Associations between bovine IGFBP2 polymorphisms with fertility, milk production, and metabolic status in UK dairy cows.

Insulin-like growth factor binding protein-2 (IGFBP2) is a key regulator of IGF activity that has been associated with insulin resistance and obesity. In cows, IGFBP2 mRNA expression is differentially regulated according to nutritional status in different tissues including the liver, reproductive tract, and mammary gland. This study investigated associations between single nucleotide polymorphisms (SNPs) in bovine IGFBP2 with fertility, milk production, and metabolic traits in Holstein-Friesian dairy cows. Fertility was assessed in heifers by measuring age at first service, age at first conception, and age at first calving. During the first and second lactation, the number of postpartum days for commencement of luteal activity (based on milk progesterone profiles), days to first service, days to conception, average milk production per day, 305-day milk yield, total milk yield, and total days in milk were recorded. Blood samples were taken at -1, +1, and +8 weeks relative to first and second calving for assessment of metabolic status (IGF1, insulin, beta-hydroxybutyrate, and glucose). Five novel SNPs were identified in IGFBP2, two of which had significant associations with fertility (age at conception in heifers and commencement of luteal activity) and 305-day milk yield in lactation 1. Trends of association were also observed with the peripartum metabolic status, in particular the glucose, insulin, and beta-hydroxybutyrate concentrations around second calving. These results indicate that IGFBP2 SNPs may influence tissue mobilization in dairy cows and may thus be of interest for marker assisted selection.

Evidence that leptin genotype is associated with fertility, growth, and milk production in Holstein cows.

This study investigated associations between single nucleotide polymorphisms (SNP) in the leptin, leptin receptor, and neuropeptide Y (NPY) genes with growth, milk production, and fertility traits. Holstein Friesian heifers from 19 UK dairy farms were recruited at birth, providing an initial population of 509. Animals were monitored until they either reached the end of their second lactation or were culled. Size (weight, height, length, girth) was measured at 1, 6, and 15 mo to assess growth traits. Heifer fertility was assessed by recording age at service, age at conception, age at first calving, and number of services. Cow fertility was assessed by recording days from calving to service and conception, services per conception, percentage of animals in calf at 100 d after calving and the calving interval in each lactation. Milk production was recorded as days in milk, total milk per lactation, 305-d yield, milk per day, and peak yield. Mixed model analyses revealed that leptin SNP were associated with early skeletal growth (height, A1457G; length, A59V), fertility (UASMS1, UASMS2, A1457G, A59V) and milk production (A59V). The leptin receptor SNP (T945M) was only weakly associated with milk per day and days to first service. The NPY SNP (NPY1) was associated with the prevalence of the animal being in calf 100 d after calving and 305-d milk yield in the first lactation. The association of leptin SNP with fertility traits in heifers, in addition to lactating cows, suggests that some effects on fertility are direct and not necessarily mediated via altered tissue mobilization. In accord with this, other work has shown that leptin can affect oocyte quality and early embryo development. These results support the use of leptin SNP to inform marker-assisted selection in dairy cows.

A descriptive study of the survival of Holstein-Friesian heifers through to third calving on English dairy farms.

A short herd lifespan severely limits opportunities for on-farm selection of breeding cows in addition to causing financial losses on dairy farms and presenting welfare issues for individual animals. This prospective study monitored survival up to third calving and reasons for culling of a cohort of 468 Holstein-Friesian heifers on 18 dairy farms across southern England. Heifers born during 2003 and 2004 were monitored from 1 mo of age through to third calving. A longevity index was calculated as the proportion of days alive spent in milk production, a good measure of lifetime performance. On average, 11% of heifers recruited at 1 mo did not survive until first calving (0% longevity index). Of those that did calve, 19% were culled in lactation 1 (total average lifetime days in milk of 322 with a longevity index of 24%) and 24% were culled during lactation 2 (total average lifetime days in milk of 623 with a longevity index of 40%). The primary cause for culling was infertility. Only 55% of replacement heifers calved successfully for a third time, ranging from 80 to 32% across individual farms. These results show that on a selection of UK farms, a large number of heifers never become productive or are culled before they reach their full lactation potential. Increasing the productive lifetime of dairy cows would improve the efficiency of dairy production by lowering replacement costs and capturing a greater proportion of potential lactation milk yield from mature cows.

