Genome-wide association study of milk fatty acid composition in Italian Simmental and Italian Holstein cows using single nucleotide polymorphism arrays.

Bovine milk is important for human nutrition, but its fat content is often criticized as a risk factor in cardiovascular disease. Selective breeding programs could be used to alter the fatty acid (FA) composition of bovine milk to improve the healthiness of dairy products for human consumption. Here, we performed a genome-wide association study (GWAS) on bovine milk to identify genomic regions or specific genes associated with FA profile and to investigate genetic differences between the Italian Simmental (IS) and Italian Holstein (IH) breeds. To achieve this, we first characterized milk samples from 416 IS cows and 436 IH cows for their fat profile by gas chromatography. Subjects were genotyped with single nucleotide polymorphism array and a single-marker regression model for GWAS was performed. Our findings confirm previously reported quantitative trait loci strongly associated with bovine milk fat composition. More specifically, our GWAS results revealed significant signals on chromosomes Bos taurus autosome 19 and 26 for milk FA. Further analysis using a gene-centric approach and pathway meta-analysis identified not only some well-known genes underlying quantitative trait loci for milk FA components, such as FASN, SCD, and DGAT1, but also other significant candidate genes, including some with functional roles in pathways related to "Lipid metabolism." Highlighted genes related to FA profile include ECI2, PCYT2, DCXR, G6PC3, PYCR1, and ALG12 in IS, and CYP17A1, ACO2, PI4K2A, GOT1, GPT, NT5C2, PDE6G, POLR3H, and COX15 in IH. Overall, the breed-specific association outcomes reflect differences in the genetic backgrounds of the IS and IH breeds and their selective breeding histories.

Administration of botanicals with the diet regulates gene expression in peripheral blood cells of Sarda sheep during ACTH challenge.

The aim of the present research was to investigate the regulation of gene expression in ovine blood leukocytes during ACTH-induced cortisol release and the effect of dietary administration of botanicals to counteract the evoked response in polymorphonucleate cells (PMNCs). Thirty-six homogeneous Sarda sheep (age, 18±4.1 mo; BW, 38.7±1.3 kg) were allotted to six groups of six sheep each. One group was used as a negative control (Saline) and five groups were treated, every 12 h for 48 h, with 0.5 mL of ACTH agonist (250 µg/mL of tetracosactrin). Before ACTH treatment, four of the five ACTH-treated groups were separated and fed for 22 d with a basal diet supplemented with extracts from Echinacea angustifolia roots (PO+ACTH), Echinacea angustifolia flowers (EA+ACTH), Andrographis paniculata (AP+ACTH), and the bark of Larix decidua milled (LB+ACTH). Control groups (Saline and ACTH) were fed with the same basal diet without botanicals. Total RNA was extracted from blood samples collected before (T0) and after 3 h (T3) and 51 h (T51) from the first ACTH injection, and transcriptome analysis was performed using a custom oligoarray, designed from 12,194 Ovis aries UniGenes on a CombiMatrix platform. At T3, treatment with ACTH caused down-regulation of transcripts (P<0.001) involved in "response to stress" (GADD45A, GADD45B, WRNIP1, and XRCC6) and in "innate immune response" (MAPK3 and NFkBIB). At T51, treatment with ACTH caused down-regulation (P<0.001) of genes involved in "immune response" (IFNG and IL2) and up-regulation (P<0.001) of NF-κB1 and TP53. Each botanical produced a different (P<0.001) molecular signature for these genes at T3 and T51. The most active botanical in modulating transcriptome modifications in PMNCs after ACTH-induced cortisol release was Larix decidua Mill bark followed by Polinacea roots. These botanicals can be viewed as promising feed supplements in ruminants to cope with conditions associated with increased concentrations of plasma cortisol.

Grape polyphenols affect mRNA expression of PGHS-2, TIS11b and FOXO3 in endometrium of heifers under ACTH-induced stress.

Stress activates the hypothalamo-pituitary-adrenal axis leading to enhanced glucocorticoid secretion and concurrently disrupts ovarian cycle. Plant polyphenols are known to posses antioxidant and anti-inflammatory proprieties. This could be of interest for ovarian cycle when stressing conditions lead to progesterone enhancement and hamper normal reproduction activity. The present study examined whether ovarian follicular development and progesterone secretory pattern are affected by exogenous ACTH administration in heifers. Moreover, the effect of grape polyphenols in endometrium of heifers, under adrenocorticotropic hormone challenge, is evaluated in terms of transcriptional patterns of genes related to inflammation, oxidative stress and endometrial functions. At day 14 of synchronized estrous cycle, Holstein Friesian heifers received injections of either saline (CTR group) or adrenocorticotropic hormone (ACT group) agonist every 12 h for 7 days. Another group (POL group) of animals received the same treatment plus an oral supplementation of 15 g/day of grape skin extract. Cortisol and progesterone were analysed in the blood samples collected at days 0, 3, 6, 9, 12, 14, 17, 21, 24 of the estrous cycle. Endometrial biopsies were collected at diestrus (day 18) and at estrus and a panel of gene expressions were quantified by real-time PCR. ACTH administration increased both cortisol (P<0.001) and progesterone concentrations (P<0.01) compared to CTR group. PGHS-2 was significantly (P<0.01) up-regulated in the POL group compared to ACT and CTR groups at diestrus and at estrus. FOXO3 and TIS11b were down-regulated in the CTR group compared to ACT and POL groups. The PGHS-2, SOD2 (P<0.05), FOXO3 and TIS11b (P<0.10) genes were down-regulated at estrus in all groups compared to diestrus. An interesting role of polyphenols in modulating the expression levels of PGHS-2 in endometrial tissue and on the activation of TIS11b and SOD2 through c-AMP-dependent signalling was suggested.