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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-4-22
pubmed:abstractText
Obesity and its physiological consequences are increasingly prevalent among women of reproductive age and are associated with infertility. To investigate, female mice were fed a high-fat diet until the onset of insulin resistance, followed by assessments of ovarian gene expression, ovulation, fertilization, and oocyte developmental competence. We report defects to ovarian function associated with diet-induced obesity (DIO) that result in poor oocyte quality, subsequently reduced blastocyst survival rates, and abnormal embryonic cellular differentiation. To identify critical cellular mediators of ovarian responses to obesity induced insulin resistance, DIO females were treated for 4 d before mating with an insulin-sensitizing pharmaceutical: glucose and lipid-lowering AMP kinase activator, 5-aminoimidazole 4-carboxamide-riboside, 30 mg/kg.d; sodium salicylate, IkappaK inhibitor that reverses insulin resistance, 50 mg/kg.d; or peroxisome proliferator activated receptor-gamma agonist rosiglitazone, 10 mg/kg.d. 5-aminoimidazole 4-carboxamide-riboside or sodium salicylate treatment did not have significant effects on the reproductive parameters examined. However, embryonic development to the blastocyst stage was significantly improved when DIO mice were treated with rosiglitazone, effectively repairing development rates. Rosiglitazone also normalized DIO-associated abnormal blastomere allocation to the inner cell mass. Such improvements to oocyte quality were coupled with weight loss, improved glucose metabolism, and changes in ovarian mRNA expression of peroxisome proliferator activated receptor-regulated genes, Cd36, Scarb1, and Fabp4 cholesterol transporters. These studies demonstrate that peri-conception treatment with select insulin-sensitizing pharmaceuticals can directly influence ovarian functions and ultimately exert positive effects on oocyte developmental competence. Improved blastocyst quality in obese females treated with rosiglitazone before mating indicates that peroxisome proliferator activated receptor-gamma is a key target for metabolic regulation of ovarian function and oocyte quality.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
149
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2646-56
pubmed:meshHeading
pubmed-meshheading:18276752-Animals, pubmed-meshheading:18276752-Blastomeres, pubmed-meshheading:18276752-Cell Differentiation, pubmed-meshheading:18276752-Cells, Cultured, pubmed-meshheading:18276752-Cytoprotection, pubmed-meshheading:18276752-Diet, pubmed-meshheading:18276752-Diet, Atherogenic, pubmed-meshheading:18276752-Embryo, Mammalian, pubmed-meshheading:18276752-Embryo Culture Techniques, pubmed-meshheading:18276752-Embryonic Development, pubmed-meshheading:18276752-Female, pubmed-meshheading:18276752-Gene Expression Regulation, pubmed-meshheading:18276752-Hypoglycemic Agents, pubmed-meshheading:18276752-Mice, pubmed-meshheading:18276752-Mice, Inbred C57BL, pubmed-meshheading:18276752-Obesity, pubmed-meshheading:18276752-Oocytes, pubmed-meshheading:18276752-Ovary, pubmed-meshheading:18276752-Ovulation, pubmed-meshheading:18276752-PPAR gamma, pubmed-meshheading:18276752-Thiazolidinediones
pubmed:year
2008
pubmed:articleTitle
Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reverses the adverse effects of diet-induced obesity on oocyte quality.
pubmed:affiliation
School of Paediatrics and Reproductive Health, Discipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, South Australia 5005, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't