The Anti-Müllerian Hormone as Endocrine and Molecular Marker Associated with Reproductive Performance in Holstein Dairy Cows Exposed to Heat Stress.

Anti-Müllerian hormone (AMH) is proposed as a biomarker for fertility in cattle, yet this associative relationship appears to be influenced by heat stress (HS). The objective was to test serum AMH and AMH-related single nucleotide polymorphisms (SNPs) as markers potentially predictive of reproductive traits in dairy cows experiencing HS. The study included 300 Holstein cows that were genotyped using BovineSNP50 (54,000 SNP). A genome-wide association study was then executed. Nine intragenic SNPs within the pathways that influence the AMH gene were found important with multiple comparisons adjustment tests (p < 1.09 × 10-6). A further validation study was performed in an independent Holstein cattle population, which was divided into moderate (MH; n = 152) and severe heat-stressed (SH; n = 128) groups and then subjected to a summer reproductive management program. Serum AMH was confirmed as a predictor of fertility measures (p < 0.05) in MH but not in the SH group. Cows were genotyped, which revealed four SNPs as predictive markers for serum AMH (p < 0.01), reproductive traits (p < 0.01), and additional physiological variables (p < 0.05). These SNPs were in the genes AMH, IGFBP1, LGR5, and TLR4. In conclusion, serum AMH concentrations and AMH polymorphisms are proposed as predictive markers that can be used in conjunction with genomic breeding value approaches to improve reproductive performance in Holstein cows exposed to summer HS conditions.

Growth Performance, Blood Metabolites and Carcass Characteristics of Black Goat Kids Fed Diets Containing Olive Cake.

This study investigated the dietary effect of incorporating different levels of olive cake (OC) on the metabolic responses, growth performance, and carcass characteristics of black goat male kids. Thirty kids (body weight = 17.3 ± 0.40 kg) were randomly distributed into one of three equally sized dietary groups: a control diet (CON), OC at 75 g/kg (OC75), and OC at 150 g/kg (OC150) of dietary dry matter (DM). The results revealed that the intake of DM, crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) was similar (p ≥ 0.11) among the three treatment groups. However, the OC150 group had the greatest (p < 0.0001) ether extract (EE) intake compared to the OC75 and CON groups. The growth measurements were similar (p ≥ 0.13) among the three groups. Feed efficiency was not affected by the inclusion of OC. In contrast to the CON diet, the cost of gain was, however, reduced (p = 0.004) in the OC diets. All three treatment groups' digestibility of DM, CP, and ADF was similar. However, when compared to the OC75 and CON groups, the digestibility of NDF was better (p < 0.05) in the OC150 group. The N intake did not differ among the three experimental groups. Nitrogen retained as g/d was higher (p = 0.04) in the OC150 and OC75 groups compared to the CON group, while retention as a percentage (g/100 g) was similar among the three groups. Except for intermuscular fat, total fat, leg fat depth, and tissue depth, the inclusion of OC did not result in any discernible treatment effects on the carcass and meat quality parameters. Only alanine aminotransferase enzyme activity was lower (p < 0.0001) in OC-treated groups compared to the CON group. In summary, incorporating OC at 75 g/kg and 150 g/kg levels into the diets of black goat kids had positive comparable effects on some parameters related to growth performance, carcass attributes, and meat quality. Importantly, utilizing olive cake led to cost savings in production and may serve as a viable alternative feed source in goat nutrition.

Genetic parameters for pulmonary arterial pressure, yearling performance, and carcass ultrasound traits in Angus cattle.

