Influence of ω3 fatty acids on maternal behavior and brain oxytocin in the murine perinatal period.

INTRODUCTION: Perinatal women often experience mood disorders and postpartum depression due to the physical load and the rapid changes in hormone levels caused by pregnancy, childbirth, and nursing. When the mother's emotions become unstable, their parental behavior (maternal behavior) may decline, the child's attachment may weaken, and the formation of mother-child bonding can become hindered. As a result, the growth of the child may be adversely affected. The objective of this study was to investigate the effect of ω3 fatty acid deficiency in the perinatal period on maternal behavior and the oxytocin concentration and fatty acid composition in brain tissue. MATERIALS AND METHODS: Virgin female C57BL/6 J mice fed a ω3 fatty acid-deficient (ω3-Def) or adequate (ω3-Adq) diet were mated for use in this study. To assess maternal behavior, nest shape was evaluated at a fixed time from gestational day (GD) 15 to postpartum day (PD) 13, and a retrieval test was conducted on PD 3. For neurochemical measurement, brains were removed from PD 1-6 dams and hippocampal fatty acids and hypothalamic oxytocin concentrations were assessed. RESULTS: Peripartum nest shape scores were similar to those reported previously (Harauma et al., 2016); nests in the ω3-Def group were small and of poor quality whereas those in the ω3-Adq group were large and elaborate. The inferiority of nest shape in the ω3-Def group continued from PD 0-7. In the retrieval test performed on PD 3, dams in the ω3-Def group took longer on several parameters compared with those in the ω3-Adq group, including time to make contact with pups (sniffing time), time to start retrieving the next pup (interval time), and time to retrieve the last pup to the nest (grouping time). Hypothalamic oxytocin concentrations on PD 1-6 were lower in the ω3-Def group than in the ω3-Adq group. DISCUSSION: Our data show that ω3 fatty acid deficiency reduces maternal behavior, a state that continued during pup rearing. This was supported by the observed decrease in hypothalamic oxytocin concentration in the ω3-Def group. These results suggest that ω3 fatty acid supplementation during the perinatal period is not only effective in delivering ω3 fatty acids to infants but is also necessary to activate high-quality parental behavior in mothers.

Maternal n-3 polyunsaturated fatty acids restructure gut microbiota of offspring mice and decrease their susceptibility to mammary gland cancer.

Our previous studies have revealed that a maternal diet rich in n-3 polyunsaturated fatty acids (PUFAs) is associated with decreased mammary cancer risk in offspring. However, the underlying mechanism remains unclear. The present study aimed to investigate the possible mechanism by which maternal n-3 PUFAs decrease the mammary cancer risk of offspring in terms of gut microbiota. C57BL/6 pregnant mice were fed a control standard chow (CON), fish oil supplemented diet (n-3 Sup-FO), flaxseed oil supplemented diet (n-3 Sup-FSO) or n-3 PUFA deficient diet (n-3 Def) (n = 10) throughout gestation and lactation. After weaning, all offspring were fed a AIN-93G diet. The tumor incidence and volume were significantly increased in n-3 Def offspring compared with the other groups. Maternal n-3 PUFA supplementation resulted in a significantly increased α-diversity of the gut microbiota in n-3 Sup-FO and n-3 Sup-FSO offspring compared with that in n-3 Def offspring. The relative abundances of Akkermansia, Lactobacillus and Mucispirillum observed in adult offspring of both the n-3 Sup-FO and n-3 Sup-FSO groups were higher than those observed in the control group, whereas the maternal n-3 Def diet was associated with decreased abundances of Lactobacillus, Bifidobacterium and Barnesiella in 7-week-old offspring. The levels of the pro-inflammatory factors IL-1ß, IL-6 and TNF-α were significantly lower in n-3 PUFA supplemented offspring than in n-3 Def offspring. In addition, the abundance of Mucispirillum was positively associated with the concentration of the anti-inflammatory factor IL-10, whereas the abundances of Bifidobacterium and Akkermansia were negatively associated with IL-1ß and IL-6, respectively. Based on the bacterial composition of the gut microbiota, metabolites were predicted and the results showed that arachidonic acid metabolism and the MAPK signaling pathways were more enriched, while the butyric acid metabolic pathway was less enriched in offspring of the n-3 Def group than in those of the other three groups. Our findings suggest that decreased pro-inflammatory factors and changed gut microbiota are associated with the protective effects of maternal n-3 PUFAs against offspring's mammary tumorigenesis.

