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

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Theriogenology 72 (2009) 408–416 www.theriojournal.com

Effect of growth and development during the rearing period on the subsequent fertility of nulliparous Holstein-Friesian heifers J.S. Brickell *, N. Bourne, M.M. McGowan 1, D.C. Wathes Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, Herts, AL9 7TA, United Kingdom Received 12 December 2008; received in revised form 11 March 2009; accepted 24 March 2009

Abstract 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  0.01 kg 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. # 2009 Elsevier Inc. All rights reserved. Keywords: Body weight; Fertility; Growth; IGF-I; Maiden heifer

1. Introduction A short herd life span is a significant economic loss to the dairy industry, with infertility being a major cause. Failure to conceive is the most common reason for the premature culling of dairy cows in the United Kingdom, accounting for approximately one third of disposals [1,2]. Fertility in maiden heifers is often superior to that of

* Corresponding author. Tel.: +44 1707 666553; fax: +44 1707 652090. E-mail address: [email protected] (J.S. Brickell). 1 Present address: School of Veterinary Science, The University of Queensland, St. Lucia, QLD 4072, Australia. 0093-691X/$ – see front matter # 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.theriogenology.2009.03.015

lactating cows, but a number of potential replacement heifers may never reach first calving because they either fail to conceive at all or are significantly delayed in conceiving [3]. The ability of replacement heifers to reach puberty, cycle normally, conceive at the desired time, sustain the pregnancy to term, calve normally, and subsequently commence their first lactation is a critical component of dairy enterprises [4]. Ovarian function is controlled primarily by an integrated gonadotropin-releasing hormone–gonadotropin–ovarian axis, with metabolites such as glucose and metabolic hormones including growth hormone (GH), insulin, and insulin-like growth factors (IGFs) also playing an important role [5]. The onset of puberty

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represents the maturation of the hypothalamic–pituitary– ovarian axis resulting in the first preovulatory surge of luteinizing hormone (LH) and thus ovulation [6]. An association between body weight (BW) gain and the timing of puberty has been reported in many species; high energy and protein intake resulting in increased growth is associated with the earlier attainment of puberty in calves [7–9]. Concentrations of IGF-I are elevated at puberty [7,10]; IGF-I may serve as a metabolic signal of nutritional status to the hypothalamus and act on the anterior pituitary to stimulate gonadotropin secretion and thus the onset of puberty [4,11]. Age at first calving (AFC) is an important factor determining the length of the nonproductive period as well as affecting subsequent fertility and productivity [12,13]. It is widely accepted that heifers should calve for the first time at approximately 2 yr, but most countries report a mean AFC of greater than 730 d [14– 16]. Gestation length is fixed; therefore, AFC depends upon the age at the commencement of breeding. The decision on when to start breeding is a management one, but variability in growth rates within groups of animals can lead to a large spread in the age at which heifers are bred for the first time [12]. The reproductive performance of heifers at this stage will then affect the age at conception and hence the AFC. A number of factors have been reported to influence the fertility of heifers, including heat detection, the inseminator, the service sire, nutrition, and health problems [17,18]. Few studies have investigated the effect of growth parameters and peripheral concentrations of hormonal regulators of metabolism and growth on the fertility of heifers in commercial dairy herds; much of the literature available is derived from research farms. Furthermore, in many dairy record-keeping systems, heifers are not recorded as herd members until after first calving, thus maiden heifer fertility is often poorly defined. The dairy industry would benefit considerably from being able to identify at a young age animals at risk of failing to conceive. The first objective of this study was to characterize Holstein-Friesian heifer fertility on UK dairy farms. The second was to determine the relationship between growth parameters and metabolic indices measured during the rearing period with maiden heifer fertility. 2. Materials and methods 2.1. Animals and farms All procedures were performed under the UK Animals (Scientific Procedures) Act, 1986. Sixteen

