D. S. van der Linden

Effects of ewe size and nutrition on fetal mammary gland development and lactational performance of offspring at their first lactation

Many environmental factors applied postnatally are known to affect milk production of the dam, but to date, the effects of different fetal environments on subsequent first lactational performance of the offspring have not been reported. Four hundred fifty heavy (H; 60.8 kg +/- 0.18) and 450 light (L; 42.5 kg +/- 0.17) dams were randomly allocated to ad libitum (A) or maintenance (M) nutritional regimens from d 21 until d 140 of pregnancy, under pastoral grazing conditions (HA, n = 151; HM, n = 153; LA, n = 155; LM, n = 153). At d 100 of pregnancy, a sub-group of twin-bearing dams was killed and fetal mammary glands collected. From 1 wk before lambing, all remaining dams were fed ad libitum until weaning. After weaning, female progeny were managed and fed under pastoral conditions as 1 group. At 2 yr of age, 72 twin-rearing ewe offspring were milked once a week for 7 wk. Fetuses from M-dams had heavier mammary glands (P = 0.03) compared with A-fetuses. Fetuses from H-dams had greater (P = 0.0008) mammary duct area compared with L-fetuses. At 2 yr of age, M-offspring had greater milk yields at d 7 (P = 0.02) and d 28 (P = 0.09) of lactation and tended to have greater accumulated milk yields (P = 0.11) compared with A-offspring. Ewes born to M-dams showed greater lactose percentage at d 14 (P = 0.002), d 21 (P = 0.06), and d 28 (P = 0.07) of lactation and greater (P = 0.049) accumulated lactose yields and CP (P = 0.06) yields compared with A-offspring. Ewes born to H-dams displayed greater milk yields at d 14 (P = 0.08) and d 21 (P = 0.02) and had greater accumulated milk yield (P = 0.08) and lactose yield (P = 0.04) compared with L-offspring. Lambs born to M-offspring were heavier at birth (P = 0.02) and grew faster until weaning (P = 0.02), matching the milk yield and composition data, compared with their ad libitum counterparts. Birth weight was not affected (P > 0.10) by grand dam size; however, lambs born to H-offspring grew faster from birth until d 49 of age (P = 0.03). In conclusion, dam nutrition during pregnancy affected the resulting milk production of the offspring and composition and growth of their lambs. In addition, dam size affected the milk production of the offspring, lactose yield, and growth of their lambs. These findings are important for furthering our understanding of how the environment to which the female fetus is exposed can affect her subsequent development and her ability to nourish the next generation.

Dam and granddam feeding during pregnancy in sheep affects milk supply in offspring and reproductive performance in grand-offspring1

In temperate climates, the cost of providing feed is greater in winter than in other seasons, causing ewes to be fed restricted rations during some periods of pregnancy. Epidemiological information indicates that undernutrition of the fetus may affect its health and performance in later life (i.e., fetal programming), and these effects may be passed between generations. The primary focus of the results presented in this paper is to examine the effects of feeding levels during pregnancy on a variety of traits from offspring at the fetal stage to 3.5 yr of age and also traits in the grand-offspring. Two studies are reported in which ewes were fed restricted diets during pregnancy, with a variety of fetal traits, offspring traits up to 3.5 yr of age, or grand-offspring traits up to 8 mo of age being measured. Study 2 also considered differences in dam size (heavy vs. light). In study 1, several fetal mammary gland measures indicated that milking ability may be enhanced in offspring from dams fed ad libitum during pregnancy. However, study 2 showed that mammary mass was greater in fetuses from dams fed at maintenance during pregnancy and that contemporaries of these fetuses produced greater protein and lactose yields in their first lactation. In the second lactation, the advantages in protein and lactose yields did not reoccur and ewes from ad libitum-fed dams produced greater fat yield. In study 2, grand-offspring whose granddams were fed at maintenance levels during pregnancy were lighter at birth in both the first and second parturitions than those whose granddams were fed ad libitum during pregnancy. First-parity grand-offspring whose granddams were fed maintenance levels during pregnancy achieved heavier BW by 40 to 50 d of age in the first lactation, which reflected the greater protein and lactose yields; however, no BW differences were present in second-parity lambs at the same age. A smaller proportion of first-parity ewe grand-offspring from heavy granddams that were fed ad libitum during pregnancy reached puberty at approximately 8 mo of age relative to the other granddam size and feeding groups. These results indicate that dam nutrition can affect the yield and composition of milk in their offspring and the BW and reproductive capability of their grand-offspring. Molecular and physiological mechanisms for these changes are being sought.

