Child Head Circumference and Placental MFSD2a Expression Are Associated to the Level of MFSD2a in Maternal Blood During Pregnancy.

Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephaly and intellectual impairments. Herein, we intended to identify early blood biomarkers that may be of use during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDM groups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects.

Effects of Arachidonic and Docosohexahenoic Acid Supplementation during Gestation in Rats. Implication of Placental Oxidative Stress.

Arachidonic and docosahexaenoic acids (ARA and DHA) are important during pregnancy. However, the effects of dietary supplementation on fetal growth and oxidative stress are inconclusive. We aimed to assess the effect of high ARA and DHA diet during rat gestation on: (1) ARA and DHA availability in plasma and placenta, (2) fetal growth, and (3) placental oxidative stress, analyzing the influence of sex. Experimental diet (ED) was prepared by substituting soybean oil in the control diet (CD) by a fungi/algae-based oil containing ARA and DHA (2:1). Rats were fed with CD or ED during gestation; plasma, placenta, and fetuses were obtained at gestational day 20. DHA, ARA, and their precursors were analyzed in maternal plasma and placenta by gas chromatography/mass spectrophotometry. Fetuses and placentas were weighed, the proportion of fetuses with intrauterine growth restriction (IUGR) determined, and placental lipid and protein oxidation analyzed. ED fetuses exhibited lower body weight compared to CD, being >40% IUGR; fetal weight negatively correlated with maternal plasma ARA, but not DHA. Only ED female placenta exhibited higher lipid and protein oxidation compared to its CD counterparts; lipid peroxidation is negatively associated with fetal weight. In conclusion, high ARA during gestation associates with IUGR, through placental oxidative stress, with females being more susceptible.

Loss in PKC Epsilon Causes Downregulation of MnSOD and BDNF Expression in Neurons of Alzheimer's Disease Hippocampus.

Oxidative stress and amyloid-ß (Aß) oligomers have been implicated in Alzheimer's disease (AD). The growth and maintenance of neuronal networks are influenced by brain derived neurotrophic factor (BDNF) expression, which is promoted by protein kinase C epsilon (PKCɛ). We investigated the reciprocal interaction among oxidative stress, Aß, and PKCɛ levels and subsequent PKCɛ-dependent MnSOD and BDNF expression in hippocampal pyramidal neurons. Reduced levels of PKCɛ, MnSOD, and BDNF and an increased level of Aß were also found in hippocampal neurons from autopsy-confirmed AD patients. In cultured human primary hippocampal neurons, spherical aggregation of Aß (amylospheroids) decreased PKCɛ and MnSOD. Treatment with t-butyl hydroperoxide (TBHP) increased superoxide, the oxidative DNA/RNA damage marker, 8-OHG, and Aß levels, but reduced PKCɛ, MnSOD, BDNF, and cultured neuron density. These changes were reversed with the PKCɛ activators, bryostatin and DCPLA-ME. PKCɛ knockdown suppressed PKCɛ, MnSOD, and BDNF but increased Aß. In cultured neurons, the increase in reactive oxygen species (ROS) associated with reduced PKCɛ during neurodegeneration was inhibited by the SOD mimetic MnTMPyP and the ROS scavenger NAc, indicating that strong oxidative stress suppresses PKCɛ level. Reduction of PKCɛ and MnSOD was prevented with the PKCɛ activator bryostatin in 5-6-month-old Tg2576 AD transgenic mice. In conclusion, oxidative stress and Aß decrease PKCɛ expression. Reciprocally, a depression of PKCɛ reduces BDNF and MnSOD, resulting in oxidative stress. These changes can be prevented with the PKCɛ-specific activators.

Sustained maternal hyperoxygenation improves aortic arch dimensions in fetuses with coarctation.

The aim was to investigate the impact of maternal hyperoxygenation (HO) on cardiac dimensions in fetuses with isolated Coarctation (CoA). Fetal echocardiography was performed serially in 48 fetuses with CoA and gestation age matched normal fetues. The Z-scores for the mitral valve (MV), tricuspid valve (TV), aortic valve (AV), ascending aorta (AAo), isthmus, pulmonary valve (PV), main pulmonary artery (MPA), and descending aorta (DAo) were measured and compared among normal fetuses, CoA fetuses with oxygen and CoA fetuses with air. In the group with oxygen, 6 L/min oxygen was administered to the mother using a face mask. Regression analyses were performed to identify potential factors for HO outcome. The left heart dimension Z-scores increased gradually during HO therapy periods, especially at 4 weeks after oxygen therapy (P < 0.05). As for the case group with air, the left heart dimension remained unchanged. The duration of HO was associated with aortic arch Z-scores (adjusted R2 = 0.199, 0.60 for AAO and isthmus, respectively). Sustained maternal middle-flow oxygenation can be safely used to improve left heart dimensions in fetuses with isolated CoA. The duration of HO were associated with treatment outcome. These findings may provide useful information for developing novel treatment strategies.

