Postnatal Conditions Research Articles

The response to naltrexone in ethanol-drinking rats depends on early environmental experiences

The opioid receptor antagonist naltrexone is currently used in the treatment of alcohol addiction. However, substantial individual differences have been reported for the efficacy of naltrexone. Genetic factors are known to contribute to these differences; however, little is known about the impact of early environmental influences. Based on previous findings that have suggested a link between ethanol, endogenous opioids and the early environment, it was hypothesised that early environmental factors affect naltrexone efficacy later in life. A population of Wistar rats was subjected to three different rearing conditions where the pups experienced a daily separation from the dam, for either 15min or 360min, or were just briefly handled. On postnatal day 26, the rats were given intermittent access to ethanol (5% and 20%) and water for six weeks before naltrexone (0.3mg/kg or 3.0mg/kg) or saline treatment using a randomised injection schedule with a one-week washout period between injections. Naltrexone reduced ethanol consumption, but there was high variability in the efficacy. In addition, there was an association between the rearing condition and the effectiveness of naltrexone. Naltrexone reduced ethanol intake in rats experiencing postnatal conditions that contrasted normal wildlife conditions, i.e., prolonged absence or continuous presence of the dam, and naltrexone had no effect on the total ethanol consumption in rats reared under naturalistic conditions, i.e., short absences of the dam. These rats reduced their intake of 5% ethanol but increased their preference for 20% ethanol. We conclude that rats with a history of early adversity responded well to naltrexone treatment, whereas rats reared in a social context similar to that found in nature did not benefit from treatment. The present study highlights the importance of not only considering genetics but also environmental factors when identifying individual responses to naltrexone.

Life-stage specific environments in a cichlid fish: implications for inducible maternal effects

Through environmentally induced maternal effects females may fine-tune their offspring’s phenotype to the conditions offspring will encounter after birth. If juvenile and adult ecologies differ, the conditions mothers experienced as juveniles may better predict their offspring’s environment than the adult females’ conditions. Maternal effects induced by the environment experienced by females during their early ontogeny should evolve when three ecological conditions are met: (1) Adult ecology does not predict the postnatal environmental conditions of offspring; (2) Environmental conditions for juveniles are correlated across successive generations; and (3) Juveniles occasionally settle in conditions that differ from the juvenile habitat of their mothers. By combining size-structured population counts, ecological surveys and a genetic analysis of population structure we provide evidence that all three conditions hold for Simochromis pleurospilus, a cichlid fish in which mothers adjust offspring quality to their own juvenile ecology. In particular we show (1) that the spatial niches and the habitat quality differ between juveniles and adults, and we provide genetic evidence (2) that usually fish of successive generations grow up in similar habitats, and (3) that occasional dispersal in populations with a different habitat quality is likely to occur. As adults of many species cannot predict their offspring’s environment from ambient cues, life-stage specific maternal effects are likely to be common in animals. It will therefore be necessary to incorporate parental ontogeny in the study of parental effects when juveniles and adults inhabit different environments.

出産前後の口腔内状態とオーラルケアに関する調査（2） ―妊婦のつわりの実態について―

出産前後の口腔内状態とオーラルケアに関する調査（2） ―妊婦のつわりの実態について―

Prefrontal cortex gyrification index in twins: an MRI study

Cortical development and folding seems to be under environmental as well as genetic control. The aim of our study was to estimate the genetic influence on gyrification and cortical volumes, comparing prefrontal gyrification index (GI) in monozygotic (MZ) and dizygotic (DZ) twin pairs, and unrelated pairs. Twenty-four subjects (6 pairs of MZ and 6 pairs of DZ twins) were included in this study. Prefrontal cortical folding (gyrification) was measured by an automated and manual version of the gyrification index (A-GI, M-GI) according to previously published protocols. MR-imaging was performed and 3 representative slices were selected from coronar MR-imaging scans. The volumes of the total brain, temporal lobes, prefrontal lobes, and cerebellum were analyzed, too. To evaluate similarity in GI, absolute differences in GI, and brain volumes as well as intraclass correlations of twin pairs were compared with regard to twin status. Finally, a control group of unrelated pairs was assembled from the first two study groups and analyzed. Compared to unrelated pairs, twin pairs exhibited more similarity concerning different brain volumes and a trend to more similarity concerning A-GI. MZ twins did not present more similarity concerning GI (automatically and manually measured) and volume measurements compared to DZ twins. Different factors, like intrauterine factors, postnatal development conditions, and especially environmental factors might account for the differences between related and unrelated pairs. The nonexistence of a pronounced similarity in MZ twins compared to DZ twins concerning prefrontal GI raises questions about the extent of genetic influence on GI.

