| First Author | Nanjappa MK | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 7 | Pages | 2909-19 |
| PubMed ID | 27145009 | Mgi Jnum | J:239467 |
| Mgi Id | MGI:5828957 | Doi | 10.1210/en.2016-1085 |
| Citation | Nanjappa MK, et al. (2016) Membrane-Localized Estrogen Receptor 1 Is Required for Normal Male Reproductive Development and Function in Mice. Endocrinology 157(7):2909-19 |
| abstractText | Estrogen receptor 1 (ESR1) mediates major reproductive functions of 17beta-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. |
