Importance of eIF2[alpha] phosphorylation as a protective mechanism against heat stress in mouse male germ cells

• Published in: Molecular reproduction and development 2017-03, Vol.84 (3), p.265
• Main Authors: Yoon, Jungbin, Park, Kyosun, Hwang, Deog Su, Rhee, Kunsoo
• Format: Article
• Language: English
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.22778

SUMMARY Mammalian male germ cells are exceptionally labile to heat stress. A temporal arrest of translation is one immediate response to heat, which involves heat-induced phosphorylation of eukaryotic initiation factor 2[alpha] (eIF2[alpha]) to block the formation of the translational initiation complex. Here, we investigated the protective mechanisms against heat stress in mouse male germ cells. All known eIF2[alpha] kinases were expressed in lineage- and developmental stage-specific manners in the testis; noteworthy was the presence of Gcn2 (General control nonderepressible 2 kinase) in spermatocytes of all seminiferous tubules. Multiple eIF2[alpha] kinases are likely activated upon heat stress in male germ cells. ISRIB (Integrated stress response inhibitor) was then used to determine the events downstream of eIF2[alpha] phosphorylation. ISRIB significantly reduced the rate of stress granule formation in spermatocytes at early-stage (III-IV) seminiferous tubules, and induced a number of apoptotic germ cells at late-stage (XI-XII) seminiferous tubules near the onset of meiosis. Thus, stress granule formation is a downstream event of eIF2[alpha] phosphorylation that may not directly protect cells from apoptosis, at least in spermatocytes of seminiferous tubules in early stages. Mol. Reprod. Dev. 84: 265-274, 2017. © 2017 Wiley Periodicals, Inc.