Pulmonary arterial pressure (PAP) can be used as an indicator of susceptibility to pulmonary hypertension and subsequent potential to develop right-sided heart failure (RHF). Previously reported heritability estimates of PAP have been moderate to high. Based on these estimates, selection for the indicator trait, PAP, could reduce the incidence of RHF due to hypoxia. Previous studies have also speculated that increased growth rates and body fat accumulation contribute to increased PAP and RHF. Research evaluating the genetic relationships between PAP and performance traits (e.g., yearling weight and postweaning gain) has yielded conflicting results, leading to ambiguity and uncertainty regarding the underlying genetic relationships. Additionally, no previous research has evaluated the relationship between PAP and ultrasound carcass traits. Therefore, the objective of this study was to estimate trait heritabilities and genetic correlations between PAP, post-weaning growth traits, and ultrasound carcass traits in Angus cattle, using data (n = 4,511) from the American Angus Association. We hypothesized that traits associated with increased growth and muscle would have a positive genetic (i.e., unfavorable) relationship with PAP. Estimates for heritability and genetic correlations were obtained using a multi-trait animal model. Heritability estimates for PAP (0.21 ± 0.04), post-weaning gain (PWG; 0.31 ± 0.04), and yearling weight (YWT; 0.37 ± 0.04) were within the range of estimates previously reported. Genetic correlations were weak (< 0.20) between PAP, PWG, and YWT. A low-to-moderate genetic correlation between PAP and ultrasound ribeye area (UREA) was found (0.25 ± 0.12). Genetic correlations between PAP, ultrasound back fat (UBF), ultrasound intramuscular fat (IMF), and ultrasound rump fat (RUMP) were weak (ranging in magnitude from -0.05 to 0.10) and therefore, do not provide strong support for the hypothesis of an antagonistic relationship between PAP and carcass ultrasound traits, while heritability estimates for UBF (0.43 ± 0.05), UREA (0.31 ± 0.04), IMF (0.35 ± 0.04), and RUMP (0.47 ± 0.05) were in the range of previously reported values.

Beef cattle residing >1,500 m are subject to reduced atmospheric oxygen levels when compared with beef cattle at lower elevations which may result in hypoxia-induced pulmonary hypertension and right-side heart failure. Breeders use pulmonary arterial pressures to identify animals at risk of right-side heart failure and to select breeding animals that are less susceptible to the problem. There is a concern that selection for growth and carcass characteristics may be increasing the incidence of heart failure in feedlot cattle at elevations <1,500 m. To address the concern, this study estimated the genetic correlations (i.e., relationships) between pulmonary arterial pressure, growth, and ultrasound carcass measures in Angus cattle. The study shows that the genetic relationships between pulmonary arterial pressure and these traits are minimal to non-existent with the exception of ultrasound ribeye area. Our estimate suggests a moderate, unfavorable relationship between pulmonary arterial pressure and ribeye area and that single-trait selection for increased ribeye area alone may result in increased susceptibility to right-side heart failure. However, selection for both traits simultaneously should overcome increases in susceptibility given the moderate strength of the genetic relationship.

Genetic Markers Associated with Milk Production and Thermotolerance in Holstein Dairy Cows Managed in a Heat-Stressed Environment.

Dairy production in Holstein cows in a semiarid environment is challenging due to heat stress. Under such conditions, genetic selection for heat tolerance appears to be a useful strategy. The objective was to validate molecular markers associated with milk production and thermotolerance traits in Holstein cows managed in a hot and humid environment. Lactating cows (n = 300) exposed to a heat stress environment were genotyped using a medium-density array including 53,218 SNPs. A genome-wide association study (GWAS) detected six SNPs associated with total milk yield (MY305) that surpassed multiple testing (p < 1.14 × 10-6). These SNPs were further validated in 216 Holstein cows from two independent populations that were genotyped using the TaqMan bi-allelic discrimination method and qPCR. In these cows, only the SNPs rs8193046, rs43410971, and rs382039214, within the genes TLR4, GRM8, and SMAD3, respectively, were associated (p < 0.05) with MY305, rectal temperature (RT), and respiratory rate. Interestingly, these variables improved as the number of favorable genotypes of the SNPs increased from 0 to 3. In addition, a regression analysis detected RT as a significant predictor (R2 = 0.362) for MY305 in cows with >1 favorable genotype, suggesting this close relationship was influenced by genetic markers. In conclusion, SNPs in the genes TLR4, GRM8, and SMAD3 appear to be involved in the molecular mechanism that regulates milk production in cows under heat-stressed conditions. These SNPs are proposed as thermotolerance genetic markers for a selection program to improve the milk performance of lactating Holstein cows managed in a semiarid environment.

