Body Weight Of Pups Research Articles

Oct4, Sox2, Klf4, c-My (OSKM) gene therapy in the hypothalamus prolongs fertility and ovulation in female rats.

In middle-aged (MA) female rats, we have demonstrated that intrahypothalamic gene therapy for insulin-like growth factor-I (IGF-I) extends the regular cyclicity of the animals beyond 10 months (the age at which MA rats stop ovulating). Here, we implemented long-term OSKM gene therapy in the hypothalamus of young female rats. The main goal was to extend fertility in the treated animals. We constructed an adenovector that harbors the GFP gene as well as 4 Yamanaka genes. An adenovector that only carries the gene for GFP or DsRed was used as control. At 4 months of age 12 female rats received an intrahypothalamic injection of our OSKM vector (treated rats); 12 control rats received a vector expressing a marker gene (control rats). At 9.3 months of age control and treated rats were mated with young males. A group of 12 young intact female rats was also mated. The rate of pregnancy recorded was 83%, 8.3 and 25% for young, MA control and MA treated animals, respectively. Pup body weight (BW) at weaning was significantly higher in the MA OSKM rats than in MA controls. At the age of estropause (10 months), OSKM treated females still showed regular estrous cycles. The particular significance of the present results is that, for the first time, it is shown that long-term OSKM gene therapy in the hypothalamus is able to extend the functionality of such a complex system as the hypothalamo-pituitary-ovarian axis.

Morphometric analysis of the intergenerational effects of protein restriction on nephron endowment in mice

BackgroundParental nutritional status is crucial in shaping offspring's kidney development. However, the association between a protein-restrictive diet and its intergenerational impact on kidney development remains unclear. MethodsWe conducted multigenerational morphometric measurements to investigate the effects of parental protein deprivation on offspring kidney development across four generations. F0 mice were divided into two groups and fed a normal protein diet (NPD) or a low-protein diet (LPD) for three weeks before mating and continued these diets throughout gestation and lactation. Body weight (BW), kidney weight (KW), KW/BW ratio, nephron counts, and blood pressure were assessed in F1 pups. To examine paternal effects, we bred CD1 females on an NPD with males on an LPD. BW, KW, KW/BW, and nephron counts were measured at P20. To measure the transgenerational effect of parental LPD on kidney development, F1 offspring (from parents on LPD) were fed NPD upon weaning. These F1 offspring were bred at 6 weeks of age to produce F2, F3 and F4 generations. Kidney metrics were evaluated across generations. ResultsThe average body weight of P0 pups from parents on NPD was 1.61g, while pups from parental LPD weighed an average of 0.869g, a decrease of 54 % (p = 6.9e-11, Wilcoxon test). F1 from parental LPD have significantly smaller kidneys than the control, with an average combined kidney weight of 0.0082g versus 0.0129g, a 37 % decrease (p = 3.2e-02, Wilcoxon test). P20 BW and KW remained low in LPD offspring. These effects persisted for 4 generations (F1 to F4) with an average glomerular count reduction of roughly 20 %. F3 and F4 showed wider variability in glomerular counts but were not statistically significant compared to controls. ConclusionsBoth maternal and paternal LPD significantly affected offspring nephron endowment. Our study underscores the complex nature of nutritional transgenerational effects on kidney development, emphasizing the importance of both maternal and paternal dietary impacts on kidney development and the developmental origin of adult disease.

Postnatal overfeeding in mice induces early lipidic changes in heart tissue and impacts cardiomyocyte proliferation

