Transcription factor ZFP38 is essential for meiosis prophase I in male mice

Abstract

The production of haploid gametes by meiosis is a cornerstone of sexual reproduction and maintenance of genome integrity.Zfp38mRNA is expressed in spermatocytes, indicating that transcription factor ZFP38 has the potential to regulate transcription during meiosis. In this study, we generatedZfp38conditional knockout mice (Zfp38flox/flox,Stra8-Cre, hereafter calledZfp38cKO) and found that spermatogenesis did not progress beyond meiosis prophase I inZfp38cKO mice. Using a chromosomal spread technique, we observed thatZfp38cKO spermatocytes exhibited a failure in chromosomal synapsis observed by SYCP1/SYCP3 double staining. Progression of DNA double-strand breaks (DSB) repair is disrupted inZfp38cKO spermatocytes, as revealed by γ-H2AX, RAD51 and MLH1 staining. Furthermore, the mRNA and protein levels of DSB repair enzymes and factors that guide their loading onto sites of DSBs, such as RAD51, DMC1, RAD51, TEX15 and PALB2, were significantly reduced inZfp38cKO spermatocytes. Taken together, our data suggest that ZFP38 is critical for the chromosomal synapsis and DSB repairs partially via its regulation of DSB repair-associated protein expression during meiotic progression in mouse.