Ewe size, pregnancy nutrition and pregnancy rank are known to affect the productive performance of ewes and their offspring. The aim of the present study was to compare the effects of two nutritional regimens, from day 21 to day 140 of pregnancy, in singleton-and twin-bearing ewes of two different mean weights, taken from a single flock. The study included Large ewes offered Ad lib (Large-Ad lib, n= 151), Large ewes offered Maintenance (Large-Maintenance, n = 153), Small ewes offered Ad lib (Small-Ad lib, n = 155) and Small ewes offered Maintenance (Small-Maintenance, n = 153) that were either singleton-or twin-bearing. During the period day 21 to day 140 Maintenance and Ad lib feeding regimens included Large and Small ewes and singleton-and twin-bearing ewes. At days 1 and 140 of pregnancy Large ewes were heavier (P < 0.05) and of greater (P < 0.05) body condition than Small ewes. Similarly, at days 1 and 140 of pregnancy twin-bearing ewes were heavier (P < 0.05) than single-bearing ewes. At day 1 of pregnancy there was no difference in ewe liveweight and body condition scores between Maintenance and Ad lib-fed ewes, but by day 140 ewes in the Ad lib regimen were heavier (P < 0.05) and had greater (P < 0.05) body condition than Maintenance ewes. There was an interaction (P < 0.05) between ewe nutritional regimen and lamb birth rank for lamb birth weight such that twin lambs born to Maintenance regimen ewes were lighter (P < 0.05) than their counterparts born to Ad lib ewes (4.52 ± 0.06 versus 5.23 ± 0.06 kg respectively). This relationship was not observed in singletons. There was also an interaction (P < 0.05) between ewe size and nutritional regimen for lamb birthweight. Birth weights did not differ between lambs born to either Small or Large ewes on the Ad lib feeding regimen. However, lambs born to Small ewes on the Maintenance feeding regimen were lighter (P < 0.05) than their counterparts born to Large ewes (5.09 ± 0.07 versus 5.37 ± 0.07 kg respectively). At day 100 of lactation lambs born to Large ewes were heavier (P < 0.05) than those born to Small ewes (32.65 ± 0.37 versus 31.16 ± 0.35 kg respectively) and those born to Ad lib ewes were heavier (P < 0.05) than those born to Maintenance ewes (32.77 ± 0.37 versus 31.03 ± 0.36 kg respectively). This study shows that level of dam pregnancy nutrition has a greater effect on twin-born lambs than their singleton-born counterparts. Furthermore, the data suggests that the heavier liveweights at weaning of lambs born to Large ewes may not have compensated for their dams' greater nutritional requirements compared to their smaller counterparts.

BackgroundThe mammary gland is a dynamic organ that undergoes dramatic physiological adaptations during the transition from late pregnancy to lactation. Investigation of the molecular basis of mammary development and function will provide fundamental insights into tissue remodelling as well as a better understanding of milk production and mammary disease. This is important to livestock production systems and human health.Here we use RNA-seq to identify differences in gene expression in the ovine mammary gland between late pregnancy and lactation.ResultsBetween late pregnancy (135 days of gestation ± 2.4 SD) and lactation (15 days post partum ± 1.27 SD) 13 % of genes in the sheep genome were differentially expressed in the ovine mammary gland. In late pregnancy, cell proliferation, beta-oxidation of fatty acids and translation were identified as key biological processes. During lactation, high levels of milk fat synthesis were mirrored by enrichment of genes associated with fatty acid biosynthesis, transport and lipogenesis. Protein processing in the endoplasmic reticulum was enriched during lactation, likely in support of active milk protein synthesis. Hormone and growth factor signalling and activation of signal transduction pathways, including the JAK-STAT and PPAR pathways, were also differently regulated, indicating key roles for these pathways in functional development of the ovine mammary gland. Changes in the expression of epigenetic regulators, particularly chromatin remodellers, indicate a possible role in coordinating the large-scale transcriptional changes that appear to be required to switch mammary processes from growth and development during late pregnancy to synthesis and secretion of milk during lactation.ConclusionsCoordinated transcriptional regulation of large numbers of genes is required to switch between mammary tissue establishment during late pregnancy, and activation and maintenance of milk production during lactation. Our findings indicate the remarkable plasticity of the mammary gland, and the coordinated regulation of multiple genes and pathways to begin milk production. Genes and pathways identified by the present study may be important for managing milk production and mammary development, and may inform studies of diseases affecting the mammary gland.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1947-9) contains supplementary material, which is available to authorized users.

