Pulmonary metabolic function in the awake lamb: effect of development and hypoxia

The effect of postnatal development and acute alveolar hypoxia on pulmonary metabolic function was studied in conscious newborn lambs. Measurements of the ability of the lungs of these animals to metabolize [3H]benzoyl-L-phenyl-alanyl-L-alanyl-L-proline ([3H]BPAP; a synthetic substrate for angiotensin-converting enzyme, ACE) and to remove 5-hydroxy-[14C]tryptamine (5-[14C]HT) were made by modified indicator-dilution techniques during normoxic and hypoxic (fraction of inspired O2 = 0.10) conditions at 1 day, 1 wk, and 1 mo of age. Six additional sheep (8-23 wk old) were studied acutely as "adult" controls. BPAP metabolism in the 1-day-old group was 48 +/- 3% and increased slowly to 57 +/- 1% (P less than 0.05) at 1 mo of age and to 79 +/- 3% (P less than 0.01) by 23 wk of age. Pulmonary 5-[14C]HT removal was adultlike at birth (69 +/- 2%). Alveolar hypoxia significantly decreased BPAP only in the 1-day-old group (41 +/- 3%; P less than 0.05) and had no significant effect on 5-[14C]HT removal over the range of ages studied. These data demonstrate a selective and gradual postnatal development of pulmonary ACE which could be due to alterations in either the affinity or maximal capacity of pulmonary ACE, or increased endothelial cell surface area secondary to rapid growth of small blood vessels in this period. Alveolar hypoxia does not appear to closely regulate either ACE activity or 5-HT removal in conscious lambs greater than 1 day old when trace amounts of substrate are used.     

The effect of chronic and acute haemorrhage on erythropoietin in the neonatal lamb.

In all mammalian species studied the haematocrit (hct) declines after birth in the absence of any known nutritional deficiencies. The glycoprotein hormone, erythropoietin (Epo), is essential for normal red blood cell production. The aims of this study were 1) to investigate the changes in plasma Epo during the normal post-natal decrease in hct in lambs; 2) to compare the effects of chronic and acute haemorrhage in neonatal lambs; and 3) to test the hypothesis that the Epo response to haemorrhage is blunted in the neonatal period. Twenty-one lambs (0-9 weeks of age) were studied; group I (n = 8) were used to document normal post-natal changes (98 samples); group II (n = 7) lambs were haemorrhaged repetitively during weeks 3-6 (95 samples); group III (n = 6) lambs were bled once in the first 3-week period. In the group I (control lambs) the hct decreased from 30.6 +/- 1.3 (weeks 1 & 2) to a nadir of 23.2 +/- 0.8 (75.8% of initial value) in the 6th week, and the plasma Epo declined from 25.7 +/- 4.9 (week 1) to 12.3 +/- 1.0 mU/ml (week 6). In group II, the lambs were bled repetitively, a total of 510 +/- 32 ml blood being removed during weeks 3-6, the hct was 18.7 +/- 0.8 (81% of hct at nadir in controls) in week 6, and Epo was 26.9 +/- 13.3 in week 3, 23.4 +/- 3.6 mU/ml in week 6.(ABSTRACT TRUNCATED AT 250 WORDS)     

Early neonatal lamb mortality: postmortem findings

An investigation of stillbirth and early neonatal lamb mortality was conducted in sheep flocks in Norway. Knowledge of actual causes of death are important to aid the interpretation of results obtained during studies assessing the risk factors for lamb mortality, and when tailoring preventive measures at the flock, ewe and individual lamb level. This paper reports on the postmortem findings in 270 liveborn lambs that died during the first 5 days after birth. The lambs were from 17 flocks in six counties. A total of 27% died within 3 h after birth, 41% within 24 h and 80% within 2 days. Most lambs (62%) were from triplet or higher order litters. In 81% of twin and larger litters, only one lamb died. The most frequently identified cause of neonatal death was infectious disease (n=97, 36%); 48% (n=47) of these died from septicaemia, 25% (n=24) from pneumonia, 22% (n=21) from gastrointestinal infections and 5% (n=5) from other infections. Escherichia coli accounted for 65% of the septicaemic cases, and were the most common causal agent obtained from all cases of infection (41%). In total, 14% of neonatal deaths resulted from infection by this bacterium. Traumatic lesions were the primary cause of death in 20% (n=53) of the lambs. A total of 46% of these died within 3 h after birth and 66% within 24 h. Severe congenital malformations were found in 10% (n=27) of the lambs, whereas starvation with no concurrent lesions was the cause of death in 6% (n=17). In 16% (n=43) of the lambs, no specific cause of death was identified, lambs from triplet and higher order litters being overrepresented among these cases. In this study, the main causes of neonatal lamb mortality were infection and traumatic lesions. Most neonatal deaths occurred shortly after birth, suggesting that events related to lambing and the immediate post-lambing period are critical for lamb survival.     

