Heat Shock Factor 5 Is Essential for Spermatogenesis in Zebrafish

Abstract

Summary: Heat shock factors (Hsfs) are transcription factors that regulate responses to heat shock and other environmental stimuli. Four heat shock factors (Hsf1-4) have been characterized from vertebrates to date. In addition to stress response, they also play important roles in development and gametogenesis. Here, we study the fifth member of heat shock factor family, Hsf5, using zebrafish as a model organism. Mutant hsf5−/− males, generated by CRISPR/Cas9 technique, were infertile with drastically reduced sperm count, increased sperm head size, and abnormal tail architecture, whereas females remained fertile. We show that Hsf5 is required for progression through meiotic prophase 1 during spermatogenesis as suggested by the accumulation of cells in the leptotene and zygotene-pachytene stages and increased apoptosis in post-meiotic cells. hsf5−/− mutants show gonadal misregulation of a substantial number of genes with roles in cell cycle, apoptosis, protein modifications, and signal transduction, indicating an important role of Hsf5 in early stages of spermatogenesis. : Saju et al. show that heat shock factor 5 (hsf5) is predominantly expressed in testis. Loss of Hsf5 leads to a drastic reduction in sperm counts and severe morphological abnormalities in spermatozoa, leading to infertility. Hsf5 appears to be required for proper progression of meiosis-I during spermatogenesis. Keywords: Hsf5, fish sex, reproduction, gonad differentiation, meiosis, CRISPR/Cas9, sexual development