Histone H3K27 demethylases inhibition restrains proliferation and promotes apoptosis of mouse spermatocyte

Spermatogenesis is pivotal to male reproduction and is tightly regulated by a variety of epigenetic regulators. However, the function of JMJD3/UTX in spermatogenesis and the molecular mechanisms underlying their activities remain poorly defined. Here, we confirmed that JMJD3/UTX is expressed in spermatocytes of testis and in a spermatocyte-derived GC-2 cells. Compared with that of control, GSK-J4 (a H3K27me3 demethylases JMJD3/UTX inhibitor) recipient mice showed no alternations in sperm quality and testis morphology, but the proliferation and apoptosis of germ cells were affected. Furthermore, by pharmacologically inhibiting JMJD3/UTX in spermatocyte-derived GC-2 cells, we demonstrated that JMJD3/UTX is implicated in spermatocyte cell proliferation and apoptosis. At the same time, an upregulated the trimethylation of histone H3 at lysine-27 (H3K27me3) and altered gene transcription associate with proliferation and apoptosis were observed. In summary, these data demonstrated that JMJD3/UTX plays a key role in the regulation of spermatocyte proliferation and apoptosis in murine spermatogenesis.