Effects of prenatal heat stress on birth weight and birth weight genetic parameters in German Holstein calves.

The aim of this study was to infer the effects of heat stress (HS) during late gestation of dams on phenotypes and on direct and maternal genetic parameters for birth weight (BiW). We considered 171,221 Holstein calves kept in 56 large-scale co-operator herds. For a clear separation of maternal effects, only calves from dams with at least 3 offspring were included in the analyses. The genotype data set comprised 41,143 SNPs from 1,883 Holstein bulls. Temperature-humidity indices (THI) during the last 8 wk of gestation were calculated in each herd to reflect prenatal HS. A further prenatal HS descriptor was the first principal component (PC1) from principal component analysis considering the daily THI during the last 56 d of gestation. Regression coefficients of BiW on prenatal THI during the last 12 wk of gestation and PC1 were estimated in 13 consecutive phenotypic analyses. The strongest BiW decline was -0.63 kg per standardized THI, identified during 50 to 56 d before birth. A reaction norm model with weekly prenatal THI or PC1 nested within maternal genetic and maternal permanent environmental effects was defined to infer maternal sensitivity in response to prenatal THI alterations. Direct BiW heritabilities were close to 0.33 in the course of prenatal THI. Maternal BiW heritabilities marginally increased from 0.07 to 0.08 with increasing THI. Genetic correlations between maternal genetic effects at maximum HS levels and remaining THI were larger than 0.95, indicating the absence of genotype by time-lagged HS interactions. In contrast, maternal permanent environmental correlations between BiW at prenatal THI indicating HS with BiW at remaining THI substantially declined with increasing THI distances. Hence, from a herd management perspective, avoiding HS during the dry period of the dams will contribute to a slight increase in fetus growth.

Effects of temperature-humidity index on blood metabolites of German dairy cows and their female calves.

Heat stress (HS) impairs productivity, health, and welfare in dairy cows, and additionally causes metabolic changes. Hence, specific metabolites could be used as HS biomarkers. Consequently, the aim of the present study was to compare blood metabolite concentrations of German Holstein dairy cows and of their female calves suffering from high temperature-humidity index (THI) during late gestation (cows) or during their first week of life (calves) or not. According to the mean daily THI (mTHI) at the day before blood sampling, animals were classified into 2 groups: high mTHI ≥60 (hmTHI) and low mTHI <60 (lmTHI). To perform a standard cross-sectional 2-group study, cow groups (n = 48) and calf groups (n = 47) were compared separately. Differences in metabolite concentrations between hmTHI and lmTHI animals were inferred based on a targeted metabolomics approach. In the first step, processed metabolomics data were evaluated by multivariate data analysis techniques, and were visualized using the web-based platform MetaboAnalyst V5.0. The most important metabolites with pronounced differences between groups were further analyzed in a second step using linear mixed models. We identified 9 thermally sensitive metabolites for the cows [dodecanedioic acid; 3-indolepropionic acid; sarcosine; triglycerides (14:0_34:0), (16:0_38:7), (18:0_32:1), and (18:0_36:2); phosphatidylcholine aa C38:1; and lysophosphatidylcholine a C20:3] and for the calves [phosphatidylcholines aa C38:1, ae C38:3, ae C36:0, and ae C36:2; cholesteryl esters (17:1) and (20:3); sphingomyelins C18:0 and C18:1; and p-cresol sulfate], most of them related to lipid metabolism. Apart from 2 metabolites (3-indolepropionic acid and sarcosine) in cows, the metabolite plasma concentrations were lower in hmTHI than in lmTHI groups. In our heat-stressed dry cows, results indicate an altered lipid metabolism compared with lactating heat-stressed cows, due to the missing antilipolytic effect of HS. The results also indicate alterations in lipid metabolism of calves due to high mTHI in the first week of life. From a cross-generation perspective, high mTHI directly before calving seems to reduce colostrum quality, with detrimental effects on metabolite concentrations in offspring.

Direct genetic effects, maternal genetic effects, and maternal genetic sensitivity on prenatal heat stress for calf diseases and corresponding genomic loci in German Holsteins.

