{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:00:26Z","timestamp":1770746426145,"version":"3.49.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["57460069"],"award-info":[{"award-number":["57460069"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German Academic Exchange Service"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Congenital defects of androgen synthesis or action in 46,XY individuals can result in impaired virilisation, despite the apparent testicular development. In a recent case, report of a young adult with complete androgen insensitivity syndrome (CAIS), tumourous gonadal tissue was shown to express HSD17B3 in Sertoli cells (SCs) and not in Leydig cells (LCs). This expression pattern differs from the typical adult human testis and resembles a foetal mouse testis, suggesting an underlying testicular development and function defect. Here, we investigate the effect of altered androgen signalling in gonads from five 46,XY individuals with defects in androgen synthesis or action.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Gonadal tissue sections from four patients with CAIS, one with CYP17A1 deficiency, and one control were immunostained for LC developmental and steroidogenic markers. The expression of some of these markers during development was investigated by reanalysing previously published single-cell RNA sequencing (scRNA-seq) data from normal human testicular tissues.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All gonadal tissues from the patients show an exclusive expression of HSD17B3 in SCs and an expression of the foetal\/immature LC marker DLK1 in a subset of LCs, suggesting an androgen-dependent differentiation defect of adult SCs and LCs. Furthermore, reanalysis of scRNA-seq data reveals an expression of HSD17B3 in foetal and neonatal SCs that is downregulated in adult SCs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Androgen signalling may affect the differentiation of adults, but possibly not foetal SCs or LCs, and may induce a shift of testosterone production from the tubular compartment in the foetal phase to the interstitial compartment in the adult phase.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvad007","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T18:19:48Z","timestamp":1675275588000},"page":"166-175","source":"Crossref","is-referenced-by-count":9,"title":["Persistence of foetal testicular features in patients with defective androgen signalling"],"prefix":"10.1093","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3020-3939","authenticated-orcid":false,"given":"Mostafa","family":"Al-Sharkawi","sequence":"first","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetology, Department of Paediatrics, University of L\u00fcbeck , 23562 L\u00fcbeck , Germany"},{"name":"Biochemical Genetics Department, Human Genetics and Genome Research Institute , 12622 Dokki, Cairo , Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8653-3849","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Calonga-Sol\u00eds","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetology, Department of Paediatrics, University of L\u00fcbeck , 23562 L\u00fcbeck , Germany"},{"name":"Medical Systems Biology Division, L\u00fcbeck Institute of Experimental Dermatology and Institute for Cardiogenetics, University of L\u00fcbeck , 23562 L\u00fcbeck , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0873-5805","authenticated-orcid":false,"given":"Franz F","family":"Dressler","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Schleswig-Holstein , Campus L\u00fcbeck, 23562 L\u00fcbeck , Germany"},{"name":"Institute of Pathology, Charit\u00e9 - Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health , 10117, Berlin , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4763-4521","authenticated-orcid":false,"given":"Hauke","family":"Busch","sequence":"additional","affiliation":[{"name":"Medical Systems Biology Division, L\u00fcbeck Institute of Experimental Dermatology and Institute for Cardiogenetics, University of L\u00fcbeck , 23562 L\u00fcbeck , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7490-4983","authenticated-orcid":false,"given":"Olaf","family":"Hiort","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetology, Department of Paediatrics, University of L\u00fcbeck , 23562 L\u00fcbeck , Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3718-3595","authenticated-orcid":false,"given":"Ralf","family":"Werner","sequence":"additional","affiliation":[{"name":"Division of Paediatric Endocrinology and Diabetology, Department of Paediatrics, University of L\u00fcbeck , 23562 L\u00fcbeck , Germany"},{"name":"Institute of Molecular Medicine, University of L\u00fcbeck , 23562 L\u00fcbeck , 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