Genomic Prediction Accuracies for Growth and Carcass Traits in a Brangus Heifer Population.

The predictive abilities and accuracies of genomic best linear unbiased prediction (GBLUP) and the Bayesian (BayesA, BayesB, BayesC and Lasso) genomic selection (GS) methods for economically important growth (birth, weaning, and yearling weights) and carcass (depth of rib fat, apercent intramuscular fat and longissimus muscle area) traits were characterized by estimating the linkage disequilibrium (LD) structure in Brangus heifers using single nucleotide polymorphisms (SNP) markers. Sharp declines in LD were observed as distance among SNP markers increased. The application of the GBLUP and the Bayesian methods to obtain the GEBV for growth and carcass traits within k-means and random clusters showed that k-means and random clustering had quite similar heritability estimates, but the Bayesian methods resulted in the lower estimates of heritability between 0.06 and 0.21 for growth and carcass traits compared with those between 0.21 and 0.35 from the GBLUP methodologies. Although the prediction ability of the GBLUP and the Bayesian methods were quite similar for growth and carcass traits, the Bayesian methods overestimated the accuracies of GEBV because of the lower estimates of heritability of growth and carcass traits. However, GBLUP resulted in accuracy of GEBV for growth and carcass traits that parallels previous reports.

Mineral supplementation (injectable) improved reproductive performance in Holstein cows managed in a warm summer environment.

Sustainability of dairy production depends largely on reproductive efficiency that is affected by heat stress due to high ambient temperature and humidity during summer. Supplementation of minerals has been proposed as a management strategy to minimize adverse impact of heat stress on fertility. The objective of this study was to determine the effects of an injectable mineral supplement (Fosfosan) containing selenium (Se), copper (Cu), potassium (K), magnesium (Mg) and phosphorus (P) on the ovarian structures, reproductive hormones and conception rate of heat-stressed Holstein cows. Sixteen cows were assigned during summer to one of two treatments, a control group (CON; n = 8) and a mineral-supplemented group (SUP; n = 8). Ambient temperature and relative humidity records were collected and processed to estimate the temperature-humidity index (THI), which confirmed a heat-stressed environment during the study (avg. THI = 79.4). Cows were subjected to a fixed-time artificial insemination (FTAI) program using the CIDR-Synch synchronization protocol. Traits indicative of ovarian activity were recorded during and after this protocol, as well as serum concentrations of reproductive hormones. Pregnancy diagnosis was made 28 and 35 d after FTAI. A completely randomized block design with repeated measures over time was performed to study ovarian functional structures and its hormonal profiles. Correlations and regressions were estimated to study relationships between ovarian structures and related hormones. Mineral supplementation did not increase follicular diameter or follicular populations (p > .05), yet tended to increase corpus luteum diameter (p < .10), and it enhanced (p < .01) oestrogen and progesterone serum concentrations and improved (p < .05) cow's conception rate. Diameter of dominant follicles and corpus luteum was correlated (p < .05) with oestrogen and progesterone levels, respectively, but only in mineral-treated cows. Two additional dairy herds were evaluated to confirm that mineral supplementation improved conception rate during the heat stress period (objective 2). Cows from dairy 1 received FTAI during winter (n = 401) and summer (n = 240), whereas cows from dairy 2 were bred after natural detected oestrus during winter (n = 558) and summer (n = 314). Conception rates were higher (p < .05) in winter than summer and they improved (p < .05) with mineral supplementation, but only in cows managed during summer. In conclusion, supplementation of minerals enhanced hormonal secretion from ovarian structures and improved conception rate in Holstein cows exposed to summer heat stress.

