonic and adult life, and suggest mechanisms by which environmental effects on the paternal germline can be transmitted trans-generationally.
2017-01-17 | GSE79226 | GEO
Project description:The mammalian sperm genome is generally thought to be condensed and transcriptionally inert. Here we show that most promoters in mouse sperm contain elongating RNA polymerase II and are flanked by several positioned nucleosomes marked by a variety of active histone modifications. The sperm genome is bound by several transcription factors, including Nanog, Oct4, Mediator, condensin, and the pioneer factor FoxA1. These proteins are found at promoters, enhancers, and super-enhancers, many of which are active in mESCs or adult tissues. CTCF and cohesin are also present in sperm DNA, where they mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results indicate that the sperm genome is rich in epigenetic information and primed for its expression during embryonic and adult life, and suggest mechanisms by which environmental effects on the paternal germline can be transmitted trans-generationally.
2017-01-17 | GSE79225 | GEO
Project description:The mammalian sperm genome is generally thought to be condensed and transcriptionally inert. Here we show that most promoters in mouse sperm contain elongating RNA polymerase II and are flanked by several positioned nucleosomes marked by a variety of active histone modifications. The sperm genome is bound by several transcription factors, including Nanog, Oct4, Mediator, condensin, and the pioneer factor FoxA1. These proteins are found at promoters, enhancers, and super-enhancers, many of which are active in mESCs or adult tissues. CTCF and cohesin are also present in sperm DNA, where they mediate interactions that organize the sperm genome into domains and compartments that overlap extensively with those found in mESCs. These results indicate that the sperm genome is rich in epigenetic information and primed for its expression during embryonic and adult life, and suggest mechanisms by which environmental effects on the paternal germline can be transmitted trans-generationally.
2017-01-17 | GSE79229 | GEO
Project description:RNAs present in mature mammalian sperm are delivered to the zygote at fertilization, where they have the potential to affect early development. The biogenesis of the small RNA payload of mature sperm is therefore of great interest, as it may be a target of signaling pathways linking paternal conditions to offspring phenotype. Recent studies have suggested the surprising hypothesis that the small RNA payload carried by mature sperm may include RNAs that were not synthesized during testicular spermatogenesis, but that are instead delivered to sperm during the process of post-testicular maturation in the epididymis. To further test this hypothesis, we characterized small RNA dynamics during testicular and post-testicular germ cell maturation in mice, confirming and extending prior observations that testicular germ cell populations carry extremely low levels of tRNA fragments (tRFs), which only become highly abundant only after sperm have entered the epididymis. We examined the sperm RNA repertoire in greater detail, finding that the majority of 5’ tRNA fragments carry a 2’-3’ cyclic phosphate at their 3’ end, pointing to a role for RNaseA or T-family nucleases in tRNA cleavage in the male reproductive tract. The process of small RNA delivery to sperm can be recapitulated in vitro, as caput epididymosomes deliver small RNAs including tRFs and microRNAs to mature testicular spermatozoa. Finally, to definitively identify the tissue of origin for small RNAs in sperm, we carried out tissue-specific metabolic labeling of RNAs in intact mice, finding that mature sperm carry small RNAs that were originally synthesized in the somatic cells of the epididymis. Taken together, our data demonstrates that soma-germline small RNA transfer occurs in male mammals, most likely via vesicular transport from the epididymis to maturing sperm.
2018-07-15 | GSE112990 | GEO