Maternal Rats Research Articles

Long-chain perfluoroalkylether carboxylic acids PFO5DoA and PFO4DA alter glucose, bile acid, and thyroid hormone homeostasis in fetal rats from 5-day maternal oral exposure

Chemical monitoring studies in North Carolina, USA and Shandong, China have reported detections of perfluoroalkylether carboxylic acids of increasing chain length with ether bonds between each fluorinated carbon. Despite detection there is limited hazard data available to inform risk assessment. Here, we exposed pregnant Sprague-Dawley rats to two of these compounds, perfluoro-3,5,7,9-butaoxadecanoic acid (PFO4DA) and perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA), from gestation days 18-22 across a series of doses (0.3 - 62.5 mg/kg/d) via oral gavage. PFO5DoA was acutely toxic to rat dams and fetuses at the top two doses (30 and 62.5 mg/kg), while PFO4DA did not cause acute toxicity at any doses tested. PFO5DoA significantly increased maternal liver weight (≥3 mg/kg; 28% increase at 10 mg/kg) while PFO4DA did not affect maternal liver weight up to 62.5 mg/kg. PFO4DA and PFO5DoA both significantly reduced serum total thyroxine in maternal (≥10 mg/kg for both) and fetal (≥1 mg/kg) rats. Both compounds significantly reduced fetal liver glycogen concentrations, increased fetal serum total bile acids, and altered expression levels of multiple genes associated with glucose metabolism in the fetal liver. Serum concentrations of PFO5DoA were higher than PFO4DA in both rat dams and fetuses at equivalent maternal oral doses indicating greater accumulation. Dose response modelling of several fetal endpoints as a function of serum molar concentration indicates PFO5DoA was ∼3-4-fold more potent than PFO4DA. PFO5DoA and PFO4DA produced maternal and fetal toxicity from short-term oral maternal exposure indicating need for additional toxicity data to evaluate potential human health risks.

Iron Level in Pregnant Rats is Associated with Caries Susceptibility in Offsprings.

Iron deficiency anemia (IDA) is a prevalent issue in pregnant women and children. However, the causal relationship between IDA in pregnancy and caries susceptivity in offspring remains unclear. This study aimed to explore the role of iron level during pregnancy on caries susceptivity of offsprings. Here, low-iron (LI) and high-iron (HI) models were established in maternal rats, and iron-related characteristics were examined in maternal rats and their offsprings. After induction of caries in rat offsprings, the carious lesions were evaluated by the Keyes scores, and microstructural damages in molars were observed by scanning electron microscopy. The results showed that LI in maternal rats induced IDA in rat offsprings, and HI only increased serum ferritin in offsprings. LI and HI in maternal rats had no effect on the morphological structure of salivary glands in rat offsprings. After inducing caries, rat offsprings in the LI group exhibited significant increase in enamel lesions at the smooth surface, and on enamel, slight dentinal, and moderate dentinal lesions at the sulcal surface. Only enamel lesions at the sulcal surface were significantly weakened in the HI group. Additionally, visible enamel damages were observed in the LI group. To sum up, iron deficiency during pregnancy enhances caries susceptibility in rat offsprings.

Effects of progesterone administered to maternal rats during the teratogenesis-sensitive period through different routes on neurobehavior and gut microbiota in offspring

Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different routes on offspring growth remain unevaluated. This study aimed to investigate and compare the effects of P4 administration through three different routes in pregnant rats during the teratogenesis-sensitive period on fertility outcomes and the behavior, plasma P4 and pregnenolone levels, and alterations in gut microbiota in the filial generation (F1) of offspring. Methods: Female rats that mated successfully were randomly classified into four groups: Group 1, the normal control group; Group 2, the IG group, in which utrogestan was administered via intragastric gavage; Group 3, the IM group, in which P4 was administered via intramuscular injection; and Group 4, the VAGIN group, in which P4 sustained-release vaginal gel was administered through the vagina. Except for the control group, P4 was administered in other groups through their respective routes for 13 consecutive days daily during the teratogenic-sensitive gestation period (days 6–18). The fertility outcomes of the maternal rats were observed, and open-field and three-chamber social preference tests were conducted to assess anxiety and social behavior, along with an exhaustive swimming experiment to evaluate the motor endurance of the offspring. Plasma P4 and pregnenolone levels in the offspring were measured, and fecal samples were assessed using gut microbiota sequencing and subsequent bioinformatics analysis. Results: No significant alterations in fertility outcomes were observed through three P4 administration routes—intragastric gavage, intramuscular injection, and vaginal administration—in rats. However, in behavioral experiments in offspring, a significant increase was observed in swimming time in the IG group than in the control group (P = 0.013). Furthermore, the offspring in the IG group exhibited a marked decrease in non-social behaviors compared with the control group (P = 0.030). No significant behavioral changes were observed in the F1 offspring in the open-field test. Additionally, the offspring in the IG group exhibited a significant elevation in plasma pregnenolone levels compared with the control group (P = 0.019) 30 days after birth. No notable differences in the α-diversity of gut microbiota were observed among the groups. However, significant differences in β-diversity were observed in both the IG and IM groups compared with the control group, indicating that P4 treatment via the two routes exhibited a significant impact on the gut microbiota composition of F1 offspring. Distinct differences were observed in the gut microbiota of the offspring among the three P4 treatment groups, with 22, 28, and 33 differential bacterial taxa identified in the IG, IM, and VAGIN groups, respectively, using linear discriminant effect size analysis, whereas Olivella appeared exclusively in the control group rather than in the P4 treatment groups. Conclusion: Oral administration of P4 to maternal rats during the teratogenesis-sensitive period enhanced motor endurance and plasma pregnenolone levels and altered the composition of the gut microbiota in the offspring. Our findings demonstrated different effects on offspring growth when P4 is administered orally, intramuscularly, or vaginally.

Reproductive and developmental safety evaluation of Thymelaea hirsuta (L.) leaves aqueous extract in Wistar albino rats

Ethnopharmacological relevanceThe popularity of herbal medicine is expanding globally due to the common belief that herbal products are natural and nontoxic. Thymelaea hirsuta leaves are traditionally used for the treatment of recurrent abortion in humans and animals. However, a lack of safety evaluation of the plant, particularly in pregnant women, raises serious concerns regarding its potential embryotoxic effects. Aim of the studyTherefore, the present study investigated the safety of Thymelaea hirsuta leaves aqueous extract (THLE) during pregnancy and lactation following maternal rat treatment. Materials and methodsTHLE phytochemical compounds were identified using high-performance liquid chromatography (HPLC). THLE was orally administered to pregnant rats and lactating dams at dosages of 0, 250, 500, and 1000 mg/kg/day. At the end of the study, dam s' and pups' body weights, serum biochemical and hematological indices, and histopathological changes were investigated. For the fetal observation and histopathological changes were also evaluated. ResultsOur findings revealed that THLE is rich in different phenolic and flavonoid compounds. However, biochemical and hormonal parameters such as ALT, AST, and prolactin were significantly increased in dams treated with a higher dosage of THLE when compared to the control dams (P ≤ 0.05). Additionally, external, visceral and skeletal examinations of fetuses revealed a marked increase of malformation rates in treated fetuses. ConclusionsThe results revealed that higher oral dosing of THLE during pregnancy could affect embryonic development in rats, while lower doses are safe and can be used during pregnancy and lactation to attain its beneficial effects.

Therapeutic effect of Momordica charantia on cardiomyopathy in a diabetic maternal rat model.

Myocardial structural and functional abnormalities are hallmarks of diabetic cardiomyopathy (DCM), a chronic consequence of diabetes mellitus (DM). Maternal DM affects and increases the risk of heart defects in diabetic mothers compared with nondiabetic mothers. Momordica charantia exhibits antidiabetic effects due to various bioactive compounds that are phytochemicals, a broad group that includes phenolic compounds, alkaloids, proteins, steroids, inorganic compounds, and lipids. Pregnant maternal rats were split into four groups: control (C), M. charantia-treated (MC), type 2 diabetes mellitus (T2DM) (DM), and diabetic (MC + DM) groups. Diabetes mothers had increased serum glucose, insulin, total cholesterol, triglyceride, and low-density lipoprotein cholesterollevels and reduced high-density lipoprotein cholesterollevels. Cardiac biomarkers such as cardiac troponin T (cTnT), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenasewere increased. Hormone levels of follicle-stimulating hormone, luteinizing hormone, progesterone, and estrogen decreased significantly. Inflammatory markers such as interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and vascular adhesion molecule-1 (VCAM-1) were elevated in diabetic mothers. Oxidative stress markers indicated increased malondialdehydeand nitric oxidelevels, while antioxidants such as glutathione, superoxide dismutase, and catalasewere decreased in maternal heart tissue. The levels of apoptotic markers such as tumor suppressor 53 (P53) and cysteine aspartic protease-3 (caspase-3) were significantly greater in diabetic maternal heart tissue. Histopathological analysis revealed heart tissue abnormalities in diabetic maternal rats. M. charantia extract improved maternal diabetes-induced changes in inflammation, antioxidant levels, and heart tissue structure.