1988). Plasma metabolite and hormone concentrations as predictors of dairy merit in young Friesian bulls: effect of metabolic challenges and fasting. ABSTRACTResponses to metabolic challenges were measured in 8-month-old Friesian bull calves with a view to identifying possible predictors of genetic merit for milk fat production. Seven 'high' breeding index bulls (mean breeding index for milk fat = 128-9 (s.d. 4-8) percentage units) were compared with six 'low' breeding index bulls (mean 107-3 (s.d. 2-4) percentage units). Bulls were from two selection lines and breeding indices calculated as the average of parental breeding index values.Challenges involved intravenous injection of the following (dose rates per kg body weight): adrenalin (1 ng); glucose (0-17 g); glucagon (0-175 ^g); insulin (0-01 mg); and arginine (40 mg). Blood samples were withdrawn prior to and after each challenge (two challenges daily). Bulls were then fasted for 3 days before being refed.Relative to the low breeding index bulls, those in the high breeding index group exhibited: (a) greater pancreatic sensitivity to circulating glucose as indicated by increased insulin concentrations following the glucose challenge; (b) more rapid clearance of glucose from plasma following the insulin challenge; (c) reduced sensitivity to the glycogenolytic/gluconeogenic effects of glucagon as indicated by lower blood glucose concentrations following intravenous injection of this hormone; (d) elevated plasma insulin and growth hormone concentrations during the fasting period; (e) elevated plasma concentrations of insulin, glucose and urea during refeeding; (f) no difference in responses to intravenous arginine or adrenalin, or in circulating concentrations of Insulin-like Growth Factor-1 or alkaline phosphatase. Results are consistent with previous observations that metabolic differences between cattle in the Massey University high and low breeding index lines are most evident in the metabolism of glucose and insulin. Metabolic challenges offer a potentially useful means of predicting genetic merit for milk fat production but the conditions under which repeatable differences between the lines can best be demonstrated are yet to be determined.

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.

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.

Photodynamic therapy regimens, which use light-activated molecules known as photosensitizers, are highly selective against many malignancies and can bypass certain challenging therapeutic resistance mechanisms. Photosensitizers such as the small cationic molecule EtNBS (5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells that reside within acidic and hypoxic tumour microenvironments. At higher doses, however, these photosensitizers induce “dark toxicity” through light-independent mechanisms. In this study, we evaluated the use of nanoparticle encapsulation to overcome this limitation. Interestingly, encapsulation of the compound within poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-EtNBS) was found to significantly reduce EtNBS dark toxicity while completely retaining the molecule’s cytotoxicity in both normoxic and hypoxic conditions. This dual effect can be attributed to the mechanism of release: EtNBS remains encapsulated until external light irradiation, which stimulates an oxygen-independent, radical-mediated process that degrades the PLGA nanoparticles and releases the molecule. As these PLGA-encapsulated EtNBS nanoparticles are capable of penetrating deeply into the hypoxic and acidic cores of 3D spheroid cultures, they may enable the safe and efficacious treatment of otherwise unresponsive tumour regions.

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.

Nutrition of the ewe at various stages of pregnancy is known to affect ewe and offspring performance. However, little is known regarding the potential interactions among differing maternal nutrition regimens in early and mid–late pregnancy. The objective of the present study was to examine the effects and potential interactions of three pastoral nutritional treatments from Day 21 of pregnancy (P21) to P50 (Sub-maintenanceP21–50 (total liveweight change achieved, SMP21-50, –0.15 ± 0.02 kg/day) v. MaintenanceP21–50 (MP21-50,–0.02 ± 0.02 kg/day) v. Ad libitumP21–50 (AdP21-50,0.15 ± 0.02 kg/day) and two pastoral nutritional treatments from P50 to P139 [MaintenanceP50–139 (designed to match change in conceptus mass, total liveweight change achieved, 0.19 ± 0.01 kg/day) v. Ad libitumP50–139 (0.26 ± 0.01 kg/day)] on 382 twin-bearing ewes and their offspring until 91 days after the mid-point of lambing (L91). Ewe liveweight and condition scores in pregnancy and lactation, and lamb liveweights, indices of colostrum uptake and survival were recorded. There were no interactions between nutritional periods for lamb liveweight, apparent colostrum intake and survival, and ewe liveweight, condition score and total weight of lamb per ewe at the end of the study. At L91, ewe nutritional treatment during P21–50 or P50–139 had no effect on either ewe liveweight or body condition score. Ewe nutritional treatment during P21–50 had no effect on lamb birthweight. Lambs born to AdP50–139 ewes were lighter (P < 0.05) than those born to MP50–139 ewes (5.32 ± 0.04 v. 5.48 ± 0.04 kg, respectively). Ewe nutritional treatment during P21–50 or P50–139 had no (P > 0.05) effect on indices of colostrum uptake in lambs at 24–36 h of age. At L91, ewe nutritional treatment during P21–50 or P50–139 had no effect on lamb liveweight, survival or total weight of lamb per ewe. In conclusion, although considerable differences in ewe liveweight were observed during pregnancy, the nutritional treatments had no effect on the production parameters measured at the end of the study. These results indicate, first, that farmers can use early pregnancy as a period to control ewe nutrition when ewes are offered at least pregnancy maintenance levels of nutrition in the mid–late pregnancy period and, second, that there is no advantage from offering twin-bearing ewes a level of nutrition above their pregnancy maintenance requirements in mid–late pregnancy.