Phase Contrast Imaging Reveals Low Lung Volumes and Surface Areas in the Developing Marsupial

Marsupials are born with immature lungs when compared to eutherian mammals and rely, to various extents, on cutaneous gas exchange in order to meet metabolic requirements. Indeed, the fat-tailed dunnart is born with lungs in the canalicular stage of development and relies almost entirely on the skin for gas exchange at birth; consequently undergoing the majority of lung development in air. Plane radiographs and computed tomography data sets were acquired using phase contrast imaging with a synchrotron radiation source for two marsupial species, the fat-tailed dunnart and the larger tammar wallaby, during the first weeks of postnatal life. Phase contrast imaging revealed that only two lung sacs contain air after the first hour of life in the fat-tailed dunnart. While the lung of the tammar wallaby was comparatively more developed, both species demonstrated massive increases in air sac number and architectural complexity during the postnatal period. In addition, both the tammar wallaby and fat-tailed dunnart had lower lung volumes and parenchymal surface areas than were expected from morphometrically determined allometric equations relating these variables to body mass during the neonatal period. However, lung volume is predicted to scale with mass as expected after the neonatal marsupial reaches a body mass of ∼1 g and no longer relies on the skin for gas exchange. Decreased lung volume in the marsupial neonate further supports the maxim that cutaneous gas exchange occurs in the marsupial neonate because the respiratory apparatus is not yet capable of meeting the gas exchange requirements of the newborn.     

Ontogenetic and lung development in Tupaia belangeri during the early postnatal period

The Belanger's tree shrew (Tupaia belangeri) has an unusual reproductive strategy. The animals are born in altricial condition and remain in the nest for the first four weeks of life, nursed only once in 48 h. This is highly demanding for the constitution of the neonates. Despite their immaturity in the external appearance at birth, newborn tree shrews have to deal with the absence of the mother. We asked if the lung structure of the neonates match the high physiological requirements of this “absentee system”. To examine the lung development of nest young tree shrews, histological and ultrastructural investigations were performed. Newborn tree shrews are at the transition stage between the saccular and the alveolar stage of lung development. In addition to small saccules, the lung has alveoli and associated structures already at birth and thus appears more mature compared with typical altricial species. The results of the present study reveal that despite their immaturity in the external appearance newborn tree shrews are relatively mature in terms of lung development. This can be interpreted as a prerequisite for thermoregulatory abilities, necessary in neonate tree shrews to cope with the restricted nature of maternal care.     

The Placentation of Eulipotyphla—Reconstructing a Morphotype of the Mammalian Placenta

Placentation determines the developmental status of the neonate, which can be considered as the most vulnerable stage in the mammalian life cycle. In this respect, the different evolutionary and ecological adaptations of marsupial and placental mammals have most likely been associated with the different reproductive strategies of the two therian clades. The morphotypes of marsupial and placental neonates, as well as the placental stem species pattern of Marsupialia, have already been reconstructed. To contribute to a better understanding of the evolution of Placentalia, a histological and ultrastructural investigation of the placenta in three representatives of Eulipotyphla, that is, core insectivores, has been carried out in this study. We studied the Musk shrew (Suncus murinus), the four‐toed hedgehog (Atelerix albiventris), and the Iberian mole (Talpa occidentalis). As a result, a eulipotyphlan placental morphotype consisting of a compact and invasive placenta was reconstructed. This supports the widely accepted hypothesis that the stem lineage of Placentalia is characterized by an invasive, either endothelio‐ or hemochorial placenta. Evolutionary transformations toward a diffuse, noninvasive placenta occurred in the stem lineages of lower primates and cetartiodactyles and were associated with prolonged gestation and the production of few and highly precocial neonates. Compared to the choriovitelline placenta of Marsupialia, the chorioallantoic placenta of Placentalia allows for a more intimate contact and is associated with more advanced neonates. J. Morphol. 275:1122–1144, 2014. © 2014 Wiley Periodicals, Inc.     

Perinatal adaptation in mammals: the impact of metabolic rate.

