Shearing during pregnancy--review of a policy to increase birthweight and survival of lambs in New Zealand pastoral farming systems.

Over the past decade, lambing percentages have risen in conjunction with a rise in the percentage of multiple lambs born. Multiple-born lambs are smaller than their singleton counterparts and are particularly susceptible to starvation-exposure. Any technique that can increase the birthweight or thermoregulatory capability, or both, of otherwise lightweight lambs has the potential to substantially increase survival of multiple-born lambs. In the United Kingdom under housed conditions, shearing during pregnancy has been shown to increase both the birthweight and thermoregulatory capability of newborn lambs. However, shearing during pregnancy under pastoral conditions has failed to consistently affect the newborn lamb's thermoregulatory capability. In contrast, under New Zealand's pastoral conditions shearing during pregnancy has been found to increase birthweight, but results have been inconsistent in both magnitude and birth-rank specificity. Increase in feed intake by the dam, types of shearing comb used and changes in gestation length do not explain the variation observed. When studies involving shearing during pregnancy are collated it becomes apparent that there are two criteria that must be met to achieve a birthweight response. Firstly, the dam must have the potential to respond and secondly, the dam must have the means to respond. Any increase in lamb survival through shearing during pregnancy would be predominantly through an increase in birthweight of otherwise lightweight lambs. However, in the few studies conducted to date, an increase in birthweight has not resulted in a statistically significant increase in survival. For an increase in birthweight to have a positive effect on lamb survival, lambs must be otherwise destined to be born within a birthweight range in which survival rate is below optimum (<4.0 kg), and the increase in birthweight observed must move a significant proportion of otherwise lightweight lambs into a higher range of survival rate.

Immunohistochemical detection of myogenic cells in muscles of fetal and neonatal lambs.

Previous studies have implied that myonuclei accumulation in a muscle is more important than myofibre number in the determination of muscle size in fetal/neonatal lambs. However, due to the lack of a reliable marker, the role of myogenic precursor nuclei (satellite cells) in myofibre hypertrophy in late fetal and postnatal life is not well understood. In this study, MyoD was shown to be a useful marker for actively proliferating satellite cells in both fetal and neonatal lambs. MyoD was used to determine whether there were differences in the number of actively proliferating satellite cells between single and twin fetuses/neonates, which may explain at least some of the difference in myofibre size observed near birth. Eighteen single-bearing and 9 twin-bearing Coopworth ewes were randomly assigned to one of three slaughter groups (100, 120 and 140 days of gestation). The remaining ewes were kept on pasture until 20 days postpartum at which time 4 single and 4 twin lambs were sacrificed. Twin fetuses/neonates had lower body weights and muscle weights compared to singles. Lower muscle weights in the twins were associated with smaller myofibre cross-sectional areas and lower total nuclei numbers and myogenic precursor cell numbers per muscle in selected hind-limb muscles. These results indicate that myofibre hypertrophy in late gestation and early postnatal life is related to myogenic precursor cell number which may have important implications for growth potential of the growth-restricted fetus.

The effect of season and monensin sodium on the digestive characteristics of autumn and spring pasture fed to sheep.

The effects of season of growth and monensin treatment on ruminal digestion of fresh-cut autumn and spring pasture were measured in a single group of ruminally fistulated castrated male sheep, housed indoors in metabolism crates. Responses were assessed in terms of ruminal volatile fatty acid molar proportions, ammonia concentration, pH, apparent digestibility of the pasture, and nitrogen balance of the animals. Blood plasma concentrations of insulin, glucose, beta-hydroxybutyrate, urea, and NEFA were also evaluated. Autumn pasture contained significantly lower proportions of water-soluble carbohydrate (P < 0.05), cellulose (P < 0.05), and lignin (P < 0.05) and increased pectin (P < 0.05), hemicellulose (P < 0.05), and crude protein (P < 0.10) concentrations when compared with spring pasture. Voluntary DMI by sheep of autumn pasture was lower (P < 0.01) than that of spring pasture and was significantly (P < 0.05) reduced by monensin treatment. Monensin treatment significantly decreased the ruminal molar proportions of acetic acid (P < 0.10) and butyric acid (P < 0.001) and increased the molar proportions of propionic acid (P < 0.001) and minor VFA (P < 0.01). Nitrogen retention of the sheep was significantly (P < 0.05) reduced by monensin treatment. Plasma glucose levels were increased (P < 0.10) by monensin treatment during the fourth 5-d collection period in both seasons. Chemical analysis suggested that the composition of autumn pasture was different from that of spring pasture and that this was manifested in vivo by increased DMI and digestibility of spring vs autumn pasture. Ruminal fermentation of autumn pasture also had an increased acetate-to-propionate ratio compared with spring pasture. Monensin treatment acted consistently across seasons by increasing the proportion of propionate and decreasing the proportion of acetate in ruminal fluid.