Effect of calving season on the parameters and components of the lactation curve in Holstein dairy cows managed in a semi-desert climate.

The lactation curve in dairy cows is influenced by the calving season, which is highly dependent on the warm climate in semi-arid regions. Objective herein was to evaluate effects of calving season on the parameters and components of the lactation curve in Holstein cows. The study included 278,317 milk records collected from 1086 cows from the 1st to 5th calving and good body condition score. The cows were grouped according to the season in which they calved: winter-calved (CS1), summer-calved (CS2), and autumn-calved cows (CS3). Ambient temperature and humidity data were used to calculate the temperature-humidity index (THI). The NLIN procedure was used to estimate the parameters of the lactation curve that served to calculate the components. The mixed procedure was executed to analyze the fixed effect of calving season. Associations between lactation curve traits were tested using correlation and regression analyses. A univariate model was utilized to calculate heritability. Average THI values during the lactation period were 73.5, 68.5, and 69.5 units for CS1, CS2, and CS3 groups, respectively. Initial milk production and increasing rate to the maximum milk yield in CS1 and CS3 groups were higher (P < 0.05) than CS2 cows. However, persistency and total milk yield during the entire lactation period were superior (P < 0.05) for CS2 and CS3 cows compared to CS1 cows, probably due to the moderate heat stress during the lactation period in the CS1 group. In cows from CS2 and CS3 groups, total milk production at 305 days was moderately correlated with initial milk production (r = 0.47; P < 0.05), and highly correlated with milk yield at peak day (r = 0.91; P < 0.05) which resulted as reliable predictor for total milk yield during the entire lactation (R2 = 0.83). In conclusion, the THI prevailing during the different calving seasons appeared to be an important factor influencing the performance of the lactation curve.

Pulmonary arterial pressure in fattened Angus steers at moderate altitude influences early postmortem mitochondria functionality and meat color during retail display.

Pulmonary hypertension is a noninfectious disease of cattle at altitudes > 1524 m (5,000 ft). Mean pulmonary arterial pressures (PAP) are used as an indicator for pulmonary hypertension in cattle. High PAP cattle (≥50 mmHg) entering the feedlot at moderate elevations have lower feed efficiency as compared to low PAP cattle (< 50 mmHg). The impact of pulmonary arterial pressure on mitochondrial function, oxidative phosphorylation (OXPHOS) protein abundance, and meat color was examined using longissimus lumborum (LL) from high (98 ± 13 mmHg; n = 5) and low (41 ± 3 mmHg; n = 6) PAP fattened Angus steers (live weight of 588 ± 38 kg) during early postmortem period (2 and 48 h) and retail display (days 1 to 9), respectively. High PAP muscle had greater (P = 0.013) OXPHOS-linked respiration and proton leak-associated respiration than low PAP muscles at 2 h postmortem but rapidly declined to be similar (P = 0.145) to low PAP muscle by 48 h postmortem. OXPHOS protein expression was higher (P = 0.045) in low PAP than high PAP muscle. During retail display, redness, chroma, hue, ratio of reflectance at 630 and 580 nm, and metmyoglobin reducing activity decreased faster (P < 0.05) in high PAP steaks than low PAP. Lipid oxidation significantly increased (P < 0.05) in high PAP steaks but not (P > 0.05) in low PAP. The results indicated that high PAP caused a lower OXPHOS efficiency and greater fuel oxidation rates under conditions of low ATP demand in premortem beef LL muscle; this could explain the lower feed efficiency in high PAP feedlot cattle compared to low PAP counterparts. Mitochondrial integral function (membrane integrity or/and protein function) declined faster in high PAP than low PAP muscle at early postmortem. LL steaks from high PAP animals had lower color stability than those from the low PAP animals during simulated retail display, which could be partially attributed to the loss of muscle mitochondrial function at early postmortem by ROS damage in high PAP muscle.