The effect of maternal HMB supplementation on bone mechanical and geometrical properties, as well as histomorphometry and immunolocalization of VEGF, TIMP2, MMP13, BMP2 in the bone and cartilage tissue of the humerus of their newborn piglets.

The presented experiment focuses on assessing the impact of HMB (hydroxy-ß-methobutyrate) supplementation of mothers during pregnancy on the development of the skeletal system of their offspring. For this purpose, an experiment was carried out on 12 clinically healthy sows of the Great White Poland breed, which were divided randomly into two groups the control and the HMB group. All animals were kept under standard conditions and received the same feed for pregnant females. In contrast, females from the HMB group between 70 and 90 days were supplemented with 3-hydroxy-3-methylbutyle in the amount of 0.2g/kg b.w/day. Immediately after birth, the piglets were also divided into groups based on: sex, and presence or lack HMB supplementation, and subsequently were euthanized and humerus bones from all piglets were collected. Mother's HMB supplementation during pregnancy affected the multiple index of their offspring. The higher humerus mass and length was observed with the greater effect in males. Maternal supplementation also influenced on the geometrical and mechanical properties of the humerus as in the case of mass, this effect was higher in males. Also, the collagen structure of the compacted and trabecular bone changed under the HMB addition. Maternal supplementation also affected the expression of selected proteins in growth cartilage and trabecular bone. The obtained results show that the administration to the mother during pregnancy by the HMB significantly affects the development of the humerus in many ways. The obtained results also confirm the utility of such experiments in understanding of the importance of the pregnancy diet as an develop and adaptable factor of offspring organisms and are the base for further research in that area as well as in the protein markers expression area.

Neonatal Piglets Can Synthesize Adequate Creatine, but Only with Sufficient Dietary Arginine and Methionine, or with Guanidinoacetate and Excess Methionine.

BACKGROUND: Suckling piglets synthesize most of their creatine requirement, which consumes substantial amounts of arginine in order to synthesize guanidinoacetic acid (GAA) and methionine in order to transmethylate GAA to creatine. OBJECTIVES: To determine whether supplemental GAA or creatine spare arginine and/or methionine for protein synthesis and, if GAA is supplemented, whether excess methionine is needed for conversion to creatine. METHODS: Yucatan miniature piglets (9-11 days old; both sexes) were fed 1 of 5 elemental diets for 5 days: 1) low arginine (0.3 g·kg-1·d-1) and low methionine (0.20 g·kg-1·d-1; Base); 2) Base plus GAA (0.093 g·kg-1·d-1; +GAA); 3) Base plus GAA plus excess methionine (0.5 g·kg-1·d-1; +GAA/Met); 4) Base plus creatine (0.12 g·kg-1·d-1; +Cre); or 5) excess arginine (1.8 g·kg-1·d-1) and excess methionine (+Arg/Met). Isotope tracers were infused to determine whole-body GAA, creatine, and protein synthesis; tissues were analyzed for creatine synthesis enzymes and metabolite concentrations. Data were analyzed by 1-way ANOVA. RESULTS: : GAA and creatine syntheses were 115% and 32% higher, respectively, with the +Arg/Met diet (P < 0.0001), in spite of 33% lower renal L-arginine: glycine amidinotransferase activity (P < 0.0001) compared to Base, suggesting substrate availability dictates synthesis rather than enzyme capacity. GAA or creatine supplementation reduced arginine conversion to creatine by 46% and 43%, respectively (P < 0.01), but did not spare amino acids for whole-body protein synthesis, suggesting that limited amino acids were diverted to protein at the expense of creatine synthesis. The +GAA/Met diet led to higher creatine concentrations in the kidney (2.6-fold) and liver (7.6-fold) than the +GAA diet (P < 0.01), suggesting excess methionine is needed for GAA conversion to creatine. CONCLUSIONS: Piglets are capable of synthesizing sufficient creatine from the precursor amino acids arginine and methionine, or from GAA plus methionine.

