{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:16:13Z","timestamp":1788434173080,"version":"build-2803163510"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Vitamin D has attracted increasing attention in male reproduction, male fertility, and sperm function, but its pharmacological relevance remains incompletely defined. This review synthesizes current evidence on the molecular mechanisms and clinical implications of vitamin D signaling in the male reproductive system. Available experimental and human data suggest that the vitamin D receptor (VDR) and vitamin D-metabolizing enzymes are present in testicular cells, the epididymis, accessory sex glands, and mature spermatozoa, supporting the possibility of both systemic and local actions. Mechanistically, vitamin D may regulate sperm capacitation and progressive motility through calcium-dependent non-genomic pathways. Ligand-activated VDR signaling may also contribute to antioxidant defense, mitochondrial stability, inflammatory control, steroidogenesis, germ-cell survival, and epigenetic regulation, although several of these pathways still require direct validation in human testicular tissue and spermatozoa. Clinically, low circulating 25-hydroxyvitamin D has been most consistently associated with impaired sperm motility, whereas associations with sperm concentration, total sperm count, reproductive hormones, and sperm DNA fragmentation index are less consistent. Interventional studies suggest that vitamin D supplementation may improve selected semen parameters in deficient men, but current trials do not support broad endocrine or fertility benefits in unselected populations. Importantly, emerging preclinical data indicate that excessive vitamin D exposure may impair spermatogenesis, highlighting a potential biphasic relationship in which both deficiency and excess are unfavorable. Thus, vitamin D should be viewed as a homeostatic modulator rather than a stand-alone treatment for male infertility. Future studies should define optimal therapeutic windows, clarify effects on sperm DNA integrity, and incorporate individual differences in VDR-related genetic and epigenetic regulation.<\/jats:p>","DOI":"10.3389\/fphar.2026.1849299","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:32:20Z","timestamp":1788431540000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Vitamin D in male reproduction: molecular mechanisms and pharmacological perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bang","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyun","family":"Qiu","sequence":"additional","affiliation":[{"name":"The Third School of Clinical Medicine, Ningxia Medical University","place":["Yinchuan, Ningxia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmei","family":"Lv","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hunan Provincial Key Laboratory of Regional Hereditary Birth Defect Prevention and Control, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University","place":["Changsha, Hunan, China"]},{"name":"Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, Key Laboratory of Reproductive Health Diseases Research and Translation (Hainan Medical University), Ministry of Education, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University","place":["Haikou, Hainan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3390\/biomedicines11010090","article-title":"The association between vitamin D and the components of Male fertility: a systematic review","volume":"11","author":"Adamczewska","year":"2022","journal-title":"Biomedicines"},{"key":"B2","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s12958-015-0032-1","article-title":"A unique view on male infertility around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod. 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