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commercial dairy farms and one primarily research farm across southern England keeping HolsteinFriesian cows (median herd size, 228; range, 105 to 540 adult cows) were recruited between August 2003 and October 2004. These farms provided a range of management practices representative of those commonly encountered on UK dairy farms. All farms selected had a target AFC for maiden heifers of approximately 730 d. No aspect of herd management was changed for the duration of the study period. The recruitment period for each individual farm generally lasted 1 to 4 mo during the main calving season, with the aim of obtaining a cohort of approximately 25 consecutively born live heifer calves per farm. The research farm provided three groups of calves (each on a different milk feeding regime); this gave a total of 19 cohorts of calves recruited to the study, with a mean cohort size of 24 (range, 15 to 30 calves per cohort). After weaning at approximately 4 to 12 wk of age, calves were offered diets of concentrate and forage. Full details on diet composition are not included due to the nature of this on-farm study based on 17 farms, each of which used a different range of ingredients. Briefly, concentrate (crude protein range, 16% to 18%) was fed at 1.5 to 4 kg/calf per day, and forage (such as barley straw, grass hay, grass silage, and maize silage) was generally offered to calves ad libitum, from weaning until approximately 6 mo of age. Calves were turned out to pasture at a mean age of 261 d (range, 100 to 431 d).

2.2. Growth parameters All heifer calves recruited (n = 457) were assessed at approximately 30 d of age (29  0.9 d, n = 457) (mean  S.E.M), 180 d (185  0.8 d, n = 440), and 450 d (447  3 d, n = 428; approximately 1 to 2 wk prior to first breeding) to measure growth and metabolic parameters. Body weight was measured using a portable weigh platform with Tru-Test loadbars connected to an Eziweigh 2 indicator (Ritchey Tagg, Ripon, North Yorkshire, UK). Weigh equipment was calibrated before each sampling session. Heart girth (girth) and crown-rump length (CRL) were measured using a tape measure, and height at withers (HT) was measured using a height stick. The 30-d measurement was subtracted from the equivalent 180-d measurement and divided by the number of days between the two time points to give the average daily change (ADC) in each growth parameter (BW, girth, HT, and CRL) from 30 to 180 d. Similarly, the 180-d measurement was subtracted from the equivalent 450-d measurement and divided by

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Table 1 Definition of fertility parameters. Fertility trait

Definition

Age at first breeding (AFB) Number of services per conception (S/C) Pregnancy rate to first AI

Number of days from birth to the day of first AI, or first contact with a bull, or first embryo transfer Number of inseminations before a positive pregnancy diagnosis, or a calving event

Age at first calving (AFC)

Number of animals pregnant to first AI divided by the total number of first inseminations given to animals that conceived Number of days from birth to day of first calving

the number of days between the two time points to give the ADC in each parameter from 180 to 450 d. 2.3. Blood sampling and assay methods Blood samples were collected from the jugular vein (at 30 and 180 d) and from the coccygeal vein or artery (at 450 d). Samples for the determination of plasma IGF-I, insulin, and urea concentrations were taken into 10-mL heparinized tubes, and 5-mL tubes containing fluoride oxalate were used for the determination of plasma glucose (both BD Vacutainer systems; Plymouth, Devon, UK). The blood samples were transported to the laboratory on ice where they were centrifuged at 1500  g at 4 8C and aliquots of the plasma stored at–20 8C. Insulin-like growth factor-I was measured in all samples; insulin, glucose, and urea were only measured in the 180- and 450-d samples once heifers had been weaned. As it was not possible to be certain of the interval between milk feeding and blood sampling in this on-farm trial, only IGF-I concentrations were considered as reliable at 30 d of age; feeding of concentrate and hay in 12-wk-old animals does not cause a significant change in plasma concentrations of insulin and glucose [19]. Insulin-like growth factor-I concentration was measured by human OCTEIA IGF-I plate kits (Immunodiagnostic Systems Ltd, Boldon, Tyne and Wear, UK), which are two-site immunoenzymometric assays as described previously [20]. Assay sensitivity was 1.9 ng/mL, and inter- and intra-assay coefficients of variation were 4.1% and 1.7%, respectively. Plasma insulin concentration was determined by a double antibody radioimmunoassay (RIA) [21], using bovine insulin standard (Sigma, Gillingham, Dorset, UK), bovine anti-insulin primary antibody (Sigma), and antiguinea pig IgG for separation (Sac-Cel, IDS, Boldon, Tyne and Wear, UK). Assay sensitivity was 0.05 ng/mL, and inter- and intra-assay coefficients of variation were 6.7% and 6.6%, respectively. Plasma glucose and urea concentrations were measured by the Dairy Herd Health and Productivity