Polymorphisms in the autosomal genes for mitochondrial function TFAM and UCP2 are associated with performance and longevity in dairy cows.

The autosomal genes mitochondrial transcription factor A (TFAM) and uncoupling protein 2 (UCP2) are both involved in moderating mitochondrial energy production. This study investigated single nucleotide polymorphisms (SNPs) in TFAM and UCP2 and their associations with growth, fertility, milk production and survival in UK dairy cows. Holstein-Friesian heifers (n = 509) were recruited at birth and monitored until they either reached the end of their second lactation or were culled. Weight, height, length and girth were measured at 1, 6 and 15 months of age to assess growth. Fertility records were obtained for both heifers and cows and production traits (milk per day, peak yield and 305-day yield) were recorded in the first and second lactation. Mixed model and survival analyses revealed that TFAM3 GG homozygotes, representing 49% of the population, were larger than the AG heterozygotes throughout the growing period, had worse fertility, produced less milk in both lactations and were more likely to be culled. TFAM3 AA homozygotes (7% of population) were generally smaller as heifers, had slightly worse fertility and also produced less milk. This suggests a clear advantage for maximizing the heterozygotic population for this SNP. Furthermore, the results for milk per day suggest an overdominant effect, as both homozygotes of TFAM3 had significantly lower yields than the heterozygote. For UCP2, the minority CG heterozygotes (6% of population) were larger as heifers, had a reduced age at first conception and a delayed return to cyclicity after calving, when compared against the majority (94%) GG homozygotes.

Association between Neospora caninum seropositivity and perinatal mortality in dairy heifers at first calving.

Associations between Neospora caninum infection and the reproductive performance of dairy heifers in their first and second pregnancy on 18 UK farms were examined. Six-month-old heifer calves were tested for N caninum-specific antibodies with a commercial ELISA, and were then monitored until their second calving. Random-effects regression analyses were performed on the data, using serological status as the explanatory variable. Of 460 heifers tested, 7.2 per cent were seropositive. Seropositive heifers were more likely to suffer gestational loss (late embryonic/early fetal loss and abortion) than seronegative heifers during their first (odds ratio [OR] 5.3, P<0.01) and second (OR 6.0, P<0.001) pregnancy. Seropositive heifers were also four times more likely to experience perinatal mortality (calf born dead or dying within 24 hours of parturition) at first (OR 3.9, P<0.01) and second (OR 4.5, P<0.1) calving. No significant association between seropositivity and the fertility parameters (age at first breeding and calving, days from calving to first service and conception, services per conception and calving interval) or conception failure was found. The results suggest that N caninum infection before pregnancy is a significant contributing factor to gestational loss and perinatal death, and thus serological screening of potential replacement heifers is recommended.

Polymorphisms in the bovine leptin gene associated with perinatal mortality in Holstein-Friesian heifers.

