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Comment |
The effect of monosaccharide sugars and pyruvate on the differentiation and metabolism of sheep granulosa cells in vitro. Campbell BK et al. The objective of this study was to investigate the effect of three monosaccharides or pyruvate on the ability of gonadotrophins to induce cellular proliferation and differentiation of cultured sheep granulosa cells. Lactate production and levels of mRNA expression for the glucose transporters SLC2A1,4,5,8 were also determined. No energy source in the culture media reduced cell number (50%) and oestradiol production. Dose and type of monosaccharide had a highly significant (P<0.001) effect on FSH-induced differentiation of the granulosa cells and there was a highly significant interaction (P<0.001). Glucose supported higher levels of oestradiol production than fructose which was in turn higher than galactose (P<0.001). In contrast, pyruvate at low doses supported similar levels of oestradiol production as glucose but higher doses were markedly inhibitory to oestradiol production (P<0.001). Cells responded positively to insulin (P<0.001) in the presence of all three monosaccharides. Glucose and the high doses of fructose resulted in the accumulation of lactate (P<0.001) but pyruvate, galactose and the low dose of fructose resulted in low lactate production. SLC2A5 expression was not detected and SLC2A8 expression was not affected but SLC2A1 and 4 expression was depressed (P<0.05) by culture in the presence of fructose and glucose. These data show that glucose, metabolized under anoxic conditions to lactate, is the preferred energy substrate to support the gonadotrophin-induced differentiation of ovine granulosa cells in vitro and that fructose and pyruvate, but not galactose, are alternative energy substrates despite marked differences in the way these substrates are metabolised.
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Mutations |
1 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: subfertile
Comment: Slc2a8 Deficiency in Mice Results in Reproductive and Growth Impairments. Adastra KL et al. SLC2A8, also known as GLUT8, is a facilitative glucose transporter expressed in the testis, brain, liver, heart, uterus, ovary and fat. In this study we examined the effect of Slc2a8 deficiency on mouse gamete, preimplantation embryo and implantation phenotype, as well as postnatal growth and physiology. For this model, the transcriptional start site and exons 1-4 were targeted and a lack of protein expression was confirmed by western immunoblot. Oocytes obtained from Slc2a8-/- mice demonstrated abnormal metabolism and ATP production. In addition, deletion of Slc2a8 resulted in impaired decidualization, a critical step in the differentiation of endometrial stromal cells (ESC), necessary for implantation. This indicates a role for SLC2A8 in decidualization, which is supported by Slc2a8 mRNA expression in both mouse and human ESCs which increases dramatically in response to hormonal changes occurring during the process of implantation. Ovarian transplantation studies confirmed that lack of SLC2A8 affects both the embryo and the implantation processes. This phenotype leads to decreased litter size, and smaller pups at weaning that continue to display an abnormally small growth phenotype into adulthood. The Slc2a8 null mice display decreased body fat by MRI and interestingly, they are resistant to a diet high in fat and carbohydrates.
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