A case of semi-combusted pregnant female in the Phoenician-Punic necropolis of Monte Sirai (Carbonia, Sardinia, Italy).

We present a case of a pregnant woman with the fetus skeletal remains in situ, belonging to the Phoenician-Punic necropolis of Monte Sirai (Sardinia, Italy). The burial dates back to the late 6th to early 5th century BCE. Of the unborn fetal cases documented in the literature this is amongst the oldest four and it represents the first documented case of a pregnant woman in the Phoenician and Punic necropolis literature. A physico-chemical investigation of bones combining X-ray diffraction and Fourier transform-infrared spectroscopy suggests that the female skeleton and fetus were subjected to an incomplete heat treatment according to a funerary practice, perhaps limited to the period of early 5th century BCE, that appears to be peculiar to this site.

Antioxidant Supplementation Modulates Age-Related Placental Bed Morphology and Reproductive Outcome in Mice.

The number of women who delay their first childbirth is increasing. This demographic shift is an important health issue because advanced maternal age is a risk factor for reproductive capacity loss and the occurrence of placental bed disorders that may lead to placenta abruption, preeclampsia, and placenta insufficiency. A redox imbalance status, resulting from the enhanced production of reactive oxygen species or their deficient neutralization, is proposed to occur in this setting. Thus, uterine redox status was evaluated in young (8- to 12-wk-old) and reproductively aged (38- to 42-wk-old) mice. In addition, it was hypothesized that specific dietary antioxidant supplementation would restore the balance and improve the reproductive outcome of aging female mice. To test this hypothesis, two different antioxidants, the nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor apocynin and the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL), were added to the drinking water of female mice prior to and during pregnancy. Compared to younger females, uteri from reproductively aged nonpregnant mice exhibited areas of endometrial cystic dilation, increased level of NOX1 expression, and enhanced protein carbonylation, especially in the apical surface of the luminal epithelium. Both antioxidants decreased protein carbonylation level in the uterus of reproductively aged mice. When reproductively aged females became pregnant, the litter size was smaller and fetuses were heavier. The change was accompanied by a significant decrease in decidua thickness. Provision of apocynin significantly increased litter size and restored decidua thickness. Reproductively aged mice provided with TEMPOL did not evidence such benefits, but whereas apocynin normalized fetal birth weight, TEMPOL further increased it. These findings emphasize that uterine redox balance is important for reproductive success and suggest that age-related redox imbalance might be compensated by specific antioxidant supplementation.

The habenulo-interpeduncular and mammillothalamic tracts: early developed fiber tracts in the human fetal diencephalon.

PURPOSE: The habenulo-interpeduncular (HI) and mammillothalamic (MT) tracts are phylogenetically ancient. The clinical relevance of these tracts has recently received attention. In this work, we map the anatomy the developing HI and MT. METHODS: To investigate the topographical anatomy of developing fiber tracts in and around the diencephalon, we examined the horizontal, frontal, and sagittal serial paraffin sections of 28 human fetuses at 8-12 weeks of gestation. RESULTS: In all specimens, eosinophilic early fiber bundles were limited to the bilateral HI and MT tracts in contrast to pale-colored later developing fibers such as the thalamocortical projections and optic tract. The HI and MT tracts ran nearly parallel and sandwiched the thalamus from the dorsal and ventral sides, respectively. The nerve tract course appeared to range from 5-7 mm for the HI tract and 3-5 mm for the MT tract in 15 specimens at 11-12 weeks. The HI tract was embedded in, adjacent to, or distant from the developing parvocellular red nucleus. CONCLUSIONS: In early human fetuses, HI and MT tracts might be limited pathways for primitive cholinergic fiber connections between the ventral midbrain and epithalamic limbic system.

Validation of the gastroschisis experimental model and the influence of the mother's diet enriched with glutamine in the fetal morphology.