Evaluation of colostrum bioactive protein transfer and blood metabolic traits in neonatal lambs in the first 24 hours of life.

Colostrum is a unique resource that contributes to the passive transfer of immunity and plays a central role in the health status of neonatal ruminants. However, digestion and absorption of colostral proteins in the gut remain incompletely understood. Therefore, this study aimed to investigate the effect of bovine colostrum feeding on blood metabolic traits and to quantify colostral bioactive proteins in the gastrointestinal digesta and blood to evaluate intestinal transfer in neonatal lambs in the first 24 h of life. Fifty-four newborn lambs were used in this study, including 27 lambs fed pooled bovine colostrum and slaughtered at 6 (C6h), 12 (C12h), or 24 h (C24h) after birth; 18 lambs not fed any colostrum or milk and slaughtered at birth (N0h) or 24 h (N24h) after birth; and 9 milk-fed lambs slaughtered at 24 h (M24h) after birth. Lambs receiving colostrum or milk were bottle-fed within the first 2 h to obtain intakes of 8% of body weight at birth. Samples of blood and digesta from the abomasum, jejunum, and ileum were collected after slaughter. Serum concentrations of glucose, insulin, total protein, and aspartate aminotransferase were higher in colostrum-fed lambs than in N0h lambs. Serum concentrations of insulin, total protein, insulin-like growth factor 1, and γ-glutamyl transpeptidase were higher in C24h lambs than in N24h or M24h lambs. Apparent efficiencies of IgG absorption in C6h, C12h, and C24h lambs were 14.4, 26.8, and 17.2%, respectively, whereas apparent efficiencies of lactoferrin (LF), α-lactalbumin (α-LA), and ß-lactoglobulin (ß-LG) absorption were very low in colostrum-fed lambs, with mean values of 0.06, 0.002, and 0.003%, respectively. Concentrations of IgG, LF, α-LA, and ß-LG in the digesta of the abomasum, jejunum, and ileum rapidly decreased from C6h to C24h lambs, and the disappearance rates of IgG, LF, α-LA, and ß-LG were higher in lambs from C6h to C12h (62.1, 75.7, 91.3, and 95.0% for IgG, LF, α-LA, and ß-LG, respectively) than from C12h to C24h (34.6, 22.5, 7.5, and 2.2% for IgG, LF, α-LA, and ß-LG, respectively). These results indicated that bovine colostrum feeding improved the metabolic and immunological status of lambs, and that ingested colostral IgG was prone to intact uptake into the blood, whereas almost all ingested LF, α-LA, and ß-LG disappeared in the lumen of the gastrointestinal tract in a time-dependent manner. The findings provide novel information for exploring selective absorption of colostral compounds in the small intestine of lambs.

Determinants of vitamin D status in Kenyan calves.

Vitamin D plays a critical role in calcium homeostasis and in the maintenance and development of skeletal health. Vitamin D status has increasingly been linked to non-skeletal health outcomes such as all-cause mortality, infectious diseases and reproductive outcomes in both humans and veterinary species. We have previously demonstrated a relationship between vitamin D status, assessed by the measurement of serum concentrations of the major vitamin D metabolite 25 hydroxyvitamin D (25(OH)D), and a wide range of non-skeletal health outcomes in companion and wild animals. The aims of this study were to define the host and environmental factors associated with vitamin D status in a cohort of 527 calves from Western Kenya which were part of the Infectious Disease of East African Livestock (IDEAL) cohort. A secondary aim was to explore the relationship between serum 25(OH)D concentrations measured in 7-day old calves and subsequent health outcomes over the following 12 months. A genome wide association study demonstrated that both dietary and endogenously produced vitamin D metabolites were under polygenic control in African calves. In addition, we found that neonatal vitamin D status was not predictive of the subsequent development of an infectious disease event or mortality over the 12 month follow up period.

Maternal High Fat Diet Programs Male Mice Offspring Hyperphagia and Obesity: Mechanism of Increased Appetite Neurons via Altered Neurogenic Factors and Nutrient Sensor AMPK.

