{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:50:43Z","timestamp":1791989443940,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM121298"],"award-info":[{"award-number":["P20 GM121298"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["U54GM115677"],"award-info":[{"award-number":["U54GM115677"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Approximately half of male factor infertility cases are idiopathic, indicating a need for new methods to supplement male fertility assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The objective of this study was to identify differences in the sperm transcriptomes of men with different clinical fertility status. We hypothesized that sperm mRNA profiling could distinguish men presenting for fertility assessment from proven fertile men.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      We compared two groups of study participants: men who presented for infertility assessment (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a053, \u201cinfertility\u201d), and men without a history of infertility who had fathered a child and were presenting for vasectomy (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a014, \u201cproven fertile\u201d control). Study participants provided a semen sample for semen analysis and sperm mRNA sequencing. Differentially abundant genes were identified, and a gene expression summary score was constructed to test the ability of RNA\u2010seq data to differentiate between study populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The semen parameter that best differentiated between study populations was motility (area under the ROC curve\u00a0=\u00a00.746). In RNA\u2010seq analysis, 1885 total differentially abundant transcripts were identified (\n                      <jats:italic>q<\/jats:italic>\n                      \u00a0&lt;\u00a00.05, fold difference\u00a0\u2265\u00a02), 1004 (53.3%) of which were downregulated in infertility study participants. The Gene Ontology term, spermatogenesis, was enriched, with 40 out of 44 differentially abundant genes downregulated in infertility study participants. A gene expression summary score consisting of 100 upregulated and 100 downregulated genes was able to differentiate between the two groups of study participants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Sperm mRNAs differed between proven fertile and infertility study men. Known fertility\u2010associated genes, including\n                      <jats:italic>PRM1<\/jats:italic>\n                      and\n                      <jats:italic>PRM2<\/jats:italic>\n                      , and potentially novel fertility markers, including\n                      <jats:italic>HOOK1<\/jats:italic>\n                      and\n                      <jats:italic>SPATA6<\/jats:italic>\n                      , were downregulated in infertility study samples. Future studies should test these results for reproducibility and test whether novel biomarker candidates can provide mechanistic information about etiologies of idiopathic male infertility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results support the hypothesis that sperm mRNA abundance differs by clinical fertility status.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70060","type":"journal-article","created":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T03:49:18Z","timestamp":1746848958000},"page":"2419-2431","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Downregulation of spermatogenesis\u2010associated transcripts in the spermatozoa of idiopathic infertile men"],"prefix":"10.1111","volume":"14","author":[{"given":"Xinran","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Brown University  Providence Rhode Island USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan J.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Brown University  Providence Rhode Island 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