The effect of maternal exposure to endocrine disrupting chemicals on fetal and neonatal development: A review on the major concerns

There is a widespread exposure of general population, including pregnant women and developing fetuses, to the endocrine disrupting chemicals (EDCs). These chemicals have been reported to be present in urine, blood serum, breast milk, and amniotic fluid. Endocrine disruptions induced by environmental toxicants have placed a heavy burden on society, since environmental exposures during critical periods of development can permanently reprogram normal physiological responses, thereby increasing susceptibility to disease later in life—a process known as developmental reprogramming. During development, organogenesis and tissue differentiation occur through a continuous series of tightly‐regulated and precisely‐timed molecular, biochemical, and cellular events. Humans may encounter EDCs daily and during all stages of life, from conception and fetal development through adulthood and senescence. Nevertheless, prenatal and early postnatal windows are the most critical for proper development, due to rapid changes in system growth. Although there are still gaps in our knowledge, currently available data support the urgent need for health and environmental policies aimed at protecting the public and, in particular, the developing fetus and women of reproductive age. Birth Defects Research (Part C) 108:224–242, 2016. © 2016 Wiley Periodicals, Inc.     

Neural factors in the development of renal function: effect of neonatal central catecholaminergic lesions with 6-hydroxydopamine.

Peripheral sympathetic neurons are thought to provide trophic regulatory signals for development of their target tissues. In the current study, we investigated the role of sympathetic tone in the functional development of the kidney in rats, using neonatal intracisternal administration of 6-hydroxydopamine (6-OHDA). This treatment destroys central catecholaminergic pathways and permanently reduces sympathetic activity without ablating peripheral nerve terminals. Renal function was evaluated over the first two postnatal weeks, when glomerular and tubular function undergo rapid development. Although basal renal clearance and the homeostatic response to fluid deprivation developed normally in the lesioned rats, the response to a maximally-effective dose of desmopressin acetate (DDAVP), a vasopressin analog, became deficient by the end of the second week. After weaning, the lesioned animals were unable to survive a chronic salt load, which requires sustained water reabsorption but high output of sodium. These data indicate that normal sympathetic tone is required for appropriate development of the responsiveness of the renal tubule to vasopressin.     

Influence of maternal nicotine exposure on neonatal rat bone: protective effect of pentoxifylline

Limited research in young adults and immature animals suggests a detrimental effect of tobacco on bone during growth. The aim of this study was to determine the adverse effects of maternal nicotine exposure during pregnancy and lactation on neonatal rat bone development, and to determine a protective effect of pentoxifylline (PTX). Gravid rats were assigned into four groups, one control (group I) and three experimental (groups II, III, and IV). In group II, pregnant rats received 3 mg/kg/day nicotine alone, subcutaneously, until 21 days postnatal. In group III, pregnant rats received nicotine (3 mg/kg/day) and PTX (60 mg/kg/day). In group IV, pregnant rats received PTX alone (60 mg/kg/day). Whole body mineral density (BMD), content (BMC), area (BA), and histopathologic and morphologic findings of the femur were determined at 21 days of age. The study revealed that nicotine exposure (group II) decreased birth weight, pregnancy weight gain, and length of femur compared with other groups (P < 0.01). Birth weight was higher in groups III (PTX + nicotine) and IV (PTX) than in group II (nicotine). Body weight at 21 days of age was higher (P = 0.009) in the PTX alone group (group IV) compared with the other groups. BMD was higher (P < 0.001) in the PTX-treated groups (group III and IV) compared with other groups. In addition, there were more apoptotic chondrocytes in the hypertrophic zone of rats exposed to nicotine alone (group II) compared with the other groups (P < 0.001). In conclusion, maternal nicotine exposure resulted in decreased birth weight, pregnancy weight gain, and bone lengthening, and increased apoptosis. Pentoxifylline supplementation was found to prevent the adverse effects of maternal nicotine exposure on BMD and birth weight.     