Antioxidant Response of Maternal and Fetal Rat Liver to Selenium Nanoparticle Supplementation Compared to Sodium Selenite: Sex Differences between Fetuses.

To compare the effects of organic selenium nanoparticles (SeNPs, Se0) and inorganic sodium selenite (NaSe, Na2SeO3, Se4+) on the antioxidant response in maternal and fetal rat liver, pregnant females were treated with two forms of selenium (Se) at equivalent doses during gestation (0.5 mg SeNPs or 0.5 mg NaSe/kg body weight/day). Structural parameters of the liver of gravid females and their fetuses were examined in a sex-specific manner. The oxidative stress parameters superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione S-transferase (GST), total glutathione (GSH) and sulfhydryl groups (SH) were established. In addition, the Se concentration was determined in the blood, liver, urine and feces of the gravid females and in the liver of the fetuses. The structure of the liver of gravid females remained histologically the same after supplementation with both forms of Se, while the oxidative stress in the liver was significantly lower after the use of SeNPs compared to NaSe. Immaturity of fetal antioxidant defenses and sex specificity were demonstrated. This study provides a detailed insight into the differences in the bioavailability of the nano form of Se compared to sodium selenite in the livers of pregnant females and fetuses.

Docosahexaenoic acid ameliorates autistic‐like behaviors by inhibiting oxidative stress and inflammatory response in neonatal maternal separation rats

AbstractAutism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by impaired social interactions and communication, repetitive, or stereotyped behavior. Docosahexaenoic acid (DHA), an essential polyunsaturated fatty acid, has been demonstrated to exert anti‐oxidative stress and anti‐inflammatory properties, while also promoting myelin development and neural differentiation and development. However, it remains uncertain whether DHA can ameliorate autistic‐like behaviors, and if so, the underlying mechanisms are still unclear. Here, we established a neonatal maternal separation (NMS) rat model and treated it with DHA (80 mg/kg/day, i.p.). The results showed DHA treatment significantly alleviated autism‐like behaviors in the NMS rats during their juvenile period. Subsequently, we employed network pharmacology analysis and molecular docking methods to screen potential targets of DHA in ASD therapy. Through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Wikipedia enrichment analysis, we identified anti‐oxidative stress, anti‐inflammatory and JNK signaling pathway that might be associated with DHA‐mediated improvement of autistic‐like behaviors. Furthermore, western blotting assays showed DHA significantly downregulated the expression levels of p‐JNK and c‐JUN, while upregulating the expression levels of NRF2, HO‐1, SOD1, and CAT. In addition, enzyme‐linked immunosorbent assay results showed DHA effectively reduced the production of pro‐inflammatory factors, such as TNF‐α, IL‐6, and IL‐1β. Collectively, our study predicted and validated that DHA exhibits the potential to improve autistic‐like behaviors induced by NMS in rats by suppressing JNK activation and inhibiting oxidative stress and inflammatory response. These findings suggest that DHA may be a potential therapeutic agent for the treatment of ASD.

