Spermatogenesis is a differentiation process during which diploid spermatogonial stem cells (SSCs) produce haploid spermatozoa. This highly specialized process is precisely controlled at the transcriptional, posttranscriptional, and translational levels. Here we report that N-methyladenosine (mA), an epitranscriptomic mark regulating gene expression, plays essential roles during spermatogenesis. We present comprehensive mA mRNA methylomes of mouse spermatogenic cells from five developmental stages: undifferentiated spermatogonia, type A spermatogonia, preleptotene spermatocytes, pachytene/diplotene spermatocytes, and round spermatids. Germ cell-specific inactivation of the mA RNA methyltransferase Mettl3 or Mettl14 with Vasa-Cre causes loss of mA and depletion of SSCs. mA depletion dysregulates translation of transcripts that are required for SSC proliferation/differentiation. Combined deletion of Mettl3 and Mettl14 in advanced germ cells with Stra8-GFPCre disrupts spermiogenesis, whereas mice with single deletion of either Mettl3 or Mettl14 in advanced germ cells show normal spermatogenesis. The spermatids from double-mutant mice exhibit impaired translation of haploid-specific genes that are essential for spermiogenesis. This study highlights crucial roles of mRNA mA modification in germline development, potentially ensuring coordinated translation at different stages of spermatogenesis.

The effective modulation of pore sizes for nanoporous silica nanoparticles still remains a great challenge not satisfactorily solved. In this paper, the pore sizes in the shell of hollow silica nanocapsules are well-tuned by a reversible Si-O bond breakage and reformation process under mildly alkaline conditions (e.g., Na(2) CO(3) solution). The pores in nanosized hollow silica capsules can be modulated from 3.2 nm to larger than 10 nm by a novel, surfactant-directing alkaline-etching (SDAE) strategy. Interestingly, the pores can be fully filled through the regrowth of the dissoluted silicates by bonding to silanols (Si-OH) on the wall surface to generate the nonporous hollow silica nanocapsules. The large-sized pore hollow silica nanocapsules exhibit excellent siRNA-loading capabilities and intracellular transfection efficiencies in vitro. In addition, the large pores in the shell of hollow silica nanocapsules are explored as channels for collecting superparamagnetic, small-sized Fe(3) O(4) nanoparticles as contrast agents for magnetic resonance imaging, initiating a special approach towards pore-size modulation and multifunctionalization of silica-based nanostructural materials for nanobiomedical applications.

Mammalian sperm capacitation is an essential prerequisite to fertilizion. Although progress had been made in understanding the physiology and biochemistry of capacitation, little is known about the potential roles of epididymal proteins during this process. Here we report that HongrES1, a new member of the SERPIN (serine proteinase inhibitor) family exclusively expressed in the rat cauda epididymis and up-regulated by androgen, is secreted into the lumen and covers the sperm head. Co-culture of caudal sperms with HongrES1 antibody in vitro resulted in a significant increase in the percentage of capacitated spermatozoa. Furthermore, the percentage of capacitated spermatozoa clearly increased in rats when HongrES1 was down-regulated by RNAi in vivo. Remarkably, knockdown of HongrES1 in vivo led to reduced fertility accompanied with deformed appearance of fetuses and pups. These results identify HongrES1 as a novel and critical molecule in the regulation of sperm capacitation and male fertility.