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Treatment of Ca(2+) channel blockers (CCB) to relieve hypertension causes reversible male infertility, suggesting deregulation of Ca(2+) homeostasis in testis is closely related with male infertility. To investigate the possible toxicity of therapeutic application of CCB in childhood, the effect of nifedipine and ethosuximide, an L-type and T-type CCB, respectively, on the spermatogenesis and testicular gene expression was examined. Following the intraperitoneal injection of either drug for 7 days to 18 days on old mice, the paired testes weights were significantly lower in mice treated with nifedipine (> or = 10 mg/kg/day) or ethosuximide (100 mg/kg/day) than vehicle controls. In mice given high drug dosing (100 mg/kg), seminiferous tubules showed immaturity with spermatogenic arrest at elongating spermatid stage and poorly developed lumen. Unexpectedly, the expression of activator isoform of transcription factor cAMP-responsive element modulator (CREM) mRNA increased together with transition protein 2 and protamine 2 mRNA in drug-treated mice testes, suggesting that CCB may deregulate expression of activator isoform of CREM in male germ cells and that spermatogenic defect following CCB treatment may attribute to ectopic expression of CREM-dependent gene battery in testis. Therapeutic application of CCB in childhood should be cautious because of their potential to cause spermatogenic defect and altered gene expression in testis.

20 nm diameter SiO(2) nanopore arrays on gradient-thickness membranes were formed by a focused electron beam with in situ transmission electron microscopy (TEM). Nanopore shrinkage was seen in nanopores on thicker membranes, with the rate of diameter change remaining constant during the shrinkage process. In contrast, pore expansion was observed in thinner membranes, with the expansion rate being constant at the initial stage but with a slight increase at the later stage. The geometry model of shrinkage and expansion of the nanopores in relation to the electron irradiation time was investigated by utilizing the TEM tilting method.

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