Maternal high-fat (HF) is associated with offspring hyperphagia and obesity. We hypothesized that maternal HF alters fetal neuroprogenitor cell (NPC) and hypothalamic arcuate nucleus (ARC) development with preferential differentiation of neurons towards orexigenic (NPY/AgRP) versus anorexigenic (POMC) neurons, leading to offspring hyperphagia and obesity. Furthermore, these changes may involve hypothalamic bHLH neuroregulatory factors (Hes1, Mash1, Ngn3) and energy sensor AMPK. Female mice were fed either a control or a high fat (HF) diet prior to mating, and during pregnancy and lactation. HF male newborns were heavier at birth and exhibited decreased protein expression of hypothalamic bHLH factors, pAMPK/AMPK and POMC with increased AgRP. As adults, these changes persisted though with increased ARC pAMPK/AMPK. Importantly, the total NPY neurons were increased, which was consistent with the increased food intake and adult fat mass. Further, NPCs from HF newborn hypothalamic tissue showed similar changes with preferential NPC neuronal differentiation towards NPY. Lastly, the role of AMPK was further confirmed with in vitro treatment of Control NPCs with pharmacologic AMPK modulators. Thus, the altered ARC development of HF offspring results in excess appetite and reduced satiety leading to obesity. The underlying mechanism may involve AMPK/bHLH pathways.

Omega-6:Omega-3 Fatty Acid Ratio and Total Fat Content of the Maternal Diet Alter Offspring Growth and Fat Deposition in the Rat.

Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) have been shown to inhibit lipogenesis and adipogenesis in adult rats. Their possible early life effects on offspring fat deposition, however, remain to be established. To investigate this, female Wistar rats (n = 6-9 per group) were fed either a 9:1 ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) or a lower 1:1.5 ratio during pregnancy and lactation. Each ratio was fed at two total fat levels (18% vs. 36% fat w/w) and offspring were weaned onto standard laboratory chow. Offspring exposed to a 36% fat diet, irrespective of maternal dietary LA:ALA ratio, were lighter (male, 27 g lighter; female 19 g lighter; p < 0.0001) than those exposed to an 18% fat diet between 3 and 8 weeks of age. Offspring exposed to a low LA (18% fat) diet had higher proportions of circulating omega-3 LCPUFA and increased gonadal fat mass at 4 weeks of age (p < 0.05). Reduced Srebf1 mRNA expression of hepatic (p < 0.01), gonadal fat (p < 0.05) and retroperitoneal fat (p < 0.05) tissue was observed at 4 weeks of age in male and female offspring exposed to a 36% fat diet, and hepatic Srebf1 mRNA was also reduced in male offspring at 8 weeks of age (p < 0.05). Thus, while offspring fat deposition appeared to be sensitive to both maternal dietary LA:ALA ratio and total fat content, offspring growth and lipogenic capacity of tissues appeared to be more sensitive to maternal dietary fat content.

Short communication: Colostrum versus formula: Effects on mRNA expression of genes related to branched-chain amino acid metabolism in neonatal dairy calves.

The objective of the current study was to elucidate the effect of feeding colostrum or milk-based formula on the tissue mRNA abundance of the most relevant branched-chain amino acids (BCAA) transporters and catabolizing enzymes in newborn calves. German Holstein calves were fed either colostrum (COL; n = 7) or milk-based formula (FOR; n = 7) with comparable nutrient composition but lower contents of free BCAA, insulin, and insulin-like growth factor-I in the formula than in the respective colostrum for up to 4 d of life. Tissue samples from liver, kidney fat, 3 different muscles [M. longissimus dorsi (MLD), M. semitendinosus (MST), and M. masseter (MM)], as well as duodenum, jejunum, and ileum were collected following euthanasia on d 4 at 2 h after feeding. The plasma-free BCAA were analyzed, and the tissue abundance of solute carrier family 1 member 5 (SLC1A5), SLC7A5, and SLC38A2 as well as mitochondrial isoform of branched-chain aminotransferase (BCATm), branched-chain α-keto acid dehydrogenase E1α (BCKDHA), and branched-chain α-keto acid dehydrogenase E1ß (BCKDHB) were assessed. The preprandial plasma concentrations of free BCAA were affected by time but did not differ between groups. The plasma concentrations of free BCAA decreased in COL, whereas they increased in FOR after feeding, resulting in higher postprandial plasma total BCAA concentrations in FOR than in COL. The mRNA abundances of BCATm, BCKDHA, BCKDHB, as well as BCAA transporters in the liver, were not affected by the diet. In kidney fat, the mRNA abundance of BCAA catabolizing enzymes did not differ between groups, but that of SLC1A5 was lower in FOR than in COL. The mRNA abundance of BCAA catabolizing enzymes in different sections of the small intestine was not affected by the diet, whereas that of SLC7A5 was or tended to be lower in the duodenum, proximal jejunum, and mid jejunum of the COL calves compared with the FOR calves. The mRNA abundance of BCKDHA was lower in MLD and MM but greater in MS for the FOR calves compared with the COL calves. The mRNA abundance of SLC7A5 in MST was lower in FOR than in COL, whereas it was unaffected by the diet in MLD and MM. The differential effect of feeding colostrum on the mRNA abundance of BCKDHA in 3 different muscle tissues might point to a muscle type-specific response. The results also indicate that the colostral BCAA might be favorably used for anabolic metabolism in the small intestine of neonatal calves. Such effects are speculated to be due to the stimulatory effects of growth factors and hormones present in colostrum.

