Milton G. Thomas

Reproductive Traits and Their Heritabilities in Beef Cattle

Fertility is a complex trait in beef production systems and genetic evaluation procedures, which is partly due to the numerous measures used to assess reproduction. Beyond beef cattle, fertility measures vary according to animal species, and even within beef cattle, they vary by breed, location, sex, and class. Fertility is of significant economic importance to beef cattle producers, and therefore should be included in their breeding objective. However, traits considered indicative of fertility are in general of low heritability, are expressed late in the life of an animal, or both. Complicating genetic analyses is the binary nature of many of these traits because of truncation of data from short-controlled breeding seasons (typically 60 to 90 d long). Additionally, implementation of genetic prediction of reproductive traits in beef cattle has previously been hampered by a lack of total-herd data reporting systems. This review evaluates historic and current measures of assessing fertility and the heritabilities of these traits in beef cattle. Successful implementation of fertility traits into genetic improvement programs is dependent on whole-herd reporting and improved analysis techniques.

Gene network analyses of first service conception in Brangus heifers: Use of genome and trait associations, hypothalamic-transcriptome information, and transcription factors

Measures of heifer fertility are economically relevant traits for beef production systems and knowledge of candidate genes could be incorporated into future genomic selection strategies. Ten traits related to growth and fertility were measured in 890 Brangus heifers (3/8 Brahman × 5/8 Angus, from 67 sires). These traits were: BW and hip height adjusted to 205 and 365 d of age, postweaning ADG, yearling assessment of carcass traits (i.e., back fat thickness, intramuscular fat, and LM area), as well as heifer pregnancy and first service conception (FSC). These fertility traits were collected from controlled breeding seasons initiated with estrous synchronization and AI targeting heifers to calve by 24 mo of age. The BovineSNP50 BeadChip was used to ascertain 53,692 SNP genotypes for ∼802 heifers. Associations of genotypes and phenotypes were performed and SNP effects were estimated for each trait. Minimally associated SNP (P < 0.05) and their effects across the 10 traits formed the basis for an association weight matrix and its derived gene network related to FSC (57.3% success and heritability = 0.06 ± 0.05). These analyses yielded 1,555 important SNP, which inferred genes linked by 113,873 correlations within a network. Specifically, 1,386 SNP were nodes and the 5,132 strongest correlations (|r| ≥ 0.90) were edges. The network was filtered with genes queried from a transcriptome resource created from deep sequencing of RNA (i.e., RNA-Seq) from the hypothalamus of a prepubertal and a postpubertal Brangus heifer. The remaining hypothalamic-influenced network contained 978 genes connected by 2,560 edges or predicted gene interactions. This hypothalamic gene network was enriched with genes involved in axon guidance, which is a pathway known to influence pulsatile release of LHRH. There were 5 transcription factors with 21 or more connections: ZMAT3, STAT6, RFX4, PLAGL1, and NR6A1 for FSC. The SNP that identified these genes were intragenic and were on chromosomes 1, 5, 9, and 11. Chromosome 5 harbored both STAT6 and RFX4. The large number of interactions and genes observed with network analyses of multiple sources of genomic data (i.e., GWAS and RNA-Seq) support the concept of FSC being a polygenic trait.

Growth characteristics, reproductive performance, and evaluation of their associative relationships in Brangus cattle managed in a Chihuahuan Desert production system.

