Year: 2021
Type: article
Study design: Observational Study
Abstract: BACKGROUND: P-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. METHODS: We 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. RESULTS: mutations. CONCLUSIONS: Our 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.).
Source: New England Journal of Medicine
Authors: Liina Nagirnaja, Nina Mørup, John E. Nielsen, Rytis Stakaitis, Ieva Golubickaite, Manon S. Oud, Sofia B. Winge, Filipa Carvalho, Kenneth I. Aston, Francesca Khani, Godfried W. van der Heijden, C. Joana Marques, Niels E. Skakkebaek, Ewa Rajpert–De Meyts, Peter N. Schlegel, Niels Jørgensen, Joris A. Veltman, Alexandra M. Lopes, Donald F. Conrad, Kristian Almstrup
Institutions: Oregon National Primate Research Center, University of Copenhagen, Lithuanian University of Health Sciences, Oregon Health & Science University, Rigshospitalet, Neuroscience Institute, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Universidade do Porto, Radboud University Medical Center, University of Utah, Newcastle University
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3189079727