Service (University of Edinburgh, UK) with an OPerationally Enhanced Random Access (OPERA) analyzer (Bayer plc, Newbury, Berks, UK) using kinetic enzymatic kits (urea: Randox Laboratories Ltd., Crumlin, Co. Antrim, UK; glucose: Bayer plc) [22]. Quality assurance was provided by including internal quality controls during each assay. 2.4. Fertility parameters For all heifers (n = 428) that reached the start of the first breeding period, service details were collected from on-farm records. Age at first breeding (AFB), method of insemination (artificial insemination [AI], natural service, or embryo transfer), number of services per conception (S/C), pregnancy rate to first AI, and AFC were recorded to create four outcome traits to define reproductive performance (Table 1). For the naturally mated heifers, the duration of the breeding period was recorded. A successful insemination, resulting in a conception, was validated by a pregnancy diagnosis (if performed) or by a subsequent calving date and gestation length of 282  14 d. The outcome (conceived or failed to conceive [FTC]) of each insemination was recorded. For FTC heifers, the total number of services given to each animal, and/or the number of times mated to a bull, before a decision was made to cull them was recorded. 2.5. Statistical analysis Associations between each fertility trait and the growth and metabolic parameters were determined using clustered regression analysis in Stata 9.2 (StataCorp, College Station, Texas, USA). The twolevel model included farm as a random effect, with the heifers (level 1 units) nested within farms (level 2 units). The random effects were represented by two sources of variation in the data: (i) the variation between the heifers within each farm, and (ii) the variation between farms. Each growth and metabolic parameter (the explanatory variable) was included one at a time as a

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fixed effect. Because of the variability in the exact age of heifers at 30, 180, and 450 d, actual age of the heifer at sample/measurement collection was initially included in each model as a fixed effect but was dropped if P > 0.1. The coefficient value represented the estimated mean change in one fertility parameter for a unit change in each explanatory variable after adjusting for the other variables in the equation. A two-level binary logistic random effects model that included farm as a random effect, with the outcome coded as 1 (FTC) or 0 (conceived), was used to investigate associations between FTC and each growth and metabolic parameter. Each growth and metabolic parameter was included one at a time as a fixed effect, with the exact age of heifers at the time of sample/ measurement collection included initially as a fixed effect. The exponential of each logistic coefficient in the model was the odds ratio (OR), usually approximated by the estimated relative risk of FTC for a unit increase in the explanatory variable. The final P values and 95% confidence intervals reported for the estimated OR were based on Wald’s test. Heifers were grouped retrospectively based on their actual AFC: <775 d and >775 d. This grouping strategy was based on the spread in the AFC observed in this study (Fig. 1b) and because calving at 700 to 750 d is usually considered economically optimum [12,13]. Body weight and IGF-I concentration at 30, 180, and 450 d and BW gain from 30 to 180 d and 180 to 450 d were compared between these two groups using independent samples t-test in Statistical Package for the Social Sciences (SPSS version 16.0; SPSS Inc., Chicago, IL, USA). 3. Results 3.1. Survival Of the 457 heifers recruited, 6% (n = 29 of 457) failed to reach the start of the first breeding period: 23 died and 6 were culled. Eleven heifers suffered late embryonic–early fetal mortality after a positive pregnancy diagnosis and were subsequently served again prior to first calving (mean AFC, 978  44 d), and six heifers aborted (days pregnant, 188 to 257) and entered their first lactation at a mean age of 698  20 d. Nineteen heifers that were served at least once failed to calve for the first time: 16 failed to conceive, 2 were identified by a veterinarian as freemartins, and 1 died shortly after breeding. Of the 392 heifers that conceived and calved without suffering reproductive loss, 3% (n = 13) failed to come into full milk production during