PURPOSE: To validate the gastroschisis experimental model in female rats and the effects on the glutamine fetal morphology during pregnancy. METHODS: Twelve pregnant rats Wistar were separated in two groups: Group I (n = 6 rats, 71 fetuses) took glutamine and Group II (n = 6 rats, 75 fetuses) took isocaloric supplementation. At the 18th day of pregnancy, female rats were taken to hysterotomy and the fetuses which were selected for the act of gastroschisis were partially removed from the womb and by the laparotomy technique, the exclusion of the intestine was done. After that, fetuses were put in the womb cavity again and the rats' abdomen sutured. At the 21st day of pregnancy, date before delivery, by C-section ordinary animals and the ones with gastroschisis were removed and studied separately. The morphometrical parameters studied were the body weight (PC); the intestine weight (PI); the intestine length (CI) and its relations (PI/PC, PI/CI e PC-PI). RESULTS: The intestine weight (PI) and the intestine length (CI) were different in fetuses with gastroschisis (p<0.05), however no difference between the groups regarding supplementation with glutamine. CONCLUSIONS: The gastroschisis experimental model is valid and reproducible. The nutritional therapy with glutamine did not change the morphometrical parameters.

Epigenetic changes in fetal hypothalamic energy regulating pathways are associated with maternal undernutrition and twinning.

Undernutrition during pregnancy is implicated in the programming of offspring for the development of obesity and diabetes. We hypothesized that maternal programming causes epigenetic changes in fetal hypothalamic pathways regulating metabolism. This study used sheep to examine the effect of moderate maternal undernutrition (60 d before to 30 d after mating) and twinning to investigate changes in the key metabolic regulators proopiomelanocortin (POMC) and the glucocorticoid receptor (GR) in fetal hypothalami. Methylation of the fetal hypothalamic POMC promoter was reduced in underfed singleton, fed twin, and underfed twin groups (60, 73, and 63% decrease, respectively). This was associated with reduced DNA methyltransferase activity and altered histone methylation and acetylation. Methylation of the hypothalamic GR promoter was decreased in both twin groups and in maternally underfed singleton fetuses (52, 65, and 55% decrease, respectively). This correlated with changes in histone methylation and acetylation and increased GR mRNA expression in the maternally underfed singleton group. Alterations in GR were hypothalamic specific, with no changes in hippocampi. Unaltered levels of OCT4 promoter methylation indicated gene-specific effects. In conclusion, twinning and periconceptional undernutrition are associated with epigenetic changes in fetal hypothalamic POMC and GR genes, potentially resulting in altered energy balance regulation in the offspring.

Prenatal programming by testosterone of hypothalamic metabolic control neurones in the ewe.

Ewes treated prenatally with testosterone develop metabolic deficits, including insulin resistance, in addition to reproductive dysfunctions that collectively mimic polycystic ovarian syndrome (PCOS), a common endocrine disease in women. We hypothesised that metabolic deficits associated with prenatal testosterone excess involve alterations in arcuate nucleus (ARC) neurones that contain either agouti-related peptide (AgRP) or pro-opiomelanocortin (POMC). Characterisation of these neurones in the ewe showed that immunoreactive AgRP and POMC neurones were present in separate populations in the ARC, that AgRP and POMC neurones co-expressed either neuropeptide Y or cocaine- and amphetamine-regulated transcript, respectively, and that each population had a high degree of co-localisation with androgen receptors. Examination of the effect of prenatal testosterone exposure on the number of AgRP and POMC neurones in adult ewes showed that prenatal testosterone excess significantly increased the number of AgRP but not POMC neurones compared to controls; this increase was restricted to the middle division of the ARC, was mimicked by prenatal treatment with dihydrotestosterone, a non-aromatisable androgen, and was blocked by co-treatment of prenatal testosterone with the anti-androgen, flutamide. The density of AgRP fibre immunoreactivity in the preoptic area, paraventricular nucleus, lateral hypothalamus and dorsomedial hypothalamic nucleus was also increased by prenatal testosterone exposure. Thus, ewes that were exposed to androgens during foetal life showed alterations in the number of AgRP-immunoreactive neurones and the density of fibre immunoreactivity in their projection areas, suggestive of permanent prenatal programming of metabolic circuitry that may, in turn, contribute to insulin resistance and an increased risk of obesity in this model of PCOS.

