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Dysregulation of long non-coding RNAs in mouse testis and sperm after exposure to cadmium

ABSTRACT: Dysregulation of long non-coding RNAs in mouse testis and sperm after exposure to cadmium

PROVIDER: PRJNA348423 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4423210_1.fastq.gz	Fastqsanger.gz
	SRR4423210_2.fastq.gz	Fastqsanger.gz
	SRR4423201_1.fastq.gz	Fastqsanger.gz
	SRR4423201_2.fastq.gz	Fastqsanger.gz
	SRR4423211_1.fastq.gz	Fastqsanger.gz

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The profile of long non-coding RNAs in mouse testis and sperm after exposure to cadmium

Project description:Increasing evidences have shown that cadmium could caused male infertility. However, the exhaustive mechanisms have not been elucidated in mammals. Here, the mice testes and sperm RNA were used to investigate lncRNA expression profiles by stranded-specific RNA-seq on the transcriptome levels after exposure to cadmium. More LncRNA expression have been changed than mRNA genes by cadmium. Furthermore, many novel LncRNA were inducible expression, suggesting that LncRNA might be a good candidate for indicating the reproductive toxicity of cadmium. The present study provides a preliminary database for further exploring the mechanisms of reproductive toxicity caused by cadmium in mammalians.

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Dysregulation of long non-coding RNAs in mouse testis and sperm after exposure to cadmium

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-02-08 | GSE88739 | GEO

Sperm-specific proteins and cancer testis antigens exist outside the blood-testis barrier

Project description:Sperm develop in the seminiferous tubules of the testis from puberty, sequestered inside the blood-testis barrier to prevent their recognition as “non-self” by the immune system. It is widely assumed that proteins expressed specifically in sperm do not have direct access to the circulation or the immune system. This assumption underlies the pursuit of cancer testis antigens (CTAs) as therapeutic targets and biomarkers for particular cancers. CTAs are aberrantly expressed in cancer but only expressed in sperm in healthy men; thus these proteins are assumed to be absent from the blood and/or to be neoantigens.

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Project description:In order to discover novel small RNAs expressed in mature sperm, we isolated mature sperm from mouse cauda epididymis, comparing with data from adult tesis and uterus. The small RNA fraction (18-40nt) was cloned and sequenced from total RNA of mature sperm, testis and uterus of mice. RNAs extracted from mature sperm, adult testis and uterus were used for high throughput sequencing analysis

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small RNA deep-sequencing of mature sperm, testis and uterus in mice

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Construction and analysis of the testis/sperm-enriched interaction network: identification of potential PPP1CC2 complexes as targets for male contraception

Project description:Phosphoprotein phosphatase 1 catalytic subunit gamma 2 (PPP1CC2), a PPP1 isoform restricted to testicular germ cells and spermatozoa, is essential for completion of spermatogenesis and highly similar PPP1C isoforms are capable of compensating for the loss of Ppp1cc in every tissue except in testis. In addition, inhibition of the enzymatic activity of PPP1C in spermatozoa stimulates motility. The key to understand the regulation of PPP1CC2 lies in the identification and characterization of its interacting partners. By integrating tissue-specific protein expression and protein-protein interaction data, we identified testis/sperm-enriched/specific PPP1CC complexes and potential key PPP1 interacting proteins (PIPs) for male reproduction. We constructed a testis/sperm-enriched network, analyzed several topological properties and specified the biological/physiological properties of the proteins in the network. Proteins were classified into modules according to their topological features and functional annotations, which clarified the mechanisms underlying testis and sperm function and, more specifically, the role of PPP1CC in spermatogenesis and sperm motility. Previously uncharacterized PIPs, such as AKAP4, were identified based on analyses of the interaction network. The PPP1CC2 interaction with AKAP4 in human sperm was also validated by different methods and the complex was proposed as potential targets for male contraception due to its significance in spermatozoa motility.

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Differential Expression Profiles and Potential Intergenerational Functions of tRNA-Derived Small RNAs in Mice After Cadmium Exposure

Project description:Cadmium (Cd) is a toxic heavy metal and ubiquitous environmental endocrine disruptor. Previous studies on Cd-induced damage to male fertility mainly focus on the structure and function of testis, and semen quality. Nevertheless, to date, no studies have investigated the effects of Cd exposure on sperm epigenetic inheritance and intergenerational inheritance. In our study, we systematically revealed the changes in sperm tRNA-derived small RNAs (tsRNA) profiles and found that 14 tsRNAs (9 up-regulated and 5 down-regulated) were significantly altered after Cd exposure. Bioinformatics of tsRNA-mRNA-pathway interactions revealed that the altered biological functions mainly were related to ion transmembrane transport, lipid metabolism and cell membrane system. In addition, we focused on two stages of early embryo development and selected two organs to study the impact of these changes on cell membrane system, especially mitochondrion and lysosome, two typical membrane-enclosed organelles. Surprisingly, we found that the content of mitochondrion was significantly decreased in 2-cell stage, whereas remarkably increased in the morula stage. The contents of mitochondrion and lysosome were significantly increased in the testes of 6-days offspring and livers of adult offspring, whereas remarkably decreased in the testes of adult offspring. This provides a possible basis to further explore the effects of paternal Cd exposure on offspring health.

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Sperm heterogeneity and DNMT/TET activities do not account for sperm DNA methylation changes observed in the epididymis

Project description:Following their production in the testis, spermatozoa enter the epididymis to gain their motility and fertilizing abilities. This post-testicular maturation coincides with sperm epigenetic profile changes that influence the progeny outcome. While recent studies underscored the dynamics of small non-coding RNAs in the maturing spermatozoa, little is known regarding sperm methylation changes and their impact at the post-fertilization level. To map out the sperm methylome dynamics, we purified spermatozoa by FACS from the testis and the different epididymal segments (i.e. caput, corpus and cauda) of CAG/su9-DsRed2; Acr3-EGFP transgenic mice. Reduced-Representation Bisulfite Sequencing (RRBS-Seq) performed on DNA from these respective sperm populations indicated that high methylation changes were observed between spermatozoa from the caput vs. testis with 5546 entries meeting our threshold values (q value < 0.01, methylation difference above 25 %). Most of these changes were transitory during epididymal sperm maturation according to the low number of entries identified between spermatozoa from cauda vs. testis.

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