Maternal supplementation of organic selenium during gestation improves sows and offspring antioxidant capacity and inflammatory status and promotes embryo survival.

Selenium (Se) is an essential trace element in humans and sows, having a biological function mediated in part by its incorporation into selenoproteins. This study was conducted to investigate the effects of maternal 2-hydroxy-4-methylselenobutanoic acid (HMSeBA), an organic Se source, on reproductive performance, antioxidant capacity and inflammatory status of sows and their offspring. Forty-three Landrace × Yorkshire sows were randomly allocated to receive one of the following three diets during gestation: control diet (control, basal diet, n = 15), sodium selenite (Na2SeO3) supplemented diet (Na2SeO3, basal diet + Na2SeO3 at 0.3 mg Se per kg, n = 13), and HMSeBA supplemented diet (HMSeBA, basal diet + HMSeBA at 0.3 mg Se per kg, n = 15). Blood samples of sows and piglets, placentas and piglet liver samples were analyzed for selenium status, antioxidant capacity and inflammatory cytokines. Results showed that, as compared to the control group, HMSeBA supplementation increased the number of born alive piglets and plasma concentrations of total selenium and selenoprotein P in both sows and piglets. Besides, the activities of antioxidant enzymes in the blood of sows, umbilical cord and piglets, placentas and piglets' liver were increased by dietary HMSeBA supplementation as compared to the control group, while malondialdehyde concentration (p < 0.05) was decreased in the blood of sows, umbilical cord and newborn piglets. In addition, maternal HMSeBA intake during gestation up-regulated antioxidant-related selenoprotein gene expression in the placenta (GPx2, GPx3, p < 0.05) and in the liver of newborn piglets (GPx1, GPx2, GPx3, TXNRD2, p < 0.05). Moreover, as compared to the control group, sows and newborn piglets in the Na2SeO3 and HMSeBA groups had a lower serum interleukin-6 (p < 0.05) concentration, and placentas in the HMSeBA group had lower IL-1ß, IL-6 and IL-8 gene expression (p < 0.05). In conclusion, maternal supplementation of HMSeBA during pregnancy improved antioxidant capacities and reduced the inflammation level in mater, placenta, and fetus. This finding may highlight the important role of selenoproteins (especially GPXs) in preventing negative consequences of over-production of free radicals and inflammatory cytokines during gestation and at births.

Selenium biofortified alfalfa hay fed in low quantities improves selenium status and glutathione peroxidase activity in transition dairy cows and their calves.