The disrupting effect of chlormequat chloride on growth hormone is associated with pregnancy

Since chlormequat chloride is widely applied as a plant growth regulator in agriculture and horticulture, its exposure through food consumption is common. We demonstrated previously that chlormequat chloride exposure during pregnancy led to embryos with bigger sizes associated with higher levels of growth hormone (GH) on gestation day 11 (GD11). However, the dose-effect relationship of chlormequat chloride at a lower dose range was not established, and the underlying mechanisms of its promoting effects on embryonic growth and development were not fully elucidated. To address these, pregnant rats were orally exposed to chlormequat chloride at 0, 0.05, 0.5 and 5 mg/kg.bw from GD0 to 11 and the embryonic growth and growth related hormones were evaluated on GD11. We found that the growth and development of the embryos was significantly promoted in a dose dependent manner by chlormequat chloride. Chlormequat chloride also increased embryonic GH, GH releasing hormone (GHRH), and somatostatin (SRIF), and inhibited the embryonic cAMP dependent protein kinase A (PKA) signaling pathway. Chlormequat chloride increased GH synthesis modulated by GHRH/SRIF-PKA-Pituitary specific transcription factor 1 (Pit-1) in the maternal rats. Intriguingly, chlormequat chloride did not show any effects on GH and PKA signaling pathways in the non-pregnant female rats. These findings together suggest that the disrupting effect of chlormequat chloride on GH is associated with pregnancy.

Early-life exposure to PM2.5 leads to ASD-like phenotype in male offspring rats through activation of PI3K-AKT signaling pathway

Previous studies have shown that early-life exposure to fine particulate matter (PM2.5) is associated with an increasing risk of autism spectrum disorder (ASD), however, the specific sensitive period of ASD is unknown. Here, a model of dynamic whole-body concentrated PM2.5 exposure in pre- and early-postnatal male offspring rats (MORs) was established. And we found that early postnatal PM2.5 exposed rats showed more typical ASD behavioral characteristics than maternal pregnancy exposure rats, including poor social interaction, novelty avoidance and anxiety disorder. And more severe oxidative stress and inflammatory responses were observed in early postnatal PM2.5 exposed rats. Moreover, the expression level of phosphatase and tensin homolog deleted on chromosome ten (PTEN) was down-regulated and the ratios of p-PI3K/PI3K and p-AKT/AKT were up-regulated in early postnatal PM2.5 exposed rats. This study suggests that early postnatal exposure to PM2.5 is more susceptible to ASD-like phenotype in offspring than maternal pregnancy exposure and the activation of PI3K-AKT signaling pathway may represent underlying mechanisms.

Paeoniflorin Alleviates Anxiety and Visceral Hypersensitivity via HPA Axis and BDNF/TrkB/PLCγ1 Pathway in Maternal Separation-induced IBS-like Rats.

Irritable Bowel Syndrome (IBS) is a prevalent gastrointestinal disorder that significantly diminishes the quality of life for affected individuals. The pathophysiology of IBS remains poorly understood, and available therapeutic options for IBS are limited. The crucial roles of brain-gut interaction, which is mediated by the Hypothalamic-Pituitary-Adrenocortical (HPA) axis and the autonomic nervous system in IBS, have attracted increasing attention. The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats. The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot. The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon. These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.

Environmental enrichment attenuates depressive-like behavior in maternal rats by inhibiting neuroinflammation and apoptosis and promoting neuroplasticity

Gestational stress can exacerbate postpartum depression (PPD), for which treatment options remain limited. Environmental enrichment (EE) may be a therapeutic intervention for neuropsychiatric disorders, including depression, but the specific mechanisms by which EE might impact PPD remain unknown. Here we examined the behavioral, molecular, and cellular impact of EE in a stable PPD model in rats developed through maternal separation (MS). Maternal rats subjected to MS developed depression-like behavior and cognitive dysfunction together with evidence of significant neuroinflammation including microglia activation, neuronal apoptosis, and impaired synaptic plasticity. Expanding the duration of EE to throughout pregnancy and lactation, we observed an EE-associated reversal of MS-induced depressive phenotypes, inhibition of neuroinflammation and neuronal apoptosis, and improvement in synaptic plasticity in maternal rats. Thus, EE effectively alleviates neuroinflammation, neuronal apoptosis, damage to synaptic plasticity, and consequent depression-like behavior in mother rats experiencing MS-induced PPD, paving the way for new preventive and therapeutic strategies for PPD.

Does Microwave Exposure at Different Doses in the Pre/Postnatal Period Affect Growing Rat Bone Development?