Placental nutrient transport is affected by pregnancy rank in sheep1

Understanding the link between placental function and fetal growth is critical to comprehend the mechanisms underlying altered fetal growth. This study investigated the relationship between fetal weight and placentome type and size in placentae of singleton and twin fetuses and fetuses within a twin pair from ad libitum-fed ewes at d 140 of pregnancy. In addition, insulin, IGF-I, metabolites, and free AA profiles in fetal, umbilical artery, and vein plasma of singleton and twin fetuses were investigated and used as an indicator of placental nutrient transport. Individual placentae per fetus were dissected, placentomes were classed per type (A to D) and size (light to heavy), and placentome number and individual weight were recorded. Twin fetuses were 16% lighter (P = 0.01) than singletons and had a smaller placenta, with 28% decreased placentome weight (P = 0.03) and 35% fewer placentomes (P = 0.001). Twins also had a different distribution of placentome type and size compared with placentae of singletons, such that twins showed a greater proportion of type B and light placentomes compared with singletons. In twins, umbilical artery plasma had less Glu (P < 0.05) and greater Gln (P < 0.05) concentrations than fetal plasma or umbilical vein plasma, but no differences in AA concentrations were observed between these pools in singletons. Glutamate is a major oxidation energy source for the placenta, and the fetal liver is the net producer of Glu using Gln as its main precursor, indicating that the functionality of the fetoplacental unit may be different between singletons and twins. Twin fetuses had 13% less insulin (P = 0.04) concentrations in umbilical artery plasma than singletons. plasma of twin fetuses had 39% less IGF-I (P = 0.003), 33% less His (P = 0.03), and 22% less Gln (P = 0.02) concentrations and tended to have 44% less Arg (P = 0.07) and 20% less Leu (P = 0.06) concentrations than singletons. Arginine, His, and Leu are examples of AA that can promote insulin secretion, and in turn, insulin can increase fetal IGF-I concentrations. In addition, insulin and IGF-I are important fetal growth factors by stimulating and regulating AA transport across the placenta. Collectively, these results indicate that the functionality of the fetoplacental unit may be different between singletons and twins and that AA transport may be reduced in twin placentae.

The effect of breeding hoggets on lifetime performance

Abstract The reported study involved mature ewes that had either been presented for breeding and had lambed as a hogget (MP), had been presented for breeding as a hogget but did not become pregnant (MNP) or were not presented for breeding as a hogget (NM). Their subsequent performance as mature ewes was examined. Although breeding as a hogget reduced (P <0.05) two-tooth mating live weight and condition score in subsequent years, the differences were either smaller or not present at all (P>0.05). Breeding as a hogget increased (P<0.05) the number of foetuses per ewe lifetime (8.2±0.08, 7.0±0.13 and 7.1±0.12 for MP, MNP and NM respectively) but did not alter ewe (P>0.05) longevity. These results indicate that hogget breeding can be used as a management option to improve lifetime reproductive performance.