Leptin is an important regulator of fetal and placental growth. This study evaluated the association of single nucleotide polymorphisms (SNP) in the leptin gene with perinatal mortality (stillbirths and mortality within 24h of parturition) in 385 Holstein-Friesian heifers on 18 dairy farms in the United Kingdom. The 3 SNP evaluated were exon 2FB, UASMS1, and UASMS2. The mean age at first calving was 27.0+/-0.2 mo. Associations between each SNP and perinatal mortality (calf alive or dead) were tested using a generalized linear model that included herd-year-season, calf sex, age at first calving, and age and pedigree of the dam. The overall level of perinatal mortality in the population was 16.9%, with significant allelic substitution effects for exon 2FB and UASMS1. These 2 SNP were in close linkage disequilibrium with each other (r(2)=0.98) but not with UASMS2 (r(2)=0.10). For exon 2FB, perinatal mortality was similar between heifers carrying the CT and TT alleles (20%), but was higher than in heifers carrying the CC allele (11%). For UASMS1, mortality was 21% with the CC and CT alleles but only 10% with the TT allele. No associations of perinatal mortality with SNP were found in the UASMS2 data set, possibly influenced by the low frequency (2%) of the TT genotype. No significant effects of herd-year-season, age at first calving, or calf sex were found. In conclusion, polymorphisms in the leptin gene were associated with 2-fold differences in perinatal mortality in dairy heifers.

Effect of growth and development during the rearing period on the subsequent fertility of nulliparous Holstein-Friesian heifers.

This study investigated the effect of growth parameters and metabolic indices during the rearing period on the fertility of nulliparous Holstein-Friesian heifers managed on 17 UK dairy farms. Growth parameters (body weight [BW], heart girth, height, and crown-rump length) and metabolic indices (insulin-like growth factor-I [IGF-I], insulin, glucose, and urea) were measured at approximately 30, 180, and 450 d of age. Fertility data collected included age at first breeding (AFB), number of services per conception, pregnancy rate to first artificial insemination (AI), and age at first calving (AFC). Of the heifers initially bred (n=428), 4% failed to conceive. The mean pregnancy rate to first AI for heifers that conceived and calved without suffering reproductive loss (n=392) was 67%, and 6% required >2 inseminations. The mean AFB and AFC was 473+/-5 d (range, 357 to 936 d) and 791+/-6 d (range, 636 to 1529 d), respectively. Increased BW, girth, and IGF-I concentration (at 30, 180, and 450 d) and increased skeletal growth (at 180 and 450 d) was associated with a reduced AFB and AFC (P<0.05 to 0.001). Heifers calving at <775 d had a mean BW gain of 0.82+/-0.01kg from 30 to 180 d. Increased glucose concentration at 180 d was associated with a reduced AFB (P<0.01), but no associations were found between insulin and urea concentrations and any of the fertility traits recorded (P>0.1). Suboptimal growth associated with an increased AFC could be alleviated by improved monitoring of replacement heifers during the rearing period.

Effect of management factors and blood metabolites during the rearing period on growth in dairy heifers on UK farms.

Growth rates during rearing affect the age and body weight (BW) of replacement heifers at first calving. Diet and disease can affect growth via altered metabolic hormone concentrations, but are difficult to monitor accurately on commercial farms. This study investigated the effect of management and metabolic indices (IGF-I, insulin, glucose and urea) on the growth rate of 509 Holstein-Friesian heifers on 19 UK dairy farms. Size (BW, heart girth, height and crown-rump length) was measured at approximately 1, 6 and 15 months. The mean daily weight gain up to 6 months for all calves was 0.77kg/day, with extreme variability both between cohorts of calves (range 0.49-1.02kg/day) and between individual calves within farms (range 0.45-1.13kg/day). Growth was enhanced by supplemental colostrum, by milk replacer as opposed to whole milk and by ad libitum milk feeding and was reduced by gradual weaning and dehorning after weaning. Larger group size slowed growth before weaning (>6 calves) but increased it post-weaning (>20 calves). These management differences were reflected in altered plasma IGF-I concentrations, which were positively associated with growth throughout the rearing period. Larger calves at 1 month had a greater weight gain up to 6 months. Sub-optimum growth of some heifers within each cohort was established at an early age and resulted in animals reaching the start of breeding at an inadequate size (BW range 209-498kg at 15 months). This could be alleviated by altered management strategies and improved monitoring of growing heifers.

Mortality in Holstein-Friesian calves and replacement heifers, in relation to body weight and IGF-I concentration, on 19 farms in England.