Metabolic responses to mid-pregnancy shearing that are associated with a selective increase in the birth weight of twin lambs.

Previous studies have shown that shearing pregnant ewes at mid- or late-pregnancy is associated with an increase in lamb birth weight. The present study was designed to investigate metabolic responses that may underlie this response. Single- and twin-bearing ewes were either unshorn or shorn at mid-pregnancy (Day 69 of pregnancy; P69), and insulin, glucose and epinephrine challenges were conducted on P109-111 and P132-134. Shearing increased the birth weight of twin lambs by over 1 kg (P < 0.001) without having any effect on singleton birth weight. This response was associated with a 10-20% reduction in the insulin response to a glucose challenge (P < 0.05) without a change in glucose clearance following either glucose or insulin challenges. The lipolytic response to epinephrine challenge increased as pregnancy progressed, but was not associated with the increased birth weight of twin lambs born to shorn ewes. By late pregnancy, a 25% reduction in maternal IGF-I concentration and a two- to threefold increase in maternal IGFBP-1 concentration (P < 0. 05) associated with shearing were observed. The increase in lamb birth weight associated with mid-pregnancy shearing may have been associated with an increase in the non-insulin dependent uptake of glucose by the placental-fetal unit.

Muscle growth, cell number, type and morphometry in single and twin fetal lambs during mid to late gestation.

Muscle growth, myofibre number, type and morphometry were studied in large hindlimb muscles of single and twin fetal lambs during mid to late gestation. Placental insufficiency, evident by lower total placentome weight and number per fetus, resulted in reduced fetal weights from 100 to 140 days gestation in twins compared with singletons (at 140 days: 5016 +/- 108 g v. 5750 +/- 246 g, respectively; P<0.05). However, competition between littermates did not consistently reduce muscle mass (15-22%) until 140 days gestation. Apparent myofibre number increased with age, indicating that the full complement of myofibres in some large hindlimb muscles may be achieved during early postnatal life. Litter size did not impact on apparent myofibre number in the semitendinosus, plantaris or gastrocnemius muscles. However, a transient effect on myofibre number in the adductor femoris muscle was observed from 80-120 days gestation. The phenotypic maturation of myofibres was unaffected by increasing litter size. Smaller muscle mass in twins was associated with smaller myofibre cross-sectional area in the semitendinosus, adductor femoris and gastrocnemius muscles at 140 days gestation. A similar trend was observed for the plantaris muscle. These results indicate that while competition between littermates for nutrients in late gestation can impact on both fetal and muscle mass, the fetus has the capacity to buffer against the effects of restricted nutrient supply on myofibre hyperplasia and phenotypic maturation, but myofibre hypertrophy is compromised.

Morphometric analysis of myofibre development in the adductor femoris muscle of single and twin fetal lambs.

Cellular development of the adductor femoris muscle from twin and single fetuses was studied at 140 days gestation to evaluate the effect of moderate fetal growth retardation on myofibre development. Twin fetuses had lower bodyweights (13%) and disproportionately small adductor femoris muscle weights (22%) compared with single fetuses. Reduced muscle mass was associated with smaller myofibre cross-sectional areas (CSA) and lower DNA content (22%), indicative of fewer myonuclei and retarded myofibre hypertrophy. Myofibre number and the phenotypic maturation of the myofibres were similar between twins and singletons. These results indicate that even modest growth restriction during fetal life can negatively influence myofibre hypertrophy, highlighting the importance of fetal nutrition for muscle growth. Large muscles, such as the adductor femoris, have intrafascicularly terminating myofibres, which necessitates accurate sampling of the muscle when investigating possible perturbations in morphological characteristics (e.g. between singletons and twins). The second objective of the present study was to investigate the impact of the sampling site on the morphological parameters of the adductor femoris muscle. The apparent total myofibre number decreased from the proximal to the distal region of the adductor femoris muscle. The apparent number of slow-twitch fibres also decreased from the proximal to the medial region, but was not different between the medial and distal regions of the muscle. Similarly, myofibre CSA differed between the medial and distal regions. These results indicate that, particularly with large muscles, such as the adductor femoris, which has intrafascicularly terminating myofibres, single site sampling for the determination of morphological fibre characteristics may generate misleading results and that careful selection of the sampling area may be necessary.