The aim of this study was to infer the effects of heat stress (HS) of dams during late gestation on direct and maternal genetic parameters for pneumonia (PNEU, 112,563 observations), diarrhea (DIAR, 176,904 observations), and omphalitis (OMPH, 176,872 observations) in Holstein calves kept in large-scale co-operator herds. The genotype dataset included 41,135 SNPs from 19,247 male and female cattle. Temperature-humidity indices (THI) during the last 8 wk of pregnancy were calculated, using the climate data from the nearest public weather station for each herd. Heat load effects were considered for average weekly THI larger than 60. Phenotypically, regression coefficients of calf diseases on prenatal THI during the last 8 wk of gestation were estimated in 8 consecutive runs. The strongest detrimental effects of prenatal HS on PNEU and DIAR were identified for the last week of pregnancy (wk 1). Thus, only wk 1 was considered in ongoing genetic and genomic analyses. In an advanced model considering prenatal HS, random regression coefficients on THI in wk 1 nested within maternal genetic effects (maternal slope effects for heat load) were considered as parameters to infer maternal sensitivity in response to prenatal THI alterations. Direct heritabilities from the advanced model ranged from 0.10 (THI 60) to 0.08 (THI 74) for PNEU and were close to 0.16 for DIAR. Maternal heritabilities for PNEU increased from 0.03 to 0.10 along the THI gradient. For DIAR, the maternal heritability was largest (0.07) at the minimum THI (THI = 60) and decreased to 0.05 at THI 74. Genetic correlations smaller than 0.80 for PNEU and DIAR recorded at THI 60 with corresponding diseases at THI 74 indicated genotype by climate interactions for maternal genetic effects. Genome-wide associations studies were performed using de-regressed proofs of genotyped sires for direct genetic, maternal genetic, and maternal slope effects. Thirty suggestive and 2 significant SNPs were identified from the GWAS. Forty-three genes located close to the suggestive SNPs (±100 kb) were annotated as potential candidate genes. Three biological processes were inferred on the basis of the these genes, addressing the negative regulation of the viral life cycle, innate immune response, and protein ubiquitination. Hence, the genetics of prenatal heat stress mechanisms are associated with immune physiology and disease resistance mechanisms.

Genome-wide associations for heat stress response suggest potential candidate genes underlying milk fatty acid composition in dairy cattle.

Contents of milk fatty acids (FA) display remarkable alterations along climatic gradients. Detecting candidate genes underlying such alterations might be beneficial for the exploration of climate sensitivity in dairy cattle. Consequently, we aimed on the definition of FA heat stress indicators, considering FA breeding values in response to temperature-humidity index (THI) alterations. Indicators were used in GWAS, in ongoing gene annotations and for the estimation of chromosome-wide variance components. The phenotypic data set consisted of 39,600 test-day milk FA records from 5,757 first-lactation Holstein dairy cows kept in 16 large-scale German cooperator herds. The FA traits were C18:0, polyunsaturated fatty acids (PUFA), saturated fatty acids (SFA), and unsaturated fatty acids (UFA). After genotype quality control, 40,523 SNP markers from 3,266 cows and 930 sires were considered. Meteorological data from the weather station in closest herd distance were used for the calculation of maximum hourly daily THI, which were allocated to 10 different THI classes. The same FA from 3 stages of lactation were considered as different, but genetically correlated traits. Consequently, a 3-trait reaction norm model was used to estimate genetic parameters and breeding values for FA along THI classes, considering either pedigree (A) or genomic (G) relationship matrices. De-regressed proofs and genomic estimated breeding values at the intermediate THI class 5 and at the extreme THI class 10 were used as pseudophenotypes in ongoing genomic analyses for thermoneutral (TNC) and heat stress conditions (HSC), respectively. The differences in de-regressed proofs and in genomic estimated breeding values from both THI classes were pseudophenotypes for heat stress response (HSR). Genetic correlations between the same FA under TNC and HSC were smallest in the first lactation stage and ranged from 0.20 for PUFA to 0.87 for SFA when modeling with the A matrix, and from 0.35 for UFA to 0.86 for SFA when modeling with the G matrix. In the first lactation stage, larger additive genetic variances under HSC compared with TNC indicate climate sensitivity for C18:0, PUFA, and UFA. Climate sensitivity was also reflected by pronounced chromosome-wide genetic variances for HSR of PUFA and UFA in the first stage of lactation. For all FA under TNC, HSC, and HSR, quite large genetic variance proportions were explained by BTA14. In GWAS, 30 SNP (within or close to 38 potential candidate genes) overlapped for HSR of the different FA. One unique potential candidate gene (AMFR) was detected for HSR of PUFA, 15 for HSR of SFA (ADGRB1, DENND3, DUSP16, EFR3A, EMP1, ENSBTAG00000003838, EPS8, MGP, PIK3C2G, STYK1, TMEM71, GSG1, SMARCE1, CCDC57, and FASN) and 3 for HSR of UFA (ENSBTAG00000048091, PAEP, and EPPK1). The identified unique genes play key roles in milk FA synthesis and are associated with disease resistance in dairy cattle. The results suggest consideration of FA in combination with climatic responses when inferring genetic mechanisms of heat stress in dairy cows.