Balancing growth and reproductive performance in beef cattle managed in desert environments is challenging. Our objectives were to 1) evaluate trends in growth and reproductive traits, and 2) assess associative relationships between growth characteristics and reproductive performance in a Brangus herd managed in a Chihuahuan Desert production system from 1972 to 2006. Data were from bull (n = 597) and heifer calves (n = 585; 1988 to 2006) and cows (n = 525; repeated records of cows, n = 2,611; 1972 to 2006). Variables describing the growth curve of each cow were estimated using a nonlinear logistic function (each cow needed 6 yr of data). Mixed-effect models and logistic regression were used to analyze trends across years in growth and reproductive traits (both continuous and categorical). For continuous traits of calves, a slight cubic response (P < 0.01) described the dynamics of birth weight, 205-d BW, and 365-d BW across years. For categorical traits of females, positive linear trends (P < 0.05) across years were observed in percent pregnant as yearlings, calved at 2 yr of age, and first-calf heifer rebreeding (slopes ranged from 0.007 to 0.014%/yr). Autumn cow BW increased gradually until 1997 (509 kg +/- 8.8) and then decreased gradually by 0.6 kg/yr, whereas pregnancy percentage decreased gradually until 1995 (78.4% +/- 1.0) and then increased slightly by 0.2%/yr. A quadratic effect best described the dynamics of these 2 variables across years (P < 0.01) as well as estimates describing the growth curve of each cow. Specifically, asymptotic BW and age increased (P < 0.05) from 1972 to 1983 and 1990, respectively. Asymptotic age then decreased by 27% from 1983 to 1996 (P < 0.05). The maturing rate index was negatively correlated with age at first calving and calving interval (r = -0.42 and -0.18, P < 0.01), which suggested that early-maturing cows had enhanced fertility in this environment and production system. In summary, minimal changes were observed in measures of growth in bulls and heifers in a Brangus herd managed in the Chihuahuan Desert. Opposing relationships were observed among measures of cow size and fertility; as growth curves shifted toward earlier maturity, measures of reproductive performance suggested that fertility improved.

Metabolic Reprogramming Regulates the Proliferative and Inflammatory Phenotype of Adventitial Fibroblasts in Pulmonary Hypertension Through the Transcriptional Corepressor C-Terminal Binding Protein-1

Background: Changes in metabolism have been suggested to contribute to the aberrant phenotype of vascular wall cells, including fibroblasts, in pulmonary hypertension (PH). Here, we test the hypothesis that metabolic reprogramming to aerobic glycolysis is a critical adaptation of fibroblasts in the hypertensive vessel wall that drives proliferative and proinflammatory activation through a mechanism involving increased activity of the NADH-sensitive transcriptional corepressor C-terminal binding protein 1 (CtBP1). Methods: RNA sequencing, quantitative polymerase chain reaction,13C–nuclear magnetic resonance, fluorescence-lifetime imaging, mass spectrometry–based metabolomics, and tracing experiments with U-13C-glucose were used to assess glycolytic reprogramming and to measure the NADH/NAD+ ratio in bovine and human adventitial fibroblasts and mouse lung tissues. Immunohistochemistry was used to assess CtBP1 expression in the whole-lung tissues. CtBP1 siRNA and the pharmacological inhibitor 4-methylthio-2-oxobutyric acid (MTOB) were used to abrogate CtBP1 activity in cells and hypoxic mice. Results: We found that adventitial fibroblasts from calves with severe hypoxia-induced PH and humans with idiopathic pulmonary arterial hypertension (PH-Fibs) displayed aerobic glycolysis when cultured under normoxia, accompanied by increased free NADH and NADH/NAD+ ratios. Expression of the NADH sensor CtBP1 was increased in vivo and in vitro in fibroblasts within the pulmonary adventitia of humans with idiopathic pulmonary arterial hypertension and animals with PH and cultured PH-Fibs, respectively. Decreasing NADH pharmacologically with MTOB or genetically blocking CtBP1 with siRNA upregulated the cyclin-dependent genes (p15 and p21) and proapoptotic regulators (NOXA and PERP), attenuated proliferation, corrected the glycolytic reprogramming phenotype of PH-Fibs, and augmented transcription of the anti-inflammatory gene HMOX1. Chromatin immunoprecipitation analysis demonstrated that CtBP1 directly binds the HMOX1 promoter. Treatment of hypoxic mice with MTOB decreased glycolysis and expression of inflammatory genes, attenuated proliferation, and suppressed macrophage numbers and remodeling in the distal pulmonary vasculature. Conclusions: CtBP1 is a critical factor linking changes in cell metabolism to cell phenotype in hypoxic and other forms of PH and a therapeutic target.