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): French Federation of Cardiology Foundation of France Background Shortly after birth, cardiomyocytes lose their ability to proliferate to switch towards a hypertrophic growth and this ability is known to be influenced by nutritional factors. Postnatal overfeeding (PNOF) induced by litter size reduction in rodents reproduces the impact of childhood overnutrition. While PNOF was shown to induce major cardiac and metabolic alterations in adulthood, little is known about its impact during the first days of life. Purpose The objective of this project was to investigate the early changes induced by PNOF induced in heart tissue in terms of lipid profile and cardiomyocyte proliferation. Methods Two days after birth, C57BL/6 male pups were randomly distributed in litters adjusted to either 9 or 3 pups to form normally fed (NF) or postnatally overfed (PNOF) group, respectively. At 7, 10 and 24 postnatal days (D7, D10 and D24, respectively), hearts were harvested for immunostaining of the proliferation marker Ki67. Cardiac and plasma lipid composition of NF and PNOF was evaluated using liquid chromatography coupled to mass spectrometry technique. Finally, cardiomyocytes from D24 hearts were isolated and counted on Malassez counting chamber. Results At D7, D10 and D24, body weight and cardiac mass of PNOF pups were significantly higher than these of NF controls. Interestingly, at D7, lipid composition of PNOF hearts was decreased in cardiolipins, fatty acids and cholesterol derivatives. Moreover, plasma triglyceride levels were lower in D10 PNOF pups. These modifications were associated with a significant reduction of cardiomyocytes’ proliferation rate and an increased hypertrophy in PNOF hearts at D7, resulting in the reduction of cardiomyocyte number at D24 in PNOF mice. Conclusion Only five days after litter size reduction, PNOF induced major lipidic changes both in the cardiac tissue and in the plasma. In parallel, PNOF shortened the cardiomyocyte proliferative window and induced earlier cardiomyocyte maturation. Given the importance of fatty acid metabolism in cardiac development and function, these early changes could be linked to the long-term cardiometabolic alterations observed later in life.

Effects of gestational intermittent hypoxia on the autoresuscitation response following anoxia-induced apneas in neonatal mice

Introduction: Sudden infant death syndrome (SIDS) is the leading cause of death in infants from one month to one year of age. Smoking is a significant risk factor in SIDS, and smoking probably causes intermittent hypoxia in the fetus. Therefore, we modeled the effects of intermittent hypoxia during gestation in mice to determine if gestational intermittent hypoxia would adversely affect the capacity of neonatal mice to autoresuscitate effectively after exposure to anoxic stimuli. A degraded capacity to autoresuscitate could explain, in part, why infants born to mothers who smoke have an increased risk of dying from of SIDS. The primary objective of this study was to investigate the effects of intermittent gestational hypoxia on the autoresuscitation responses to anoxia-induced apneas in neonatal mice. Our hypothesis was that pups born to intermittently hypoxic dams would struggle more to recover from anoxic apneas — would have impaired cardiorespiratory responses to anoxic stress compared to the control mice born to dams exposed to room air during gestation. Methods: We studied C57Bl/6 dams who previously had one litter to prove their capability to breed and rear pups. Dams were placed in either an hypoxic or room air chamber at approximately embryonic day 5 (E5; fifth day of pregnancy). The fractional inspired oxygen concentration (FIO2) was reduced to 11% for 10 minutes, three times per hour, with 10 minute periods of 21% oxygen between them. Each hour of intermittent hypoxia was followed by an hour breathing 21% FiO2. The room air control chamber was maintained at a constant FIO2 of 21% with inflows of compressed air that mimicked the noise and flow of nitrogen in the hypoxic chamber. The dams spent the entirety of their pregnancies in the environmental chambers. Once the pups were delivered, the cages were placed in room air, housing environments. The pups were allowed to stay with their mothers until approximately post-natal day 8 (P8). On P8, each pup was fitted into a head out plethysmograph to measure respiratory flow using a pneumotachograph. We recorded respiratory activity, ECG activity, and body movements (using a piezo sensitive film). The pups were maintained at ~34 degrees C in the pneumotachographic chamber. We measured the highest respiratory rate, highest heart rate, longest apnea, gasp latency, mean heart rate recovery, and mean respiratory rate recovery. Results: The mean heart rate recovery and mean longest apnea (in seconds) doubled in the mice exposed to gestational intermittent hypoxia compared to pups born to dams exposed to room air during gestation. The mean heart rate recovery and mean longest apnea in gestationally hypoxic pups was 41.0 +/- 13.7 seconds and 22.05 +/- 12.0 seconds, respectively. The mean heart rate recovery and mean longest apnea in normal, room air-exposed pups was 22.4 +/- 11.1 seconds and 10.3 +/- 7.0 seconds, respectively. The longest apnea in gestational intermittent hypoxic pups was significantly longer than in control pups (53.0 +/- 13.7 seconds and 19.1 +/- 15.0 seconds). Pups exposed to gestational intermittent hypoxia also had increased mean respiratory rate recovery times and gasp latency times (start of apnea until the first gasp). The average body weight of hypoxic pups was 4.3 grams while the average body weight for the normal pups was 4.9 grams. Conclusion: Gestational intermittent hypoxia was associated with delayed and prolonged the autoresuscitation responses in neonatal mice following acute anoxic exposure. We hypothesize that this is due to changes in the brain’s serotonin system. We are investigating how intrauterine hypoxia may decrease serotonin and serotonergic signaling pathways as changes in serotonergic function may degrade the capacity of mice to autoresuscitate following anoxic gas exposure. NIH/NICHD. HD100823 and NIH/NICHD. HD 107060. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effectiveness of Adas Leaf Infusion (Foeniculum vulgare L.) in Post-Best White Rats (Rattus Sp.) On The Growth Of Children

