Sex-specific expression and function of TRIM28 during mouse primordial germ differentiation

Mammalian primordial germ cells (PGCs) are embryonic precursors to the adult germline and must facilitate high-fidelity transfer of genomic material from one generation to the next. Transposable elements (TEs) represent an ongoing threat to genomic fidelity and are therefore tightly controlled during embryonic germline development. Here, we find that some TEs change in accessibility during normal PGC differentiation, while others are constitutively repressed by tripartite motif-containing 28 (TRIM28), a master TE regulator. We find that TRIM28 itself is regulated in a sex-specific manner and represses sex-specific TEs. In both testicular and ovarian PGCs, TRIM28 protects against upregulation of 2-cell (2C)-associated genes, dysregulation of PGC differentiation, and incomplete activation of DAZL. This perturbs testicular and ovarian PGCs differently, with testicular PGCs failing to differentiate in embryonic life while ovarian PGCs inefficiently enter meiosis leading to a diminished ovarian reserve by the onset of sexual maturity.