Behavioural patterns in ewe–lamb pairs and vulnerability to predation by wolverines

In Norway domestic sheep Ovis aries range unattended in mountainous areas during the summer season. Wolverines Gulo gulo re-established in the alpine regions of southern Norway during recent decades and are viewed as a substantial predator on lambs. Reducing predation on sheep by wolverines would not only reduce the economic loss to farmers but also promote the acceptance of wolverines in their summer ranges. We hypothesized that male lambs would be more prone to wolverine predation, because of higher locomotor activity, lower behavioural ewe–lamb synchrony and larger ewe–lamb distance. We studied ewe and lamb behavioural patterns, synchrony and ewe–lamb distance on a summer range in Knutshøi, south-central Norway. Although no differences were found in ewe–lamb distance or locomotor activity in gender, female lambs synchronized their behaviour more with their mother than males. Only for female lambs, increased synchrony resulted in closer ewe–lamb distances. Overall losses to wolverines based on long-term data indicate that male lambs are more prone to predation than females later in the season. These sex-specific behavioural differences in lambs affect the spatial and social relationships between ewe and lamb, and are likely to increase with age eventually leading to sexual segregation. Male lambs can therefore be expected to be more prone to wolverine predation towards the end of the season, when lambs become independent from the ewe.     

Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats

The renin-angiotensin system (RAS) has been implicated in pulmonary hypertension and pulmonary fibrosis. In the present study, we examined the effects of maternal exposure to captopril (2.85 mg/kg/day) during late pregnancy (G13-G21) on postnatal rat lung development. Treatment with captopril during late pregnancy caused a significant decrease in ACE activity in P0 rats. Body weight decreased at P0 (p<0.001), P8 and P15 (p<0.01) in captopril-treated rats. Lung weight of P0 and P8 pups was lower in treated-animals (p<0.05). Lungs from captopril-treated animals showed impaired alveolar formation, with enlarged distal airway spaces at P8, P15 and P30. Interalveolar wall distance measured by mean linear intercept increased in treated vs. age-matched animals at P8, P15 (p<0.001) and P30 (p<0.05) resembling new bronchopulmonary dysplasia. In control animals, the proliferating cell nuclear antigen (PCNA) marker was higher at P0 and then drops gradually, while in captopril-treated animals PCNA marker remains higher at all stages studied. α-Smooth muscle actin (α-SMA), a marker of fibroblast differentiation into myofibroblasts, was higher at the tips of developing secondary septa in captopril-treated lungs at P8 and P15. The increased expression of PCNA and α-SMA in treated pups suggest that beyond the effect caused by captopril, the developing lungs have the capacity to recover once the treatment was stopped. Taking together the low weight, histomorphological changes and increased expression of cellular markers caused by ACE inhibition during late pregnancy, it appears that the RAS could be an intrinsic factor involved in secondary septa formation during lung development.     

Interaction between maternal effect and zygotic effect mutations during maize seed development

Double fertilization of the embryo sac by the two sperm cells of a pollen grain initiates seed development. Proper development of the seed depends not only on the action of genes from the resulting embryo and endosperm, but also on maternal genes acting at two stages. Mutations with both sporophytic maternal effects and gametophytic maternal effects have been identified. A new maternal effect mutation in maize, maternal effect lethal1 (mel1), causes the production of defective seed from mutant female gametophytes. It shows reduced pollen transmission, suggesting a requirement in the male gametophyte, but has no paternal effect on seed development. Interestingly, the defective kernel phenotype of mel1 is conditioned only in seeds that inherit mel1 maternally and are homozygous for the recessive allele (endogenous to the W22 inbred line) of either of two genes, sporophyte enhancer of mel1 (snm1) or snm2, suggesting redundancy between maternally and zygotically required genes. Both mel1 and snm1 map to the short arm of chromosome 2, and snm2 maps to the long arm of chromosome 10. The mode of action of mel1 and the relationship between mel1 and snm1 and snm2 are discussed.     