Mammalian birth is accompanied by profound changes in metabolic rate that can be described in terms of body size relationship (Kleiber's rule). Whereas the fetus, probably as an adaptation to the low intrauterine pO2, exhibits an "inappropriately" low, adult-like specific metabolic rate, the term neonate undergoes a rapid metabolic increase up to the level to be expected from body size. A similar, albeit slowed, "switching-on" of metabolic size allometry is found in human preterm neonates whereas animals that are normally born in a very immature state are able to retard or even suppress the postnatal metabolic increase in favor of weight gain and O2 supply. Moreover, small immature mammalian neonates exhibit a temporary oxyconforming behavior which enhances their hypoxia tolerance, yet is lost to the extent by which the size-adjusted metabolic rate is "locked" by increasing mitochondrial density. Beyond the perinatal period, there are no other deviations from metabolic size allometry among mammals except in hibernation where the temporary "switching-off" of Kleiber's rule is accompanied by a deep reduction in tissue pO2. This gives support to the hypothesis that the postnatal metabolic increase represents an "escape from oxygen" similar to the evolutionary roots of mitochondrial respiration, and that the overall increase in specific metabolic rate with decreasing size might contribute to prevent tissues from O2 toxicity.     

Loss of Hox5 function results in myofibroblast mislocalization and distal lung matrix defects during postnatal development

Alveologenesis is the final stage of lung development and is responsible for the formation of the principle gas exchange units called alveoli. The lung mesenchyme, in particular the alveolar myofibroblasts, are drivers of alveolar development, however,few key regulators that govern the proper distribution and behavior of these cells in the distal lung during alveologenesis have been identified. While Hox5 triple mutants(Hox5 aabbcc) exhibit neonatal lethality, four-allele, compound mutant mice(Hox5 AabbCc) are born in Mendelian ratios and are phenotypically normal at birth. However, they exhibit defects in alveologenesis characterized by a BPD-like phenotype by early postnatal stages that becomes more pronounced at adult stages. Invasive pulmonary functional analyses demonstrate significant increases in total lung volume and compliance and a decrease in elastance in Hox5 compound mutants. SMA+ myofibroblasts in the distal lung are distributed abnormally during peak stages of alveologenesis and aggregate, resulting in the formation of a disrupted elastin network. Examination of other key components of the distal lung ECM, as well as other epithelial cells and lipofibroblasts reveal no differences in distribution. Collectively, these data indicate that Hox5 genes play a critical role in alveolar development by governing the proper cellular behavior of myofibroblasts during alveologenesis.     

Perinatal adaptation in mammals: the impact of metabolic rate

Mammalian birth is accompanied by profound changes in metabolic rate that can be described in terms of body size relationship (Kleiber's rule). Whereas the fetus, probably as an adaptation to the low intrauterine pO₂, exhibits an “inappropriately” low, adult-like specific metabolic rate, the term neonate undergoes a rapid metabolic increase up to the level to be expected from body size. A similar, albeit slowed, “switching-on” of metabolic size allometry is found in human preterm neonates whereas animals that are normally born in a very immature state are able to retard or even suppress the postnatal metabolic increase in favor of weight gain and O₂ supply. Moreover, small immature mammalian neonates exhibit a temporary oxyconforming behavior which enhances their hypoxia tolerance, yet is lost to the extent by which the size-adjusted metabolic rate is “locked” by increasing mitochondrial density. Beyond the perinatal period, there are no other deviations from metabolic size allometry among mammals except in hibernation where the temporary “switching-off” of Kleiber's rule is accompanied by a deep reduction in tissue pO₂. This gives support to the hypothesis that the postnatal metabolic increase represents an “escape from oxygen” similar to the evolutionary roots of mitochondrial respiration, and that the overall increase in specific metabolic rate with decreasing size might contribute to prevent tissues from O₂ toxicity.     

Electron microscopy and microcalorimetry of the postnatal rat heart (Rattus norvegicus)

The interplay of ultrastructure and tissue metabolism was examined in neonatal, infant and adult rat hearts by electron microscopy and microcalorimetry. Morphometry was used to determine parameters of oxygen diffusion capacity (distance between capillaries and mitochondria, capillary surface density) and oxidative metabolic capacity (mitochondrial volume fraction). Thin slices and large samples of living tissue were examined calorimetrically to quantify aerobic metabolism and ischemia tolerance, respectively. After birth, rat hearts grow in parallel to body mass and show characteristics of cellular hypertrophy. Capillary surface density increases from neonatal to infant rats, and decreases to an intermediate value in adult rats. The distance between capillaries and mitochondria shows no significant changes throughout postnatal development. Mitochondrial volume fraction increases continuously until adulthood. The specific aerobic tissue metabolic rate is higher in the neonatal than in the infant and adult rat. However, the ischemic decline in metabolic rate is much slower in the neonatal rat, reflecting an elevated hypoxia tolerance. In conclusion, the neonatal rat heart exhibits a high metabolic rate despite a low mitochondrial volume fraction. The subsequent structural rearrangements can be interpreted as long-term adaptations to the increased postnatal workload and may contribute to the progressive loss of hypoxia tolerance.     