Cortical Development in the Fetus and the Newborn

Brain function is tightly linked to the development of the cortex. Until recently, assessing the human cortical development and folding was not possible in vivo. It is magnetic resonance imaging and new post-processing image analysis tools that have improved the understanding of cortical development. The combination of conventional magnetic resonance imaging and diffusion tensor imaging has further allowed depiction of the relationship of changes in intracortical layering and cortical folding. Being able to follow these early developmental processes has elucidated changes in early brain development due to changed environmental conditions in fetal life such as twinning and fetal growth restriction and postnatal conditions such as prematurity. This review further illustrates new data on brain structural asymmetries linked to the emergence of early language functions.

CANTAB delayed matching to sample task performance in juvenile baboons

This study reports the administration of the Cambridge Neuropsychological Test Automated Battery system's delayed matching to sample (DMTS) task to juvenile baboons. Nine subjects (female = 5, male = 4) were trained with delay intervals ranging from 0 to 80 s. Trial unique stimuli were utilized in combination with matching to sample, in contrast to non-matching to sample, to more accurately assess components of medial temporal lobe (hippocampal formation) mediated working memory. These parameters force subjects to rely on recognition for matching stimuli and overcome their innate tendency to choose novel stimuli (non-matching), thus increasing task difficulty. Testing with delays intervals of 0–2, 4, 8, and 16 s revealed decreased percent correct responding as delay intervals increased. An effect of 1 vs. 3 distractor stimuli on accuracy was also noted. Increasing the number of distractors resulted in decreased observing response latencies. The increase in choice response latency seen with increasing delay interval was independent of number of distractor stimuli presented. There were no sex differences in task performance. Our laboratory is focused on understanding the functional consequences of suboptimal conditions during pregnancy and early postnatal life in offspring. The ability of juvenile baboons to perform the DMTS task demonstrates the utility of this non-human primate model in examining pre- and post-natal conditions that impact the development of working memory. Evaluation of causes and consequences of impaired working memory in a variety of human diseases will be assisted by the use of this task in nonhuman primate models of human health and disease.

Color Doppler myocardial imaging demonstrates reduced diastolic tissue velocity in growth retarded fetuses with flow redistribution

ObjectivesIn fetuses suffering from intrauterine growth retardation with cerebroplacental redistribution (IUGR CPR), the diastolic heart function may be particularly susceptible to hypoxemia as described in postnatal pathological conditions. Using the newly introduced ultrasound technique, color Doppler myocardial imaging (CDMI), we investigated the correlation between diastolic tissue velocities and diastolic blood flow velocities and compared diastolic myocardial tissue velocities in fetuses with IUGR CPR and normal fetuses. Study designPeak early and active atrial tissue velocities (E’ and A’) were acquired from both ventricular free walls in 18 fetuses with IUGR CPR and 42 normal fetuses. In 35 normal fetuses, blood flow across the atrio-ventricular valves was also recorded. Umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV) flows were obtained in all fetuses. Nonparametric tests were used for statistical analysis. ResultsThere was a tendency towards increased E’ and A’ with fetal age in normal pregnancies. No correlation between tissue velocity and blood flow velocity was established. IUGR CPR fetuses had significantly lower E’ and A’, but when indexing to heart length, only A’ remained significantly lower. E’/A’ ratio was increased in the left ventricle but unchanged in the right. ConclusionCDMI is easily applicable during standard fetal echocardiography and provides new information on the diastolic properties of the fetal myocardium. In fetuses with IUGR CPR, diastolic tissue velocities are abnormal and especially A’ may be a marker of diastolic dysfunction.

