The amount of attention to age-related hearing loss (ARHL) has been growing, not only from the perspective of being one of the most common health conditions affecting older adults, but also from the perspective of its relation to cognition. Results from a number of epidemiological and laboratory studies have demonstrated a significant link between ARHL and cognitive decline. The Lancet International Commission on Dementia, Prevention, Intervention, and Care has estimated that mid-life hearing loss, if eliminated, might decrease the risk of dementia by nine percent, since hearing loss is a modifiable age-associated condition linked to dementia. Despite numerous research efforts, elucidation of the underlying causal relationships between auditory and cognitive decline has not yet reached a consensus. In this review article, we focused on the hypotheses of etiological mechanisms between ARHL and cognitive decline: (1) cognitive load hypothesis; (2) common cause hypothesis; (3) cascade hypothesis; and (4) overdiagnosis or harbinger hypothesis. Factual evidence obtained in previous studies was assessed to understand the link between ARHL and cognitive decline or dementia. Additionally, an overview of the conceivable effects of hearing intervention, e.g., hearing aids and cochlear implants, on cognition were presented, and the role of hearing aid use was considered for the relevant hypotheses. We should continue to strive for social enlightenment towards the importance of 'hearing well', and cultivate a necessity for hearing screening among patients at risk of cognitive decline.

Spermatogenesis is a highly specialized process of cellular differentiation to produce spermatozoa. This differentiation process accompanies morphological changes that are controlled by a number of genes expressed in a stage-specific manner during spermatogenesis. Here we show that in mice, the absence of a testis-specific, cytoplasmic polyadenylate [poly(A)] polymerase, TPAP, results in the arrest of spermiogenesis. TPAP-deficient mice display impaired expression of haploid-specific genes that are required for the morphogenesis of germ cells. The TPAP deficiency also causes incomplete elongation of poly(A) tails of particular transcription factor messenger RNAs. Although the overall cellular level of the transcription factor TAF10 is unaffected, TAF10 is insufficiently transported into the nucleus of germ cells. We propose that TPAP governs germ cell morphogenesis by modulating specific transcription factors at posttranscriptional and posttranslational levels.

We have previously indicated that at least in mouse, sperm serine protease(s) other than acrosin probably act on the limited proteolysis of egg zona pellucida to create a penetration pathway for motile sperm, although the participation of acrosin cannot be ruled out completely. A 42-kDa gelatin-hydrolyzing serine protease present in mouse sperm is a candidate enzyme involved in the sperm penetration of the zona pellucida. In this study, we have PCR-amplified an EST clone encoding a testicular serine protease, termed TESP5, and then screened a mouse genomic DNA library using the DNA fragment as a probe. The DNA sequence of the isolated genomic clones indicated that the TESP5 gene is identical to the genes coding for testicular testisin and eosinophilic esp-1. Immunochemical analysis using affinitypurified anti-TESP5 antibody revealed that 42-and 41-kDa forms of TESP5 with the isoelectric points of 5.0 to 5.5 are localized in the head, cytoplasmic droplet, and midpiece of cauda epididymal sperm probably as a membranous protein. Moreover, these two forms of TESP5 were selectively included into Triton X-100-insoluble microdomains, lipid rafts, of the sperm membranes. These results show the identity between TESP5/testisin/esp-1 and the 42-kDa sperm serine protease. When HEK293 cells were transformed by an expression plasmid carrying the entire protein-coding region of TESP5, the recombinant protein produced was released from the cell membrane by treatment with Bacillus cereus phosphatidylinositol-specific phospholipase C, indicating that TESP5 is glycosylphosphatidylinositol-anchored on the cell surface. Enzymatic properties of recombinant TESP5 was similar to but distinguished from those of rat acrosin and pancreatic trypsin by the substrate specificity and inhibitory effects of serine protease inhibitors.Mammalian fertilization involves a complex set of molecular events, including adhesion and binding of sperm to the zona pellucida (ZP), 1 an extracellular glycoprotein matrix surrounding the egg, acrosome reaction, penetration of sperm through the ZP, and fusion between sperm and egg (for reviews, see Refs. 1-4). Of these events, the acrosome reaction is a fusion between the outer acrosomal and plasma membranes at the anterior region of sperm head. Consequently, the acrosomal components are released and interact with the ZP. The sperm penetration of the ZP is believed to require both sperm motility and enzymatic hydrolysis by acrosomal protease(s) (1, 5).A sperm serine protease, acrosin, is localized in the acrosomal matrix as an enzymatically inactive zymogen, proacrosin, which is then converted into the active form during the acrosome reaction (6, 7). The role of acrosin in fertilization has long been considered to participate in the limited proteolysis of ZP, which enables sperm to penetrate the ZP. However, our previous work (8) using acrosin-deficient mutant mice conclusively showed that acrosin is not essential both for the sperm penetration of the egg ZP and for fertilization. The deficiency of acrosin cause...

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