Zygotic chromatin undergoes extensive reprogramming immediately after fertilization. It is generally accepted that maternal factors control this process. However, little is known about the underlying mechanisms. Here we report that maternal RAD9A, a key protein in DNA damage response pathway, is involved in post-zygotic embryo development, via a mouse model with conditional depletion of Rad9a alleles in oocytes of primordial follicles. Post-zygotic losses originate from delayed zygotic chromatin decondensation after depletion of maternal RAD9A. Pronucleus formation and DNA replication of most mutant zygotes are therefore deferred, which subsequently trigger the G2/M checkpoint and arrest development of most mutant zygotes. Delayed zygotic chromatin decondensation could also lead to increased reabsorption of post-implantation mutant embryos. In addition, our data indicate that delayed zygotic chromatin decondensation may be attributed to deferred epigenetic modification of histone in paternal chromatin after fertilization, as fertilization and resumption of secondary meiosis in mutant oocytes were both normal. More interestingly, most mutant oocytes could not support development beyond one-cell stage after parthenogenetic activation. Therefore, RAD9A may also play an important role in maternal chromatin reprogramming. In summary, our data reveal an important role of RAD9A in zygotic chromatin reprogramming and female fertility.

Although single-atomically dispersed metal-N_x on carbon support (M-NC) has great potential in heterogeneous catalysis, the scalable synthesis of such single-atom catalysts (SACs) with high-loading metal-N_x is greatly challenging since the loading and single-atomic dispersion have to be balanced at high temperature for forming metal-N_x. Herein, we develop a general cascade anchoring strategy for the mass production of a series of M-NC SACs with a metal loading up to 12.1 wt%. Systematic investigation reveals that the chelation of metal ions, physical isolation of chelate complex upon high loading, and the binding with N-species at elevated temperature are essential to achieving high-loading M-NC SACs. As a demonstration, high-loading Fe-NC SAC shows superior electrocatalytic performance for O₂ reduction and Ni-NC SAC exhibits high electrocatalytic activity for CO₂ reduction. The strategy paves a universal way to produce stable M-NC SAC with high-density metal-N_x sites for diverse high-performance applications.