Multi-Tissue Omics Analyses Reveal Molecular Regulatory Networks for Puberty in Composite Beef Cattle

Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e. hypothalamus, pituitary gland, ovary, uterus, and endometrium) as well as tissues known to be relevant to growth and metabolism needed to achieve puberty (i.e., longissimus dorsi muscle, adipose, and liver). These tissues were collected from pre- and post-pubertal Brangus heifers (3/8 Brahman; Bos indicus x 5/8 Angus; Bos taurus) derived from a population of cattle used to identify quantitative trait loci associated with fertility traits (i.e., age of first observed corpus luteum (ACL), first service conception (FSC), and heifer pregnancy (HPG)). In order to exploit the power of complementary omics analyses, pre- and post-puberty co-expression gene networks were constructed by combining the results from genome-wide association studies (GWAS), RNA-Seq, and bovine transcription factors. Eight tissues among pre-pubertal and post-pubertal Brangus heifers revealed 1,515 differentially expressed and 943 tissue-specific genes within the 17,832 genes confirmed by RNA-Seq analysis. The hypothalamus experienced the most notable up-regulation of genes via puberty (i.e., 204 out of 275 genes). Combining the results of GWAS and RNA-Seq, we identified 25 loci containing a single nucleotide polymorphism (SNP) associated with ACL, FSC, and (or) HPG. Seventeen of these SNP were within a gene and 13 of the genes were expressed in uterus or endometrium. Multi-tissue omics analyses revealed 2,450 co-expressed genes relative to puberty. The pre-pubertal network had 372,861 connections whereas the post-pubertal network had 328,357 connections. A sub-network from this process revealed key transcriptional regulators (i.e., PITX2, FOXA1, DACH2, PROP1, SIX6, etc.). Results from these multi-tissue omics analyses improve understanding of the number of genes and their complex interactions for puberty in cattle.

Genomic regions associated with fertility traits in male and female cattle: Advances from microsatellites to high-density chips and beyond

A current challenge in genetic improvement of cattle is to identify genomic selection strategies that could work across breeds. Breed differences, scarcity of data, and lack of quantitative trait loci (QTL) validation contribute to this challenge. We conducted a review of the literature to identify QTL, markers, and candidate genes that are associated with fertility across breeds to arrive at an integrated view of bovine fertility genomics and to guide the direction of future studies. This review considers both male and female fertility traits as these are economically relevant for all breeds and production systems. Regions associated with fertility traits were found in each of the 30 bovine chromosomes, confirming the complexity of these polygenic traits. Across breeds, regions on chromosomes 1, 5, 14, and 16 were associated with female reproductive traits. The X chromosome was associated with male reproductive traits in both dairy and beef bulls. It has recently been proposed that a Y chromosome anomaly may be involved in infertility in cows. Knowledge of these QTL may assist discovery of causative mutations and has the potential to improve the accuracy of genomic selection, especially across breeds of cattle.

Increased prevalence of EPAS1 variant in cattle with high-altitude pulmonary hypertension

High-altitude pulmonary hypertension (HAPH) has heritable features and is a major cause of death in cattle in the Rocky Mountains, USA. Although multiple genes are likely involved in the genesis of HAPH, to date no major gene variant has been identified. Using whole-exome sequencing, we report the high association of an EPAS1 (HIF2α) double variant in the oxygen degradation domain of EPAS1 in Angus cattle with HAPH, mean pulmonary artery pressure >50u2009mmu2009Hg in two independent herds. Expression analysis shows upregulation of 26 of 27 HIF2α target genes in EPAS1 carriers with HAPH. Of interest, this variant appears to be prevalent in lowland cattle, in which 41% of a herd of 32 are carriers, but the variant may only have a phenotype when the animal is hypoxemic at altitude. The EPAS1 variant will be a tool to determine the cells and signalling pathways leading to HAPH.

