The amyloid beta (Aβ) peptide in the brains of patients with Alzheimer's disease (AD) is cytotoxic to neurons and has a central role in the pathogenesis of the disease. Peroxiredoxin 6 (Prdx6) is an antioxidant protein and could act as a cytoprotective protein. However, the role of Prdx6 in neurodegenerative disease has not been studied. Thus, the roles and action mechanisms in the development of AD were examined. Aβ1-42-induced memory impairment in Prdx6 transgenic mice was worse than C57BL/6 mice, and the expression of amyloid precursor protein cleavage, C99, β-site APP-cleaving enzyme 1, inducible nitric oxide synthase, and cyclooxygenase-2 was greatly increased. In addition, the astrocytes and microglia cells of Aβ-infused Prdx6 transgenic mice were more activated, and Aβ also significantly increased lipid peroxidation and protein carbonyl levels, but decreased glutathione levels. Furthermore, we found that translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus was increased in Aβ-infused Prdx6 transgenic mice. These results suggest that the overexpression of Prdx6 could accelerate the development of AD through increased amyloidogenesis through independent PLA2 activation and Nrf2 transcription.

Abstract. Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may affect adversely the development of the male reproductive system. Twenty-one days old ICR mice weaned from dams fed with a casein-based AIN-76A diet during gestation and lactation were exposed to genistein (2.5 and 5.0 mg/kg/day, p.o.) for 5 weeks. 17β-Estradiol (7.5 µg/kg/day) and corn oil were used for the positive and negative vehicle controls, respectively. The animals were fed the casein-based AIN-76A diet throughout the experiment. There were no significant differences in body weights of mice between the genistein groups and the negative control group. No significant differences in relative reproductive organ weights were found among all experimental groups. Sperm counts in epididymis and testes were slightly decreased in the genistein-exposed groups compared with control group. Sperm motile characteristics in genistein-exposed groups were slightly higher than those of the control group. Levels of phospholipid hydroxide glutathione peroxidase mRNA in the testis, epididymis, and prostate of mice exposed to genistein or estradiol were significantly higher than those of the controls (P<0.05). Exposure to genistein caused hyperplasia of Leydig cells in the testis and a slight increase of interstitial fibroblasts in the epididymis, while estradiol treatment caused severe damage to the testis and epididymis. These results suggest that dietary uptake of genistein during the juvenile period may affect male reproductive development, resulting in a slight decrease in sperm count, but with an increase in sperm motion quality.

Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may adversely affect the development of male reproductive system. Twenty one-day-old ICR mice weaned from dams fed with a soybean-based diet throughout gestation and lactation were exposed by gavage to genistein (2.5 mg/kg b.w./day) or 17beta-estradiol (7.5 microg/kg b.w./day) for five weeks. Corn oil was used as a negative control. The animals were fed with a casein-based AIN-76A diet throughout the experimental periods. There were no significant differences in body and organ weights of mice among experimental groups. No significant differences in sperm counts and sperm motile characteristics were found between control and genistein groups. Treatment of 17beta-estradiol caused a significant decrease in prostate weight and epididymal sperm counts compared to the control (p<0.05). The levels of phospholipid hydroxide glutathione peroxidase in the testis and prostate of mice exposed to genistein or 17beta-estradiol were significantly higher than that of the control mice (p<0.05). 17beta-estradiol treatment caused degeneration and apoptosis of germ cells in the testis, depletion and degeneration in the epididymal epithelium, and hyperplasia of mucosal fold region in the prostate of mice. Genistein treatment did not cause any lesion in the testis, epididymis, and prostate. These results suggest that dietary uptake of genistein during juvenile period may not affect male reproductive development and functions.

Abstract. The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) is highly expressed in testes under gonadotropin control. The expression patterns of PHGPx mRNA by 17β-estradiol (E2) as an estrogen and tamoxifen (Tam) as an estrogen antagonist were investigated in the reproductive organs of male rats. Twelve-week-old male Sprague-Dawley rats were subcutaneously injected with E2 (7.5 µg/kg/day) or Tam (5 mg/kg/day) for 1 week. The E2 treatment significantly increased the levels of PHGPx mRNA in both testes and prostates, whereas the Tam treatment significantly decreased the levels of PHGPx mRNA, compared to the vehicle control (p<0.01). The treatment with E2 or Tam slightly decreased the levels of PHGPx mRNA in epididymides. In histopathological examination, severe vacuolization and depletion of germ cells in the seminiferous tubules, cell debris in the tubular lumen, and mild proliferative changes in interstitial tissues were observed in the testes of Tam-treated rats, whereas only mild spermatogonial proliferation was observed in the seminiferous tubules of E2-treated rats. There were no typical histopathological changes in the epididymides of any of the laboratory rats but mild epithelial proliferation in the prostates of E2-and Tam-treated rats. These results suggest that PHGPx mRNA expression may be influenced by estrogen in the male reproductive organs.