Elimination of the maternally induced adaptive immune response allows uniform achievement of high level allogeneic chimerism by in utero hematopoietic cell transplantation and postnatal minimal conditioning BMT

Elimination of the maternally induced adaptive immune response allows uniform achievement of high level allogeneic chimerism by in utero hematopoietic cell transplantation and postnatal minimal conditioning BMT

出産前後の口腔内状態とオーラルケアに関する調査（１） ―妊婦の実態について

出産前後の口腔内状態とオーラルケアに関する調査（１） ―妊婦の実態について

The Long-Term Economic Impact of In Utero and Postnatal Exposure to Malaria

This paper examines the long-term economic impact of in utero and postnatal exposure to malaria using historical data from the United States. Recent research shows that individuals who were exposed to early-life health shocks have worse outcomes as adults, all else being equal. Because malaria has an acute impact on in utero and postnatal health conditions, such exposure may have significant economic effects over the life cycle. To test this conjecture, I match adults in the 1960 Decennial Census to the malaria death rate in their state-year of birth. Because malaria death rates are potentially correlated with important omitted variables and measured with error, I employ a novel identification strategy that uses variation in interacted hot and rainy weather conditions to instrument for malaria exposure. The IV estimates indicate that adults exposed to malaria around the time of birth had significantly lower levels of educational attainment.

Sex allocation in yellow-legged gulls (Larus michahellis) depends on nutritional constraints on production of large last eggs

Male and female offspring can differ in their susceptibility to pre-natal (e.g. egg quality) and post-natal (e.g. sib-sib competition) conditions, and parents can therefore increase their individual fitness by adjusting these maternal effects according to offspring sex. In birds, egg mass and laying/hatching order are the main determinants of offspring viability, but these effects can act differently on each sex. In a previous study, relatively large last-laid (c-)eggs of yellow-legged gulls (Larus michahellis) were more likely to carry a female embryo. This suggests compensatory allocation of maternal resources to daughters from c-eggs, which suffer reduced viability. In the present study, we supplemented yellow-legged gulls with food during the laying period to experimentally test whether their nutritional conditions were responsible for the observed covariation between c-egg sex and mass. As predicted, food supplementation enhanced female c-eggs' mass more than that of male c-eggs. Thus, this experiment indicates that mothers strategically allocated their resources to c-eggs, possibly in order to compensate for the larger susceptibility of daughters to hatching (and laying) order. The results also suggested that mothers decided on resource allocation depending on the sex of already ovulated c-eggs, rather than ovulating ova of either sex depending on food availability.

Differential Biomechanical Development of Elastic Tissues in the Bovine Fetus

Mechanical loading conditions are important factors in the gestational development of fetal tissues. However, little is known about how mechanical loading during development modulates the structure and function of elastic tissues. We hypothesized that developing elastic tissues functionally adapt to their loading conditions. To test this hypothesis, we assessed the changes in the composition, viscoelasticity, and thermoelastic properties of elastic tissue from bovine aortas (functional during gestation) and nuchal ligaments (nonfunctional during gestation). Clear differences in the developmental timeline of elastic tissue structure and function were observed between aortic and ligament elastic tissue. Elastic tissue in the aorta developed earlier than that of the nuchal ligament, indicating a role for loading conditions in the timeline of development. Ligament elastic tissue, however, underwent rapid remodeling in late gestation-likely as a preadaptation to the sudden-onset of tensile load it experiences at birth. Finally, while the same fundamental structure-mechanical relationships were seen in both tissues, there was a clear difference in mechanical properties between the elastic tissues from the adult nuchal ligament and the adult aorta, indicating that postnatal loading conditions continue to influence tissue structure and mechanical properties, tailoring them to their functional roles in adult life.