Placental development and fetal growth in growth hormone-treated ewes.

The effects of recombinant bovine growth hormone (bGH) treatment of pregnant ewes on maternal metabolism, placental development and fetal growth were examined in two studies. In a preliminary study (experiment one), single-bearing ewes were treated by twice-daily subcutaneous injection for 7 days with bGH (n = 8) at a dose of 0.15 mg/kg LW/day or with saline (n = 8) between days 101 and 107 of gestation inclusive. In experiment two, single- and twin-bearing ewes were treated for 14 days with bGH (0.15 mg/kg L W/day) (n = 10) or saline (n = 10) between days 70 and 83 or days 98 and 111 of gestation inclusive. Ewes were killed on the day following termination of bGH treatment and fetal and placental measurements recorded. Maternal plasma concentrations of GH, IGF-I and insulin were higher (P < 0.001) in bGH-treated ewes relative to saline-treated ewes in both experiments. Consistent across experiments was an increase (P < 0.05) in the weight of the myoendometrium in bGH-treated ewes. Treatment with bGH also increased the total weight of the gravid uterus (P < 0.05) in both experiments. Weights of the uterine fluids were increased by bGH in experiment one (P < 0.05), but an effect of the same magnitude could not be repeated in experiment two. In experiment one, there was a tendency towards increased mean fetal body weights after growth hormone treatment, although the effect was non-significant. In experiment two, treatment with bGH was associated with significantly (P < 0.05) higher fetal weights, but only at the later stage of gestation (day 112). This effect was additive with that of fetal rank. Exogenous bGH treatment had little discernible effect on measures of placental size. It is concluded that administration of exogenous bGH to pregnant ewes can stimulate fetal growth, but only after about day 100 of gestation. This response seems most likely to reflect changes in maternal nutrient partitioning or placental function, rather than placental size. These studies suggest a role for growth hormone of maternal or placental origin in the regulation of fetal growth.

Ontogeny of IGF-I responsiveness to bGH in young lambs.

The ontogeny of hepatic growth hormone (GH) receptors (GHR), as measured by responses of both plasma insulin-like growth factor-I (IGF-I) and hepatic GHR to an exogenous bGH stimulus, was examined using sheep of different ages (Days 1-7, 14-21, 28-35, and 56-63 of life, and yearlings). The IGF-I response to bGH was first examined in yearling sheep using two doses of bGH (0.1 and 0.2 mg/kg LW/d). Based on these results, lambs in four groups up to Day 63 of life were treated for 5 d with bGH (n = 10) at a dose of 0.15 mg/kg LW/d or with saline (n = 10). Jugular blood samples were taken once daily on Days - 1, 4, and 5 of treatment. bGH treatment in lambs up to Day 63 of life had little effect on plasma concentrations of GH, insulin, glucose or urea, but significantly (P < 0.05) increased circulating concentrations of IGF-I at all ages and of NEFA at Day 62/63 of life. In contrast, bGH treatment at either dose in yearlings significantly increased these parameters, except for plasma urea concentrations which were decreased in bGH-treated yearlings. However, the responses of plasma IGF-I concentration to bGH stimulus in lambs up to Day 63 of life were small compared to those in yearling sheep. Consistent with this, bGH treatment failed to affect hepatic GH binding in young lambs, but up-regulated it in yearling sheep. Furthermore, basal (unstimulated) GH binding did not differ between sheep of 7 vs. 63 vs. 365 d of age, despite the greater IGF-I responses to bGH in the latter group. It is suggested that hepatic GHR in lambs up to Day 63 of life are not fully functional compared to the situation in yearlings.

