ArticleHuman molecular genetics2014
Epigenetic regulation of the RHOX homeobox gene cluster and its association with human male infertility.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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.
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Who cites it
26 citing papers in PubMed, 48 citations in OpenAlex.
- SpermThe world journal of men's health · 2024Article
- Sperm epigenetics and male infertility: unraveling the molecular puzzle.Human genomics · 2024Review
- Article
- Mammal Reproductive Homeobox (Rhox) Genes: An Update of Their Involvement in Reproduction and Development.Genes · 2023Review
- Identification ofTranslational andrology and urology · 2023Article
- A higher preconceptional paternal body mass index influences fertilization rate and preimplantation embryo development.Andrology · 2022Article
- Epigenetic Modifications, A New Approach to Male Infertility Etiology: A Review.International journal of fertility & sterility · 2022Review
- TheProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Epigenetics of Male Infertility: The Role of DNA Methylation.Frontiers in cell and developmental biology · 2021Review
- Profiling the DNA methylation patterns of imprinted genes in abnormal semen samples by next-generation bisulfite sequencing.Journal of assisted reproduction and genetics · 2020Article
- High-resolution analysis of germ cells from men with sex chromosomal aneuploidies reveals normal transcriptome but impaired imprinting.Clinical epigenetics · 2019Article
- Epigenetics of Male Fertility: Effects on Assisted Reproductive Techniques.The world journal of men's health · 2019Review
- Transcription factors SOHLH1 and SOHLH2 coordinate oocyte differentiation without affecting meiosis I.The Journal of clinical investigation · 2017Article
- The human RHOX gene cluster: target genes and functional analysis of gene variants in infertile men.Human molecular genetics · 2016Article
- Rhox13 is required for a quantitatively normal first wave of spermatogenesis in mice.Reproduction (Cambridge, England) · 2016Article
- The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment.Cell reports · 2016Article
- Spermatogonial stem cell autotransplantation and germline genomic editing: a future cure for spermatogenic failure and prevention of transmission of genomic diseases.Human reproduction update · 2016Review
- lncRHOXF1, a Long Noncoding RNA from the X Chromosome That Suppresses Viral Response Genes during Development of the Early Human Placenta.Molecular and cellular biology · 2016Article
- Epigenetics: A key paradigm in reproductive health.Clinical and experimental reproductive medicine · 2016Review
- The role of epigenetics in idiopathic male infertility.Journal of assisted reproduction and genetics · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The X-linked RHOX cluster encodes a set of homeobox genes that are selectively expressed in the reproductive tract. Members of the RHOX cluster regulate target genes important for spermatogenesis promote male fertility in mice. Studies show that demethylating agents strongly upregulate the expression of mouse Rhox genes, suggesting that they are regulated by DNA methylation. However, whether this extends to human RHOX genes, whether DNA methylation directly regulates RHOX gene transcription and how this relates to human male infertility are unknown. To address these issues, we first defined the promoter regions of human RHOX genes and performed gain- and loss-of-function experiments to determine whether human RHOX gene transcription is regulated by DNA methylation. Our results indicated that DNA methylation is necessary and sufficient to silence human RHOX gene expression. To determine whether RHOX cluster methylation associates with male infertility, we evaluated the methylation status of RHOX genes in sperm from a large cohort of infertility patients. Linear regression analysis revealed a strong association between RHOX gene cluster hypermethylation and three independent types of semen abnormalities. Hypermethylation was restricted specifically to the RHOX cluster; we did not observe it in genes immediately adjacent to it on the X chromosome. Our results strongly suggest that human RHOX homeobox genes are under an epigenetic control mechanism that is aberrantly regulated in infertility patients. We propose that hypermethylation of the RHOX gene cluster serves as a marker for idiopathic infertility and that it is a candidate to exert a causal role in male infertility.
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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.