Placental imprinted gene expression mediates the effects of maternal psychosocial stress during pregnancy on fetal growth.

Imprinted genes uniquely drive and support fetoplacental growth by controlling the allocation of maternal resources to the fetus and affecting the newborn's growth. We previously showed that alterations of the placental imprinted gene expression are associated with suboptimal perinatal growth and respond to environmental stimuli including socio-economic determinants. At the same time, maternal psychosocial stress during pregnancy (MPSP) has been shown to affect fetal growth. Here, we set out to test the hypothesis that placental imprinted gene expression mediates the effects of MPSP on fetal growth in a well-characterized birth cohort, the Stress in Pregnancy (SIP) Study. We observed that mothers experiencing high MPSP deliver infants with lower birthweight (P=0.047). Among the 109 imprinted genes tested, we detected panels of placental imprinted gene expression of 23 imprinted genes associated with MPSP and 26 with birthweight. Among these genes, five imprinted genes (CPXM2, glucosidase alpha acid (GAA), GPR1, SH3 and multiple ankyrin repeat domains 2 (SHANK2) and THSD7A) were common to the two panels. In multivariate analyses, controlling for maternal age and education and gestational age at birth and infant gender, two genes, GAA and SHANK2, each showed a 22% mediation of MPSP on fetal growth. These data provide new insights into the role that imprinted genes play in translating the maternal stress message into a fetoplacental growth pattern.

Timing of prenatal exposure to trauma and altered placental expressions of hypothalamic-pituitary-adrenal axis genes and genes driving neurodevelopment.

Prenatal maternal stress increases the risk for negative developmental outcomes in offspring; however, the underlying biological mechanisms remain largely unexplored. In the present study, alterations in placental gene expression associated with maternal stress were examined to clarify the potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating foetal hypothalamic-pituitary-adrenal axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy. Objective prenatal traumatic stress was defined as whether mothers were exposed to Superstorm Sandy during pregnancy. Among the 275 mother-infant dyads, 181 dyads were delivered before Superstorm Sandy (ie, Control), 66 dyads were exposed to Superstorm Sandy during the first trimester (ie, Early Exposure) and 28 were exposed to Superstorm Sandy during the second or third trimester (ie, Mid-Late Exposure). Across all trimesters, expression of HSD11B2, MAOA, ZNF507 and DYRK1A was down-regulated among those exposed to Superstorm Sandy during pregnancy. Furthermore, trimester-specific differences were also observed: exposure during early gestation was associated with down-regulation of HSD11B1 and MAOB and up-regulation of CRHBP; exposure during mid-late gestation was associated with up-regulation of SRD5A3. The findings of the present study suggest that placental gene expression may be altered in response to traumatic stress exposure during pregnancy, and the susceptibility of these genes is dependent on the time of the exposure during pregnancy. Further studies should aim to clarify the biological mechanisms that underlie trimester-specific exposure by evaluating the differential impact on offspring neurodevelopment later in childhood.

Imprinted gene expression in fetal growth and development.

Experimental studies showed that genomic imprinting is fundamental in fetoplacental development by timely regulating the expression of the imprinted genes to overlook a set of events determining placenta implantation, growth and embryogenesis. We examined the expression profile of 22 imprinted genes which have been linked to pregnancy abnormalities that may ultimately influence childhood development. The study was conducted in a subset of 106 placenta samples, overrepresented with small and large for gestational age cases, from the Rhode Island Child Health Study. We investigated associations between imprinted gene expression and three fetal development parameters: newborn head circumference, birth weight, and size for gestational age. Results from our investigation show that the maternally imprinted/paternally expressed gene ZNF331 inversely associates with each parameter to drive smaller fetal size, while paternally imprinted/maternally expressed gene SLC22A18 directly associates with the newborn head circumference promoting growth. Multidimensional Scaling analysis revealed two clusters within the 22 imprinted genes which are independently associated with fetoplacental development. Our data suggest that cluster 1 genes work by assuring cell growth and tissue development, while cluster 2 genes act by coordinating these processes. Results from this epidemiologic study offer solid support for the key role of imprinting in fetoplacental development.

Effects of the rearing season on carcass and meat quality of suckling Apennine light lambs.

The aim of this study was to evaluate the effects of the rearing season (autumn vs winter) on the carcass and meat quality of light lambs, obtained according to the traditional farming system usual in central Italy. Eighty carcasses from 60 d+/-3 old unweaned Apennine single birth male lambs, permanently reared indoor, half in autumn (receiving milk from ewes permanently pastured) and half in winter (which dams did never acceded to pasture), were weighed, classified according to the EU classification system for light lambs, and their Longissimus lumborum meat was analysed for pH, colour, drip and cooking losses, proximate composition and fatty acids profile of intramuscular fat. Most of the carcasses fully responded to the 1st quality EU requirements and no effects of the rearing season was evident on carcass characteristics. On the contrary, L. lumborum of lambs born and reared in autumn, receiving milk from ewes permanently pastured, evidenced a lower Lightness L* (P=0.02), a higher Chroma C* (P=0.01), with a higher fat content (P=0.04) than lambs reared in winter, which dams were permanently stall-fed. Moreover the intramuscular fat of the former was characterized by a greater PUFA concentration (P=0.01), a more favourable n-6/n-3 ratio (P<0.001), and a higher CLA content (P<0.001) than the latter, as a result of the difference related to the sheep traditional feeding system.