Effect of Previous Experience on Grazing Patterns and Diet Selection of Brangus Cows in the Chihuahuan Desert

Abstract The ability to adapt to different environments is critical when livestock are moved because of drought or other management considerations. The impact of previous experience on grazing patterns and diet selection of Brangus cows in desert conditions was evaluated. Cows originating from a humid-subtropical environment (Leona, Texas) were brought to the Chihuahuan Desert (naïve) and evaluated against cows that spent their life in the Chihuahuan Desert (native) and cows that were born and raised in the Chihuahuan Desert but were moved to Leona, Texas during the preceding 3 yr (tourist). In addition, native cows with recent experience in desert conditions were compared with naïve cows and tourist cows that had not been in the Chihuahuan Desert for at least 3 yr. All cows were mature and had similar pedigrees (nu200au200a=u200au200a21). Cows from the three groups were tracked in three extensive pastures (>u200a1u200a000 ha) for three 8–10-d periods during winter, early summer, and later summer. Cows never grazed in the experimental pastures before the study, but native and tourist cows had grazed adjacent pastures. Fecal near-infrared spectroscopy was used to estimate diet quality. Naïve cows used 335 hau200a±u200a83 standard error (SE) less area (Pu200au200a=u200au200a0.06) and were 479 mu200a±u200a105 SE closer to water (Pu200au200a=u200au200a0.03) than cows born and raised in the Chihuahuan Desert (native and tourist cows pooled) when first evaluated in winter. After pooling all data, native cows were farther (Pu200au200a=u200au200a0.06) from water (730 mu200a±u200a283 SE) and spent less time at water (10.53%u200a±u200a3.93 SE) than cows that did not spend their entire life in the desert (naïve and tourist pooled). During winter and early summer (drought conditions), naïve cows selected diets with lower (Pu200a<u200a0.05) crude protein (CP) than cows born in the desert, but during late summer after abundant precipitation naïve cows selected a diet with higher (Pu200au200a=u200au200a0.07) CP. Although Brangus cows are highly adaptable, animals raised in nearby pastures appear to have advantages over naïve animals when grazing Chihuahuan Desert rangeland.

Breed and stocking rate effects on Chihuahuan Desert cattle production.

Productivity of Barzona, Brangus, and Beefmaster cattle was evaluated on conservatively (n=2) (40 ha AU-1) and moderately (28.5 ha AU-1) stocked pastures (n=2) in the Chihuahuan Desert of south-central New Mexico. Equivalent numbers of suckled, first-calf heifers of each breed (n=31) weighing 333+/-11 kg were randomly assigned to the study pastures in the spring of 1992. Pastures were grazed continuously and herd productivity data were collected from 1992-1994. In late August 1994, all pastures were destocked due to onset of severe drought. No effect of breed (P>0.10) was detected in the analyses, so data were pooled across breeds and compared between the stocking rates. Calf crop percentages (1993, 1994) were higher in conservative than moderate stocked pastures (82 vs 62%, respectively, P 0.10) between stocking rates. However, the main effect of year and stocking rate X year interaction were significant (p<0.05). These analyses suggest that the drought in 1994 lowered returns per ha compared to 1993 when precipitation was near average and that conservative stocking may present less financial risk than moderate stocking when drought occurs. These data are consistent with other studies from arid and semi-arid rangelands demonstrating that conservative stocking can give financial returns from cattle production equal to or greater than those from moderate stocking. DOI:10.2458/azu_jrm_v53i1_winder

Metabolic Hormone Profiles and Evaluation of Associations of Metabolic Hormones with Body Fat and Reproductive Characteristics of Angus, Brangus, and Brahman Heifers1

Metabolic hormone profiles and their associations with measures of body fat and reproduction were evaluated among Angus, Brangus, and Brahman heifers (n = 8/breed). Heifers of similar age from breeding programs in semi-arid environments were pen-fed for 10 wk prior to