{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:57:46Z","timestamp":1787317066806,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["KK.01.1.1.01.0008"],"award-info":[{"award-number":["KK.01.1.1.01.0008"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Non-obstructive azoospermia (NOA) is a form of male infertility caused by disorders of the testicular parenchyma and impaired spermatogenesis. This study aimed to investigate the nature of Leydig cell changes in patients with NOA, especially whether their actual proliferation occurred. Methods: 48 testicular biopsies from infertile patients with NOA and 24 testicular biopsies originating from azoospermic patients suffering from obstructive azoospermia (OA) were included in the study. Leydig cells and their possible proliferative activity were analysed by immunohistochemistry and morphometry (stereology). Results: Unlike in the OA group, Leydig cells in NOA patients were sometimes organised into larger clusters and displayed an abundant cytoplasm\/hypertrophy. Moreover, significant fibrosis of the interstitial compartment was demonstrated in some NOA samples, often accompanied by inflammatory cells. Stereological analysis showed no increase\/proliferation of Leydig cells; on the contrary, these cells decreased in number in the NOA group. Conclusions: The decrease in the number of Leydig cells can be explained by previous inflammatory changes within the testicular interstitium and consequent interstitial fibrosis. The interstitial fibrosis might have a deteriorating effect on Leydig cells.<\/jats:p>","DOI":"10.3390\/life11111266","type":"journal-article","created":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T21:00:50Z","timestamp":1637528450000},"page":"1266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Leydig Cells in Patients with Non-Obstructive Azoospermia: Do They Really Proliferate?"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7151-6512","authenticated-orcid":false,"given":"Dinko","family":"Hauptman","sequence":"first","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Urology, University Hospital Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2143-6968","authenticated-orcid":false,"given":"Marta Himelreich","family":"Peri\u0107","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tihana","family":"Mari\u0107","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Katu\u0161i\u0107","family":"Bojanac","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Medical Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nino","family":"Sin\u010di\u0107","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Medical Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran","family":"Zimak","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Urology, University Hospital Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljko","family":"Ka\u0161telan","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Urology, University Hospital Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1528-5462","authenticated-orcid":false,"given":"Davor","family":"Je\u017eek","sequence":"additional","affiliation":[{"name":"Scientific Centre of Excellence for Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Histology and Embryology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Transfusion Medicine and Transplantation Biology, University Hospital Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/humupd\/dmm029","article-title":"Which is the best sperm retrieval technique for non-obstructive azoospermia? 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