The hypothesis of the study was that feeding a relatively low amount of Se biofortified alfalfa hay during the dry period and early lactation would improve selenium status and glutathione peroxidase activity in dairy cows and their calves. Ten Jersey and 8 Holstein primiparous dairy cows were supplemented with Se biofortified (TRT; n = 9) or non-biofortified (CTR; n = 9) alfalfa hay at a rate of 1 kg/100 kg of BW mixed with the TMR from 40 d prior parturition to 2 weeks post-partum. Se concentration in whole blood, liver, milk, and colostrum, the transfer of Se to calves, and the glutathione peroxidase (GPx) activity were assessed. TRT had 2-fold larger (P < 0.05) Se in blood v. CTR that resulted in larger Se in liver and colostrum but not milk and larger GPx activity in plasma and erythrocytes but not in milk. Compared to CTR, calves from TRT had larger Se in blood but only a numerical (P = 0.09) larger GPx activity in plasma. A positive correlation was detected between Se in the blood and GPx activity in erythrocytes and plasma in cows. Our results demonstrated that feeding pregnant primiparous dairy cows with a relatively low amount of Se-biofortified alfalfa hay is an effective way to increase Se in the blood and liver, leading to greater antioxidant activity via GPx. The same treatment was effective in improving Se concentration in calves but had a modest effect on their GPx activity. Feeding Se biofortified hay increased Se concentration in colostrum but not in milk.

Iron deficiency during pregnancy and lactation modifies the fatty acid composition of the brain of neonatal rats.

Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam's milk and neonates' brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring's brain and suggests that these effects can be reduced by iron repletion of the dam's diet at birth.

Flaxseed oil supplementation improves intestinal function and immunity, associated with altered intestinal microbiome and fatty acid profile in pigs with intrauterine growth retardation.

Flaxseed oil (FO), enriched in n-3 polyunsaturated fatty acids (PUFAs), is an important oil source for intestinal development and health. We aimed to study the different effects of FO versus soybean oil (SO) on growth, intestinal health and immune function of neonates with intrauterine growth retardation (IUGR) using a weaned piglet model. Forty pairs of male IUGR and normal birth weight piglets, weaned at 21 ± 1 d, were fed diets containing either 4% FO or SO for 3 weeks consecutively. Growth performance, nutrient digestibility and intestinal function parameters, immunology and microbiota composition were determined. IUGR led to a poor growth rate, nutrient digestibility and abnormal immunology variables, whereas feeding FO diet improved systemic and gut immunity, as indicated by increased plasma concentration of immunoglobulin G and decreased CD3+CD8+ T lymphocytes, and down-regulated intestinal expression of genes (MyD88, NF-κB, TNF-α, IL-10). Although IUGR tended to decrease villous height, feeding FO diet tended to increase the villi-crypt ratio and up-regulated expressions of tight junction genes (Claudin-1 and ZO-1), together with increased mucosa contents of n-3 PUFAs and a lower Σn-6/Σn-3 ratio. Besides, FO diet decreased the abundance of pathogenic bacteria Spirochaetes, and increased phylum Actinobacteria, and genera Blautia and Bifidobacterium in colonic digesta. Our findings indicate that IUGR impairs growth rate, nutrient digestibility, and partly immunology variables, whereas feeding FO-supplemented diet could improve intestinal function and immunity of both IUGR and NBW pigs, associated with the altered gut microbiome and mucosal fatty acid profile.

Neonatal treatment with clomipramine modifies the expression of estrogen receptors in brain areas of male adult rats.

The participation of estrogens in depression has been well recognized. To exert its effects, estradiol binds mainly to estrogen receptors ESR1 and ESR2 (α and ß, respectively), expressed in brain regions including the hippocampus, limbic regions and hypothalamic nuclei. In rodents, modified estrogen receptors expression in brain areas have been implicated in different signs similar to those observed in depressive patients. Neonatal clomipramine (CMI) treatment is a pharmacological manipulation that generates behavioral and neurochemical changes that persist throughout adulthood and resemble human depression. The aim of this study was to analyze whether CMI neonatal treatment modifies the expression of nuclear ESR1 and ESR2 in the hippocampus, amygdala basolateral (BLA), amygdala medial (MeA), hypothalamic medial preoptic area (mPOA) and raphe nucleus in male rats. Our results indicate that CMI treatment significantly induced an mRNA increase of ESR1 in the hypothalamus, additionally produce a reduction in the mRNA ESR2 expression in raphe accompanied of an increase in hypothalamus and amygdala. CMI treated rats show more immunorreactive cells to ESR1 (ESR1-ir) in mPOA, BLA, MeA, together with a reduction of these cells in the hippocampal CA1 region. Moreover, an increase in the number of immunorreactive cells to ESR2 (ESR2-ir), in BLA and MeA, was observed in CMI treated rats. Additionally, the hippocampal CA2 region and raphe nucleus showed a decrease in these cells. Also, neonatal CMI treatment induced a decrease in the number of cells of the pyramidal layer in CA1. Overall, the results suggest that neonatal CMI treatment in rats (during brain development) induces changes in estrogen receptors in different brain areas involved with the regulation of depressive-like behaviors.