The effects of ovine placental lactogen and bovine growth hormone on hepatic and mammary gene expression in lactating sheep.

The ability of ovine placental lactogen (oPL) to bind to the growth hormone receptor (GHR) raises the possibility that oPL may exert a growth hormone (GH)-like action on galactopoiesis. We have compared the effects of treating lactating ewes for 5 days with an equimolar dose (0.1 mg/kg/day, administered as two equal doses 12 hourly) of either bovine growth hormone (bGH) (n = 10), oPL (n = 10) or saline (n = 9) on hepatic and mammary GHR, insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) gene expression and hepatic GHR number. Hepatic GHR and IGFBP-3 mRNA were unaltered by bGH or oPL treatment. Hepatic IGF-I mRNAs increased following bGH (P < 0.05) but not oPL treatment. GHR gene expression was greater in liver compared to mammary gland extracts. There was no effect of either bGH or oPL treatment on mammary GHR, IGF-I or IGFBP-3 mRNA or hepatic GHR number. These studies confirm the galactopoietic effects of bGH in lactating ruminants and suggest that the mechanism of this action is not via increased hepatic GHR number or gene expression. In addition, the increase in hepatic but not mammary IGF-I mRNA with bGH treatment suggests an endocrine action of IGF-I on milk synthesis. These studies also demonstrate that an equimolar dose of oPL is not galactopoietic or somatogenic in the lactating ewe.

Comparative effects of recombinant ovine placental lactogen and bovine growth hormone on galactopoiesis in ewes.

The effects of recombinant ovine placental lactogen and bovine growth hormone on milk yield, milk composition, and concentrations of blood hormones and metabolites were compared in ewes during an established lactation. Beginning on d 17 of lactation, ewes were treated for 5 d with twice daily subcutaneous injections of ovine placental lactogen (n = 9), bovine growth hormone (n = 10) at a dose of 0.10 mg/d per kg of body weight, or saline (n = 10). Circulating concentrations of ovine placental lactogen were 24.6 +/- 1.6 ng/ml on d 5 for ewes treated with ovine placental lactogen, but concentrations of ovine placental lactogen were undetectable in ewes treated with either saline or bovine growth hormone. Treatment with bovine growth hormone increased circulating concentrations of growth hormone, insulin-like growth factor-I, and nonesterified fatty acids and decreased urea concentrations relative to those in ewes treated with ovine placental lactogen or saline. Compared with saline treatment, no parameters were affected by treatment with ovine placental lactogen. Treatment with bovine growth hormone or ovine placental lactogen treatment had no significant effects on plasma concentrations of insulin, glucose, or creatinine. Treatment with bovine growth hormone, but not ovine placental lactogen, increased yields of milk, fat, and lactose. Weight of the mammary gland was increased by bovine growth hormone, but not by ovine placental lactogen. Despite the fact that ovine placental lactogen is a potent somatogen, it does not appear to exhibit the same galactopoietic activity as bovine growth hormone in lactating ewes.

Maternal constraint influences muscle fibre development in fetal lambs.

The objective was to examine myogenesis in two situations expected to be characterized by maternal constraint: (i) in fetuses due to be born in spring (n=10) or autumn (n=10); and (ii) in single (n=16) and twin (n=20) fetal lambs. Maternal constraint operating through limitation of placental size, as measured by placentome weight per fetus, was evident in each study. Although a lower placental weight did not influence body and muscle weights of fetuses due to be born in the spring or autumn, twins had lower body and muscle weights than singles. Fibre number and average fibre cross-sectional (CS) area were differentially affected by season and fetal number. The differences in muscle fibre morphology between spring- and autumn-born fetuses suggest that muscle fibre development was influenced by maternal constraint in the absence of an effect on fetal weight. The differences in muscle fibre number and CS area in particular muscles from twin and single fetuses suggest that more severe maternal constraint, reflected in a lower placental size per fetus, not only influences fetal weight but can also affect muscle development.

Manipulation of adult body composition by treatment of the neonatal rat with growth hormone and prolactin.

