Ddx25, also known as Gonadotropin-regulated testicular RNA helicase (GRTH), is a DEAD-box RNA helicase. It is an essential post-transcriptional regulator in spermatogenesis, mainly expressed in germ cells (meiotic spermatocytes and round spermatids) and Leydig cells [1,2]. It is involved in transporting target mRNAs to the cytoplasm for storage in chromatoid bodies of spermatids and regulating their translation during spermatogenesis [1,2].

Male mice lacking GRTH/ Ddx25 are sterile due to spermatogenic arrest at the step of round spermatids failing to elongate [1,2,3,5]. GRTH/ Ddx25-KO and GRTH Knock-In (KI) mice with R242H mutation (lacking phosphorylated GRTH) show similar spermatogenic arrest, indicating the importance of phosphorylated GRTH in spermatid development [3,4,5]. RNA-Seq analysis of germ cells from KI and WT mice revealed that absence of phosphorylated GRTH impairs histone ubiquitination and acetylation essential for spermatid elongation during spermiogenesis [4].

In conclusion, Ddx25 is a multifunctional RNA helicase essential for spermatogenesis. Studies using KO and KI mouse models have revealed its crucial role in spermatid development and chromatin remodeling, providing insights into male infertility mechanisms. These models contribute to understanding the biological functions of Ddx25 in the context of male reproductive diseases [1,2,3,4,5].