Alterations of the circular RNA profile in the jejunum of neonatal calves in response to colostrum and milk feeding.

Circular RNA (circRNA) have been suggested to contribute to regulating gene expression in various tissues and cells of eukaryotes. However, little is known regarding the expression pattern of circRNA and their potential function in the small intestine of neonatal calves that receive colostrum. In the current study, jejunum tissue samples were collected from control calves (2 h after birth; CT; n = 3) and neonatal calves that ingested colostrum (24 h after birth; CO; n = 3) or milk (24 h after birth; MK; n = 3) to compare the circRNA expression patterns using a high-throughput RNA sequencing approach. A total of 21,213, 17,861, and 21,737 circRNA were identified in the CT, CO, and MK groups, respectively. Only 13,254 of these circRNA were common to the 3 groups, suggesting high specificity of circRNA expression depending on nutrient type. In total, 243, 249, and 283 circRNA were differentially expressed in the CO versus CT, CO versus MK, and MK versus CT comparisons, respectively. Gene ontology analysis showed that the differentially expressed circRNA and their predicted or known target genes from the CO and MK groups were mainly involved in macromolecule metabolic process, response to stress, and vesicle-mediated transport. Moreover, pathway analysis showed that the Rap1 signaling pathway, focal adhesion, ubiquitin-mediated proteolysis, and extracellular matrix-receptor interaction were the most significantly enriched pathways. These data collectively indicate that circRNA are abundant and dynamically expressed when calves receive colostrum and act as microRNA sponges to regulate their target genes for jejunum function during the early development of newborn calves.

Neuroprotective effect of astaxanthin on newborn rats exposed to prenatal maternal seizures.

Maternal epilepsy during pregnancy is associated with an increased incidence of brain damage and cognitive deficits in offspring. Oxidative stress is believed to play a critical role in this process. Astaxanthin, a natural carotenoid and dietary supplement, possesses potent antioxidant properties. This study was designed to investigate whether astaxanthin ameliorates the hippocampal damage in newborn rats induced by maternal epileptic seizures in utero and to explore the underlying mechanisms. Female Sprague-Dawley rats underwent chronic amygdalar kindling. After being fully kindled, all rats were allowed to mate, and electrical stimulation in the amygdala was performed every other day throughout the pregnancy. Astaxanthin was intraperitoneally injected at a dose of 30 mg/kg/d throughout pregnancy. Prenatal astaxanthin administration ameliorated neuronal lesions, decreased oxidative stress and induced the expression of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the hippocampus of pups. Astaxanthin also ameliorated placental ischemic damage in epileptic mothers. Based on the results of the present study, we concluded that astaxanthin might serve as a therapeutic agent for preventing brain damage in offspring exposed to prenatal maternal seizures.

Deleterious effects of perinatal exposure to potassium bromate on the development of offspring of Swiss mice.

The present study aimed to investigate the impact of perinatal potassium bromate (KBrO3) exposure on the development of sensorimotor reflexes and redox status, and on the histological architecture of the brain, liver, and kidney of newborn mice. Pregnant mice received 1-ml bottled drinking water daily by oral intubation and served as the control group. Another group of pregnant mice were supplemented orally with 200 mg/kg body weight KBrO3 dissolved in drinking water from gestation day 5 to postnatal day 21. KBrO3 induced a decrease in the postnatal body weight in the newborn mice. KBrO3-exposed newborn mice showed poor performance and delayed development of the sensorimotor reflexes. Histological changes, increased lipid peroxidation, and altered antioxidants were reported in the cerebrum, cerebellum, medulla oblongata, liver, and kidney of the KBrO3-exposed newborn mice. In conclusion, these findings demonstrated that perinatal exposure to bromate induced oxidative stress, histological and behavioral alterations, and was a potential teratogen in newborn mice.

Colostrum feeding shapes the hindgut microbiota of dairy calves during the first 12 h of life.