Previous studies involving fetal decapitation or hypophysectomy, and the treatment of neonates with hormones or antibodies, have suggested that changes in pituitary hormone status during the perinatal period may influence later body composition. In the present study, rats were treated for the first 21 days of life with twice daily subcutaneous injections of saline, recombinant bovine growth hormone (bGH) or pituitary ovine prolactin (oPRL). The bGH and oPRL were administered at doses of 0.2 or 0.4 microgram/g bodyweight/day. One-third of the rats in each treatment group were slaughtered at each of days 21, 60 and 120 of life and measurements made of: length and weight of the body; weights of bones and muscle groups in the hindlimb; weights of four fat depots (120-day group only); and the content of nitrogen (N) and fat in the carcass. bGH, but not oPRL, treatment increased weight of the femur and humerus (across ages) but neither treatment had marked effects on weights of muscle groups, carcass weight or carcass N content at any age. Both bGH and oPRL treatment significantly reduced weight of the subcutaneous scapular fat depot and reduced carcass fat content, but only in animals aged 120 days (i.e. 99 days after the cessation of treatment). It is concluded that treatment of rats with bGH and oPRL during the immediate postnatal period specifically retards the ability of animals to deposit body fat in later life by mechanisms which differ from those involved in the classical lipolytic/antilipogenic effects of bGH.

Differential effects of maternal ovine placental lactogen and growth hormone (GH) administration on GH receptor, insulin-like growth factor (IGF)-1 and IGF binding protein-3 gene expression in the pregnant and fetal sheep.

The role of placental lactogen (PL) in the regulation of maternal metabolism and fetal growth is not understood. Both PL and growth hormone (GH) have been suggested as possible regulators of mammogenesis. Our aim was to compare the effects of recombinant ovine placental lactogen (oPL) and bovine growth hormone (bGH) on maternal mammary gland development and fetal growth. Pregnant ewes were treated from day 101 to 107 of gestation with twice daily subcutaneous injections of recombinant oPL (n = 7), bGH (n = 8) (0.15 mg/kg live weight/day) or saline (n = 8). On day 108 of gestation, fetal and maternal tissues were collected. The relative abundance of growth hormone receptor (GHR), insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) mRNA was assessed in mammary gland, maternal liver and heart, and in fetal and placental tissues. There was no detectable change in mammary tissue GHR, IGF-1 or IGFBP-3 gene expression with either bGH or oPL treatment. Maternal administration of bGH, but not oPL, during pregnancy caused an increase in maternal hepatic IGF-1 gene expression (P < 0.005). Treatment with oPL, but not bGH, resulted in a significant increase (P < 0.025) in the relative abundance of fetal hepatic IGFBP-3 mRNA. Maternal hepatic GHR gene expression was not affected by treatment. This study suggests that while bGH treatment of pregnant ewes induces characteristic somatogenic responses, oPL treatment does not have comparable effects. However, oPL may indirectly influence the fetal somatotropic axis by altering fetal hepatic IGFBP-3 production.

Growth-promoting effects of ovine placental lactogen (oPL) in young lambs: comparison with bovine growth hormone provides evidence for a distinct effect of oPL on food intake.

The growth-promoting and metabolic effects of recombinant ovine placental lactogen (oPL) were compared with those of recombinant bovine growth hormone (bGH) in young lambs. Lambs were treated by twice daily subcutaneous injection with oPL (n = 16) or bGH (n = 16) at a dose of 0.1 mg/kg live weight/day or with saline (n = 16) for 21 days commencing on day 3 of life. Jugular blood samples were taken on days 0, 10 and 20 of treatment. Half the lambs in each group were slaughtered at 24 days, and the other half at 9 months of age. Both bGH and oPL treatments induced small but significant (P < 0.05) increases in circulating concentrations of insulin-like growth factor-I (IGF-I) on day 10 of treatment, but not on day 20. Neither treatment altered plasma concentrations of glucose, non-esterified fatty acids, urea or creatinine compared to those in saline-treated lambs. Relative to those of bGH-treated (0.24 +/- 0.01 kg/day) or saline-treated (0.25 +/- 0.01 kg/day) lambs, live weight gains of oPL-treated lambs (0.28 +/- 0.01 kg/day) were significantly (P < 0.05) increased during treatment and differences in live weight were still apparent at 9 months of age. Similarly, treatment with oPL, but not bGH, significantly (P < 0.01) increased daily energy intake. It is concluded that placental lactogen and growth hormone do not have identical biological actions. While oPL is growth-promoting in young lambs, this effect may be mediated by stimulating voluntary feed intake rather than by elevating circulating concentrations of IGF-I.