The impact of pulmonary arterial pressure (PAP) on mitochondrial function, oxidative phosphorylation protein abundance, and meat color was examined using longissimus lumborum (LL) from high (98 ± 13 mmHg) and low (41 ± 3 mmHg) PAP fattened Angus steers (live weight of 588 ± 38 kg) during early postmortem period (2 and 48 h) and retail display (days 1 to 9), respectively. The results indicated that high PAP caused a lower oxidative phosphorylation efficiency and greater fuel oxidation rates under conditions of positive energy balance in beef LL muscle. This could explain the lower feed efficiency in high PAP feedlot cattle compared to low PAP counterparts. Mitochondrial integral function declined faster in high PAP than low PAP muscle at early postmortem. LL steaks from high PAP animals had lower color stability than those from the low PAP animals during simulated retail display, which could be partially attributed to the loss of muscle mitochondrial function at early postmortem in high PAP muscle.

A SNP within the PMCH gene as a molecular marker associated with fertility traits in Angus and Brangus beef heifers raised under a desert environment.

Components of the GH/IGF1 endocrine axis regulate growth and reproductive traits in cattle. The pro-melanin-concentrating hormone (PMCH) gene located within chromosome 5 belongs to this axis. Objective herein was to evaluate PMCH single-nucleotide polymorphisms (SNPs) as molecular markers associated with age at first calving, calving interval, and age at second calving in Angus and Brangus beef heifers raised in desert conditions. Five SNPs within the PMCH gene were included in the study. Three of these SNPs had minor allele frequency > 10% and only one SNP did not deviate from Hardy-Weinberg equilibrium. A genotype to phenotype association analyses was performed using a mixed-effects model which included phenotype as the response variable, SNP genotype, breed, year of birth and age of dam as fixed terms, and sire as a random effect. Genotypes from the SNP rs135033882 were found to be associated (P < 0.05) with all evaluated fertility traits, and the term breed resulted as a significant source of variation only for age at second calving. The allele A was the favorable allele because it decreased the age at first calving 98.6 days, the calving interval 85.3 days, and the age at second calving 183.1 days, in Angus and Brangus heifers. In conclusion, we proposed a SNP within the PMCH gene as a potential candidate marker associated with reproductive performance in Angus and Brangus beef heifers raised in a desert climate.

Differential response from selection for high calving ease vs. low birth weight in American Simmental beef cattle.

Data on calving ease (CE) and birth, weaning weight (WW), and yearling weight (YW) were obtained from the American Simmental Association (ASA) and included pedigree and performance information on 11,640,735 animals. Our objective was to quantify differential response from selection for high CE vs. low birth weight (LBW) in first-calf Simmental heifers. We hypothesized that direct selection for CE should be used as the primary approach to reduce dystocia and mitigate losses in growth-related traits. WW and YW were adjusted to 205 and 365 d of age, respectively. Sire and maternal grandsire (co)variance components for CE, birth weight (BW), and 205-d weaning weight (205-d WW), and sire covariance components for 160-d postweaning gain (160-d gain) were estimated using a sire-maternal grandsire model. Direct and maternal expected progeny differences (EPD) for CE, BW, and 205-d WW and direct EPD for 160-d gain and 365-d yearling weight (365-d YW) for first-calf Simmental heifers population (465,710 animals) were estimated using a threshold-linear multivariate maternal animal model. This population was used to estimate genetic trends and as a selection pool (control) for various selection scenarios. Selection scenarios were high CE (HCE), LBW, the all-purpose selection index (API = -1.8 BW + 1.3 CE + 0.10 WW + 0.20 YW) of the ASA and its two derived subindices: (API1 = 1.3 CE + 0.20 YW) and (API2 = -1.8 BW + 0.20 YW), and lastly Dickerson's selection index (DSI = -3.2 BW + YW). Data for each selection scenario were created by selecting sires with EPD greater than or equal to the average along with the top 75% of dams. Comparison between selection scenarios involved evaluating the direct and maternal genetic trends from these scenarios. Direct heritabilities for CE, BW, 205-d WW, 160-d gain, and 365-d YW of Simmental cattle were 0.23, 0.52, 0.28, 0.21, and 0.33, respectively. The single trait, HCE, selection scenario, as opposed to LBW, increased the intercept for CE by 57.7% and the slopes (P < 0.001) for BW, 205-d WW, 160-d gain, and 365-d YW by 27.9%, 37.5%, 16%, and 28%, respectively. Comparisons of various selection scenarios revealed that the CE-based selection scenarios (HCE, API, and API1) had a greater response for CE and growth traits.

