ArticleThe New England journal of medicine2021
Variant
Open access · bronzeAbstract read
In one paragraph
Article in The New England journal of medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
16.6field-weighted citation impact, top 1% of its field
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
66 citing papers in PubMed, 95 citations in OpenAlex.
- ER-Localized DeadenylaseExploration (Beijing, China) · 2026Article
- Comprehensive profiling of cell-free RNA in seminal plasma reveals functional links to spermatogenic impairment.Clinical and translational medicine · 2026Article
- Unraveling the role of PIWI/piRNAs in stem cell therapy: Epigenetic mechanisms and therapeutic potentials.Genes & diseases · 2026Review
- PIWI-Interacting RNAs in brain health and disease: biogenesis, mechanisms, and therapeutic horizons.Psychopharmacology · 2026Review
- Molecular Advances in Male Infertility and Fertility: Importance of Redox Regulation and Oxidative Stress.International journal of molecular sciences · 2026Review
- A mammalian-like piRNA pathway in Axolotl reveals the origins of piRNA-directed DNA methylation.The EMBO journal · 2026Article
- Changes in circulating small non-coding RNAs after castration in a cohort of prostate cancer patients.Scientific reports · 2026Article
- PIWIL4: from biological characteristics to disease pathogenesis and clinical applications.Frontiers in oncology · 2026Review
- Small Non-coding RNAs and Male Infertility.Advances in experimental medicine and biology · 2026Review
- Pathogenic Variants in PET Complex Encoding GenesHuman mutation · 2026Article
- The Role of Whole Exome Sequencing in the Genetic Evaluation of the Infertile Man.Advances in experimental medicine and biology · 2026Review
- High-Resolution Multiplexed Sequencing of Single-Cell Full-length Transcriptome Via Combinational Barcoded Tn5 Transposon Insertion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic and epigenetic insights into non-obstructive azoospermia: mechanisms, biomarkers, and clinical perspectives.Reproductive biology and endocrinology : RB&E · 2025Review
- GASZ directly recruits MILI to the intermitochondrial cement for piRNA biogenesis and male germ cell development.Nucleic acids research · 2025Article
- Ribonucleases in Mendelian disease: Characterization and insight from model organisms.Genes & diseases · 2025Review
- Introduction to androgenetics: terminology, approaches, and impactful studies across 60 years.Andrology · 2025Review
- Genetic and functional analysis reveals novel mutations in meiotic genes underlying non-obstructive azoospermia.Journal of assisted reproduction and genetics · 2025Article
- How exome sequencing improves the diagnostics and management of men with non-syndromic infertility.Andrology · 2025Review
- Review
- Epigenetics of nonobstructive azoospermia.Asian journal of andrology · 2025Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Commented on by
Authors and funding
20 authors at 1 institution in 6 countries.
Liina NagirnajaFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Nina MørupFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).ORCID 0000-0002-7332-4116
John E NielsenFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Rytis StakaitisFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).ORCID 0000-0001-5946-1731
Ieva GolubickaiteFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).ORCID 0000-0003-2739-8576
Manon S OudFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Sofia B WingeFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Filipa CarvalhoFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Kenneth I AstonFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Francesca KhaniFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Godfried W van der HeijdenFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
C Joana MarquesFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Niels E SkakkebaekFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Ewa Rajpert-De MeytsFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Peter N SchlegelFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Niels JørgensenFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Joris A VeltmanFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Alexandra M LopesFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Donald F ConradFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).
Kristian AlmstrupFrom the Division of Genetics, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton (L.N., D.F.C.); the Center for Embryonic Cell and Gene Therapy, Oregon Health and Science University, Portland (D.F.C.); the Department of Growth and Reproduction (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.) and the International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (N.M., J.E.N., R.S., I.G., S.B.W., N.E.S., E.R.-D.M., N.J., K.A.), Rigshospitalet, and the Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences (K.A.), University of Copenhagen, Copenhagen; the Laboratory of Molecular Neurooncology, Neuroscience Institute (R.S.), and the Institute of Biology Systems and Genetic Research (I.G.), Lithuanian University of Health Sciences, Kaunas, Lithuania; the Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior (M.S.O., G.W.H.), and the Department of Obstetrics and Gynecology (G.W.H.), Radboud University Medical Center, Nijmegen, the Netherlands; Serviço de Genética, Departamento de Patologia, Faculdade de Medicina da Universidade do Porto (F.C., C.J.M.), Instituto de Investigação e Inovação em Saúde, Universidade do Porto (F.C., C.J.M., A.M.L.), and the Institute of Molecular Pathology and Immunology of the University of Porto (A.M.L.) - all in Porto, Portugal; the Andrology and In Vitro Fertilization Laboratory, Department of Surgery (Urology), University of Utah School of Medicine, Salt Lake City (K.I.A.); the Departments of Pathology and Laboratory Medicine (F.K.) and Urology (P.N.S.), Weill Cornell Medicine, New York; and the Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom (J.A.V.).ORCID 0000-0002-1832-0307
Oregon National Primate Research Center · US
Funding
Project IIIP50HD096723 · NICHD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Kyle Edwin Orwig · 2019 to 2026
$15.0MGENOMICS OF SPERMATOGENIC IMPAIRMENTR01HD078641 · NICHD · WASHINGTON UNIVERSITY · PI Kenneth Ivan Aston, DONALD F. CONRAD · 2014 to 2026
$6.3MNICHD NIH HHS P50 HD096723NICHD NIH HHS R01 HD078641NIH HHS P50HD096723NIH HHS R01HD078641Wellcome Trust 209451Wellcome Trust 209451/Z/17/Z
Abstract
backgroundP-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are short (21 to 35 nucleotides in length) and noncoding and are found almost exclusively in germ cells, where they regulate aberrant expression of transposable elements and postmeiotic gene expression. Critical to the processing of piRNAs is the protein poly(A)-specific RNase-like domain containing 1 (PNLDC1), which trims their 3' ends and, when disrupted in mice, causes azoospermia and male infertility.
methodsWe performed exome sequencing on DNA samples from 924 men who had received a diagnosis of nonobstructive azoospermia. Testicular-biopsy samples were analyzed by means of histologic and immunohistochemical tests, in situ hybridization, reverse-transcriptase-quantitative-polymerase-chain-reaction assay, and small-RNA sequencing.
resultsFour unrelated men of Middle Eastern descent who had nonobstructive azoospermia were found to carry mutations in
conclusionsOur results suggest a direct mechanistic effect of faulty piRNA processing on meiosis and spermatogenesis in men, ultimately leading to male infertility. (Funded by Innovation Fund Denmark and others.).
Indexed as
MutationAdultAzoospermiaBiopsyExome SequencingExoribonucleasesGene ExpressionHumansInfertility, MaleMaleMeiosisPhenotypePolymerase Chain ReactionRNA, Small InterferingSequence Analysis, RNATestisExoribonucleasesRNA, Small Interfering
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.