Biology subjects

Dou, Q.

Publications and source records attributed to Dou, Q..

3 recordsLinked to original sources

bioRxiv2021

TXNRD3 supports male fertility via the redox control of spermatogenesis

Thioredoxin/glutathione reductase (TGR, TXNRD3) is a thiol oxidoreductase of unknown function composed of thioredoxin reductase and glutaredoxin domains. This NADPH-dependent enzyme evolved by gene duplication within the Txnrd family, is expressed in the testes and can reduce both thioredoxin and glutathione in vitro. To characterize the function of TXNRD3 in vivo, we generated a strain of mice with the deletion of Txnrd3 gene. We show that Txnrd3 knockout mice are viable and without discernable gross phenotypes, but TXNRD3 deficiency leads to fertility impairment in male mice. Txnrd3 knockout animals exhibit a lower fertilization rate in vitro, a sperm movement phenotype and an altered redox status of thiols. Proteomic analyses revealed a broad range of substrates reduced by TXNRD3 during sperm maturation, presumably as a part of quality control. The results show that TXNRD3 plays a critical role in male reproduction via the thiol redox control of spermatogenesis.

biochemistry↗

bioRxiv2021

Redox regulation by TXNRD3 during epididymal maturation underlies capacitation-associated mitochondrial activation and sperm motility in mice

During epididymal transit, redox remodeling protects mammalian spermatozoa, preparing them for survival in the subsequent journey to fertilization. However, molecular mechanisms of redox regulation in sperm development and maturation remain largely elusive. In this study, we report that TXNRD3, a thioredoxin reductase family member particularly abundant in elongating spermatids at the site of mitochondrial sheath formation, regulates redox homeostasis to support male reproduction. Using Txnrd3-/- mice, our biochemical, ultrastructural, and live cell imaging analyses revealed impairments in sperm morphology and motility under conditions of TXNRD3 deficiency. We reveal that mitochondria develop more defined cristae during capacitation in wild type sperm. Absence of TXNRD3 alters redox status in both the head and tail during sperm maturation and capacitation, resulting in defective mitochondrial ultrastructure and activity under capacitating conditions. These findings provide insights into molecular mechanisms of redox homeostasis and bioenergetics during sperm maturation, capacitation, and fertilization.

physiology↗

bioRxiv2017

Gut Microbiota Composition Related With Clostridium difficile-Positive Diarrhea And C. Difficile Type (A+B+, A-B+, And A-B-) In ICU Hospitalized Patients

BackgroundGut microbiota composition of intensive care unit (ICU) patients suffering from Clostridium difficile-positive diarrhea (CDpD) is still poorly understood. This study aims to use 16S rDNA (and metagenome) sequencing to compare the microbiota composition of 58 (and 5) ICU patients with CDpD (CDpD group), 33 (and 4) ICU patients with C. difficile negative diarrhea (CDnD group), and 21 (and 5) healthy control subjects (control group), as well as CDpD patients in A+B+ (N=34; A/B: C. difficile TcdA/B), A-B+ (N=7), and A-B- (N=17) subgroups. For 16S rDNA data, OTU clustering (tool: UPARSE), taxonomic assignment (tool: RDP classifier), -diversity and {beta}-diversity analyses (tool: QIIME) were conducted. For metagenome data, metagenome assembly (tool: SOAP), gene calling (tools: MetaGeneMark, CD-HIT, and SoapAligner), unigene alignment (tool: DIAMOND), taxon difference analysis (tool: Metastats), and gene annotation (tool: DIAMOND) were performed.\n\nResultsThe microbial diversity of CDpD group was lower than that of CDnD and control groups. The abundances of 10 taxa (e.g. Deferribacteres, Cryptomycota, Acetothermia) in CDpD group were significantly higher than that in CDnD group. The abundances of Saccharomycetes and Clostridia were significantly lower in CDpD in comparison with control. A+B+, A-B+ and A-B- subgroups couldnt be separated in principal component analysis, while some taxa are significantly different between A+B+ and A-B- subgroups.\n\nConclusionCDpD might relate to the decrease of beneficial taxa (i.e. Saccharomycetes and Clostridia) and the increase of harmful taxa (e.g. Deferribacteres, Cryptomycota, Acetothermia) in gut microbiota in ICU patients. C. difficile type might be slightly associated with gut microbiota composition.

molecular biology↗