Ythdc2, a member of the YT521-B homology (YTH) gene family, is an N6-methyladenosine (m6A) binding protein and RNA helicase. It plays a crucial role in RNA metabolism, regulating processes such as translation efficiency and mRNA abundance. Ythdc2 is involved in multiple biological pathways, with its function being essential for proper cell state transitions, especially during germ cell development [2,3,5].

Ythdc2 knockout (KO) mice are infertile. In males, testes are significantly smaller, and in females, ovaries are smaller compared to littermates. Germ cells in Ythdc2 KO mice do not develop past the zygotene stage, indicating its importance in spermatogenesis [2]. Conditional knockout (CKO) of Ythdc2 after meiotic prophase initiation allows germ cells to reach the pachytene stage but they fail to transition to the diplotene stage, revealing its role in meiotic progression in late spermatocytes [3]. In breast cancer, knockdown of Ythdc2 in cell lines attenuates sphere-forming and metastatic abilities, suggesting its involvement in tumorigenesis and metastasis [1]. In colorectal cancer, downregulation of Ythdc2 increases the stability and expression of LIMK1 mRNA, which promotes 5-fluorouracil (5-FU) chemoresistance [4].

In summary, Ythdc2 is vital for mammalian spermatogenesis and germ cell differentiation. Its KO and CKO mouse models have provided insights into its role in infertility and cancer-related processes. These findings suggest that Ythdc2 could be a potential target for treating infertility and certain cancers.