T.M. Sullivan

Nutrient intake in the bovine during early and mid-gestation causes sex-specific changes in progeny plasma IGF-I, liveweight, height and carcass traits

Fetal and postnatal growth are mediated by insulin-like growth factors (IGFs) and their binding proteins (IGFBPs). Maternal nutrient intake during gestation can program the postnatal IGF-axis. This may have significant economic implications for beef cattle production. We investigated the effect of high (H=240%) and low (L=70%) levels of recommended daily crude protein (CP) intake for heifers during the first and second trimesters of gestation in a two-by-two factorial design on progeny (n=68) plasma IGF-I, IGF-II, total IGFBP (tIGFBP), postnatal growth and carcass traits. Calves were heavier at birth following high CP diets during the second trimester (P=0.03) and this persisted to 29d. Plasma IGF-I concentrations of males were greater for HL compared to LL (P<0.01) and HH (P>0.04) from 29 to 657d, and for LH compared to LL from 29 until 379d (P=0.02). Exposure to low CP diets during the first trimester resulted in heavier males from 191d onwards (P=0.04) but a tendency for lighter females from 552d onwards (P=0.07) that had lighter carcass weights (P=0.04). Longissimus dorsi cross-sectional area of all carcasses was greater following exposure to low CP diets during the second trimester (P=0.04). Heifer nutrient intake during the first and second trimesters causes persistent and sex-specific programming of progeny plasma IGF-I, postnatal liveweight and carcass weight. Refining heifer nutritional programs during early gestation may optimize production objectives in progeny.

Heifer nutrition during early- and mid-pregnancy alters fetal growth trajectory and birth weight.

Maternal nutrient intake during gestation can alter fetal growth. Whilst this has been studied extensively in the sheep, less is known about effects in the bovine. Composite-breed beef heifers were allocated to either a high (H/-=76 MJ metabolisable energy (ME) and 1.4 kg crude protein (CP)) or low (L/-=62 MJ ME and 0.4 kg CP daily) nutritional treatment at artificial insemination. Half of each nutritional group changed to an opposite nutritional group at the end of the first trimester (-/H=82 MJ ME and 1.4 kg CP; -/L=62 MJ ME and 0.4 kg CP daily), resulting in 4 treatment groups: HH (n=16); HL (n=19); LH (n=17); LL (n=19). During the third trimester all heifers were fed the same diets. Fetuses were measured at 4-weekly intervals beginning at day 39 of gestation. Calves were also measured at birth for physical body variables. Low maternal nutrient intake was associated with decreased crown-rump length at day 39 (P<0.01) and increased thoracic diameter at day 95 (P<0.01). Umbilical cord diameter was reduced in L/- fetuses in the first trimester (P<0.05) but was greater in -/L fetuses in the second trimester compared to their respective H counterparts (P<0.05). Calf birth weight was decreased in association with -/L maternal diets (P<0.05). In conclusion, fetal development of cattle may be affected by maternal nutrition as early as day 39 of gestation. This may be followed by either compensatory fetal growth, or alternatively, preferential fetal tissue growth that is dependant upon maternal nutrition. Clearly, calf birth weight may be altered by maternal nutrition during mid-gestation.

Protein intake during gestation affects postnatal bovine skeletal muscle growth and relative expression of IGF1, IGF1R, IGF2 and IGF2R

Expression of insulin-like growth factor (IGF)1 and IGF2 and their receptor (IGF1R and IGF2R) mRNA in fetal skeletal muscle are changed by variations in maternal nutrient intake. The persistence of these effects into postnatal life and their association with phenotype in beef cattle is unknown. Here we report that the cross-sectional areas of longissimus dorsi and semitendinosus (ST) muscles were greater for mature male progeny born to heifers fed low protein diets (70% vs. 240% of recommended) during the first trimester. In ST, this was accompanied by greater IGF1, IGF2 and IGF2R mRNA at 680 d. Females exposed to low protein diets during the first trimester had decreased IGF2 mRNA in ST at 680 d, however this did not result in an effect to phenotype. Exposure to low protein diets during the second trimester increased IGF1R mRNA in ST of all progeny at 680 d. Changes to expression of IGF genes in progeny skeletal muscle resulting from variations to maternal protein intake during gestation may have permanent and sex-specific effect on postnatal skeletal muscle growth.