Effects of pre/postnatal 2.45 GHz continuous wave (CW), Wireless-Fidelity (Wi-Fi) Microwave (MW) irradiation on bone have yet to be well defined. The present study used biochemical and histological methods to investigate effects on bone formation and resorption in the serum and the tibia bone tissues of growing rats exposed to MW irradiation during the pre/postnatal period. Six groups were created: one control group and five experimental groups subjected to low-level different electromagnetic fields (EMF) of growing male rats born from pregnant rats. During the experiment, the bodies of all five groups were exposed to 2.45 GHz CW-MW for one hour/day. EMF exposure started after fertilization in the experimental group. When the growing male rats were 45 days old in the postnatal period, the control and five experimental groups' growing male and maternal rats were sacrificed, and their tibia tissues were removed. Maternal rats were not included in the study. No differences were observed between the control and five experimental groups in Receptor Activator Nuclear factor-kB (RANK) biochemical results. In contrast, there was a statistically significant increase in soluble Receptor Activator of Nuclear factor-kB Ligand (sRANKL) and Osteoprotegerin (OPG) for 10 V/m and 15 V/m EMF values. Histologically, changes in the same groups supported biochemical results. These results indicate that pre/postnatal exposure to 2.45 GHz EMF at 10 and 15 V/m potentially affects bone development.

Ultrastructural Changes in Thyroid Gland from Fetus and Maternal Rats Rattus Norvegicus with Induced Hypothyroidism

Ultrastructural Changes in Thyroid Gland from Fetus and Maternal Rats Rattus Norvegicus with Induced Hypothyroidism

Perinatal maternal exposure to high-dose sodium phenobarbital in the modified Comparative Thyroid Assay: no significant reduction in thyroid hormones in pups despite notable effects in dams.

We propose a modified Comparative Thyroid Assay (CTA, USEPA) utilizing a smaller number of Sprague-Dawley rats (N=10/group) that assesses brain thyroid hormone (TH) concentrations and periventricular heterotopia while maintaining assay sensitivity. Our recent findings demonstrated that a prenatal test cohort of the modified CTA detected a dose-dependent decrease in maternal serum T3 (up to -26%) and T4 (up to -44%) with sodium phenobarbital (NaPB) exposure at 1000 ppm and 1500 ppm, equivalent to intakes of 60 and 84 mg/kg/day, respectively. On gestation day (GD) 20, fetuses exhibited reduced serum (-26%) and brain (-29%) TH concentrations, although these reductions were not dose dependent. The present study expanded the treatment in a postnatal test cohort, with maternal exposure to NaPB (81-93 mg/kg/day) from GD6 to lactation day (LD) 21. We assessed serum and brain TH concentrations, and periventricular heterotopia in pups on postnatal days (PND) 4, 21, and 28. While LD21 dams showed significant reductions in serum T3 (up to -34%) and T4 (up to -54%), the pups did not exhibit significant TH suppression or periventricular heterotopia at any test point. Instead, a compensatory increase in T4 was observed in serum and brain of PND21 pups. The present study confirmed that perinatal maternal exposure to high doses of NaPB leads to a moderate decrease in maternal TH concentrations; however, the exposure of maternal rats to a similar dose of NaPB did not significantly reduce serum or brain TH concentrations in their postnatal offspring.

Pre-weaning antibiotic exposure in maternal rat (F0) causes neurobehavioral effects in adult rat offspring (F1) via activation of HPA axis, and down-regulation of NR3C1 and TPH2 gene

Pre-weaning antibiotic exposure in maternal rat (F0) causes neurobehavioral effects in adult rat offspring (F1) via activation of HPA axis, and down-regulation of NR3C1 and TPH2 gene

Protective effects of gestational folic acid and egg yolk powder solution intubation on motor coordination, anxiety, cognition, acetylcholinesterase activity and DNA fragmentation in prenatal alcohol exposed rats

