{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:08:16Z","timestamp":1789996096974,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reinke crystals are a defining histological feature of human adult Leydig cells, the testosterone\u2010producing cells of the testis. These structures are present in the cytoplasm and the nucleus and display quantitative alterations in a variety of physiological and pathological contexts. The functional significance and protein composition of Reinke crystals have remained elusive for over a century.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We sought to explore the protein composition of Reinke crystals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Double labelling immunofluorescence for the purine nucleotide\u2010synthesizing enzymes inosine monophosphate dehydrogenase (IMPDH) and phosphoribosyl pyrophosphate synthetase (PRPS) and confocal microscopic imaging were performed on samples of human Leydig cell tumours and adjacent non\u2010neoplastic testis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrate that Reinke crystals are intensely immunoreactive for IMPDH and PRPS, two key rate\u2010limiting enzymes in the de novo synthesis of purine nucleotides.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>IMPDH and PRPS are two of several metabolic enzymes that are capable of forming mesoscale filamentous aggregates as a mechanism to regulate enzyme activity. IMPDH is also able to form crystals in cellulo. Our observations potentially link Reinke crystal formation to purine nucleotide metabolism in Leydig cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>If confirmed in future studies, this finding may have important implications for understanding metabolic contributions to male reproductive disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70302","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T12:17:33Z","timestamp":1783340253000},"page":"2063-2070","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reinke Crystals are Immunoreactive for Purine\u2010Synthesising Metabolic Enzymes"],"prefix":"10.1111","volume":"14","author":[{"given":"John","family":"Woulfe","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Ottawa and Ottawa Hospital Research Institute  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor A.","family":"Flood","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharlene","family":"Faulkes","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Munoz","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine St. Michael's Hospital Unity Health &amp; Department of Laboratory Medicine and Pathobiology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioy059"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02975071"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/andr.13201"},{"issue":"2","key":"e_1_2_11_5_1","first-page":"252","article-title":"Intranuclear Reinke's Crystals in a Testicular Leydig Cell Tumor Diagnosed by Aspiration Cytology. 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