Obese women often have certain degree of reproductive dysfunction with infertility. Although the clinical impact of obesity on female infertility has been extensively studied, the effective and... Show moreObese women often have certain degree of reproductive dysfunction with infertility. Although the clinical impact of obesity on female infertility has been extensively studied, the effective and targeted treatment is still lacking. Melanocortin-4-receptor knock-out (MC4R KO) mouse is an over-eating obese model with hyperphagia, hyperinsulinemia, reduced growth hormone (GH), and insulin resistance. Dapagliflozin improved the metabolic and hormonal parameters in MC4R KO mice. MC4R KO female mice were treated with dapagliflozin for 14 weeks from 14-week age. Age-matched WT littermates and non-treated MC4R KO mice were used as control groups. Food intake was measured daily. Body weight was measured twice a week. Estrous cycles, GH, and luteinizing hormone (LH) profiles were measured. Selected tissues were collected at the end of experiments for gene expression profiles and hematoxylin-eosin staining. Regularity and mode of hormonal profiles were restored by the dapagliflozin treatment. Estrous cycle was partially normalized, number of CL was significantly increased, and the expression of Kiss1 and Gnrh1 in the hypothalamus and LH in the pituitary was markedly increased by the dapagliflozin treatment. It is conclsuded that dapagliflozin may recover LH and GH profiles partially through modification of relevant gene expression in the hypothalamus and pituitary, and result in an improved ovulation rate in obese mouse model. Dapagliflozin may therefore improve fertility in obese patients. Show less
Transition metals are widespread in aquatic environments and can be harmful when concentrations exceed thresholds. Especially for fish, an important component of the human diet, low concentrations... Show moreTransition metals are widespread in aquatic environments and can be harmful when concentrations exceed thresholds. Especially for fish, an important component of the human diet, low concentrations of transition metals will directly affect their well-being. Different taxa are protected by unified water quality criteria (WQC) thresholds, which rarely consider the ecological status and economic value of different species. There is therefore an urgent need to study taxon-specific sensitivity. The present study established the species sensitivity distributions of nine typical transition metals (Cr, Mn, Fe, Ni, Cu, Zn, Ag, Cd and Hg) for protecting freshwater and seawater fish based on non-parametric kernel density estimation methods, and then derived their acute and chronic HC5-values. The results showed that Ag and Hg have the highest acute toxic potency to fish in freshwater as well as seawater. Compared with marine fish, freshwater fish were more tolerant to acute exposure to Cr, Fe, Ni and Zn, whilst being more sensitive to Ag and Cd. Moreover, edible fish are more sensitive than other fish to these metals in both freshwater and seawater, encouraging more protection of economically valuable fish that may potentially affect human health. The study provides a strong reference for future research on taxon-specific WQC for transition metals. Show less
Huisman, M.V.; Rothman, K.J.; Paquette, M.; Teutsch, C.; Diener, H.C.; Dubner, S.J.; ... ; Frappe, T 2017