Prematurity and insulin sensitivity

Premature infants of low and extremely low birth weight represent a challenge for neonatal intensive care units and paediatricians. These neonates may be at increased risk of insulin resistance and diabetes perinatally and during childhood. During the first week of postnatal life, infants born prematurely are at risk of abnormalities in glucose homeostasis. Additionally, there are major differences in their glucose/insulin homeostasis compared with infants born at term. Preterm infants are at risk of hypoglycaemia, due to decreases in deposits of glycogen and fat that occur during the third trimester, and also to transient hyperinsulinaemia. Hyperglycaemia may also be observed in preterm infants during the perinatal period. These infants are unable to suppress glucose production within a large range of glucose and insulin concentrations, insulin secretory response is inappropriate, insulin processing is immature and there is an increased ratio of the glucose transporters Glut-1/Glut-2 in fetal tissues, which limits sensitivity and hepatocyte reaction to increments in glucose/insulin concentration during hyperglycaemia. In addition, increased concentrations of tumour necrosis factor alpha present in intrauterine growth retardation (IUGR) and induce insulin resistance. It has been proposed that the reduced insulin sensitivity may result from adaptation to an adverse in utero environment during a critical period of development. We have investigated postnatal insulin resistance in 60 children born with very low birth weight and either small for gestational age or at an appropriate size for gestational age. This study showed that IUGR, rather than low birth weight itself, was associated with increased fasting insulin levels. As poor fetal growth may be associated with the development of obesity, type 2 diabetes and the metabolic syndrome in later life, it is important that we continue to increase our understanding of the effects of IUGR on postnatal growth and metabolism.     

Maternal reproductive experience enhances early postnatal outcome following gestation and birth of rats in hypergravity

A major goal of space life sciences research is to broaden scientific knowledge of the influence of gravity on living systems. Recent spaceflight and centrifugation studies demonstrate that reproduction and ontogenesis in mammals are amenable to study under gravitational conditions that deviate considerably from those typically experienced on Earth (1 x g). In the present study, we tested the hypothesis that maternal reproductive experience determines neonatal outcome following gestation and birth under increased (hyper) gravity. Primigravid and bigravid female rats and their offspring were exposed to 1.5 x g centrifugation from Gestational Day 11 either through birth or through the first postnatal week. On the day of birth, litter sizes were identical across gravity and parity conditions, although significantly fewer live neonates were observed among hypergravity-reared litters born to primigravid dams than among those born to bigravid dams (82% and 94%, respectively; 1.0 x g controls, 99%). Within the hypergravity groups, neonatal mortality was comparable across parity conditions from Postnatal Day 1 through Day 7, at which time litter sizes stabilized. Maternal reproductive experience ameliorated neonatal losses during the first 24 h after birth but not on subsequent days, and neonatal mortality was associated with changes in maternal care patterns. These results indicate that repeated maternal reproductive experience affords protection against neonatal losses during exposure to increased gravity. Differential mortality of neonates born to primigravid versus bigravid dams denotes gravitational load as one environmental mechanism enabling the expression of parity-related variations in birth outcome.     

Review: Maternal programming of development in the pig and the lactocrine hypothesis

Maternal effects on development are profound. Together, genetic and epigenetic maternal effects define the developmental trajectory of progeny and, ultimately, offspring phenotype. Maternally provisioned environmental conditions and signals affect conceptus, fetoplacental and postnatal development from the time of conception until weaning. In the pig, reproductive tract development is completed postnatally. Porcine uterine growth and uterine endometrial development occur in an ovary-independent manner between birth (postnatal day = PND 0) and PND 60. Milk-borne bioactive factors (MbFs), exemplified by relaxin, communicated from lactating dam to nursing offspring via a lactocrine mechanism, represent an important source of extraovarian uterotrophic support in the neonatal pig. Lactocrine deficiency from birth affects both the neonatal porcine uterine developmental program and trajectory of uterine development, with lasting consequences for endometrial function and uterine capacity in adult female pigs. The potential lactocrine signaling window extends from birth until the time of weaning. However, it is likely that the maternal lactocrine programming window – that period when MbFs communicated to nursing offspring have the greatest potential to affect critical organizational events in the neonate – encompasses a comparatively short period of time within 48 h of birth. Lactocrine deficiency from birth was associated with altered patterns of endometrial gene expression in neonatally lactocrine-deficient adult gilts during a critical period for conceptus–endometrial interaction on pregnancy day 13, and with reduced litter size, estimated at 1.4 pigs per litter, with no effect of parity. Data were interpreted to indicate that reproductive performance of female pigs that do not receive sufficient colostrum from birth is permanently impaired. Observations to date suggest that lactocrine-dependent maternal effects program postnatal development of the porcine uterus, endometrial functionality and uterine capacity. In this context, reproductive management strategies and husbandry guidelines should be refined to ensure that such practices promote environmental conditions that will optimize uterine capacity and fecundity. This will entail careful consideration of factors affecting lactation, the quality and abundance of colostrum/milk, and practices that will afford neonatal pigs with the opportunity to nurse and consume adequate amounts of colostrum.     