Responses of young energy-restricted sheep to chronically administered insulin-like growth factor I (IGF-I): evidence that IGF-I suppresses the hepatic growth hormone receptor.

We have shown previously that chronic administration (8 weeks) of insulin-like growth factor-I (IGF-I) has little growth-promoting effect in well fed sheep. The aim of this study was to investigate the anabolic effects of IGF-I in energy-restricted conditions in which circulating concentrations of IGF-I in control animals were expected to be low. Young castrate male sheep were offered chaffed lucerne at a rate equivalent to 110% maintenance and were treated by sc injection three times per day for either 8 or 12 weeks with recombinant human IGF-I (150 micrograms/kg live wt x day) or saline in a 2 x 2 factorial design (eight animals per cell). IGF-I treatment significantly increased plasma IGF-I concentrations, but reduced plasma concentrations of IGF-II, GH, urea, and creatinine. Treatment with IGF-I also decreased (P < 0.1) GH secretion in response to a GRF load, but significantly (P < 0.05) increased the nonesterified fatty acid response to an epinephrine load. The reduction in circulating GH levels was accompanied by a suppression of [125I]oGH binding to hepatic microsomal membranes. This effect, if apparent in other tissues, may act as a feedback mechanism to limit the local synthesis of IGF-I and could explain why IGF-I treatment had little effect on the growth rate of the sheep, although it did increase nitrogen digestibility of the feed consumed and decreased the fat content of the hind leg. It also differentially promoted the growth of the spleen, thymus, and mandibular salivary gland and increased blood counts of eosinophils. It is concluded that IGF-I does not have marked effects on growth rate or body composition in sheep fed a near-maintenance diet. Possible reasons include the associated suppression of GH secretion and action, which limits the ability of treated animals to repartition absorbed nutrients.

A homologous radioimmunoassay for ovine insulin-like growth factor-binding protein-2: ontogenesis and the response to growth hormone, placental lactogen and insulin-like growth factor-I treatment in sheep.

Although insulin-like growth factor-binding protein-2 (IGFBP-2) is an abundant IGFBP in fetal and postnatal plasma, its regulation is not yet clearly understood. To address this question in sheep, we purified ovine IGFBP-2 and developed a homologous radioimmunoassay. We have studied its ontogenesis and measured serum concentrations of ovine IGFBP-2 after bovine growth hormone (bGH), ovine placental lactogen (oPL) and IGF-I treatment. Concentrations of IGFBP-2 were high at 125 days of gestation (550 +/- 15 micrograms/l) but fell after birth (P < 0.05) and plateaued after 1 year of age (340 +/- 20 micrograms/l). In lactating ewes, bGH treatment for 7 days significantly reduced (21%; P < 0.05) IGFBP-2 relative to the saline-treated group. Similarly, in neonatal lambs, bGH treatment from day 3 to day 23 of life reduced (P < 0.05) IGFBP-2 by 23% relative to the saline-treated group. oPL had no effect on serum levels of IGFBP-2 in the ewe or the neonatal lamb. In well-fed yearling lambs, treatment with IGF-I reduced IGFBP-2 values by 27% (P < 0.05) relative to control animals. In yearling lambs, reduced nutrition increased plasma IGFBP-2 (41%; P < 0.05). However this increase was abolished by IGF-I treatment. The changes in plasma levels of IGFBP-2 were positively related to changes in IGF-II while there was a negative relationship between circulating IGF-I and IGFBP-2 such that both IGF-I and IGF-II may play a role in the regulation of IGFBP-2 in serum.

Influence of fetal and maternal genotype for circulating insulin-like growth factor I on fetal growth in mice.