Adas leaf (Foeniculum vulgare L.) was known by the people around the mountain sides of Merbabu as one type of vegetable to increase breast milk secretion. Increased breast milk secretion has positive effect on pups development in early period of life. The aim of this study is to determine the effect of infusion of adas leaves, the effective dose of infusion against the growth of body weight and body length of pups and the levels of flavonoids, steroids, and stigmasterol on adas leaf. The study was conducted using 12 post-partum rats that have each 5 pups. White rats were divided into 4 groups: control group; the G1 (20 grams/300 ml dose infusion); the G2 (40 grams/300 ml dose infusion); and G3 (60 grams/300 ml dose infusion). Each group consisted of three replications. All of rats mother treated with the adas leaves by infuse feeding (sonde). Adas leaves was infused by 1 ml for 2 times a day on the rats mother (morning and evening). Rats mother were given pellets and also drinking water by adlibitum. Both mother and inbred rats were weighed, length of its body weight was measured every 5 days for 15 days. Data were analyzed by Analysis of Variance (ANOVA) two way and continued by Duncan Multiple Range Test (DMRT). Quantitatively measurements of total flavonoids, steroids and stigmasterol of adas leaves analyzed using Thin Layer Chromatography (TLC). The results showed that infusion of adas leaves significant difference in the growth of body weight and body length between control and treatment groups (p < 0.05). A dose of 60 grams/300 ml of distilled water can effectively increase the growth of body weight and body length of pups. Levels of total flavonoids, steroids and stigmasterol of adas leaves, respectively, are 0.43 %, 0.029 %, and < 0.011 %.

Early life exposure to low-dose perfluorooctane sulfonate disturbs gut barrier homeostasis and increases the risk of intestinal inflammation in offspring

Perfluorooctane sulfonate (PFOS), one of the legacy per- and poly-fluoroalkyl substances (PFAS), is associated with multiple adverse health effects on children. However, much remains to be known about its potential impacts on intestinal immune homeostasis during early life. Our study found that PFOS exposure during pregnancy in rats significantly increased the maternal serum levels of interleukin-6 (IL-6) and zonulin, a gut permeability biomarker, and decreased gene expressions of Tight junction protein 1 (Tjp1) and Claudin-4 (Cldn4), the tight junction proteins, in maternal colons on gestation day 20 (GD20). Being exposed to PFOS during pregnancy and lactation in rats significantly decreased the body weight of pups and increased the offspring's serum levels of IL-6 and tumor necrosis factor-α (TNF-α) on postnatal day 14 (PND14), and induced a disrupted gut tight junction, manifested by decreased expressions of Tjp1 in pup's colons on PND14 and increased pup's serum concentrations of zonulin on PND28. By integrating high-throughput 16S rRNA sequencing and metabolomics, we demonstrated that early-life PFOS exposure altered the diversity and composition of gut microbiota that were correlated with the changed metabolites in serum. The altered blood metabolome was associated with increased proinflammatory cytokines in offspring. These changes and correlations were divergent at each developmental stage, and pathways underlying immune homeostasis imbalance were significantly enriched in the PFOS-exposed gut. Our findings provide new evidence for the developmental toxicity of PFOS and its underlying mechanism and explain in part the epidemiological observation of its immunotoxicity.

Reproductive Toxicity Evaluation of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes on Reproduction and Offspring Health.

