ArticleHuman reproduction (Oxford, England)2012
A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility.
Article in Human reproduction (Oxford, England), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07684339 (Assessing the Correlation Between Phospholipase C Zeta), which is not on this map. Cited by 60 papers, 2 of them syntheses that pooled it.
What it found
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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.
Assessing the Correlation Between Phospholipase C Zeta (PLCZeta) Measurements and Semen Parameters
Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 133 citations in OpenAlex.
- Clinical Applications of Assisted Oocyte Activation in Couples with Various Reproductive Problems: A Systematic Review.Reproductive sciences (Thousand Oaks, Calif.) · 2024Pooled it
- Phospholipase C Zeta in Human Spermatozoa: A Systematic Review on Current Development and Clinical Application.International journal of molecular sciences · 2024Pooled it
- N6-Methyladenosine and 5-Methylcytosine Epitranscriptomic Regulation of Male Reproduction and Fertility.Biology · 2026Review
- A comprehensive review for defining cut-off values of oocyte, zygote, and embryo maturation arrest (OZEMA) due to maternal-effect genes: towards the establishment of clinical criteria.Human reproduction (Oxford, England) · 2026Review
- Clinical Features and PLCZ1 Gene Variants in Two Cases of Male Infertility: A Case Series and Literature Review.Molecular genetics & genomic medicine · 2026Review
- A Homozygous Frameshift Mutation inHuman mutation · 2026Article
- Pathogenic homozygous PLCZ1 mutation reduces sperm protein levels with a simulated reduction of PIP2 binding: a case report.Reproduction & fertility · 2026Article
- PLCZ1 gene mutation leads to fertilization disorder: a case report.JBRA assisted reproduction · 2025Article
- Phospholipases: Paving the Way for a New Life.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Phospholipase Cζ, the Molecular Spark of Fertilization and Male Infertility: Insights from Bench to Bedside.Medicina (Kaunas, Lithuania) · 2025Review
- Structural Implications of H233L and H398P Mutations in Phospholipase Cζ: A Full-Atom Molecular Dynamics Study on Infertility-Associated Dysfunctions.International journal of molecular sciences · 2025Article
- Identification of housekeeping gene for future studies exploring effects of cryopreservation on gene expression in shrimp.Scientific reports · 2025Article
- Phospholipase C zeta: a hidden face of sperm for oocyte activation and early embryonic development.Obstetrics & gynecology science · 2024Article
- Novel PLCZ1 mutation caused polyspermy during in vitro fertilization.Asian journal of andrology · 2024Article
- The mammalian sperm factor phospholipase C zeta is critical for early embryo division and pregnancy in humans and mice.Human reproduction (Oxford, England) · 2024Article
- Molecular Mechanism of Oocyte Activation in Mammals: Past, Present, and Future Directions.Biomolecules · 2024Review
- High rate of detected variants in maleHuman reproduction open · 2024Article
- Assessment of Expression Levels and Localization Patterns of Phospholipase C zeta in Different Grades of HOST in Human Sperm.International journal of fertility & sterility · 2023Article
- Transition nuclear protein 1 as a novel biomarker in patients with fertilization failure.Clinical and experimental reproductive medicine · 2023Article
- Advances in the study of genetic factors and clinical interventions for fertilization failure.Journal of assisted reproduction and genetics · 2023Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundMale factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLCζ). Previously, we identified a point mutation in an infertile male resulting in the substitution of histidine for proline at position 398 of the protein sequence (PLCζ(H398P)), leading to abnormal PLCζ function and infertility. METHODS AND
resultsHere, using a combination of direct-sequencing and mini-sequencing of the PLCζ gene from the patient and his family, we report the identification of a second PLCζ mutation in the same patient resulting in a histidine to leucine substitution at position 233 (PLCζ(H233L)), which is predicted to disrupt local protein interactions in a manner similar to PLCζ(H398P) and was shown to exhibit abnormal calcium oscillatory ability following predictive 3D modelling and cRNA injection in mouse oocytes respectively. We show that PLCζ(H233L) and PLCζ(H398P) exist on distinct parental chromosomes, the former inherited from the patient's mother and the latter from his father. Neither mutation was detected utilizing custom-made single-nucleotide polymorphism assays in 100 fertile males and females, or 8 infertile males with characterized oocyte activation deficiency.
conclusionsCollectively, our findings provide further evidence regarding the importance of PLCζ at oocyte activation and forms of male infertility where this is deficient. Additionally, we show that the inheritance patterns underlying male infertility are more complex than previously thought and may involve maternal mechanisms.
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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.