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their first lactation: two heifers were culled immediately after first calving, and 11 were subsequently culled at <100 d. 3.2. Reproductive performance The reproductive performance of the 392 heifers that conceived and calved without suffering reproductive loss is summarized in Table 2. Heifers were on average 473  5 d and 791  6 d at first breeding and at calving, respectively (Fig. 1). Median AFC was 759 d, and 28% and 11% of heifers calved before 720 d (24 mo) and after 900 d (30 mo), respectively. Six percent of heifers required >2 inseminations to conceive. The mean pregnancy rate to first AI was 67%, and heifers required on average 1.4  0.1 S/C (range, 1 to 5). These measures showed considerable variation between farms (pregnancy rate to first AI 50% to 89% and S/C 1.1 to 1.8, respectively). This also led to considerable variation in the AFC both between and within farms (Fig. 2). Greater growth during the rearing period was associated with a reduced age at first breeding and at calving. Larger heifers in terms of weight and girth (at 30, 180, and 450 d) and skeletal size (at 180 and 450 d) were on average younger at first breeding and at calving (P < 0.001 to 0.05; Table 3). Calves with a higher weight gain from 30 to 180 d had a lower AFB and AFC; for every 1 kg/d increase, the mean AFB and AFC was reduced by on average 124 and 94 d, respectively (P < 0.001 to 0.01; Table 4). Similarly, for every 1 kg/d increase in weight gain from 180 to 450 d, heifers were on average 158 and 180 d younger at first breeding and at calving, respectively (P < 0.001). Some metabolic indices during the rearing period were also associated with the age at first breeding and at calving (Table 3). Increased IGF-I concentration at 30, 180, and 450 d was associated with a reduced AFB and AFC (P < 0.001 to 0.05), and an increased glucose concentration at 180 d was also associated with a reduced AFB (P < 0.01). Concentrations of insulin and urea (at 180 and 450 d) and glucose (at 450 d) were not Table 2 Reproductive performance of 392 heifers that conceived and calved without suffering reproductive loss. Parameter

Mean  SEM

Range

AFB, d Number of S/C (AI only)a Pregnant to first AI, % (n)a AFC, d

473  5 1.4  0.1 67% (133 of 200) 791  6

357 to 936 1 to 5

a

n = 200 for heifers served by AI only.

636 to 1529

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Fig. 1. Histogram of frequency of (a) AFB and (b) AFC in days for 392 heifers that conceived and calved without suffering reproductive loss.

associated with either AFB or AFC (P > 0.05, data not shown). Collectively, heifers calving at <775 d were heavier (at 30 and 180 d) and had higher IGF-I concentrations (at 30, 180, and 450 d) than those calving at >775 d (P < 0.001; Table 5). Most difference was apparent at 180 d of age; the mean weight and IGF-I concentration of heifers calving at <775 d was 183 kg and 100 ng/mL, respectively, compared with 160 kg and 67 ng/mL, respectively, for heifers calving at a mean age of >775 d (P < 0.001). These differences were associated with a higher average daily weight gain from 30 to 180 d, and 180 to 450 d for heifers calving at <775 d. For example, the ADG in BW from 30 to 180 d was 0.82  0.01 kg/d

(<775 d) compared with 0.67  0.02 kg/d (>775 d) (P < 0.001). Some aspects of calf growth were associated with the number of S/C (Table 3). For example, calves that were longer at 30 d, had a larger girth measurement at 180 d, and that were heavier at 450 d, required on average more S/C (P < 0.05). Growth rate from 30 to 180 d was not significantly associated with the number of S/C, although there was a tendency for increased girth growth to be associated with more S/C (coefficient value 2.3, P = 0.06). Elevated growth (in terms of BW and girth) over the entire rearing period from 30 to 450 d was associated with more S/C (P < 0.01 to 0.05; Table 4). For example, the mean weight gain of heifers that required 1 S/C was 0.81  0.03 kg/d compared Table 3 Coefficient values for size parameters and metabolic indices during the rearing period associated with AFB, AFC, and number of S/C (n = 392). Sample collection Variable 30 d

180 d

450 d Fig. 2. Box and whisker plot showing AFC for 392 heifers summarizing the median, the 25th and 75th percentiles, the minimum and maximum observed values, and the outliers (o) and extreme values (*) for each individual farm. Farms 2 3, and 5 represented the three cohorts of heifers on the one research farm that were fed different preweaning diets.