Mercury and selenium concentrations in maternal and neonatal scalp hair: relationship to amalgam-based dental treatment received during pregnancy

Mercury and selenium concentrations were determined in scalp hair samples collected postpartum from 82 term pregnancy mothers and their neonates. Maternal mercury and selenium had median concentrations of 0.39 μg/g (range 0.1–2.13 μg/g) and 0.75 μg/g (range 0.1–3.95 μg/g), respectively, and corresponding median neonatal values were 0.24 μg/g (range 0.1–1.93 μg) and 0.52 μg/g (range (0.1–3.0 μg/g). Amalgam-based restorative dental treatment received during pregnancy by 27 mothers (Group I) was associated with significantly higher mercury concentrations in their neonates (p<0.0001) compared to those born to 55 mothers (Group II) whose most recent history of such dental treatment was dated to periods ranging between 1 and 12 yr prior to pregnancy. In the Group I mother/neonate pairs, amalgam removal and replacement in 10 cases was associated with significantly higher mercury concentrations compared to 17 cases of new amalgam emplacement. Selenium concentrations showed no significant integroup differences. However, the selenium/mercury molar ratio values were lowest in the Group I neonates, compared to their mothers and to the Group II mother/neonate pairs. This ratio decreased as mercury concentration increased, and this interrelation was statistically significant in both groups of mother/neonate pairs. The data from this preliminary study suggest that amalgam-based dental treatment during pregnancy is associated with higher prenatal exposure to mercury, particularly in cases of amalgam removal and replacement. The ability of a peripheral biological tissue, such as hair, to elicit such marked differences in neonatal mercury concentrations provides supporting evidence of high fetal susceptibility to this form of mercury exposure. The data are discussed in relation to the differences between maternal and fetal mercury metabolisms and to mercury—selenium metabolic intereactions in response to mercury exposure.     

Why Baja? A bioenergetic model for comparing metabolic rates and thermoregulatory costs of gray whale calves (Eschrichtius robustus)

A bioenergetic model is developed from empirically derived equations of morphometric, ventilatory and thermoregulatory variables to compare estimated field metabolic rates (FMR) of gray whale calves to estimates of unregulated body heat losses and consequent required thermogenesis at birth, natal lagoon departure, and weaning. Estimates of FMR are based on rates of oxygen consumption. Body surface and ventilatory heat fluxes are evaluated separately, then combined to estimate minimum total heat losses from birth to weaning at three ambient water temperature regimes typical of winter natal lagoons and Oregon coastal waters and arctic conditions during summer. Modeled heat losses of neonates in winter lagoons are half their estimated mean FMR. Neonates in good body condition appear to be capable of tolerating heat losses experienced in 10°C water without additional thermogenic activities above their estimated resting metabolic rates. This study provides new evidence that no thermoregulatory advantage accrues to neonates or to their mothers by being born in warm winter natal lagoons or by remaining there several weeks longer than other gray whales. Consequently, avoidance or reduced risk of killer whale predation seems a more likely candidate than reduced heat loss as the principal fitness benefit of low-latitude winter migrations.     