The role of insulin-like growth factor I in the regulation of fetal growth was investigated in two lines of mice selected for high or low concentrations of this factor in plasma. In Expt 1, females from each line were mated with males of the reciprocal line to generate fetuses of equivalent genotype. Females with low concentration of the factor in plasma exhibited the typical negative relationship between mean fetal mass and litter size (b = -0.032 +/- 0.006 g per fetus, P < 0.01). However, dams of the line with high concentrations of the factor did not exhibit this relationship (b = -0.004 +/- 0.006 g per fetus), despite the fact that they had 26% larger litters (P < 0.05) at a common maternal body mass. This difference in maternal constraint apparently reflects a greater capacity for nutrient transfer to the fetuses in the dams with more insulin-like growth factor I in plasma, as suggested by the absence of a relationship between mean placental mass and mean fetal mass in that line. In Expt 2, the effect of fetal genotype for insulin-like growth factor I was investigated by transferring embryos of the two lines into females of an unrelated strain. Fetuses from the line with high concentrations of the factor in plasma were heavier at term (1.51 versus 1.37 g, pooled SE = 0.05 g, P < 0.05) than fetuses from the line with low concentrations in plasma. It is therefore concluded that fetal growth is influenced by both the maternal and fetal genotypes for insulin-like growth factor I, but in qualitatively different manners.

IGFBP-2 expression in liver and mammary tissue in lactating and pregnant ewes.

Binding proteins for the insulin-like growth factors (IGFBPs) modulate the actions of IGF I and IGF II. IGFBP-2 is particularly high in plasma of pregnant and fetal animals and in milk. We investigated the peri-lactational control of IGFBP-2 expression and secretion. Fifteen singleton-bearing pregnant ewes at day 101 of gestation were injected sc twice daily for 8 days with bovine growth hormone (bGH) or ovine placental lactogen (oPL) both at 0.15 mg.kg-1.d-1 or saline. A further fifteen ewes at day 17 of lactation were injected sc twice daily for 5 days with bGH or oPL at 0.1 mg.kg-1.d-1 or saline. On the last day of injection blood samples were taken and the animals were sacrificed. Liver and mammary tissue samples were immediately frozen and subsequently extracted to provide total RNA for evaluation by Northern blot analysis using a rat IGFBP-2 cDNA probe. Plasma samples were analysed by Western ligand blotting for IGFBP-2. The comparison of the two saline-treated groups (pregnant vs lactating ewe) revealed no difference in the plasma concentrations of IGFBP-2. IGFBP-2 mRNA expression in the liver of the lactating ewes was markedly increased compared to that in the pregnant ewes. In contrast, in mammary tissue the expression was significantly lower in lactating than in pregnant sheep. In pregnant animals treatment with bGH, but not oPL, decreased the expression of IGFBP-2 in liver. There was a similar trend in the lactating ewe.(ABSTRACT TRUNCATED AT 250 WORDS)

Elevating maternal insulin-like growth factor-I in mice and rats alters the pattern of fetal growth by removing maternal constraint.

Fetal growth is normally constrained by maternal factors. This constraint is demonstrated by the usual inverse linear relationship between litter size and mean fetal weight. Cross-breeding experiments between mice of lines selected for high or low plasma insulin-like growth factor (IGF-I) levels suggested that elevations in maternal IGF-I abolish (P less than 0.01) this constraining effect and reverse the usual positive relationship between fetal and placental size in late gestation. This was confirmed by treating mice and rats throughout pregnancy with IGF-I. In normal mice and in low IGF-I line mice treatment with IGF-I (10 micrograms 8-hourly s.c. from day 1 to 19 of pregnancy) abolished maternal constraint whereas 0.9% (w/v) NaCl treatment did not. In Wistar rats osmotic pumps were implanted to deliver IGF-I (1 microgram/g body weight per day), bovine GH (bGH; 0.6 microgram/g body weight per day) or saline from day 1 to 19 of pregnancy. IGF-I therapy but not bGH or saline abolished (P less than 0.01) maternal constraint and altered (P less than 0.01) the relationship between placental and fetal weight. When high or low IGF-I line mice embroys were transplanted into a normal line of mice, the expected negative relationship (P less than 0.05) between mean fetal weight and litter size was maintained. However, the embryos of the high line were heavier (P less than 0.05) than those from the low line irrespective of fetal number, suggesting a direct role for IGF-I in the regulation of fetal growth.(ABSTRACT TRUNCATED AT 250 WORDS)