BW (kg) Girth (cm) CRL (cm) IGF-I (ng/mL) BW (kg) Girth (cm) CRL (cm) HT (cm) IGF-I (ng/mL) Glucose (mmol/L) BW (kg) Girth (cm) CRL (cm) HT (cm) IGF-I (ng/mL)

AFB

AFC

S/C

1.7*** 2.4** 0.3* 0.6*** 2.5*** 1.6*** 3.4*** 0.7*** 24.4** 0.6*** 3.0*** 0.7* 2.7*** 0.5***

0.02* 0.5** 0.4** 2.0*** 0.01* 1.6*** 2.4** 0.8*** 0.5*** 0.004* 2.2*** 2.2* 0.5**

P values: ***P < 0.001, **P < 0.01, *P < 0.05. Non-significant variables have not been included.

J.S. Brickell et al. / Theriogenology 72 (2009) 408–416 Table 4 Coefficient values for growth parameters during the rearing period associated with AFB, AFC, and number of S/C (n = 392). Growth period

Variable

30 to 180 d

BW (kg/d) Girth (cm/d) CRL (cm/d) HT (cm/d) BW (kg/d) Girth (cm/d) BW (kg/d) Girth (cm/d) HT (cm/d)

180 to 450 d 30 to 450 d

AFB

AFC

124*** 370*** 253*** 531*** 158*** 302* 278*** 731*** 646*

S/C

94** 346*** 253*** 490*** 180*** 235*** 648** 908**

1.7** 6.5*

P values: ***P < 0.001, **P < 0.01, *P < 0.05. Non-significant variables have not been included.

with 0.91  0.05 kg/d for heifers that required >2 S/C. No associations between the metabolic indices during the rearing period, or AFB, and the number of S/C were found (P > 0.05, data not shown). 3.3. Growth parameters and metabolic indices associated with failure to conceive A total of 428 heifers were served at least once, of which 4% (n = 16 of 428) were subsequently culled due to infertility. These FTC heifers were bred for the first time at a mean age of 488  22 d (range, 416 to 678 d, n = 16), which was not much different than the AFB for heifers that conceived (473  5 d, n = 392) (P = 0.5). Eight of these FTC animals received a mean of 3.3  0.8 inseminations (range, 1 to 8) over a period of up to 427 d. Six animals were run with a bull for about 4 mo but failed to conceive, while two were mated to a bull after failure to conceive to AI and again failed to conceive. A further two heifers were culled at this stage after being diagnosed by the veterinarian as freemartins; one received two inseminations, and the other was run with a bull.

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No significant differences were found in the growth parameters or metabolic indices during the rearing period between heifers that failed to conceive and those that conceived. Because of the small number of FTC heifers in the analysis, trends of P < 0.1 are reported. Failed-to-conceive heifers tended to have a higher BW and girth measurement at 450 d (391 vs. 368 kg, and 178 vs. 173 cm, respectively, P < 0.1). These differences were associated with a higher ADC from 30 to 450 d in BW (0.81 vs. 0.76 kg/d, P < 0.1) and girth (0.22 vs. 0.20 cm/d, P < 0.05). Heifers that failed to conceive also tended to have lower plasma urea concentrations at 450 d (2.9 vs. 3.8 mmol/L, P < 0.1) but higher glucose concentrations (4.4 vs. 4.2 mmol/L, P < 0.1). 4. Discussion There is a perception within the dairy industry that maiden heifer fertility is not a problem and that difficulties only arise once cows are lactating. However, we found that 6% of heifers required >2 inseminations to conceive, and 11% were significantly delayed in conceiving and calved for the first time after 30 mo of age. This indicates that suboptimal fertility and infertility (4% of heifers failed to conceive at all) are also problems in nonlactating animals. The number of FTC heifers was lower than a previous estimate of 6.5% all on one farm (n = 7 of 107) [20]. Farm policies differ in the length of time animals are bred before a decision is made to cull them, resulting in differences in the culling rate. In this study, heifers that failed to conceive were given on average three inseminations, in agreement with previous observations [23,24], but some farms allowed heifers up to five inseminations before they were culled. The pregnancy rate to first insemination of 67% was similar to previous observations in the UK of both high (64%) and average (71%) genetic merit Holstein

