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Neuroplastin-deficient (Nptn\u2212\/\u2212) male mice cannot sire offspring. By immunohistochemistry, we characterized neuroplastin expression in the testis. Breeding, mating behavior, hormonal regulation, testicular development, and spermatogenesis were analyzed in cell-type specific neuroplastin mutant mice. Leydig, Sertoli, peritubular myoid, and germ cells express Np, but spermatogenesis and sperm number are not affected in Nptn\u2212\/\u2212 males. Neuroplastin lack from CNS neurons or restricted to spermatogonia or Sertoli cells permitted reproduction. Normal luteinizing hormone (LH) and follicle-stimulating hormone (FSH) blood levels in Nptn\u2212\/\u2212 males support undisturbed hormonal regulation in the brain. However, Nptn\u2212\/\u2212 males lack mounting behavior accompanied by low testosterone blood levels. Testosterone rise from juvenile to adult blood levels is absent in Nptn\u2212\/\u2212 males. LH-receptor stimulation raising intracellular Ca2+ in Leydig cells triggers testosterone production. Reduced Plasma Membrane Ca2+ ATPase 1 (PMCA1) in Nptn\u2212\/\u2212 Leydig cells suggests that Nptn\u2212\/\u2212 Leydig cells produce sufficient testosterone for testis and sperm development, but a lack of PMCA-Np complexes prevents the increase from reaching adult blood levels. Behavioral immaturity with low testosterone blood levels underlies infertility of Nptn\u2212\/\u2212 males, revealing that Np is essential for reproduction.<\/jats:p>","DOI":"10.3390\/ijms25010177","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T01:19:42Z","timestamp":1703207982000},"page":"177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Neuroplastin Expression in Male Mice Is Essential for Fertility, Mating, and Adult Testosterone Levels"],"prefix":"10.3390","volume":"25","author":[{"given":"Juanjuan","family":"Chen","sequence":"first","affiliation":[{"name":"Neurogenetics, Leibniz Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Neurogenetics, Leibniz Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumee","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Neurogenetics, Leibniz Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7174-9954","authenticated-orcid":false,"given":"Caroline","family":"Wieseh\u00f6fer","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University Hospital, University Duisburg-Essen, Hufelandstr. 55, D-45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-2475","authenticated-orcid":false,"given":"Gunther","family":"Wennemuth","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University Hospital, University Duisburg-Essen, Hufelandstr. 55, D-45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1749-4863","authenticated-orcid":false,"given":"Karin","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Zoo and Wildlife Research IZW, Alfred-Kowalke-Str. 17, D-10315 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4964-1330","authenticated-orcid":false,"given":"Dirk","family":"Montag","sequence":"additional","affiliation":[{"name":"Neurogenetics, Leibniz Institute for Neurobiology, Brenneckestr. 6, D-39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"ref_1","first-page":"E1","article-title":"Mendelian genetics of male infertility","volume":"1214","author":"Hwang","year":"2011","journal-title":"Ann. 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