Dietary protein during gestation affects placental development in heifers

The influence of nutritional protein during the first and second trimesters of pregnancy on placental measures at term and caruncle numbers in the uteri of adult offspring was determined in composite beef heifers. At artificial insemination (AI), heifers were divided by weight and composite genotype into four dietary treatment groups, identified by the level of protein components fed during the first and second trimesters: high/high (HH), high/low (HL), low/high (LH), low/low (LL). Expelled placentas were collected and weighed, and cotyledons were dissected, counted, weighed, and measured. Uteri from mature female offspring were dissected at slaughter and caruncles counted. The number of cotyledons in the expelled placenta was increased by high dietary protein in the second trimester (P=0.02) and varied with genotype (P=0.03). Placental weight was influenced by maternal undernutrition during early gestation dependent on dam genotype (P=0.001). Placental efficiency, as determined by calf weight:placental weight, increased with dam age (P=0.03). Calf birth weight was closely associated with placental weight (P=0.002) and cotyledonary weight (P=0.001) and surface area (P=0.04), but not with the number of cotyledons. Leptin concentrations during early (R=-0.29) and late gestation (R=-0.25) correlated with placental weight, and Insulin-like growth factor binding proteins throughout gestation correlated with the number of cotyledons (R=-0.28 to-0.33). The number of uterine caruncles in the nonpregnant adult offspring did not correlate with the dams genotype, nutrition treatment, or cotyledon number in the expelled placenta.

Heifer nutrient intake during early- and mid-gestation programs adult offspring adiposity and mRNA expression of growth-related genes in adipose depots

Changes in maternal nutrient intake during gestation alter IGF receptor abundance and leptin (LEP) mRNA expression in fetal adipose tissue. It is not known whether such changes persist into adult life and whether they are associated with an effect on phenotype. We investigated the effect of high (240%) and low (70%) levels of recommended daily crude protein intake for beef heifers during the first and second trimesters of gestation on singleton progeny (n=68): subcutaneous (SC) adipose tissue depth at rump (P8) and rib (RF) sites from 65 until 657 days of age; plasma leptin concentrations from birth until 657 days and expression of IGF1 and IGF2, their receptors (IGF1R and IGF2R) and LEP mRNA in perirenal (PR), omental (OM) and SC adipose tissue at 680 days of age. High-protein diets during the first trimester increased LEP and IGF1 mRNA in PR of males and females, respectively, compared with low-protein diets, and decreased IGF1R mRNA in SC of all progeny but increased RF depth of males between 552 and 657 days. High-protein diets compared with low-protein diets during the second trimester increased IGF1R mRNA in PR and OM of all progeny; LEP mRNA in PR of males; and IGF2 and IGF2R mRNA in OM of all progeny. Conversely, LEP mRNA in OM and IGF2 mRNA in PR of all progeny were decreased following exposure to high- compared with low-protein diets during the second trimester. Heifer diet during gestation has permanent sex- and depot-specific effects on the expression of adipogenic and adipocytokine genes and offspring adiposity.

Dietary manipulation of Bos indicus × heifers during gestation affects the prepubertal reproductive development of their bull calves

We determined the influence of nutritional protein and energy during the first and second trimesters of pregnancy in composite beef heifers on prepubertal reproductive parameters of their male calves. At artificial insemination, heifers were stratified by weight within each composite genotype into 4 treatment groups: High/High (HH=250% crude protein (CP) and 243% metabolisable energy (ME) for first and 229% CP and 228% ME for second trimester of pregnancy), High/Low (HL=250% CP and 243% ME for first trimester and 63% CP and 176% ME for second trimester) Low/High (LowH=75% CP and 199% ME for first trimester and 229% CP and 228% ME for second trimester) or Low/Low (LL=75% CP and 199% ME for first trimester and 63% CP and 176% ME for second trimester). At 5 months of age, male calves were castrated, and gonadotrophins and testosterone (pre- and post-GnRH challenge), IGF-I and leptin were measured along with testicular parameters. Lower maternal dietary protein and energy levels during gestation were associated with increased prepubertal FSH concentrations (P=0.03) and paired testicular volume (P=0.04) in male offspring. Serum LH (P<0.001) and FSH concentrations (P=0.04) were correlated with seminiferous tubule diameter. Testosterone concentrations were positively correlated with testis measures: paired testicular weight (P<0.001), volume (P=0.03) and seminiferous tubule diameter (P<0.001). Although leptin concentrations were associated with prepubertal age (P=0.04) and body weight (P=0.006), they were not associated with any of the measures of reproductive development, but insulin-like growth factor-I was associated with prepubertal FSH (P=0.005). In conclusion, prepubertal reproductive development of bulls may be affected by prenatal nutrition during early and mid gestation.

Dystocia in 3-year-old beef heifers; Relationship to maternal nutrient intake during early- and mid-gestation, pelvic area and hormonal indicators of placental function