Effects of loading methods on rabbit welfare and meat quality.

The effects of different loading methods on the welfare, carcass characteristics and meat quality traits of hybrid commercial rabbits were investigated. 384 male rabbits, 82 days old, were transported from the farm to the slaughterhouse. At the farm, 192 rabbits were loaded onto the truck smoothly (S) and 192 rabbits were loaded roughly (R). The S loading method consisted of carefully placing each rabbit into the transport crates. In the R method, the loading was hurriedly and carelessly executed by the transport operator, throwing each animal into the crates fixed on the truck. Live weight before and after transport as well as slaughter data were recorded for each rabbit, and a subset of 80 carcasses were evaluated for meat quality. Blood samples from 80 rabbits were analysed for haematological and biochemical parameters. A significant neutrophilia (P<0.001), lymphocytopaenia (P<0.001) and an increase in serum aspartate aminotransferase (AST) (P<0.01), alanine aminotransferase (ALT) (P<0.001) and creatine kinase (CK) activities (P<0.001) were recorded in all rabbits after transport, independent of the loading method. A twofold increase in serum corticosterone concentration (6.23 vs. 14.88 ng/mL; P=0.001) was observed in all rabbits following transport. Results suggest that the stress parameters analysed were more influenced by transport and handling itself rather than by the different loading methods. The results showed that there was no adverse effect of loading method on carcass traits. Furthermore, the stress condition evidenced by haematological and biochemical parameters prior to slaughter did not affect meat quality.

Effects of selenium source and level of supplementation on the performance and meat quality of lambs.

Objective of this study was to evaluate the performance, the quality and oxidative stability of meat, the total Se and specific selenoamino-acids content of muscle of lambs that were fed diets supplemented from different Se sources and at different levels. Forty-eight Apennine lambs 30day old (12.78±0.94kg) received, during a 63day period, a total mixed ration (TMR) which was either Se unsupplemented (Control group - background only- 0.13mg/kg Se) or supplemented with Na selenite (0.30mg/kg Se as sodium selenite) or selenium enriched yeast (0.30mg/kg and 0.45mg/kg Se as Se-yeast). Growth performance, feed to gain ratio, carcass and meat quality (pH, drip and cooking losses, colour, GSH-Px activity and chemical analysis) did not show any difference between the treatments. Meat colour and oxidative stability during 9 days of refrigerated storage were unaffected by dietary supplementation, suggesting that, at the levels of Se used in this experiment, dietary Se, even from an organic source, had limited potential for reducing lipid oxidation. Selenium supplementation raised the Se content in muscle (P<0.001) with the greatest increase when Se-yeast was fed. Although selenite increased total Se, it did not influence total or specific selenoamino-acids in this tissue. On the contrary, Se-yeast supplementation led to an increase in muscle Se-methionine content. We conclude that Se supplementation can increase significantly muscle Se levels and produce, particularly when Se-yeast is fed, a source of Se enriched meat as Se-methionine.

The atpIBEXF operon coding for the F0 sector of the ATP synthase from the purple nonsulfur photosynthetic bacterium Rhodobacter capsulatus.

The atpIBEXF operon coding for the F0 sector of the ATP synthase from Rhodobacter capsulatus was cloned and sequenced. The genes for the five subunits were present in the order: atpI (subunit I), atpB (subunit a), atpE (subunit c), atpX (subunit b'), and atpF (subunit b). The transcription initiation site was defined by primer-extension analysis. A duplicated and divergent copy of the b subunit gene (subunit b') was present. This duplication is found only in photosynthetic prokaryotes and in plant chloroplasts. F0 deletion mutants formed tiny colonies during anaerobic growth in the dark but could not sustain continuous growth. Based on the results of the present work, we conclude that a functioning ATP synthase is essential for normal growth under all conditions tested.

Pulse oximetry monitoring during non-sedated upper gastrointestinal endoscopy.

Fifty consecutive patients judged fit for non-sedated upper gastrointestinal endoscopy were monitored by pulse oximetry before, during and after the procedure. Transient hypoxia developed during intubation in five subjects (10%) but treatment was not required nor was the test halted. Only one patient with pre-existing respiratory problems became hypoxaemic to the extent that oxygen had to be given and the procedure halted. The chance of hypoxia was unrelated to age, sex, smoking, anxiety, or the duration of intubation. Routine pulse oximetry is not necessary for non-sedated gastroscopy but oximetry monitoring may be important in selected cases.

Effect of gamma-aminobutyric acid on cyclic nucleotides content of guinea-pig cerebral cortex slices.