AbstractBackgroundDevelopment of neurobehavioural disorders can occur in the postnatal life of foetuses prenatally exposed to alcohol, regardless of the alcohol type consumed during pregnancy. Hence, the need to investigate the efficacy of proposed pharmaco‐nutritional therapy in mediating potential behavioural and cholinergic impairments in prenatal alcohol exposed (PAE) fetuses.MethodWe investigated whether PAE exacerbates anxiety, motor coordination, cognitive function, cerebral cortex acetylcholinesterase (ACh) activity, DNA fragmentation and assessed associations among parental and PAE rats’ cerebral cortex ACh activity. Thirty female Wistar rats were mated in the following groups (n = 6): 1: Negative control (distilled water only), 2: Positive control (40% EtOH), 3: local gin (LG), 4: local gin+egg yolk solution(LGEY) 5: local gin +egg yolk solution+folic acid(LGEYFA). Statistical significance of obtained data was measured at p<0.05 using regression model, ANOVA and Tukey’s PostHoc tests (GraphPad 5).ResultWhen compared to the negative control, all alcohol groups (supplemented or not) had significantly lower latency of fall, working memory, percentage alternation etc. Although the brain weight of PAE rats in group 2 (positive control) did not change significantly (p = 0.159), critically reduced brain weights seen in group 3 (LG, p<0.001) were normalized in the supplemented groups (4‐LGEY and 5‐LGE). Cortex protein levels was unchanged in all maternal rats regardless of alcohol intubation. However, ACh cerebral cortex activity was significantly reduced in PAE rats from non‐supplemented groups (2 and 3). Necrosis and fragmentation were also seen in agarose gel electrophoregram (AGE) of gDNA isolated from PAE rats’ brain.ConclusionPrenatal alcohol exposure predisposes to severe neurobehavioural and cognitive deficits while gestational folic acid+egg yolk solution may be a therapeutic target for high risk PAE pregnancies.

Reduction of compulsive overeating in rats caused by maternal deprivation in early ontogenesis with the use of a new ghrelin receptor antagonist agrelax

BACKGROUND: Factors that may trigger episodes of binge eating include mental and physical stress, dietary restrictions of high-calorie foods. In a rodent model it has been shown that intermittent consumption of high-calorie foods causes binge eating regardless of body weight gain.
 AIM: To investigate the effect of a novel ghrelin receptor antagonist Agrelax on binge eating in in adult rats after maternal deprivation in early ontogeny.
 MATERIALS AND METHODS: Animals were weaned for 180 min from day 2 to day 12 after birth; males 90100 days of age were used in the experiments. In the development of binge eating, animals received a high-carbohydrate diet (Nutella paste based chocolate mixture) for 1 h every day or every third day for 1.5 months. Fifteen minutes before feeding, the chocolate paste was placed within 5 cm of reach with visual contact. Agrelax, a novel ghrelin receptor antagonist, was administered intranasally 1g/1l, 20l for 7 days.
 RESULTS: Maternal deprivation induced bindge eating of high-calorie foods in adult rats. When chocolate was given 3 times a week, its consumption increased (p 0.001) in the maternal deprivation group relative to the control group. After a course of administration of agrelax, chocolate consumption did not differ significantly from that in the control group. The daily consumption of standard food did not differ relative to the control group both before and after the course of agrelax administration. When chocolate was given daily, the maternal deprivation rats did not develop food addiction. At the same time agrelax did not induce a change in chocolate consumption relative to the control group.
 CONCLUSIONS: The findings suggest new ways to synthesize pharmacological agents of peptide nature based on ghrelin and its antagonists for correction of food addiction caused by psychogenic stresses in ontogenesis.

Bovine milk osteopontin improved intestinal health of pregnant rats fed a high-fat diet through improving bile acid metabolism

The main purpose of the current study was to investigate the ameliorative effects of bovine milk osteopontin (bmOPN) on the gut dysfunction of pregnant rats fed a high-fat diet (HFD). Bovine milk osteopontin was supplemented at a dose of 6 mg/kg body weight. Bovine milk osteopontin supplementation during pregnancy reduced colonic inflammation of HFD dams, and it also increased the colonic expression of ZO-1 and claudin-4 of HFD dams. Bovine milk osteopontin significantly enriched the relative abundance of Bacteroidetes, whereas it decreased Proteobacteria, Helicobacteraceae, and Desulfovibrionaceae in feces of HFD dams. The levels of isobutyric acid and pentanoic acid in the HFD + bmOPN group were higher than that of the HFD group. Functional predication analysis of microbial genomes revealed that bmOPN supplementation to HFD pregnancies changed 4 Kyoto Encyclopedia of Genes and Genomes pathways including bile acid biosynthesis. Further, bmOPN enriched hepatic taurochenodeoxycholic acid and tauroursodeoxycholic acid plus taurohyodeoxycholic acid in the gut of HFD maternal rats. Our findings suggested that bmOPN improved the gut health of HFD pregnant rats partially through modulating bile acid biosynthesis.