Maternal creatine supplementation from mid-pregnancy protects the diaphragm of the newborn spiny mouse from intrapartum hypoxia-induced damage.

We hypothesized that maternal creatine supplementation from mid-pregnancy would protect the diaphragm of the newborn spiny mouse from the effects of intrapartum hypoxia. Pregnant mice were fed a control or 5% creatine-supplemented diet from mid-gestation. On the day before term, intrapartum hypoxia was induced by isolating the pregnant uterus in a saline bath for 7.5-8 min before releasing and resuscitating the fetuses. Surviving pups were placed with a cross-foster dam, and diaphragm tissue was collected at 24 h postnatal age. Hypoxia caused a significant decrease in the cross-sectional area (∼19%) and contractile function (26.6% decrease in maximum Ca2=-activated force) of diaphragm fibers. The mRNA levels of the muscle mass-regulating genes MuRF1 and myostatin were significantly increased (2-fold). Maternal creatine significantly attenuated hypoxia-induced fiber atrophy, contractile dysfunction, and changes in mRNA levels. This study demonstrates that creatine loading before birth significantly protects the diaphragm from hypoxia-induced damage at birth.

Using Z-scores to compare biometry data obtained during prenatal ultrasound screening by midwives and physicians.

OBJECTIVE: To compare retrospectively the distribution of foetal biometry data as measured by midwives and physicians during second and third trimester screening of an unselected population of pregnant women. METHODS: Standard measurements of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL) were performed by four midwives and ten physicians at 20 to 24 weeks of gestation and at 30 to 34 weeks of gestation as part of routine ultrasound examinations over a 26-month period (Jan. 2005-Mar. 2007). All measurements were converted into Z-scores using different prediction equations. The reference chart best fitting our practice was determined for each fetal parameter (French College of Sonographers for BPD, Chitty et al. for HC and FL, Snidjers and Nicolaides for AC). The means and SDs of the Z-score distributions for data collected by midwives and physicians were compared using Student's t-test for means and the Fisher-Snedecor test for SDs. RESULTS: We retrieved 1566 and 1631 measurements made by midwives and physicians respectively between 20 and 24 weeks of gestation, and 1710 and 1578 measurements made by midwives and physicians respectively between 30 and 34 weeks of gestation. Mean values recorded by midwives were significantly closer to 0 (p < 0.05) for many foetal parameters. SD values were also significantly lower and were below 1. CONCLUSION: In this study, midwives have a greater tendency than physicians to normalize biometry data. Such normalization may hamper the sensitivity of routine ultrasound screening for abnormal foetal growth.

Oogenesis and cell death in human prenatal ovaries: what are the criteria for oocyte selection?

Prenatal oogenesis produces hundreds of thousands of oocytes, most of which are discarded through apoptosis before birth. Despite this large-scale selection, the survivors do not constitute a perfect population, and the factors at the cellular level that result in apoptosis or survival of any individual oocyte are largely unknown. What then are the selection criteria that determine the size and quality of the ovarian reserve in women? This review focuses on new data at the cellular level, on human prenatal oogenesis, offering clues about the importance of the timing of entry to meiotic prophase I by linking the stages and progress through MPI with the presence or absence of apoptotic markers. The characteristics and responsiveness of cultured human fetal ovarian tissue at different gestational ages to growth factor supplementation and the impact of meiotic abnormalities upon apoptotic markers are discussed. Future work will require the use of a tissue culture model of prenatal oogenesis in order to investigate the fate of individual live oocytes at different stages of development.

The probability of finding nerve branches to the external anal sphincter.