Effects of ewe size and nutrition during pregnancy on performance of 2-year-old female offspring

The current study investigated the effects of dam weight and nutrition during gestation on the reproductive performance of female primiparous offspring at 2 years of age. Four hundred and fifty heavy (H) (mean± s.e.m .: 60·8 kg±0·18) and 450 light (L) (42·5 kg±0·17) dams were randomly allocated to ad libitum (A) or maintenance (M) nutritional regimens from day 21 until day 140 of pregnancy, under pastoral grazing conditions. One week prior to lambing, all dams and their lambs were provided with ad libitum feeding through to weaning. After weaning, female progeny were managed and fed to requirements as one group. At 2 years of age, the oestrous cycles of the female offspring ( n =207) were synchronized and the offspring were naturally mated. Ewes were scanned for pregnancy by ultrasound at day 70 of pregnancy. Within 24 h of birth, lambs were weighed and body dimensions were measured. Lambs were also weighed at day 24 (L24) and weaning. No effects of dam nutrition or dam weight were found ( P >0·10) on the reproductive performance of the ewe offspring. Lambs of M-grand-dams were heavier at birth ( P =0·024) and weaning ( P =0·031) than lambs of A-grand-dams. Twin lambs of H-grand-dams were heavier at birth ( P =0·014) than twin lambs of L-grand-dams; however, grand-dam weight had no effect ( P >0·10) on lamb weaning weight. In summary, dam weight had no effect on reproductive performance of the female offspring, with only a minor effect on the weight of grand-offspring. Thus, being born to a larger dam has no advantages over being born to a smaller dam, in terms of number of lambs born and weight of lambs at birth and weaning. Grand-dam maintenance nutrition had no effect on reproductive performance although it increased lamb birth and weaning weight and lamb growth rates of the grand-offspring. Therefore, this indicates that ewes born to dams fed at maintenance during pregnancy have an advantage over A-ewes in physiological stressful situations including pregnancy or lactation.

Effects of ewe size and nutrition during pregnancy on glucose metabolism, fat metabolism and adrenal function of postpubertal female twin offspring.

Little is known about the long-term metabolic effects of maternal constraint on the offspring and whether a possible interaction of dam size and nutrition during gestation exists, affecting postnatal metabolic functions in the offspring. Four hundred and fifty heavy (H) (60.8 ± 0.18 kg) and 450 light (L) (42.5 ± 0.17 kg) Romney dams were allocated to ad libitum (A) or maintenance (M) nutritional regimens under New Zealand pastoral grazing conditions, from Day 21 to 140 after insemination. One week before lambing, all dams and offspring were managed as one group and provided with ad libitum feeding. At 16 months of age, female twin-born offspring (n = 12 per size by nutrition group) were catheterised and given intravenous insulin (0.15 IU/kg) (ITT), glucose (0.17 g/kg) (GTT) and epinephrine (1 μg/kg) (ETT) challenges to assess their glucose and fat metabolism and adrenal function. No effects of dam size or interactions between dam size and dam nutrition were found on glucose or fat metabolism or adrenal function. In response to the ETT, M-dam offspring showed greater (P < 0.05) peak glucose concentrations, increased (P < 0.05) glucose area under the curve and tended (P < 0.10) to have increased maximum change in glucose and non-esterified free fatty acid concentrations compared with A-ewes. No effects of dam nutrition were found on glucose tolerance, insulin resistance or adrenal function in response to GTT and ITT. In conclusion, dam size had no effect on glucose metabolism, adrenal function or fat metabolism in 16-month-old female twin offspring. Dam nutrition during pregnancy from Day 21 to 140 had no major effect on glucose metabolism, adrenal function or lipolysis; however, it did potentially affect gluconeogenesis and/or glycogenolysis, as increased glucose concentrations in ewes born to M-fed dams were observed in response to ETT. These results indicate that M-ewes could have an advantage over A-ewes in physiological stressful situations in life (e.g. pregnancy, lactation) as their liver may be able to supply more glucose to support their growing conceptus and milk production to increase the chances of survival of their offspring.

Relationships between early postnatal growth and metabolic function of 16-month-old female offspring born to ewes exposed to different environments during pregnancy.

