{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:08:28Z","timestamp":1790845708526,"version":"4.1.0"},"reference-count":48,"publisher":"The Endocrine Society","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,7,1]]},"abstract":"<jats:p>Estrogen receptor 1 (ESR1) mediates major reproductive functions of 17\u03b2-estradiol (E2). Male Esr1 knockout (Esr1KO) mice are infertile due to efferent ductule and epididymal abnormalities. The majority of ESR1 is nuclear\/cytoplasmic; however, a small fraction is palmitoylated at cysteine 451 in mice and localized to cell membranes, in which it mediates rapid E2 actions. This study used an Esr1 knock-in mouse containing an altered palmitoylation site (C451A) in ESR1 that prevented cell membrane localization, although nuclear ESR1 was expressed. These nuclear-only estrogen receptor 1 (NOER) mice were used to determine the roles of membrane ESR1 in males. Epididymal sperm motility was reduced 85% in 8-month-old NOER mice compared with wild-type controls. The NOER mice had decreased epididymal sperm viability and greater than 95% of sperm had abnormalities, including coiled midpieces and tails, absent heads, and folded tails; this was comparable to 4-month Esr1KO males. At 8 months, daily sperm production in NOER males was reduced 62% compared with controls. The NOER mice had histological changes in the rete testes, efferent ductules, and seminiferous tubules that were comparable with those previously observed in Esr1KO males. Serum T was increased in NOER males, but FSH, LH, and E2 were unchanged. Critically, NOER males were initially subfertile, becoming infertile with advancing age. These findings identify a previously unknown role for membrane ESR1 in the development of normal sperm and providing an adequate environment for spermatogenesis.<\/jats:p>","DOI":"10.1210\/en.2016-1085","type":"journal-article","created":{"date-parts":[[2016,5,4]],"date-time":"2016-05-04T17:57:00Z","timestamp":1462384620000},"page":"2909-2919","source":"Crossref","is-referenced-by-count":74,"title":["Membrane-Localized Estrogen Receptor 1 Is Required for Normal Male Reproductive Development and Function in Mice"],"prefix":"10.1210","volume":"157","author":[{"given":"Manjunatha K.","family":"Nanjappa","sequence":"first","affiliation":[{"name":"Department of Physiological Sciences (M.K.N., T.I.M., S.H.L., P.S.C.), University of Florida, Gainesville, Florida 32610;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rex A.","family":"Hess","sequence":"first","affiliation":[{"name":"Department of Comparative Biosciences (R.A.H.), University of Illinois at Urbana-Champaign, 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