Evaluation of the sensitivity of pulmonary arterial pressure to elevation using a reaction norm model in Angus Cattle.

Pulmonary arterial pressure (PAP) is a diagnostic measure used to determine an individual's susceptibility to developing high-altitude disease. The importance of PAP measures collected at elevations lower than the intended breeding elevation of the bulls (i.e., ≥1,520 m) is unknown. Therefore, the objective of this study was to determine the genetic relationship between PAP measures collected in a range of elevations using reaction norm models. A total of 9,177 PAP and elevation observations on purebred Angus cattle, which averaged 43.49 ± 11.32 mmHg and 1,878.6 ± 296.8 m, respectively, were used in the evaluation. The average age of the individuals in the evaluation was 434.04 ± 115.9 d. A random regression model containing the effects of sex, a linear covariate of age, a quadratic fixed covariate of elevation, and random effects consisting of a contemporary group and a linear regression of PAP on elevation was used for the evaluation of PAP. Two forms of PAP were evaluated with this model. First, to address the non-normality of the data, PAP was raised to the power of -2.6 (ptPAP) based on the results of a Box-Cox analysis. Second, raw PAP (rPAP) phenotypes were evaluated to compare the results to those obtained from the transformed data. For ptPAP, heritability ranged from 0.25 to 0.37 corresponding to elevations of 1,900 and 1,215 m, respectively. For rPAP, heritability ranged from 0.22 to 0.41 corresponding to elevations of 1,700 and 2,495 m, respectively. Generally, lower elevations corresponded to decreased heritabilities while higher elevations corresponded to increased heritability estimates. For ptPAP, genetic correlations ranged from 0.18 (elevation: 1,215 and 2,495 m) to 1.00. For rPAP, genetic correlations ranged from 0.08 (elevation: 1,215 and 2,495 m) to 1.00. In general, the closer the elevations in which PAP was measured, the greater the genetic relationship. The greater the difference in elevation between PAP measures resulted in lower genetic correlations. The rank correlation between expected progeny differences (EPD) for 1,215 and 2,495 m was 0.65 and 0.49 for the ptPAP and rPAP, respectively. These results suggested that PAP measures collected in lower elevations may be used as an indicator of high-altitude adaptability. In the estimation of EPD to rank sires for their suitability for use in high-elevation production systems, it is important to account for the relationships among varied altitudes.

Proteomics Recapitulates Ovarian Proteins Relevant to Puberty and Fertility in Brahman Heifers (Bos indicus L.).