INTRODUCTION: Normal defecation is a combination of several elements of reflex and voluntary functions. The issue of external anal sphincter innervation is of theoretical and clinical significance; however, literature on the subject is still scarce. Most study reports discuss the course of the pudendal nerve with no close insight into inferior rectal nerves supply to the external anal sphincter. We have not found any statistical "mapping" of the site of the nerve branches insertion into the external anal sphincter. Thus, the purpose of the present study was to determine the least and most typical location of nerve branches to the external anal sphincter. One hundred and ten pudendal nerve preparations were analysed. Following the dissection of the pudendal nerve and its branches, a beam compass was used to take linear measurements from the apex of the coccygeal bone to the point of nerve branch insertion to the external anal sphincter. The distance between coccygeal bone apex and the central tendon of the perineum was also measured. For the purpose of comparison, results are presented as relative Bi/A values. Computer programmes devised by the author of this paper within Turbo Pascal were then used to determine the probability of finding nerve branches to the external anal sphincter. RESULTS: Based on the analysis of 110 preparations of the pudendal nerve and its branches, one might conclude that the former was the main although not necessarily the only source of external anal sphincter innervation. While analysing the most and the least probable location of nerve branches to the external anal sphincter, the muscle length was expressed as percentage, i.e., 0% of sphincter length = the apex of the coccygeal bone; 100% of sphincter length = the central tendon of the perineum. The length was then divided into 5% intervals with the probability of finding nerve branches determined by programmes written in Pascal. Within 30-85% of external anal sphincter length, the probability of finding nerve branches to the external anal sphincter is greater than 0.3 with peak probability of 0.68 in the interval between 55 and 65%. DISCUSSION: Sphincter innervation and clinicoanatomical function of anal canal closure apparatus has been discussed with reference to external anal sphincter injury. Transcutaneous electrostimulation of the pudendal nerve and the use of anal canal electrodes have also been mentioned. CONCLUSIONS: The most probable location of nerve branches to the external anal sphincter is half way of its length, i.e., at hour 3 or 9 of the knee-elbow position or lithotomy position. The external anal sphincter can also be directly supplied by nerve branches originating from the sacral nerve root S4; the branches then go towards the posterior part of the sphincter.

A comparison study of effects of Echinacea extract and levamisole on phenytoin-induced cleft palate in mice.

There are many reports that the teratogenic effects of phenytoin, especially cleft palate can be decreased by stimulation of maternal immune system. Also, there is some evidence that Echinacea extract and levamisole are immunomodulator drugs. So, in this study, we compared the prophylactic effects of levamisole and Echinacea extract on teratogenic effects of phenytoin. This study was performed on 32 pregnant mice that were divided into four groups. The first group (control group) received normal saline intraperitoneally and the other groups (test groups) received phenytoin (65 mg/kg intraperitoneally) at 10th day of gestation. Levamisole and extract of Echinacea purpurea were administrated at dose of 10 and 360 mg/kg intraperitoneally, respectively, in along with and 12h later after phenytoin injection, in two groups. Fetuses were carried out in 19th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Cleft palate incidence was 16, 5.3, and 3.2% in fetuses of mice that received only phenytoin, phenytoin with levamisole, and phenytoin with Echinacea extract, respectively. Mean weight and length of fetuses of animals that received levamisole and Echinacea extract were significantly greater than those received only phenytoin. It is concluded that Echinacea can stimulate immune system more than levamisole and has better prophylactic effect on incidence of phenytoin-induced cleft palate, but it is not significant.

Dietary zinc supplementation ameliorates LPS-induced teratogenicity in mice.

Maternal infection during the first trimester of pregnancy has been associated with preterm birth, spontaneous abortion, growth retardation, and congenital anomalies. Previously, our group has shown that subcutaneous injection of zinc prevents endotoxin [lipopolysaccharide (LPS)]-induced teratogenicity. The purpose of this study was to investigate whether increasing or decreasing dietary zinc alters the teratogenic effects of LPS. Female C57BL6 mice were mated and fed diets containing 5, 35, or 100 mg/kg zinc. On gestational day (GD) 8, pregnant dams were injected with either LPS (0.5 mg/kg s.c.) or saline and killed on GD18. LPS-treated fetuses from dams fed 5 and 35 mg/kg zinc diet had a significantly higher number of abnormalities per litter (2- and 1- fold saline controls, respectively) compared with those from LPS + zinc supplemented dams, which were not significantly different from the saline control groups. The beneficial effect and importance of zinc was also reflected in the larger size of fetuses (weight and crown-rump length) from the LPS + zinc-supplemented treatment group. We have demonstrated that low dietary zinc during exposure to infection (i.e. LPS) in pregnancy augments the negative impact of LPS alone, and that dietary zinc supplementation throughout pregnancy ameliorates LPS-induced teratogenicity.

[Sonographic cerebral sulcal pattern in normal fetuses]. / Repères échographiques de gyration cérébrale foetale normale.

