{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:07:00Z","timestamp":1790626020733,"version":"4.1.0"},"reference-count":34,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Working Hypothesis:<\/jats:title><jats:p>Mutations in the CYP2R1 gene, highly expressed in the testis and encoding vitamin D 25-hydroxylase, result in a vitamin D deficiency and a defective calcium homeostasis leading to rickets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective:<\/jats:title><jats:p>Our aim was to investigate CYP2R1 expression in pathological testis samples and relate this to vitamin D metabolism in testiculopathic patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Patients, Setting:<\/jats:title><jats:p>Testis samples for in vitro study and 98 young men were transversally evaluated at Padova's Center for Male Gamete Cryopreservation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>CYP2R1 mRNA expression and protein production were evaluated by quantitative RT-PCR, Western blot analysis, and immunofluorescence. Hormonal and bone-marker levels, and bone densitometry by dual-energy x-ray absorptiometry, were determined in patients with Sertoli-cell-only syndrome and severe hypospermatogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>We found a lower gene and protein expression of CYP2R1 in samples with hypospermatogenesis and Sertoli-cell-only syndrome (P &amp;lt; 0.05) and a colocalization with INSL-3, a Leydig cell marker, at immunofluorescence. In all testiculopathic patients 25-hydroxyvitamin D levels were significantly lower and PTH levels higher compared to controls (P &amp;lt; 0.05). Furthermore, testiculopathic patients showed osteopenia and osteoporosis despite normal testosterone levels compared with controls both with increased bone-marker levels and altered dual-energy x-ray absorptiometry in the femoral neck and lumbar spine (for all parameters, P &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Our data show an association between testiculopathy and alteration of the bone status, despite unvaried androgen and estrogen levels and no other evident cause of vitamin D reduction. Further studies in larger cohorts are needed to confirm our results.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2010-1628","type":"journal-article","created":{"date-parts":[[2011,1,27]],"date-time":"2011-01-27T02:46:57Z","timestamp":1296096417000},"page":"E646-E652","source":"Crossref","is-referenced-by-count":80,"title":["Bone Mineral Density and Testicular Failure: Evidence for a Role of Vitamin D 25-Hydroxylase in Human Testis"],"prefix":"10.1210","volume":"96","author":[{"given":"Carlo","family":"Foresta","sequence":"first","affiliation":[{"name":"Department of Histology (C.F., G.S., L.D.T., L.P., A.D.M., R.S.), Microbiology, and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova, 35128 Padova, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Strapazzon","sequence":"additional","affiliation":[{"name":"Department of Histology (C.F., G.S., L.D.T., L.P., A.D.M., R.S.), Microbiology, and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova, 35128 Padova, Italy;"},{"name":"EURAC Institute of Mountain Emergency Medicine (G.S.), 39100 Bozen\/Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"De Toni","sequence":"additional","affiliation":[{"name":"Department of Histology (C.F., G.S., L.D.T., L.P., A.D.M., R.S.), Microbiology, and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova, 35128 Padova, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Perilli","sequence":"additional","affiliation":[{"name":"Department of Histology (C.F., G.S., L.D.T., L.P., A.D.M., R.S.), Microbiology, and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova, 35128 Padova, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Di Mambro","sequence":"additional","affiliation":[{"name":"Department of Histology (C.F., G.S., L.D.T., L.P., A.D.M., R.S.), Microbiology, and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova, 35128 Padova, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Muciaccia","sequence":"additional","affiliation":[{"name":"Department of Histology (B.M.) and Medical Embryology, University of Rome \u201cLa Sapienza,\u201d 00161 Rome, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Sartori","sequence":"additional","affiliation":[{"name":"Clinica Medica I (L.S.), Department of Medical and Surgical Sciences, University of Padova, 35128 Padova, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Selice","sequence":"additional","affiliation":[{"name":"Department of Histology (C.F., G.S., L.D.T., L.P., A.D.M., R.S.), Microbiology, and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete Cryopreservation, University of Padova, 35128 Padova, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613595104600_B1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00198-005-2039-5","article-title":"Review: developmental origins of osteoporotic fracture.","volume":"17","author":"Cooper","year":"2006","journal-title":"Osteoporos Int"},{"key":"2020071613595104600_B2","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1359\/jbmr.2002.17.4.563","article-title":"Sex steroids, mice, and men: when androgens and estrogens get very close to each 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