ArticleJCI insight2018
Deficient LRRC8A-dependent volume-regulated anion channel activity is associated with male infertility in mice.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- Function of manchette and intra-manchette transport in spermatogenesis and male fertility.Cell communication and signaling : CCS · 2025Review
- Hormonal regulation of non-cystic fibrosis transmembrane conductance regulator ion channels in the endocervix.F&S science · 2023Article
- Trends in volume-regulated anion channel (VRAC) research: visualization and bibliometric analysis from 2014 to 2022.Frontiers in pharmacology · 2023Article
- Expression and functional maintenance of volume-regulated anion channels in myometrial smooth muscles of pregnant mice.Experimental animals · 2022Article
- Recent Advances in the Structural Biology of the Volume-Regulated Anion Channel LRRC8.Frontiers in pharmacology · 2022Review
- Late adolescence mortality in mice with brain-specific deletion of the volume-regulated anion channel subunit LRRC8A.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Profiling Cisplatin Resistance in Head and Neck Cancer: A Critical Role of the VRAC Ion Channel for Chemoresistance.Cancers · 2021Article
- Zinc pyrithione activates the volume-regulated anion channel through an antioxidant-sensitive mechanism.American journal of physiology. Cell physiology · 2021Article
- Flow fluorometry quantification of anion channel VRAC subunit LRRC8A at the membrane of living U937 cells.Channels (Austin, Tex.) · 2020Article
- LRRC8A-dependent volume-regulated anion channels contribute to ischemia-induced brain injury and glutamatergic input to hippocampal neurons.Experimental neurology · 2020Article
- Cell death in the gut epithelium and implications for chronic inflammation.Nature reviews. Gastroenterology & hepatology · 2020Review
- RNA-sequencing and bioinformatics analysis of long noncoding RNAs and mRNAs in the asthenozoospermia.Bioscience reports · 2020Observational
- The LRRC8 volume-regulated anion channel inhibitor, DCPIB, inhibits mitochondrial respiration independently of the channel.Physiological reports · 2019Article
- Inhibition of angiotensin II-induced cerebrovascular smooth muscle cell proliferation by LRRC8A downregulation through suppressing PI3K/AKT activation.Human cell · 2019Article
- Review
- Chloride Channels in Astrocytes: Structure, Roles in Brain Homeostasis and Implications in Disease.International journal of molecular sciences · 2019Review
- A 30-year journey from volume-regulated anion currents to molecular structure of the LRRC8 channel.The Journal of general physiology · 2019Review
- Cellular basis of ClC-2 ClThe Journal of biological chemistryArticle
Corrections and comments
- Retracted
Authors and funding
25 authors at 6 institutions in 4 countries.
Funding
Abstract
Ion channel-controlled cell volume regulation is of fundamental significance to the physiological function of sperm. In addition to volume regulation, LRRC8A-dependent volume-regulated anion channel (VRAC) activity is involved in cell cycle progression, insulin signaling, and cisplatin resistance. Nevertheless, the contribution of LRRC8A and its dependent VRAC activity in the germ cell lineage remain unknown. By utilizing a spontaneous Lrrc8a mouse mutation (c.1325delTG, p.F443*) and genetically engineered mouse models, we demonstrate that LRRC8A-dependent VRAC activity is essential for male germ cell development and fertility. Lrrc8a-null male germ cells undergo progressive degeneration independent of the apoptotic pathway during postnatal testicular development. Lrrc8a-deficient mouse sperm exhibit multiple morphological abnormalities of the flagella (MMAF), a feature commonly observed in the sperm of infertile human patients. Importantly, we identified a human patient with a rare LRRC8A hypomorphic mutation (c.1634G>A, p.Arg545His) possibly linked to Sertoli cell-only syndrome (SCOS), a male sterility disorder characterized by the loss of germ cells. Thus, LRRC8A is a critical factor required for germ cell development and volume regulation in the mouse, and it might serve as a novel diagnostic and therapeutic target for SCOS patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.