Prenatal and infant conditioning, the mother schema, and the origins of music and religion

Existing theories of the origins of music and religion fail to account directly and convincingly for their universal emotional power and behavioural costliness. The theory of prenatal origins is based on empirically observable phenomena and involves prenatal classical conditioning, postnatal operant conditioning and the adaptive value of mother-infant bonding. The human fetus can perceive sound and acceleration from gestational week 20. The most salient sounds for the fetus are internal to the mother's body and associated with vocalisation, blood circulation, impacts (footfalls), and digestion. The protomusical sensitivity of infants may be based on prenatal associations between the mother's changing physical and emotional state and concomitant changes in both hormone levels in the placental blood and prenatally audible sound/movement patterns. Protomusical aspects of motherese, play and ritual may have emerged during a multigenerational process of operational conditioning on the basis of prenatally established associations among sound, movement and emotion. The infant's multimodal cognitive representation of its mother (mother schema) begins to develop before birth and may underlie music's personal qualities, religion's supernatural agents, and the link between the two. Prenatal theory can contribute to an explanation of musical universal such as specific features of rhythm and melody and associations between music and body movement, as well as universal commonalities of musical and religious behaviour and experience such as meaning, fulfilment, and altered states of consciousness.

Microcephaly: a radiological review

Microcephaly results from inadequate brain growth during development. It may develop in utero, and therefore be present at birth, or may develop later as a result of perinatal events or postnatal conditions. The aetiology of microcephaly may be congenital (secondary to cerebral malformations or metabolic abnormalities) or acquired, most frequently following an ischaemic insult. This distinct radiological and pathological entity is reviewed with a specific focus on aetiology.

Fetoscopic Surgery Followed by Caesarean Section Appears Beneficial for Postnatal Muscle Condition in Spina Bifida Aperta

Fetoscopic Surgery Followed by Caesarean Section Appears Beneficial for Postnatal Muscle Condition in Spina Bifida Aperta

Developmental programming and hypertension.

There is a growing body of evidence linking adverse events or exposures during early life and adult-onset diseases. After important epidemiological studies from many parts of the world, research now focuses on mechanisms of organ dysfunction and on refining the understanding of the interaction between common elements of adverse perinatal conditions, such as nutrition, oxidants, and toxins exposures. This review will focus on advances in our comprehension of developmental programming of hypertension. Recent studies have unraveled important mechanisms of oligonephronia and impaired renal function, altered vascular function and structure as well as sympathetic regulation of the cardiovascular system. Furthermore, interactions between prenatal insults and postnatal conditions are the subject of intensive research. Prematurity vs. intrauterine growth restriction modulate differently programming of high blood pressure. Along with antenatal exposure to glucocorticoids and imbalanced nutrition, a critical role for perinatal oxidative stress is emerging. While the complexity of the interactions between antenatal and postnatal influences on adult blood pressure is increasingly recognized, the importance of postnatal life in (positively) modulating developmental programming offers the hope of a critical window of opportunity to reverse programming and prevent or reduce related adult-onset diseases.

Haploidentical In Utero Hematopoietic Cell Transplantation Improves Phenotype and Can Induce Tolerance for Postnatal Same-Donor Transplants in the Canine Leukocyte Adhesion Deficiency Model

In the murine model, in utero hematopoietic cell transplantation (IUHCT) has been shown to achieve low levels of allogeneic chimerism and associated donor-specific tolerance permitting minimal conditioning postnatal hematopoietic stem cell transplantation (HSCT). In this pilot study, we investigated IUHCT in the canine leukocyte adhesion deficiency (CLAD) model. Haploidentical IUHCT resulted in stable low-level donor cell chimerism in all dogs that could be analyzed by sensitive detection methodology (4 of 10) through 18 months of follow-up. In the 2 CLAD recipients, low-level chimerism resulted in amelioration and complete reversal of the CLAD phenotype, respectively. Six recipients of IUHCT (5 carriers and 1 CLAD) subsequently received postnatal HSCT from the same haploidentical prenatal donor after minimal conditioning with busulfan 10 mg/kg. Chimerism in 2 of 5 CLAD carriers that underwent HSCT increased from < 1% pre-HSCT to sustained levels of 35% to 45%. Control animals undergoing postnatal haploidentical HSCT without IUHCT had no detectable donor chimerism. These results demonstrate that haploidentical IUHCT in the CLAD model can result in low-level donor chimerism that can prevent the lethal phenotype in CLAD dogs, and can result in donor-specific tolerance that can facilitate postnatal minimal conditioning HSCT.

