A SNP in the HSP90AA1 gene 5′ flanking region is associated with the adaptation to differential thermal conditions in the ovine species

Molecular chaperones have long been understood to be preferentially transcribed in response to multiple perturbations of the cellular homeostasis. In this study, several polymorphisms in the gene encoding the inducible form of the cytoplasmic Hsp90 (HSP90AA1) were addressed in 24 sheep breeds reared in different climatic regions of Europe, Africa, and Asia. Significant differences in the genotype frequencies for a C/G single nucleotide polymorphism (SNP) located at position −660 in the HSP90AA1 5′flanking region were found between the different breeds. Regression analyses reflected significant correlations (from 0.41 to 0.62) between the alternative genotypes of this polymorphism and several climatic and geographic variables characteristic of the regions where these breeds are reared. Real-time analysis revealed that animals bearing the CC−660 genotype presented higher expression levels than those presenting the CG−660 or GG−660 in summer, but not in spring. Mutation at −660 site seems to affect HSP90AA1 transcription rates which could have important effects on the adaptation to different environmental conditions in sheep. Thus, the variability found in the genotype frequencies for the SNP at −660 in the ovine HSP90AA1 locus could be the result of the different environmental pressures occurring in the regions where these breed are maintained.AGRAMA breeders association, CSIC-León (Spain), CITA-Aragón (Spain), Centro Nacional de Referencia de EETs (Spain), Universidad de Zaragoza (Spain), NEIKER-Vitoria (Spain), Centro de Investigación La Orden-Valdesequera Junta de Extremadura (Spain), Dr. Julián Garde from the Universidad de Castilla-La Mancha (Spain), INIA-Madrid (Spain), and Dr Maziek Murawski from the University of Cracow (Poland) have provided biological samples. We are also very grateful to Dr. Jaime Cubero from INIA for his logistic support and to Helen Neumann for the English corrections. RTA2006-00104-00-00 and RZ2004-28 INIA projects have provided refunding to develop the experimental work

Endometrial expression of progesterone, estrogen, and oxytocin receptors and of 20α-hydroxysteroid dehydrogenase and cyclooxygenase II 2 and 5 days after ovulation in induced short and normal estrous cycles in dairy cows

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The effect of diet on fatty acid composition of elongated bovine conceptuses

AbstraktiConceptus elongation is crucial for establishment of pregnancy in ruminants. During the elongation step, endometrium secreted lipids are required as a source of energy and for the remodeling and proliferation of cellular membranes (Ribeiro et al., Reprod 2016;152:R115-R126). The present study investigated the effects of diets designed to cause 15 % reduction in milk fat synthesis (milk fat depression) on fatty acid (FA) composition of elongated bovine conceptuses. The day-14 conceptuses were collected from 22 Nordic Red multiparous dairy cows during two sequential indoor housing periods. Treatments comprised a grass silage based basal diet (CO; 10 cows), basal diet supplemented with 12 g/d of rumen protected trans-10, cis-12 CLA (Lutrell Pure, BASF, Germany) (CLA; 8 cows), and grass silage based diet containing high-starch concentrate components and supplemented with 26.7 g/kg diet dry matter of sunflower oil and 13.3 g/kg diet dry matter of fish oil (MFD; 4 cows). CLA supplement was mixed in total mixed ration and administered in two equal proportions per day. Oil supplements replaced concentrate ingredients. Cows were randomly allocated to the treatments immediately after parturitions. The diets were total mixed rations with 55:45 forage:concentrate ratio on dry matter basis. In total of 45, 35 and 13 conceptuses having visible embryonic discs were used after recovery from the superovulated CO, CLA and MFD donors 130 days after parturitions, respectively. Lipids were extracted separately from each cryopreserved conceptus using a mixture of hexane and 2-propanol (3:2, vol/vol). FA were transesterified to methyl esters using methanolic sodium methoxide and analyzed with a gas chromatograph equipped with a flame ionization detector (Shingfield et al., Anim Sci 2003;77:165–179). Data were analyzed using linear mixed models with MIXED procedure in SAS 9.4. The proportions of the most abundant FA in conceptuses, cis-9 18:1 (30-32 g/100g FA, %), 16:0 (25-26 %), and 18:0 (12-14 %), did not differ between treatments (P > 0.10). In addition, total proportions of cis unsaturated FA (53-54 %) and saturated FA (43-45 %) and ratio of cis unsaturated FA to saturated FA was not different among treatments (P > 0.10). CLA had no effect on the conceptus’ FA composition compared with CO. However, MFD induced higher (P < 0.01) 22:6n-3, and lower (P < 0.05) 22:4n-6 and 22:5n-6 proportions compared with CLA and CO. The proportion of cis-12 18:1 and trans-9, cis-12 18:2, which are biohydrogenation products of 18:2n-6 found in rich amounts in sunflower oil, tended to be higher (P < 0.10) in MFD compared with other treatments. In conclusion, although CLA and MDF caused changes in lipogenesis in the mammary gland and milk fat depression, a substantial effect on the FA composition of conceptuses was not observed. However, unsaturated FA deriving from the MFD diet and metabolized in the rumen biohydrogenation processes had a specific impact on conceptus FA profiles during elongation stage.201

Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, a Mechanism for Vitamin D Deficiency in Diabetes

Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes; however, the mechanisms remain uncertain. Here, we show that nutritional deprivation-responsive mechanisms regulate vitamin D metabolism. Both fasting and diabetes suppressed hepatic cytochrome P450 (CYP) 2R1, the main vitamin D 25-hydroxylase responsible for the first bioactivation step. Overexpression of coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), induced physiologically by fasting and pathologically in diabetes, resulted in dramatic downregulation of CYP2R1 in mouse hepatocytes in an estrogen-related receptor alpha (ERR alpha)-dependent manner. However, PGC-1 alpha knockout did not prevent fasting-induced suppression of CYP2R1 in the liver, indicating that additional factors contribute to the CYP2R1 repression. Furthermore, glucocorticoid receptor (GR) activation repressed the liver CYP2R1, suggesting GR involvement in the regulation of CYP2R1. GR antagonist mifepristone partially prevented CYP2R1 repression during fasting, suggesting that glucocorticoids and GR contribute to the CYP2R1 repression during fasting. Moreover, fasting upregulated the vitamin D catabolizing CYP24A1 in the kidney through the PGC-1 alpha-ERR alpha pathway. Our study uncovers a molecular mechanism for vitamin D deficiency in diabetes and reveals a novel negative feedback mechanism that controls crosstalk between energy homeostasis and the vitamin D pathway

Fasting-induced transcription factors repress vitamin D bioactivation, a mechanism for vitamin D deficiency in diabetes

Abstract Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes; however, the mechanisms remain uncertain. Here, we show that nutritional deprivation–responsive mechanisms regulate vitamin D metabolism. Both fasting and diabetes suppressed hepatic cytochrome P450 (CYP) 2R1, the main vitamin D 25-hydroxylase responsible for the first bioactivation step. Overexpression of coactivator peroxisome proliferator–activated receptor γ coactivator 1-α (PGC-1α), induced physiologically by fasting and pathologically in diabetes, resulted in dramatic downregulation of CYP2R1 in mouse hepatocytes in an estrogen-related receptor α (ERRα)–dependent manner. However, PGC-1α knockout did not prevent fasting-induced suppression of CYP2R1 in the liver, indicating that additional factors contribute to the CYP2R1 repression. Furthermore, glucocorticoid receptor (GR) activation repressed the liver CYP2R1, suggesting GR involvement in the regulation of CYP2R1. GR antagonist mifepristone partially prevented CYP2R1 repression during fasting, suggesting that glucocorticoids and GR contribute to the CYP2R1 repression during fasting. Moreover, fasting upregulated the vitamin D catabolizing CYP24A1 in the kidney through the PGC-1α-ERRα pathway. Our study uncovers a molecular mechanism for vitamin D deficiency in diabetes and reveals a novel negative feedback mechanism that controls crosstalk between energy homeostasis and the vitamin D pathway

A SNP in the HSP90AA1 gene 5′ flanking region is associated with the adaptation to differential thermal conditions in the ovine species

Molecular chaperones have long been understood to be preferentially transcribed in response to multiple perturbations of the cellular homeostasis. In this study, several polymorphisms in the gene encoding the inducible form of the cytoplasmic Hsp90 (HSP90AA1) were addressed in 24 sheep breeds reared in different climatic regions of Europe, Africa, and Asia. Significant differences in the genotype frequencies for a C/G single nucleotide polymorphism (SNP) located at position −660 in the HSP90AA1 5′flanking region were found between the different breeds. Regression analyses reflected significant correlations (from 0.41 to 0.62) between the alternative genotypes of this polymorphism and several climatic and geographic variables characteristic of the regions where these breeds are reared. Real-time analysis revealed that animals bearing the CC−660 genotype presented higher expression levels than those presenting the CG−660 or GG−660 in summer, but not in spring. Mutation at −660 site seems to affect HSP90AA1 transcription rates which could have important effects on the adaptation to different environmental conditions in sheep. Thus, the variability found in the genotype frequencies for the SNP at −660 in the ovine HSP90AA1 locus could be the result of the different environmental pressures occurring in the regions where these breed are maintained