Carotenoids like xanthophylls include those present in microalgae, such as astaxanthin (ASTX), canthaxanthin and fucoxanthin. ASTX has been reported to improve the male fertility dysfunctions in human trial. Our previous results also showed that the polyene structure of ASTX may interact with selenite and further protect lens proteins. Therefore, during the first year, we will aim to evaluate the differences among xanthophylls on their bindings with selenite by isothermal titration calorimetry. The effects of ASTX on spermatogenesis in excess selenite or selenite deficiency-induced male fertility dysfunctions animal model will be assessed to correlate the reproductive functions with the levels of selenite, oxidative status and cytokines. Besides, since our preliminary data shows that supplemented ASTX modulated arachidonic acid (AA) infusion induced vascular resistance and similar to the anti-inflammatory medicine-indomethacin. Therefore, during the second year, docking virtual screening will be used to provide predictive results for xanthophylls which capable of interacting with the action sites of two metabolic enzymes (cyclo-oxygenases and 5-lipoxygenease) of AA. Confirmation of selected xanthophylls will be further determined by spectroscopy (UV/Vis and circular dichroism) and in lipopolysaccharide induced cytokines/COX-2 or other expressions in macrophage. Their immuno-modulatory effects in high-glucose induced TLR and CD14 expression in macrophage will be further explored during the third year of this proposal. The mechanisms and the effects of the most potent compound will then investigated using streptozotocin-induced diabetes as a model of infertility to elucidate the possible role for the xanthophylls in diabetic infertility improvement.
|Effective start/end date||8/1/10 → 7/31/11|
- male fertility dysfunction animal model