{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:02:07Z","timestamp":1787007727465,"version":"build-2736575974"},"reference-count":51,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,7,29]]},"abstract":"<jats:p>Mumps commonly affects children 5\u20139 yr of age, and can lead to permanent adult sterility in certain cases. However, the etiology of this long-term effect remains unclear. Mumps infection results in progressive degeneration of the seminiferous epithelium and, occasionally, Sertoli cell\u2013only syndrome. Thus, the remaining Sertoli cells may be critical to spermatogenesis recovery after orchitis healing. Here, we report that the protein farnesylation\/geranylgeranylation balance is critical for patients\u2019 fertility. The expression of geranylgeranyl diphosphate synthase 1 (GGPPS) was decreased due to elevated promoter methylation in the testes of infertile patients with mumps infection history. When we deleted GGPPS in mouse Sertoli cells, these cells remained intact, whereas the adjacent spermatogonia significantly decreased after the fifth postnatal day. The proinflammatory MAPK and NF-\u03baB signaling pathways were constitutively activated in GGPPS\u2212\/\u2212 Sertoli cells due to the enhanced farnesylation of H-Ras. GGPPS\u2212\/\u2212 Sertoli cells secreted an array of cytokines to stimulate spermatogonia apoptosis, and chemokines to induce macrophage invasion into the seminiferous tubules. Invaded macrophages further blocked spermatogonia development, resulting in a long-term effect through to adulthood. Notably, this defect could be rescued by GGPP administration in EMCV-challenged mice. Our results suggest a novel mechanism by which mumps infection during childhood results in adult sterility.<\/jats:p>","DOI":"10.1084\/jem.20121806","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T00:30:22Z","timestamp":1372725022000},"page":"1559-1574","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":63,"title":["Altered protein prenylation in Sertoli cells is associated with adult infertility resulting from childhood mumps infection"],"prefix":"10.1084","volume":"210","author":[{"given":"Xiu-Xing","family":"Wang","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center and Jiangsu Key Laboratory of Molecular Medicine of the School of Medicine, Nanjing University, National Resource Center for Mutant Mice, Nanjing 210061, China 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