Table 5 Body weight and IGF-I concentration at 30, 180, and 450 d of age according to AFC <775 d (n = 216) and AFC >775 d (n = 176). Variable

Sample collection

AFC <775 d

>775 d

BW, kg

30 d 180 d 450 d 30 d 180 d 450 d 30 to 180 d 180 to 450 d

60  1 183  2 368  2 48.5  2 100.1  2 112.4  2 0.82  0.01 0.80  0.01

53  1 160  3 367  5 34.6  2 67.2  3 98.9  2 0.67  0.02 0.70  0.01

IGF-I, ng/mL

BW growth rate, kg/d

t-test

<0.001 <0.001 NS <0.001 <0.001 <0.001 <0.001 <0.001

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heifers [25], and for U.S. Holstein heifers of 62% [12]. Other studies have, however, reported lower first service conception rates for maiden heifers, for example 47% [26], 53% [27], and 55% [20]. The discrepancy between studies may arise from the animals included in the calculation, for example we only included heifers that conceived and excluded those that subsequently failed to conceive. Furthermore, there was considerable variation in conception rates between individual farms. The mean age of heifers at first breeding was 473 d (16 mo), and the AFC was 791 d (26 mo), which reflects the average number of services required per conception of 1.4. This compares well with previous data of 1.38 for Holstein heifers [28], 1.4 and 1.5 for Holstein heifers of average and high genetic merit respectively [25], and 1.5 for Holstein-Friesian heifers [23]. It is widely accepted that heifers should calve for the first time close to 2 yr of age, but similar to our observation, most countries report a mean AFC >24 mo. For example, 26.4 mo in Ireland [15], 26.9 mo in the United States [16], 27.7 mo in Costa Rica [29], and 28.1 mo in Italy [14]. Furthermore, we excluded animals from the mean AFC figure that suffered reproductive loss and were thus subsequently older at first calving. On commercial farms, decisions regarding the time of first breeding are often based on heifer body size, typically assessed by sight and not by actual weight. Therefore, a delayed AFB may in part be due to poor heifer growth, irrespective of the timing of puberty. In our study, poor growth and low circulating concentrations of IGF-I during the rearing period were the main factors associated with delayed first breeding and first calving. Most differences were apparent at 180 d of age, highlighting the importance of early growth and development. Similarly, we have previously reported that animals failing to conceive at 450 d were lighter at 270 d of age than those that conceived [30]. Insulin-like growth factor-I is a mediator of growth and development, which is strongly influenced by nutrition. Prepubertal IGF-I concentrations are highly correlated with both the growth rate from 30 to 180 d and BW at 180 d [31]. Both BW gain and IGF-I are thought to be important signals for the initiation of puberty [4]. Holstein-Friesian heifers reach puberty at approximately 9 mo of age [32]. Body weight gain has previously been associated with the timing of estrus cyclicity; for example, heifers with accelerated growth were 1.9 mo younger at first standing estrus than those fed to grow at slower rates [33]. Likewise, heifers on accelerated growth regimes (1 vs. 0.7 kg/d) were younger at puberty (10 vs. 11 mo) [8]. To maximize