Maternal-Periconceptional Vitamin B12 Deficiency in Wistar Rats Leads to Sex-Specific Programming for Cardiometabolic Disease Risk in the Next Generation

BackgroundMaternal vitamin B12 deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts. ObjectivesThis study assessed the effects of diet-induced maternal vitamin B12 deficiency on F1 offspring in terms of cardiometabolic health and normalization of these effects by maternal-periconceptional vitamin B12 supplementation. MethodsA diet-induced maternal vitamin B12 deficient Wistar rat model was generated in which female rats were either fed a control AIN-76A diet (with 0.01 g/kg vitamin B12) or the same diet with vitamin B12 removed. Females from the vitamin B12-deficient group were mated with males on the control diet. A subset of vitamin B12-deficient females was repleted with vitamin B12 on day 1 of conception. The offspring in the F1 generation were assessed for changes in body composition, plasma biochemistry, and molecular changes in the liver. A multiomics approach was used to obtain a mechanistic insight into the changes in the offspring liver. ResultsWe showed that a 36% reduction in plasma vitamin B12 levels during pregnancy in F0 females can lead to continued vitamin B12 deficiency (60%–70% compared with control) in the F1 offspring and program them for cardiometabolic adversities. These adversities, such as high triglycerides and low high-density lipoprotein cholesterol, were seen only among F1 males but not females. DNA methylome analysis of the liver of F1 3-mo-old offspring highlights sexual dimorphism in the alteration of methylation status of genes critical to signaling processes. Proteomics and targeted metabolomics analysis confirm that sex-specific alterations occur through modulations in PPAR signaling and steroid hormone biosynthesis pathway. Repletion of deficient mothers with vitamin B12 at conception normalizes most of the molecular and biochemical changes. ConclusionsMaternal vitamin B12 deficiency has a programming effect on the next generation and increases the risk for cardiometabolic syndrome in a sex-specific manner. Normalization of the molecular risk markers on vitamin B12 supplementation indicates a causal role.

Maternal rat prenatal and neonatal treatment with pequi pulp reduces anxiety and lipid peroxidation in brain tissue of rat offspring at adolescence

The Pequi fruit (Caryocar Brasiliense cambess), typical of the Brazilian cerrado or savannah, is a source of essential fatty acids, carotenoids, and phenolic compounds. The aim of this study was to analyze the effects of consuming this fruit on anxiety behavior and lipid peroxidation in the brains of rats whose mothers were treated (by gavage) during pregnancy and lactation with Pequi fruit (pulp or nuts) at 2000 mg/kg of body weight. Anxiety parameters were assessed using the open field (OF), elevated plus maze (EPM), and light/dark box (LDB) tests. The brain was removed to measure malondialdehyde (MDA) levels. Data were analyzed using One-way Anova (p < 0.05). In the OF, the animals in the pulp group presented more time spent in the central area (20.37 ± 0.73 vs Control: 12.51 ± 0.39; Nuts: 8.28 ± 0.40) and increased locomotion (159.7 ± 6.10) compared to the other groups (Control: 127.3 ± 5.54; Nuts: 139.08 ± 6.57). In the EPM, the pulp group entered into the open arms (8.57 ± 0.36) and stayed more time in the central area (19.44 ± 1.17) compared to the Nuts group (7.14 ± 0.34; 13.00 ± 1.57). In the LDB the pulp group entered more (8.00 ± 0.42 vs Control: 7.16 ± 0.16 and Nuts: 7.42 ± 0.75) and stayed longer in the clear light side (92.18 ± 6.42) than all the other groups (Control: 71.44 ± 3.53; Nuts: 80.57 ± 6.50), respectively. Pulp group presented lower MDA in the brain (55.34 ± 3.04) compared to Control (72.06 ± 4.66) and Nuts (66.57 ± 2.45). We conclude that Pequi pulp consumption during pregnancy and lactation reduces lipid peroxidation in brain tissue and induces anxiolytic-like behavior in rat offspring. These effects were not observed in the Pequi nuts group.