The incidence of mortality and culling in Holstein-Friesian heifers from birth through first calving was determined on 19 dairy farms selected from across southern England. The outcome of 1097 calvings was determined. Size (BW, heart girth, crown-rump length and height at withers) and insulin-like growth factor-I concentration of live heifer calves were measured at a mean age of 26 ± 0.7 days (n = 506). Associations between the heifer-level variables and mortality were determined using clustered binary logistic regression. Perinatal mortality (stillbirths and mortality within the first 24 h of birth) of male and female calves was 7.9%. This figure was significantly higher in cases where calving assistance was required (19.1% v. 5.6%, P < 0.001) and in twin births (18.5% v. 7.0%, P < 0.05), and was lower in pluriparous v. primiparous dams (5.6% v. 12.1%, P < 0.01). On average, 6.8% of heifers died or were culled between 1 day and 6 months of age. Low BW at 1 month was associated with reduced subsequent survival up to 6 months. Between 6 months and first calving, a further 7.7% of heifers either died (42%) or were culled (58%); accidents and infectious disease accounted for the majority of calf deaths between 6 and 15 months, whereas infertility (16/450 animals served, 3.5%) was the main reason for culling following the start of the first breeding period. In total, 11 heifers (2.2%) were culled as freemartins; eight at birth and three around service. Overall, 14.5% of liveborn potential replacement heifers died or were culled before first calving.

Factors influencing heifer survival and fertility on commercial dairy farms.

The average dairy cow survives only three lactations, reducing the availability of replacement heifers. Prenatal losses occur due to early embryonic mortality (about 40%), later embryo loss (up to 20% in high-yielding herds) or abortion (about 5%). A recent survey of 19 UK herds showed that 7.9% of calves were born dead and 3.4% died within 1 month. During the rearing phase, 6.7% of animals were lost before reaching first service at 15 months due to disease or accident and another 2.3% failed to conceive. Many potential replacements therefore never enter the milking herd. This severely limits opportunities for on-farm selection of breeding cows in addition to presenting a welfare issue and causing economic loss. The most profitable animals once lactation is reached combine good milk production with a regular calving pattern. Some aspects of performance are related to age at first calving (AFC), which in turn is influenced by heifer growth rates. Poorly growing animals required more services to conceive, calved later and subsequently performed badly. Optimum fertility and maximum yield in the first lactation were associated with an AFC of 24 to 25 months. However, heifers calving at 22 to 23 months performed best in terms of total milk yield and survival over the first 5 years, partly because good heifer fertility was associated with better fertility later. We have investigated some possible juvenile predictors of future performance. Low-birth-weight calves were more likely to come from either primiparous mothers or older dams (3+ lactations) with higher peak milk yields, suggesting that the uterine environment may limit prenatal calf growth due to competition for nutrients with maternal growth or milk production. Linear trait classification scores for frame size show genetic correlations with longevity. The skeletal measures of height and crown rump length in 1-month-old calves was correlated to subsequent stature, and frame size was correlated to weight at 15 months. It may thus be possible to predict performance from simple size measurements as juveniles. Neither endogenous nor stimulated growth hormone (GH) release in 6-month-old calves were related to milk yield in the first three lactations, but size of a stimulated GH peak was positively related to milk energy values in the first lactation. Cows with delayed ovulation (>45 days) in the first lactation had a higher GH pulse amplitude and lower IGF-I as a juvenile. Cows that partition excess energy into milk in their first lactation may suffer reduced longevity.

Serotype 1 and 2 bovine noroviruses are endemic in cattle in the United kingdom and Germany.

The genomically and antigenically distinct bovine noroviruses Bo/Jena/1980/DE and Bo/Newbury2/1976/UK have been associated with calf diarrhea. In the present seroprevalence study, both were found to be endemic in cattle from Germany and the United Kingdom, a finding in contrast to previous virus prevalence studies. They were less common than group A rotaviruses, particularly in calves, suggesting a different epidemiology.