PURPOSE: Define normal sulcation patterns and their chronological order of appearance on transabdominal ultrasound by comparing them with brain maturation references available in fetopathological studies and MRI findings. PATIENTS AND METHODS: By means of a prospective study, 158 normal fetal brains aged 21 to 34 gestational weeks have been analyzed with standardized data by transabdominal ultrasound in eleven different views using axial, coronal and sagittal orientation. RESULTS: The sequential development of cerebral sulci has been described according to the gestational age. This chronology was consistent with anatomo-pathologic references presenting a mean late period of one week and with MRI but without any late period. This study is available on the following website: CONCLUSION: This ultrasound study provides accurate landmarks and imaging features of normal fetal brain sulcation. The analysis and the knowledge of this sulcation provide better understanding of the brain cortex maturation and may be helpful in diagnosing brain diseases.

Axonal projections from the hypothalamus to the pituitary intermediate lobe in rats during ontogenesis: DiI tracing study.

This study has determined ontogenetic schedule of axonal arrival from the hypothalamus in the pituitary intermediate lobe (IL) in rats using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) as a retrograde tracer. The brains with attached pituitaries were dissected in rats from the 20th embryonic day (E20) to the 20th postnatal day (P20). Anterior lobe was mechanically detached from the IL, material fixed in paraformaldehyde, and DiI crystals were applied on the IL laying on the posterior lobe (PL). The labeling of IL + PL resulted in staining of hypothalamic magnocellular neurons, which send their axons to the PL, and hypothalamic parvocellular neurons contributing to the innervation of the IL. Therefore, the magnocellular neurons were not taken into account when identifying the neurons projecting axons to the IL. Rare fluorescent neurons projecting their axons to the IL were detected as early as on E20 in the ventral part of the periventricular nucleus (Pe) and in the rostral part of the arcuate nucleus. Few DiI-labeled neurons were seen in Pe from P1 to P3. At P5, the fluorescent neurons were accumulated giving rise to the prominent cluster in the Pe, which was enlarged on later stages and occupied all the Pe. In addition to the Pe, fluorescent neurons first appeared in the retrochiasmatic region and around the ventromedial nucleus in young rats. Thus, the axons of hypothalamic neurons of the Pe and mediobasal hypothalamus first arrive in the IL in rats at the end of intrauterine development, although the principal innervation of the IL is the postnatal event.

Can maternal vitamin e supplementation prevent lung hypoplasia in the nitrofen-induced rat model of congenital diaphragmatic hernia?

Recent studies suggest a role for antioxidants in the prevention of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH). We studied the effects of vitamin E in the nitrofen-rat model of CDH. After an initial fast, timed-pregnant Sprague-Dawley rats were gavage-fed nitrofen at gestational day 11 (term is 22 d). On the same day, one group was given a s.c. injection of vitamin E in alcohol; a second group was given an injection of alcohol alone. A third group received no treatment (control). Fetuses were delivered on day 21, and static pressure-volume curves were measured by immersion. Lungs were analyzed for total DNA and protein content by standard methods. A total of 203 fetuses were studied. Of 151 nitrofen-exposed fetuses, 77% had CDH; 92% of these were right-sided. CDH was present in 82% of vehicle-treated fetuses and 71% of vitamin E-treated fetuses (p=0.17). Nitrofen-exposed fetuses not only were smaller than control fetuses but also had disproportionately smaller lungs and poorer lung function, even when CDH was absent; however, lung function was worse when CDH was present. Vitamin E treatment did not improve either lung growth or function, although there was a trend toward less CDH. We have shown, for the first time, that the lung hypoplasia seen in nitrofen-exposed rat fetuses is associated with a dramatic reduction in static lung function, even when CDH is not present. Finally, our findings support the notion that lung hypoplasia in the nitrofen-rat model is independent of CDH formation.

Fetal magnetoencephalography--a multimodal approach.

Past studies have shown the feasibility of recording fetal evoked responses to external stimuli using a non-invasive technique called magnetoencephalography (MEG). These studies were all performed using either auditory or visual stimuli and showed a fairly low detection rate for each modality, thus making this technology currently unreliable for fetal clinical applications. This study is based on the hypothesis that a multimodal approach of applying both auditory and visual stimulation paradigms in successive recording sessions could improve the probability of obtaining a fetal evoked response. A total of 34 studies were performed on 11 normal healthy fetuses at different stages of gestation starting as early as 28 weeks with a 151-channel fetal MEG system. The success rate of obtaining a response to either (or both) stimuli from a study at a given gestation age was 91%. All the 11 fetuses showed a response at least once over the gestation period the recordings were performed. A multimodal testing approach can improve the ability of the MEG technique to reliably monitor the functional development of the fetal brain.