breeding performance, heifers should have multiple periods of estrus before insemination [8]; heifers bred at later estrous cycles have better fertility than those bred at first estrus [34]. A high glucose concentration at 180 d was also associated with a reduced AFB. Glucose is the main source of energy for ovarian function, with LH secretion also modulated directly by glucose availability [35]. It was not possible to determine the age at the onset of puberty for heifers in this on-farm study. However, the finding that heifers with faster growth rates and higher concentrations of IGF-I and glucose at 180 d were bred earlier supports the important role of body size and these metabolic indices in the regulation of the attainment of puberty. Insulin also serves as a metabolic signal influencing LH release; reduced LH pulse frequency may result in a smaller dominant follicle secreting less estradiol and ovulation failure [36]. High dietary protein intake, resulting in raised circulating concentrations of urea, has previously been reported to reduce the fertility of heifers [37]. We, however, found no significant association between the fertility parameters and concentrations of either insulin or urea during the rearing period. This might in part be due to differences in diets between farms and/or to some variation in the timing of sample collection with respect to the timing of feeding. These sources of variation were impossible to avoid in an on-farm study. In this respect, the use of IGF-I measurement is likely to be more reliable as this does not show short-term variations in concentration after feeding [32]. Larger calves with faster growth rates and higher IGF-I concentrations had a lower AFB and AFC. We also found significant positive relationships between BW and girth increases between 30 and 450 d with the number of S/C. This result indicated that the fastest growing heifers required more S/C, although these heifers presumably reached puberty earlier and were bred earlier and were still younger at first calving than heifers with poor growth rates. In addition, there was a tendency for heifers failing to conceive at all to have higher growth rates during the rearing period with respect to weight and girth. Information is limited regarding the relationship between the growth of animals and conception rate with few significant findings. Cows with a small body size have previously been reported to require fewer S/C than do cows with a large body size [38]. Similarly, the number of S/C was 1.8 and 1.4 for Italian Holstein-Friesian heifers grown at 0.8 and 0.7 kg/d, respectively [39]. Likewise, heifers with accelerated growth rates (1.1 kg/d) needed 2.1

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services compared with 1.5 for heifers grown at conventional rates of 0.8 kg/d, although data were skewed by one heifer in the accelerated regime requiring 8 services [33]. One possible explanation for this discrepancy could be that an increased growth rate, associated with a reduced AFB and more S/C, may indicate physiological immaturity at the time when animals are first bred. Heifers are typically about 60% of their mature BW at the start of the breeding period [40]; at this stage, they are partitioning nutrients into their own growth as well as reproduction. Breeding heifers at a younger age (350 vs. 462 d) has previously been associated with lower conception rates at first service (38% vs. 47%) [41]. We, however, found no significant association between the AFB and the number of S/C, similar to previous findings that reported no effect of heifer age on conception rate [26]. Exposure of a fetus to poor nutrition resulting in a low birth weight is associated with subsequent increases in growth that are thought to cause changes in insulin metabolism [42]. Therefore, it is possible that infertile heifers and those with suboptimal fertility were born with a low BW and subsequently displayed signs of early catch-up growth, causing alterations in their fat distribution, insulin sensitivity, and subsequent reproductive potential. Further work is needed to confirm the role of birth weight and early growth on subsequent fertility. The results do, however, suggest that optimal growth rates to maximize fertility should neither be too fast nor too slow. In conclusion, suboptimal growth during the first 6 mo of life resulted in animals being bred at an older age and calving at >775 d of age. Heifers calving at <775 d had a mean weight gain of 0.8 kg/d during the first 6 mo of life. Such growth rates could be achieved by improved monitoring of growing heifers during the rearing period. This research work has encouraged some farmers on the trial to start weighing their calves routinely with the aim of improving heifer growth during the rearing period. We have also highlighted that 4% of heifers fail to conceive at all, limiting the number of potential herd replacements and so reducing the opportunity for selection. Acknowledgments The authors thank both the farm staff and the veterinarians who contributed to this study. Dr. Z. Cheng assisted with the insulin RIA, and Ms. A. Petrie assisted with the data analysis. The study was funded by the Dairy Co (Cirencester, Gloucestershire, UK) and Defra (London, UK).

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