High fertility and early puberty in Bos indicus heifers are desirable and genetically correlated traits in beef production. The hypothalamus-pituitary-ovarian (HPO) axis synthesizes steroid hormones, which contribute to the shift from the pre-pubertal state into the post-pubertal state and influence subsequent fertility. Understanding variations in abundance of proteins that govern steroid synthesis and ovarian signaling pathways remains crucial to understanding puberty and fertility. We used whole ovaries of six pre-pubertal and six post-pubertal Brahman heifers to conduct differential abundance analyses of protein profiles between the two physiological states. Extracted proteins were digested into peptides followed by identification and quantification with massspectrometry (MS) by sequential window acquisition of all instances of theoretical fragment ion mass spectrometry (SWATH-MS). MS and statistical analysis identified 566 significantly differentially abundant (DA) proteins (adjusted p < 0.05), which were then analyzed for gene ontology and pathway enrichment. Our data indicated an up-regulation of steroidogenic proteins contributing to progesterone synthesis at luteal phase post-puberty. Proteins related to progesterone signaling, TGF-ß, retinoic acid, extracellular matrix, cytoskeleton, and pleiotrophin signaling were DA in this study. The DA proteins probably relate to the formation and function of the corpus luteum, which is only present after ovulation, post-puberty. Some DA proteins might also be related to granulosa cells signaling, which regulates oocyte maturation or arrest in ovaries prior to ovulation. Ten DA proteins were coded by genes previously associated with reproductive traits according to the animal quantitative trait loci (QTL) database. In conclusion, the DA proteins and their pathways were related to ovarian activity in Bos indicus cattle. The genes that code for these proteins may explain some known QTLs and could be targeted in future genetic studies.

Coding RNA Sequencing of Equine Endometrium during Maternal Recognition of Pregnancy.

Equine maternal recognition of pregnancy (MRP) is a process whose signal remains unknown. During MRP the conceptus and endometrium communicate to attenuate prostaglandin F2α (PGF) secretion, sparing the corpus luteum and maintaining progesterone production. Recognition of a mobile conceptus by the endometrium is critical by days 14-16 post-ovulation (PO), when endometrium produces PGF, initiating luteolysis. The objective of this study was to evaluate endometrial gene expression changes based upon pregnancy status via RNA sequencing. This experiment utilized a cross-over design with each mare serving as both a pregnant and non-mated control on days nine, 11, and 13 PO (n = 3/status/day). Mares were randomly assigned to collection day and pregnancy confirmed by terminal uterine lavage at the time of endometrial biopsy. Total RNA was isolated and libraries prepared using Illumina TruSeq RNA sample preparation kit. Reads were mapped and annotated using HISAT2 and Stringtie. Expression values were evaluated with DESEQ2 (P ≤ 0.05 indicated significance). On day nine, 11, and 13 there were 1435, 1435 and 916 significant transcripts, respectively. Multiple genes with splice variants had different expression patterns within the same day. These are the first data to evaluate the endometrial transcriptome during MRP on days nine, 11, and 13.

Cardiopulmonary remodeling in fattened beef cattle: a naturally occurring large animal model of obesity-associated pulmonary hypertension with left heart disease.

The obesity epidemic in developed societies has led to increased cardiovascular diseases including pulmonary hypertension associated with left heart disease (PH-LHD), the largest and fastest-growing class of PH. Similar to obese humans, PH and heart failure (HF) are increasingly recognized in North American fattened beef cattle. We hypothesized that PH and HF in fattened beef cattle are novel, phenotypically distinct manifestations of bovine PH arising from left ventricular (LV) dysfunction similar to obesity-related PH-LHD in humans. We conducted a semi-quantitative histopathological assessment of cardiopulmonary tissues obtained from fattened beef cattle suffering end-stage HF compared to asymptomatic cattle of equivalent age undergoing the same fattening regimens. In HF animals we observed significant LV fibrosis, abundant cardiac adipose depots, coronary artery injury, and pulmonary venous remodeling recapitulating human obesity-related PH-LHD. Additionally, striking muscularization, medial hypertrophy, adventitial fibrosis, and vasa vasorum hyperplasia in the pulmonary arterial circulation were associated with sequela of pathologic right ventricular (RV) remodeling suggesting combined pulmonary venous and arterial hypertension. The association between obesity, pathologic cardiopulmonary remodeling, and HF in fattened beef cattle appears to recapitulate the complex pathophysiology of obesity-associated PH-LHD in humans. This novel, naturally occurring, and large animal model may provide mechanistic and translational insights into human disease.