This study evaluated the effect of feeding non-heated and heated colostrum on the mucosa- and digesta-associated microbiota in the colon of dairy calves during the first 12 h of life. Thirty-two neonatal Holstein male calves were fed: no colostrum (NC, n = 8), non-heated colostrum (FC, n = 12) and heated colostrum (HC (60 °C, 60 min), n = 12) immediately after birth. The abundances of mucosa- and digesta-associated total bacteria were higher in the colon of FC fed calves compared to those fed no colostrum (NC) at 12 h of life. Compare to NC calves, a higher proportion of mucosa- and digesta-associated Clostridium cluster XIVa and Bifidobacterium, and a lower abundance of mucosa and digesta-associated E. coli were detected in the colon of FC and HC fed calves, as well as a tentatively lower relative abundance of Escherichia-Shigella genus in colon mucosa of HC fed calves. In addition, HC calves had lower abundances of E. coli and higher abundances of Bifidobacterium in mucosa-associated microbiota than FC fed calves. Our results suggest that feeding non-heated colostrum immediately after birth benefit neonatal calves with increased Bifidobacterium and decreased opportunistic pathogenic E. coli and Escherichia-Shigella genus in the colon, and feeding heated colostrum can fortify such effects.

Exploration of the Relationship between Intestinal Colostrum or Milk, and Serum Metabolites in Neonatal Calves by Metabolomics Analysis.

In contrast to colostral immunoglobulins, changes in metabolite composition of ingested colostrum in the gut have received little attention. Here, we characterized the metabolite profiles of colostrum and milk, ingested colostrum and milk, and serum of neonatal calves by liquid chromatography tandem-mass spectrometry and gas chromatography-mass spectrometry metabolomics approaches. Colostrum and milk underwent similar changes in metabolite profiles in the gut after being ingested. These changes were characterized by increases in methionine, glutamate, thymine, and phosphorylcholine. After ingestion, colostrum concentrations of several metabolites, such as γ-aminobutyric acid, glutamate, cinnamic acid, and thymine increased, whereas concentrations of d-ribose, and arginine decreased. These increases and decreases occurred in a time-dependent manner and were associated with alanine, aspartate, glutamate, and pyrimidine metabolism, and valine, leucine, and isoleucine biosynthesis, respectively. Meanwhile, similar changes in serum metabolites were also observed in neonatal calves fed colostrum, which implies that colostrum metabolites are transported across the small intestine and into the bloodstream. In addition, several metabolites of ingested milk were detected in the gut, and were also transferred to the bloodstream. These metabolites were related to phenylalanine, tyrosine, tryptophan, valine, leucine, and isoleucine biosynthesis, the citrate cycle, and histidine metabolism. These findings reveal that the serum metabolome of neonatal calves' changes as a result of ingesting colostrum, which can provide health-related benefits in early life.

Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota.

BACKGROUND: The early-life gut microbiota plays a critical role in host metabolism in later life. However, little is known about how the fatty acid profile of the maternal diet during gestation and lactation influences the development of the offspring gut microbiota and subsequent metabolic health outcomes. RESULTS: Here, using a unique transgenic model, we report that maternal endogenous n-3 polyunsaturated fatty acid (PUFA) production during gestation or lactation significantly reduces weight gain and markers of metabolic disruption in male murine offspring fed a high-fat diet. However, maternal fatty acid status appeared to have no significant effect on weight gain in female offspring. The metabolic phenotypes in male offspring appeared to be mediated by comprehensive restructuring of gut microbiota composition. Reduced maternal n-3 PUFA exposure led to significantly depleted Epsilonproteobacteria, Bacteroides, and Akkermansia and higher relative abundance of Clostridia. Interestingly, offspring metabolism and microbiota composition were more profoundly influenced by the maternal fatty acid profile during lactation than in utero. Furthermore, the maternal fatty acid profile appeared to have a long-lasting effect on offspring microbiota composition and function that persisted into adulthood after life-long high-fat diet feeding. CONCLUSIONS: Our data provide novel evidence that weight gain and metabolic dysfunction in adulthood is mediated by maternal fatty acid status through long-lasting restructuring of the gut microbiota. These results have important implications for understanding the interaction between modern Western diets, metabolic health, and the intestinal microbiome.