Genotype by heat stress interactions for production and functional traits in dairy cows from an across-generation perspective.

The aim of this study was to analyze time-lagged heat stress (HS) effects during late gestation on genetic co(variance) components in dairy cattle across generations for production, female fertility, and health traits. The data set for production and female fertility traits considered 162,492 Holstein Friesian cows from calving years 2003 to 2012, kept in medium-sized family farms. The health data set included 69,986 cows from calving years 2008 to 2016, kept in participating large-scale co-operator herds. Production traits were milk yield (MKG), fat percentage (fat%), and somatic cell score (SCS) from the first official test-day in first lactation. Female fertility traits were the nonreturn rate after 56 d (NRR56) in heifers and the interval from calving to first insemination (ICFI) in first-parity cows. Health traits included clinical mastitis (MAST), digital dermatitis (DD), and endometritis (EM) in the early lactation period in first-parity cows. Meteorological data included temperature and humidity from public weather stations in closest herd distance. The HS indicator was the temperature-humidity index (THI) during dams' late gestation, also defined as in utero HS. For the genetic analyses of production, female fertility, and health traits in the offspring generation, a sire-maternal grandsire random regression model with Legendre polynomials of order 3 for the production and of order 2 for the fertility and health traits on prenatal THI, was applied. All statistical models additionally considered a random maternal effect. THI from late gestation (i.e., prenatal climate conditions), influenced genetic parameter estimates in the offspring generation. For MKG, heritabilities and additive genetic variances decreased in a wave-like pattern with increasing THI. Especially for THI >58, the decrease was very obvious with a minimal heritability of 0.08. For fat% and SCS, heritabilities increased slightly subjected to prenatal HS conditions at THI >67. The ICFI heritabilities differed marginally across THI [heritability (h2) = 0.02-0.04]. For NRR56, MAST, and DD, curves for heritabilities and genetic variances were U-shaped, with largest estimates at the extreme ends of the THI scale. For EM, heritability increased from THI 25 (h2 = 0.13) to THI 71 (h2 = 0.39). The trait-specific alterations of genetic parameters along the THI gradient indicate pronounced genetic differentiation due to intrauterine HS for NRR56, MAST, DD, and EM, but decreasing genetic variation for MKG and ICFI. Genetic correlations smaller than 0.80 for NRR56, MAST, DD, and EM between THI 65 with corresponding traits at remaining THI indicated genotype by environment interactions. The lowest genetic correlations were identified when considering the most distant THI. For MKG, fat%, SCS, and ICFI, genetic correlations throughout were larger than 0.80, disproving concerns for any genotype by environment interactions. Variations in genetic (co)variance components across prenatal THI may be due to epigenetic modifications in the offspring genome, triggered by in utero HS. Epigenetic modifications have a persistent effect on phenotypic responses, even for traits recorded late in life. However, it is imperative to infer the underlying epigenetic mechanisms in ongoing molecular experiments.