A socio‐historical hypothesis for the diabetes epidemic in Chinese—Preliminary observations from Hong Kong as a natural experiment

It has been hypothesized that the emerging epidemic of diabetes in economically transitioning or recently transitioned populations is due to mismatch between developmental and mature environments. We took advantage of migration within an ethnically homogenous population to investigate this hypothesis, and the potentially modifying role of postnatal growth conditions, proxied by greater height. We used multivariable logistic regression in a population-based cross-sectional study from 1994 to 1996 of 2,341 long-term Hong Kong residents aged 25-74 years, either born in contemporaneously developed Hong Kong or migrants from economically undeveloped Guangdong. Migrant status was not associated with clinically diagnosed diabetes, odds ratio 1.05 (95% confidence interval 0.69-1.58) in adult migrants compared to Hong Kong-born natives and 1.22 (0.83-1.80) in preadult migrants, adjusted for age, sex, socio-economic position, and lifestyle. However, the association of diabetes with migrant status varied with height, suggesting a potentially complex relationship between indicators of prenatal and postnatal nutritional exposures. Compared to tall Hong Kong-born natives, the odds ratio of diabetes was 2.36 (1.20-4.61) in tall migrants, 1.94 (1.07-3.53) in short Hong Kong-born natives, but 1.04 (0.48-2.23) in short adult migrants. Additionally adjusting for body mass index and waist-hip ratio had little effect, apart from attenuating the association between short height and diabetes prevalence in Hong Kong-born natives. Whether the current epidemic of diabetes is a long-standing effect of such mismatch or a "first-generation through effect" generated by rapid economic development causing disproportionate growth remains to be determined.

Cross-fostering effect on postnatal development of rat pups exposed to methamphetamine during gestation and preweaning periods

There are studies showing that drug abuse during pregnancy may have a long-term effect on progeny of drug-abusing mothers. Our previous work demonstrated that prenatal and/or postnatal methamphetamine injections impair maternal behavior. The purpose of the present study was to assess the effect of prenatal methamphetamine or stress exposure and postnatal breeding on postnatal development of rat pups. Female rats were injected with methamphetamine (5mg/kg daily) or physiological saline prior, during and after gestation. Absolute controls did not receive any injections. On postnatal day 1, pups were cross-fostered so that each mother received some of her own and some of the pups from the mothers with the other two treatments. Pups were weighted daily for the entire lactation period. Postural motor reaction development was examined daily by righting reflex between postnatal day 1 and 12. On postnatal day 15 homing test examining pups’ nest-seeking behavior was performed. On postnatal day 23 rotarod and bar-holding tests were used to investigate sensorimotor coordination of pups. We demonstrated that prenatal methamphetamine exposure impairs performance of sensorimotor tests (righting reflex on surface and rotarod test). Moreover, the effect of methamphetamine as well as the effect of prenatal stress induced by saline injections was affected by postnatal breeding conditions in sensorimotor tests as well as in the test of homing. Our results support the hypothesis that the variation in rat maternal care could serve as a mechanism for a nongenomic behavioral mode of transmission of traits.

Hedgehog signaling is essential for normal wound healing

The hedgehog family of morphogens (sonic [Shh], Indian, and desert hedgehog) are central regulators of embryologic growth and tissue patterning. Although recent work implicates Shh in postnatal tissue repair and development, conclusive evidence is lacking. Here, we demonstrated the importance of Shh in wound repair, by examining the effects of cyclopamine, a specific inhibitor of the Shh signaling cascade, on tissue repair. Using a murine-splinted excisional wound model, which attenuates wound contraction in this loose-skinned rodent, we established that, by all measures (wound closure, epithelialization, granulation formation, vascularity, and proliferation), wound healing was profoundly impaired when Shh signaling was disrupted. Because embryonic disruption of Shh is associated with distinct phenotypic defects, our findings invite investigation of the potential role of Shh signaling under postnatal conditions associated with disregulated wound healing.