The influence of nutrition during the first and second trimesters of gestation on the occurrence of dystocia was investigated in 3-year-old composite-breed beef heifers. Heifers were allocated according to stratification by weight and genotype to either a high (H/-=76 MJ metabolisable energy (ME) and 1.4 kg crude protein (CP)), or low (L/-=62 MJ ME and 0.4 kg CP daily) nutritional treatment on the day of artificial insemination (day 0) to the same Senepol bull. Half of each nutritional group changed to an opposite nutritional group on day 93 of gestation (-/H=82 MJ ME and 1.4 kg CP; -/L=63 MJ ME and 0.4 kg CP daily), resulting in four treatment groups: HH (n=16); HL (n=19); LH (n=17); LL (n=19). From 180 days until calving all heifers were fed the same diets. Pelvic area measures were taken at heifer selection (-72 days) and at 117 days. Maternal circulating concentrations of estrone sulphate (ES), bovine placental lactogen (bPL), bovine pregnancy associated glycoprotein and progesterone were monitored throughout gestation. Heifers were observed continuously over the calving period and delivery type classified as being either eutocic or dystocic. The occurrence of dystocia was 14.1%. Increased calf birth weight increased the odds of occurrence of dystocia (odds ratio (OR)=1.40; 95% confidence interval (95% CI) 1.12-1.76; P<0.01). High diets in the second trimester were associated with heavier calves at birth (P=0.01). The mean pelvic area of eutocic heifers on -72 d, tended to be greater compared to that of dystocic heifers (P=0.08) such that a 1-cm(2) difference in pelvic area tended to decrease the risk of dystocia (OR=0.97; 95% CI 0.93-1.01; P=0.09). Longer gestation length was associated with an increased risk of dystocia (P=0.03). ES (P=0.04) and bPL (P=0.09) at calving were positively associated with the risk of dystocia. In conclusion, the current study demonstrates (a) that pelvic area measurement at selection in 3-year-old Bos indicusxBos taurus heifers may be useful for identifying heifers at an increased risk of dystocia and (b) increased ES and bPL concentrations at calving are associated with increased risk of dystocia. Pelvic area measurements obtained prior to conception remain valid in their assessment of the relationship between pelvic area and likelihood of dystocia occurring in the event of changing maternal nutrient intake during gestation. This is an important finding given maternal diets high in protein and energy during the second trimester of gestation increased calf birth weight and calf birth weight was associated with an increase in the occurrence of dystocia in heifers calving as 3-year olds.

Influences of diet during gestation on potential postpartum reproductive performance and milk production of beef heifers.

The influences of nutritional protein and energy during early and mid pregnancy on milk production and postpartum reproductive parameters were determined in 70 beef heifers of two composite breeds (Bos indicus X Bos taurus). At artificial insemination (AI), heifers were divided into four dietary treatment groups identified by the level of protein, and to a lesser extent energy, fed during the first and second trimesters: high/high (HH), high/low (HL), low/high (LH), and low/low (LL). Milk production was lower in the heifers receiving high treatment in first trimester than that in heifers receiving the low treatment (P=0.01). Milk production was negatively associated with dam body condition score (BCS; P=0.01), nonesterified fatty acids (P=0.001), and leptin (P=0.02) and positively associated with urea (P<0.001) concentrations during lactation. Increased dietary protein in the first trimester increased or decreased concentrations of colostral protein dependent upon genotype (P=0.03). Colostral protein was positively associated with bovine pregnancy associated glycoprotein from late gestation (P=0.007). Milk fat was negatively associated with BCS (P=0.007) and influenced by genotype (P=0.003). Dietary treatment did not affect the postpartum reproductive performance of beef heifers. Gestation length (P<0.001) and the postpartum interval to first estrus (PPI; P=0.02) were positively associated with calf size. Placental size was negatively associated with placental expulsion time (P<0.01). Prepartum BCS of the heifers was negatively associated with PPI (P=0.01). Overall, high levels of nutrition during early gestation are detrimental to milk production in beef heifers.

Fibrillins and latent TGFβ binding proteins in bovine ovaries of offspring following high or low protein diets during pregnancy of dams

The microsatellite D19S884, located in intron 55 of fibrillin-3 (FBN3) gene, associates with polycystic ovary syndrome (PCOS) in familial studies. The family of fibrillin proteins (FBN1-3), which includes latent TGF-beta binding proteins (LTBP-1 to -4), are extracellular matrix proteins. We localized and examined the expression of these proteins in the adult bovine ovaries (n=7-10 per group, average age 681 days) born to mothers fed high (13% protein per total dry weight) or a low protein diet (5%) in each of the first and second trimesters of pregnancy (n=4 groups). FBN1 and LTBP-1 and -2 were the major members expressed in the mature ovary. Each protein had a unique localization pattern but all were associated with stromal tissue including the tunica albuginea (FBN1 and LTBP-2 near surface, and FBN1 and LTBP-1 deeper in the tunica), cortical stroma (FBN1 and LTBP-1) and follicular thecal layers (FBN1 in theca interna, LTBP-1 in the inner regions of the theca externa, and LTBP-2 in the outer regions of the theca externa). No significant (P>0.05) effects of maternal diet were observed on either the localization or the levels of mRNA of any of these proteins in the tunica. Expression levels of all three FBNs were positively correlated with each other, and FBN1 and 2 were positively correlated with LTBP-2, suggesting some level of co-ordinate regulation. This is the first study to investigate the expression and localization of these genes affecting TGFbeta bioavailability in the ovary.