The effect of spray washing on the development of bacterial numbers and storage life of lamb carcases

Total bacterial numbers at the most highly contaminated sites on lamb carcases (in the crutch region and adjacent to the abdominal incision) were significantly reduced to log₁₀ 3.3/cm² when spray washed with unchlorinated water at 80°C and to log₁₀ 2.8 when water at 80°C containing 450 μg/ml chlorine was used, whereas numbers on carcases which were cloth cleaned or spray washed with water at 10°C remained at approximately log₁₀ 4.0. During refrigerated storage, however, carcases treated by all methods developed similar numbers of bacteria and had the same storage life, evidently because spray washing did not affect numbers of bacteria on the diaphragm. Although initial numbers of bacteria at this site were low (log₁₀ 2.9), their numbers, and also the amount of slime, increased more rapidly there than at other sites. In addition, spray washing did not significantly affect numbers of Pseudomonas spp or Brochothrix thermosphacta , which accounted for <1% of the microflora after slaughter at each site but whose numbers were between log₁₀ 6.1 and 7.5/cm² when carcases were rejected as spoiled.     

The effect of maternal cytomegalovirus infection on preimplantation development in the mouse.

Mice were inoculated with murine cytomegalovirus at 14 and 7 days before and 1 and 4 days after mating. The effects of maternal infection on early pregnancy were investigated. Inoculation 7 days before and 1 day after mating, i.e. around ovulation and implantation, significantly reduced pregnancy rate. Embryos in these females were developmentally retarded, perhaps because of the inflammatory effect of the infection on the genital tract. Retarded embryos developed normally when cultured.     

The influence of antenatal and maternal factors on stillbirths and neonatal deaths in New South Wales, Australia

This study identified the influences of maternal socio-demographic and antenatal factors on stillbirths and neonatal deaths in New South Wales, Australia. Bivariate and multivariate analyses were used to explore the association of selected antenatal and maternal characteristics with stillbirths and neonatal deaths. The findings of this study showed that stillbirths and neonatal deaths significantly varied by infant sex, maternal age, Aboriginality, maternal country of birth, socioeconomic status, parity, maternal smoking behaviour during pregnancy, maternal diabetes mellitus, maternal hypertension, antenatal care, plurality of birth, low birth weight, place of birth, delivery type, maternal deaths and small gestational age. First-born infants, twins and infants born to teenage mothers, Aboriginal mothers, those who smoked during the pregnancy and those of lower socioeconomic status were at increased risk of stillbirths and neonatal deaths. The most common causes of stillbirths were conditions originating in the perinatal period: intrauterine hypoxia and asphyxia. Congenital malformations, including deformities and chromosomal abnormalities, and disorders related to slow fetal growth, short gestation and low birth weight were the most common causes of neonatal deaths. The findings indicate that very low birth weight (less than 2,000 g) contributed 75.6% of the population-attributable risks to stillbirths and 59.4% to neonatal deaths. Low gestational age (less than 32 weeks) accounted for 77.7% of stillbirths and 87.9% of neonatal deaths. The findings of this study suggest that in order to reduce stillbirths and neonatal deaths, it is essential to include strategies to predict and prevent prematurity and low birth weight, and that there is a need to focus on anti-smoking campaigns during pregnancy, optimizing antenatal care and other healthcare programmes targeted at the socially disadvantaged populations identified in this study.     

Amplitude modulation of the nightly melatonin rise in the neonatal lamb and the subsequent timing of puberty

Spring-born female lambs require a decrease in day length for the normal timing of puberty the following autumn. If this decrease occurs early in postnatal life (i.e. 0-10 weeks), puberty is delayed. This study tested the hypothesis that failure of the neonatal lamb to respond to the critical long-day to short-day signal is due to inadequate nocturnal melatonin secretion. The approach was to artificially increase, to adult levels, the low nighttime rises of melatonin during the early postnatal period. Eight female lambs served as controls; they were raised on short days until 17 wk of age, and then exposed to 5 wk of long days, after which they were returned to short days. This alternating sequence of photoperiods during mid-development would be expected to induce normal puberty. Sixteen experimental females were exposed to the critical block of long days much earlier; they were placed in long days between 2 and 7 wk of age and in short days thereafter. Half (n = 8) received no further treatment. The other half (n = 8) were infused nightly with melatonin during the 8-h dark phase of the 5-wk, long-day photoperiod. This increased the amplitude of the natural nighttime melatonin rises 3- to 4-fold, well into the adult range.(ABSTRACT TRUNCATED AT 250 WORDS)