Early identification of neonates at risk: traits of newborn piglets with respect to survival

Despite technological changes and improved management, piglet mortality remains a problem for both production and welfare. Most preweaning mortality occurs within the first 3 days after birth because of problems with adaptation and development. Thus, the purpose of our study was to determine the physiologic state of newborn pigs with respect to piglet survival. Data were collected from 1024 live-born piglets of 106 primiparous German Landrace sows to analyze relationships between farrowing traits, early postnatal vitality and blood chemistry, including immunity of piglets at birth. Surviving piglets were compared with those that died during the first 10 days of life. The survivors were significantly heavier at birth (P=0.001), were born earlier in the birth order (P=0.04), reached the udder and took in first colostral milk more quickly (P=0.001) and had a smaller drop in rectal temperature I h after birth (P=0.001) than dead. However, dead piglets had significantly higher blood levels of inorganic phosphorus (P=0.0001), calcium (P=0.04) and urea (P=0.05), but a lower concentration of alpha2-macroglobulin and lower lymphocyte proliferation indices in response to pokeweed mitogen (P=0.05). Models fitted for discrimination between survivors and piglets that died included, in addition to birth weight and litter size, the foraging behavior of neonates (time from birth to first suckle) and their thermoregulatory capacity (rectal temperature 1 h after birth) in the first experimental unit, as well as prenursing biochemical measures (inorganic phosphorus, calcium and glucose) in the second experimental unit. These ethophysiological and biochemical traits of early postnatal vitality are important determinants of maturity and development at birth. Hence, breeding programs and perinatal housing and feeding conditions should ensure a high physiological maturity to improve mortality rates of neonates.     

High Incidence of Neonatal Danger Signs and Its Implications for Postnatal Care in Ghana: A Cross-Sectional Study

Background

Reducing neonatal mortality is a major public health priority in sub-Saharan Africa. Numerous studies have examined the determinants of neonatal mortality, but few have explored neonatal danger signs which potentially cause morbidity. This study assessed danger signs observed in neonates at birth, determined the correlations of multiple danger signs and complications between neonates and their mothers, and identified factors associated with neonatal danger signs.

Methods

A cross-sectional study was conducted in three sites across Ghana between July and September in 2013. Using two-stage random sampling, we recruited 1,500 pairs of neonates and their mothers who had given birth within the preceding two years. We collected data on their socio-demographic characteristics, utilization of maternal and neonatal health services, and experiences with neonatal danger signs and maternal complications. We calculated the correlations of multiple danger signs and complications between neonates and their mothers, and performed multiple logistic regression analysis to identify factors associated with neonatal danger signs.

Results

More than 25% of the neonates were born with danger signs. At-birth danger signs in neonates were correlated with maternal delivery complications (r = 0.20, p < 0.001), and neonatal complications within the first six weeks of life (r = 0.19, p < 0.001). However, only 29.1% of neonates with danger signs received postnatal care in the first two days, and 52.4% at two weeks of life. In addition to maternal complications during delivery, maternal age less than 20 years, maternal education level lower than secondary school, and fewer than four antenatal care visits significantly predicted neonatal danger signs.

Conclusions

Over a quarter of neonates are born with danger signs. Maternal factors can be used to predict neonatal health condition at birth. Management of maternal health and close medical attention to high-risk neonates are crucial to reduce neonatal morbidity in Ghana.     

Developmental changes in hepatocyte growth factor mRNA and its receptor in rat liver, kidney and lung.

Hepatocyte growth factor (HGF) is a mesenchymal-derived factor which induces mitosis, cell movement and morphogenesis of tissue-like structure. We analyzed changes in HGF mRNA and its receptor, the c-met proto-oncogene product, in the liver, kidney and lung during late fetal and postnatal development in rats. In the liver, the HGF-mRNA level was very low during late gestation and in neonates, it increased remarkably and reached a maximum two weeks postnatally, to be followed by a decrease to 33% of the maximum. HGF mRNA in the kidney and lung was either undetectable or very low during late gestation and the neonatal period and increased markedly to reach a maximum, respectively, 3-4 weeks postnatally. HGF-mRNA level in the adult rat lung was fivefold higher than that in the liver and kidney. The number of HGF receptors on plasma membranes of these tissues was low in neonates but there was a rapid increase after birth and a maximum was reached within three weeks. The number of HGF receptors/ng plasma membrane protein at the maximal level was highest in the liver and lowest in the lung. c-met/HGF-receptor mRNA in the liver was also low during late-gestation or in early neonatal periods and increased postnatally. Since HGF-mRNA and HGF-receptor levels changed differently in liver, kidney and lung, the expression of HGF and its receptor may be independently regulated in each organ. However, in these organs, HGF mRNA and the HGF receptor increased within a few weeks of birth, HGF may play roles in organ growth, organ maturation and the maintenance of tissue homeostasis during the postnatal period, presumably through its potential to act as mitogen, motogen and morphogen.     