The effect of GABA and related drugs on 3'5' cAMP and 3'5' cGMP was investigated in slices of guinea-pig cerebral cortex, kept at rest or electrically stimulated. GABA 1 X 10(-4) - 1 X 10(-3) M raised the cAMP basal levels, bud reduced its increase due to electrical stimulation. These effects were antagonized by picrotoxin 1.6 X 10(-5) M. On the contrary, endogenous GABA did not influence cAMP and cGMP content. In fact, neither ethanolamine-O-sulphate 2 X 10(-3) M nor picrotoxin 1.6 X 10(-5) M affected the normal nucleotide values at all. Higher picrotoxin concentrations (3.2 - 8 X 10(-5) M), however, increased both cyclic nucleotides. Phentolamine counteracted the actions of both GABA 1 X 10(-4) M and picrotoxin 8 X 10(-5) M: therefore, the observed increase in cyclic nucleotides were due to norepinephrine release. Tetrodotoxin antagonized GABA but not picrotoxin metabolic effects. Thus it is suggested that the exogenous amino acid released norepinephrine through a sodium-dependent process, while picrotoxin released the monoamine directly from its storage sites. Clearly, attention must be paid when putative transmitters or their antagonists are added at high concentrations to isolated tissue to study the effect of endogenous compounds.

Pyroglutamic acid administration modifies the electrocorticogram and increases the release of acetylcholine and GABA from the guinea-pig cerebral cortex.

Pyroglutamic acid (1-PCA), a cyclic derivative of glutamic acid, was administered i.p. (7.7 mmol/kg) or intracerebroventricularly (25 - 50 mumol) to freely moving guinea-pigs, provided with semi-permanently implanted epidural cups. The effect of this compound on cortical Acetylcholine (ACh) and GABA outflow, as well as on gross behaviour and electrocorticogram (E.Co.G.) was investigated. 1-PCA increased the release of ACh and GABA from the cortical surface, did not change their cortical content, decreased the spontaneous motor activity and synchronized the E.Co.G.. These results suggest that 1-PCA increases GABA release, possibly by changing amino acid transport through the biological barrier or by acting as antagonist on the receptors for glutamic acid. In turn, the activation of the GABA system increases, as previously demonstrated, the cortical ACh release and causes mild sedation and E.Co.G. synchronization.

Effect of adenosine, adenosine triphosphate, adenosine deaminase, dipyridamole and aminophylline on acetylcholine release from electrically-stimulated brain slices.

The effect of adenosine on release of acetylcholine (ACh) was investigated in slices of rat cortex perfused with Krebs solution, at rest and during electrical stimulation at frequencies between 0.2 and 20 Hz. Electrical stimulation brought about a linear increase in release of ACh. Adenosine, in concentrations ranging from 1 to 100 microM, reduced in a dose-dependent manner the release of ACh and was more active on the stimulated than on the resting release. However, the fractional reduction by adenosine of stimulated release of ACh did not vary with increasing stimulation rate. Adenosine triphosphate was less active than adenosine in reducing release of ACh. The inhibitory effect of adenosine was antagonized by aminophylline (0.5 mM) and did not occur when the stimulated release of ACh was enhanced by blocking muscarinic autoreceptors with atropine (15 nM). Aminophylline (0.1 and 0.5 mM) itself exerted a biphasic effect on release of ACh, increasing it at rest and during stimulation at low frequencies, and decreasing it at higher stimulation rates. The manipulation of endogenous adenosine concentrations by adding adenosine deaminase or diphyridamole, an inhibitor of adenosine uptake, had little effect on release of ACh. Dipyridamole, (4 microM), only significantly decreased release of ACh at the 20 Hz stimulation rate.

[Stimulation of cholinergic receptors and changes in cyclic nucleotide levels in the cerebral cortex of the guinea pig]. / Stimolazione dei recttori colinergici e variazioni dei nucleotidi ciclici nella corteccia cerebrale di cavia.

The effect of Atropine and Physostigmine on 3'5' AMP and 3'5' GMP content was investigated in slices of guinea-pig cerebral cortex maintained at rest or electrically-stimulated. Atropine and Physostigmine did not modify either the basal content or the electrically-evoked increase of 3'5' AMP and 3'5' GMP. On the contrary, Betanechol 25 micro M significantly increased 3'5' GMP and 3'5' AMP content in slices kept at rest. The effect was abolished by Atropine 1,5 x 10(-7) M and d-tubocurarine 7 x 10(-6) M, respectively.

[Addition of amino acids and oligopeptides to the diet of piglets. II. Effects on apparent digestion of some alimentary principles]. / Aggiunta di aminoacidi ed oligopeptidi a diete per suinetti. Nota II-Effetti sulla digeribilita' apparente di alcuni principi alimentari.

The apparent digestibility coefficients of some nutrients in connection with the addition of small quantities of amino acid and oligopeptide pools to balanced diets were determined on 15 piglets divided into three groups (1: Control; 2: amino acid pool; 3: amino acid and oligopeptide pool). Piglets receiving pools, and especially those belonging to the second group, show better results in comparison with the control animals. Besides the digestibility significantly increases with the time.