It was hypothesized that exposure of the fetus to adverse conditions in utero due to either maternal constraint or nutrition may result in developmental adaptations altering metabolism and postnatal growth of the offspring. Heavy (H) and light (L) Romney dams (G0) were allocated to ad libitum (A) or maintenance (M) nutritional regimens, from day 21-day 140 of pregnancy. Female twin-born offspring (G1) born to the dams in the four treatment groups will be referred to as HA-ewes, LA-ewes, HM-ewes and LM-ewes. At 16 months of age, offspring were catheterized and given intravenous insulin tolerance test (ITT), glucose tolerance test (GTT) and epinephrine tolerance test challenges to assess their glucose and fat metabolism in relation to their birth weight and postnatal growth. In HA-ewes, the regression coefficients of growth rates prior to puberty on insulin and glucose curves in response to GTT (InsAUCGTT) and ITT (GluAUCITT), respectively, were different from 0 (P < 0.05) and were different from the regression coefficients of HM-ewes. This may indicate that HA-ewes may have showed puberty-related insulin resistance at 16 months of age with increasing growth rates prior to puberty compared to HM- or LM-ewes. In HM-ewes, the regression coefficients of growth rates after puberty on InsAUCGTT and GluAUCITT were different from 0 (P < 0.05) and were different from those of HA-ewes. These results may indicate that offspring born to heavy dams fed maintenance during pregnancy and with greater postnatal growth rates after puberty could develop glucose intolerance and insulin resistance in later life.

Nutritional plane of twin-bearing ewes alters fetal mammary gland biochemical composition and mTOR/MAPK pathway signaling.

Identifying the biochemical changes and molecular pathways that regulate fetal mammary development in response to maternal nutrition is important for understanding the link between fetal programming of mammary development and future lactation performance. Although there are published studies regarding biochemical changes in the developing mammary gland, there are currently no data on molecular pathway involvement in regulating ruminant fetal mammary development. This study investigated changes in fetal mammary biochemical indices and mechanistic target of rapamycin (mTOR)/mitogen activated protein kinase (MAPK) signaling at d 100 and 140 of gestation in an ovine model of restricted maternal nutrition. Ewes were randomly allocated to ad libitum (A) or maintenance (M) nutritional regimens, under New Zealand pastoral grazing conditions, from d 21 to 140 of pregnancy. At d 100 and 140 of pregnancy, a subgroup of twin-bearing dams was euthanized, and whole fetal mammary glands (fiber, skin, fat, and ducts) were collected. Mammary glands of fetuses carried by M-fed dams were heavier at d 100 than those of fetuses carried by A-fed dams ( = 0.03), with no difference in the abundance of mTOR/MAPK signaling proteins observed. At d 140, mammary glands of fetuses carried by M-fed dams were lighter ( = 0.07) than fetuses carried by A-fed dams because of decreased hyperplasia ( = 0.04) and hypertrophy ( = 0.09) but had increased protein synthetic capacity ( = 0.02). Increased protein synthetic capacity was associated with increased abundance of MAPK pathway signaling proteins eukaryotic intiation factor 4E (eIF4E)/eIF4E and mTOR pathway signaling proteins eukaryotic initiation factor 4E-binding protein 1 (4E-BP1)/4E-BP1 and ribosomal protein S6 (RPS6)/RPS6 ( ≤ 0.05). Increased abundance of MAPK/mTOR pathway proteins is proposed to mediate increased protein synthetic capacity via ribosome biogenesis and the availability of factors required to initiate protein translation. The primary regulator of 4E-BP1 phosphorylation at Ser65 and RPS6 at Ser235/236 is the activated form of mTOR: mTOR. To study potential tissue-specific mTOR, mTOR abundance mammary glands, separated into parenchyma and fat pad, were collected from d 140 fetuses carried by dams fed a lucerne-based pellet diet formulated to meet 100% of the NRC-recommended maintenance requirements. Results showed that the abundance of mTOR was primarily localized to the fat pad, indicating that the fat pad plays a potential role in regulating development of the fetal mammary gland.