Role of dam and pups in the absence of nursing in CPB-B rats (rattus norvegicus)

In rats of the CPB-B strain, the female shows normal parturition behaviour and normal capacity of milk secretion, but the young - all born alive - die within few days of birth. Here, we report that this postnatal mortality is eliminated when CPB-B neonates are crossfostered to mothers of the Wu:Cpb strain; conversely, Wu:Cpb neonates (which are successfully reared by dams of their own strain) die within few days of birth when crossfostered to newly parturient CPB-B rats. It is suggested that pup mortality in CPB-B rats is due to inadequate maternal care resulting, supposedly, from susceptibility of the mother to disturbing environmental stimuli.     

Plasma prostaglandin levels during early neonatal life following term and pre-term delivery

The concentrations of prostaglandin E (PGE), prostaglandin F (PGF) and 13,14-dihydro-15-oxo-PGF (PGFM) have been measured by sensitive and specific radioimmunoassays in neonatal plasma after term and pre-term delivery. Blood samples were taken in the term delivery group from the umbilical artery at birth and on the sixth post-natal day and after pre-term delivery at 2–4 days, on the sixth day, at 2–4 weeks and at 5–8 weeks after birth. The levels of prostaglandins circulating during the first month of life were far greater than those found in normal adults. In neonates delivered at term the plasma concentration of PGE was significantly lower six days after delivery compared with the concentration at delivery whereas the concentrations of PGF and PGFM were essentially unchanged. Following pre-term delivery prostaglandin concentrations declined with increasing neonatal age although only levels of PGE at 5–8 weeks of age were within the normal range of adult values. Comparison of prostaglandin levels six days after delivery between neonates born at term and pre-term showed no significant differences. These results suggest that prematurity is not associated with marked abnormalities in the ability of the neonate to synthesize or metabolize prostaglandins.     

Lung development and the host response to influenza A virus are altered by different doses of neonatal oxygen in mice

Oxygen exposure in preterm infants has been associated with altered lung development and increased risk for respiratory viral infections later in life. Although the dose of oxygen sufficient to exert these changes in humans remains unknown, adult mice exposed to 100% oxygen between postnatal days 1-4 exhibit alveolar simplification and increased sensitivity to influenza virus infection. Additionally, two nonlinear thresholds of neonatal oxygen exposures were previously identified that promote modest (between 40% and 60% oxygen) and severe (between 80% and 100% oxygen) changes in lung development. Here, we investigate whether these two thresholds correlate with the severity of lung disease following respiratory viral infection. Adult mice exposed to 100% oxygen at birth, and to a lesser extent 80% oxygen, demonstrated enhanced body weight loss, persistent inflammation, and fibrosis following infection compared with infected siblings exposed to room air at birth. In contrast, the host response to infection was indistinguishable between mice exposed to room air and 40% or 60% oxygen. Interestingly, levels of monocyte chemoattractant protein (MCP)-1 were equivalently elevated in infected mice that had been exposed to 80% or 100% oxygen as neonates. However, reducing levels of MCP-1 using heterozygous Mcp-1 mice did not affect oxygen-dependent changes in the response to infection. Thus lung development and the host response to respiratory viral infection are disrupted by different doses of oxygen. Our findings suggest that measuring lung function alone may not be sufficient to identify individuals born prematurely who have increased risk for respiratory viral infection.     

Selective accumulation of Th2-skewing immature erythroid cells in developing neonatal mouse spleen

Environmental factors likely regulate neonatal immunity and self-tolerance. However, evidence that the neonatal immune system is suppressed or deviated is varied depending on the antigen and the timing of antigen exposure relative to birth. These disparate findings may be related to the availability of the appropriate antigen presenting cells but also point to the possibility of homeostatic changes in non-lymphoid cells in the relevant lymphoid tissues. Here we show that, while leukocytes are the most abundant cell population present in spleen during the first 4-5 days after birth, a massive accumulation of nucleated immature erythroid population in the spleen takes places on day 6 after birth. Although the relative frequency of these immature erythorid cells slowly decreases during the development of neonates, they remain one of the most predominant populations up to three weeks of age. Importantly, we show that the immature erythroid cells from neonate spleen have the capacity to modulate the differentiation of CD4 T cells into effector cells and provide a bias towards a Th2 type instead of Th1 type. These nucleated erythroid cells can produce cytokines that participate in the Th2/Th1 balance, an important one being IL-6. Thus, the selective accumulation of immature erythroid cells in the spleen during a specific period of neonatal development may explain the apparent differences observed in the type(s) of immune responses generated in infants and neonates. These findings are potentially relevant to the better management of immune deficiency in and to the design of vaccination strategies for the young.