Opposite effects of high- and low-dose di-(2-ethylhexyl) phthalate (DEHP) exposure on puberty onset, oestrous cycle regularity and hypothalamic kisspeptin expression in female rats.

Di-(2-ethylhexyl) phthalate (DEHP) is ubiquitous in the environment and has been proposed to lead to reproductive disruption. In this study, we systematically investigated the effects of different doses of DEHP exposure on female hypothalamic-pituitary-gonadal axis development. Female Sprague-Dawley rats were gavaged with vehicle (corn oil) or DEHP (5 or 500mgkg-1 day-1) during postnatal Days (PNDs) 22-28 or PNDs 22-70. Results demonstrated that the low and high doses of DEHP exerted opposite effects on puberty onset, circulating luteinising hormone, serum oestradiol and progesterone levels, with the low dose (5mgkg-1) promoting and the high dose (500mgkg-1) inhibiting these parameters. Significant dose-related differences were also found in the D500 group with longer oestrous cycle duration, lower ovarian/bodyweight ratio, fewer corpus lutea and more abnormal ovarian stromal tissue in comparison with the oil or D5 groups. Molecular data showed that the hypothalamic Kiss1 mRNA expression in the anteroventral periventricular but not in the arcuate nucleus significantly decreased in the D500 rats and increased in the D5 rats relative to the rats in the oil group. These findings suggested that the kisspeptin system is a potential target for DEHP to disrupt reproductive development and function.

Selenium inhibits high glucose-induced cyclooxygenase-2 and P-selectin expression in vascular endothelial cells.

Selenium as a component of glutathione peroxidase may be beneficial in insulin resistance, hence potentially may modify the risk of diabetes and cardiovascular disease. The aim of our study was to evaluate whether selenium can also alter high glucose (HG), advanced glycation end products (AGE), high insulin (HI) and H2O2-induced expression of cyclooxygenase (COX)-2 and P-selectin. Human umbilical vein endothelial cells (HUVECs) were pretreated with selenium and stimulated by HG, AGE, HI and H2O2. Selenium significantly inhibited HG, AGE, HI and H2O2-induced expression of COX-2 and P-selectin. Moreover, selenium also inhibited HG, AGE, HI and H2O2-induced activation of p38 mitogen-activated protein kinase (p38 MAPK), which indicated that the preventive effects of selenium on COX-2 and P-selectin may be associated with p38. Our results indicated that selenium supplementation can reduce HG, AGE, HI and H2O2-induced expression of COX-2 and P-selectin by inhibition of the p38 pathway.

[Effect of selenium on expression of P38 mitogen-activated protein kinase and monocyte chemoattractant protein-1 in diabetic endothelial cells].

AIM: To study the relationship between P38MAPK and MCP-1 in diabetic HUVEC and the mechanism of anti-atherosclerosis of selenium. METHODS: HUVEC were treated with high concentration of glucose, advanced glycosylation end products (AGE), high concentration of insulin or H(2)O(2) with or without pre-treatment with SB203580 (P38MAPK specific inhibitor) or selenium. The expression of phospho-P38MAPK and MCP-1 in HUVEC was detected by Western blot or RT-PCR, respectively. RESULTS: High concentration of glucose, AGE, high concentration of insulin and H(2)O(2) can activate P38MAPK and increase the expression of MCP-1 in HUVEC. The expression of MCP-1 was inhibited by SB203580. Selenium inhibited the activation of P38MAPK and reduced the expression of MCP-1. CONCLUSION: P38MAPK is an upstream signaling molecule of MCP-1. P38MAPK may be one of the initiating signals of diabetic atherosclerosis. Selenium can inhibit the expression of MCP-1 by repressing P38MAPK signaling pathway and therefore prevent the development of atherosclerosis.