Intravenous maternal -arginine administration to twin-bearing ewes, during late pregnancy, is associated with increased fetal muscle mTOR abundance and postnatal growth in twin female lambs.

The aims of this study were to determine whether parenteral Arg administered to well-fed twin-bearing ewes from 100 to 140 d of pregnancy influences fetal skeletal muscle growth, the abundance and activation of mechanistic target of rapamycin (mTOR) protein, and postnatal muscle growth of the offspring. Ewes fed 100% of NRC-recommended nutrient requirements for twin-bearing ewes were administered an intravenous bolus of either 345 μmol Arg HCl/kg BW or saline solution (Control) 3 times per day. At 140 d of pregnancy (P140), a group of 11 Control and 9 Arg-treated ewes were euthanized and hind leg muscles and longissimus dorsi (LD) were excised and weighed. A sample of LD was snap frozen in liquid nitrogen for later analysis of free AA (FAA) concentration, mTOR abundance and phosphorylation, and biochemical indices (DNA, RNA, and protein content). For the remaining 25 ewes (Arg, = 13, and Control, = 12), Arg administration was continued until the initiation of parturition and ewes were allowed to lamb. Lambs were weaned at postnatal Day 82 and grazed on pasture until postnatal day 153 (PN153), when a subset of 20 lambs ( = 10 per group) was euthanized. At P140, only the psoas major was heavier in the Arg-administered group compared with the Control group. Female lambs from ewes supplemented with Arg (Arg-F) had increased abundance of total mTOR, RNA concentration, and RNA:DNA ratio in LD compared with female lambs from Control ewes (Con-F), whereas males did not differ. At PN153, Arg-F were heavier than Con-F and had heavier LD and plantaris and a trend for heavier psoas major muscles compared with Con-F. In contrast, BW and individual muscle weights did not differ in male lambs. Lambs from Arg-treated ewes had heavier semimembranosus and tended to have heavier biceps femoris compared with Control lambs. The RNA concentration in LD was greater in Arg-F compared with Con-F, and DNA concentration was greater in the Arg group compared with the Control group. In conclusion, Arg administration to the ewe during gestation increases female lamb weight and muscle weight after birth and these changes are associated with altered mTOR protein abundance and have potential implications for sheep production.

Carry-over effects of ewe nutrition and birth rank during the previous pregnancy on the milking performance during the subsequent lactation of Romney ewes

This study investigated whether selection for ewe size and nutrition during the previous pregnancy would affect the lactational performance of the ewe and liveweight gain of her lamb(s) in the subsequent year. A subgroup of singleton-bearing Romney ewes were milked once a week, for 7 consecutive weeks. Singleton-bearing ‘light’ ewes that gave birth to twins in the previous year had reduced milk yields from Day 21 of lactation (L21) onwards in the present year compared with those that gave birth to singletons in the previous year. Lambs born to light ewes had reduced liveweight gain from birth to L21 compared with those born to ‘heavy’ ewes. Singleton-bearing ewes in the present year that were fed maintenance and gave birth to twins in the previous year, produced less milk from L21 onwards compared with those that were maintenance-fed and singleton-bearing in the previous year. Singleton lambs born to milked ewes that were fed maintenance and gave birth to twins in the previous year, had lower liveweight gain from birth to L21 in the present year compared with lambs born to ewes fed maintenance and gave birth to singletons in the previous year. In the entire population, lambs born to ewes fed maintenance and that gave birth to twins in the previous year were lighter at L21 than lambs born to ewes fed ad libitum and bearing twins in the previous year. This indicates that if nutrition is suboptimal, or the ewes are lighter in the previous year, those that were twin-bearing are more likely to rear lighter lambs in the present year. Therefore, farmers need to take these points into consideration when devising feeding plans for the present year.