Loss of Dead end1 induces testicular teratomas from primordial germ cells that failed to undergo sexual differentiation in embryonic testes

Abstract

Spontaneous testicular teratomas (STTs) are tumours comprising a diverse array of cell and tissue types, which are derived from pluripotent stem-like cells called embryonal carcinoma cells (ECCs). Although mouse ECCs originate from primordial germ cells (PGCs) in embryonic testes, the molecular basis underlying ECC development remains unclear. This study shows that the conditional deletion of mouse Dead end1 (Dnd1) from migrating PGCs leads to STT development. In Dnd1-conditional knockout (Dnd1-cKO) embryos, PGCs colonise the embryonic testes but fail to undergo sexual differentiation; subsequently, ECCs develop from a portion of the PGCs. Transcriptomic analyses reveal that PGCs not only fail to undergo sexual differentiation but are also prone to transformation into ECCs by upregulating the expression of ECC-specific genes in the testes of Dnd1-cKO embryos. Thus, our results clarify the role of Dnd1 in developing STTs and developmental process of ECC from PGC, providing novel insights into pathogenic mechanisms of STTs.

Investigation of extragonadal teratomas in two Poecilia wingei

“…The aetiology of teratomas of various locations in fish remains to be fully understood. In future work, it will be interesting to study the presence of genetic predisposition to gonadal and extragonadal teratomas in fish and to identify possible genetic factors, as recently shown in the example of testicular teratomas in mice (Imai et al., 2023; Naser et al., 2021). The presence of structures of varying degrees of differentiation in teratomas and the probable possibility of inheritance contribute to further studies of the histogenesis and biological behaviour of teratomas in cartilaginous and teleost fish, including in light of the evolution of tumours (Boutry et al., 2022; Kozlov, 2023).…”