title: Maternal Diabetes Leads to Adaptation in Embryonic Amino Acid Metabolism during Early Pregnancy.
abstract: During pregnancy an adequate amino acid supply is essential for embryo development and fetal growth. We have studied amino acid composition and branched chain amino acid (BCAA) metabolism at day 6 p.c. in diabetic rabbits and blastocysts. In the plasma of diabetic rabbits the concentrations of 12 amino acids were altered in comparison to the controls. Notably, the concentrations of the BCAA leucine, isoleucine and valine were approximately three-fold higher in diabetic rabbits than in the control. In the cavity fluid of blastocysts from diabetic rabbits BCAA concentrations were twice as high as those from controls, indicating a close link between maternal diabetes and embryonic BCAA metabolism. The expression of BCAA oxidizing enzymes and BCAA transporter was analysed in maternal tissues and in blastocysts. The RNA amounts of three oxidizing enzymes, i.e. branched chain aminotransferase 2 (Bcat2), branched chain ketoacid dehydrogenase (Bckdha) and dehydrolipoyl dehydrogenase (Dld), were markedly increased in maternal adipose tissue and decreased in liver and skeletal muscle of diabetic rabbits than in those of controls. Blastocysts of diabetic rabbits revealed a higher Bcat2 mRNA and protein abundance in comparison to control blastocysts. The expression of BCAA transporter LAT1 and LAT2 were unaltered in endometrium of diabetic and healthy rabbits, whereas LAT2 transcripts were increased in blastocysts of diabetic rabbits. In correlation to high embryonic BCAA levels the phosphorylation amount of the nutrient sensor mammalian target of rapamycin (mTOR) was enhanced in blastocysts caused by maternal diabetes. These results demonstrate a direct impact of maternal diabetes on BCAA concentrations and degradation in mammalian blastocysts with influence on embryonic mTOR signalling.
authors.affiliation: Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Halle (Saale), Germany.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gürke
authors.affiliation: Department of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hirche
authors.affiliation: Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Halle (Saale), Germany.
authors.forename: René
authors.initials: R
authors.lastname: Thieme
authors.affiliation: Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Halle (Saale), Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Haucke
authors.affiliation: Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Halle (Saale), Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Schindler
authors.affiliation: Department of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Gabriele I
authors.initials: GI
authors.lastname: Stangl
authors.affiliation: Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Halle (Saale), Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Fischer
authors.affiliation: Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Halle (Saale), Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Navarrete Santos
mesh_terms: D000222:Adaptation, Physiological; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000473:pathology; D005260:Female; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D027283:Large Neutral Amino Acid-Transporter 1; D058570:TOR Serine-Threonine Kinases