A new graphene-based fluorescent nanoprobe for tumor cell nucleus (GTTNs) was synthesized in our laboratory that penetrates the cell membrane and particularly targets cancer cell nucleus and displays tremendous potential for clinical applications. Although acute and subacute toxicity studies have been conducted on GTTNs, a primary result could be drawn that GTTNs appear to have almost no acute and subacute toxicity. However, as an important part of safety evaluation, the influences on reproductive and offspring developmental toxicity are still absent. In this study, male mice were injected intravenously with GTTNs, and the survival status, histopathology of the testes and epididymides, proliferation and apoptosis of testicular tissue, and sperm motility of mice were measured. To evaluate the short- and long-term fertility in male mice, different male mice resided with untreated female mice on days 1 and 30 after the end of the last treatment, and the offspring health parameters were assessed by measuring pup numbers, body weight, and organ indexes of the pups. The results indicated that GTTNs-exposed male mice retained good fertility, healthy structure of testes and epididymides, and production of healthy sperm. Meanwhile, there were no significant differences between the offspring and the control group. In consideration of GTTNs with broad prospects for biomedical applications, our results contribute a basis for further understanding of its biosafety.

Protein-Energy Malnutrition during Gestation and Lactation in Rats Affects Growth Rate, Brain Development and Essential Fatty Acid Metabolism

The influence of feeding a low protein diet to rat dams during gestation and lactation on lipid metabolism in pups was studied. Wistar rats were fed 5, 10, 15 and 25% dietary protein during gestation and lactation. Pup growth was monitored until weaning, and brain weight, protein concentration, proteolipid concentration and total lipid phosphorus concentration of brain were analyzed. The levels of fatty acids in dam milk as well as in pup liver phospholipids and brain prosphatidylcholine and phosphatidylethanolamine were determined. The progressive deprivation of maternal dietary protein produced a reduction in the total saturated fatty acid concentration of dam milk and an increment in the concentration of nonmetabolized linoleic acid. Pup body and brain weights as well as proteolipid, protein and total lipid phosphorus concentrations in brain were reduced in proportion to the degree of dietary protein deficiency. The products:precursor ratio of (n-6) fatty acids in liver phospholipids revealed an impairment in the elongation-desaturation pathway due to maternal protein deficiency. Both (n-6) and (n-3) polyunsaturated fatty acids within brain phosphatidylethanolamine were decreased by reduced maternal dietary protein intake, whereas only the linoleic acid-derived products were similarly affected in the corresponding phosphatidylcholine fraction. These results demonstrate the widespread and profound deleterious effects of low protein levels of maternal diet on the growth rate, brain development and fatty acid metabolism of rat pups.

Dietary Calcium and Lead Interact to Modify Maternal Blood Pressure, Erythropoiesis, and Fetal and Neonatal Growth in Rats during Pregnancy and Lactation

We studied the effects of dietary calcium and lead exposure on lead toxicity, fetal and neonatal growth, erythropoiesis and blood pressure during pregnancy and lactation in rats. Pregnant Sprague-Dawley rats (n = 43) were randomly assigned to one of six treatment groups of 7–8 rats each. Half of the rats were fed diets of low (0.1%), normal (0.5%) or high (2.5%) calcium as calcium carbonate and exposed to 250 mg/L of lead in their drinking water for the duration of the pregnancy and for 1 wk of lactation. Three control groups were fed the same diets without lead exposure. Pups were studied at 1 d and 1 wk of age. Maternal and fetal blood and organ samples from the groups fed the low calcium diet had the highest lead concentrations, whereas the lowest lead concentrations were found in the groups fed the high calcium diet. Dam and pup hemoglobin concentrations, hematocrits, and body weights and lengths were reduced by lead exposure and by the high calcium diet. The latter also reduced organ iron concentrations and prevented lead-induced increases in free erythrocyte protoporphyrin. Dam systolic blood pressures during the third trimester of gestation were significantly higher in rats exposed to lead and fed the low calcium diet than in rats in the other five treatment groups. The results demonstrate that dietary calcium and lead exposure interact in rats to influence maternal blood pressure, erythropoiesis, and fetal and neonatal growth during pregnancy and lactation.

Decrease in Body Weight and Liver Weight of Pups in Swiss Albino Mice by Spearmint Leaves Extract

Objective: To evaluate the effects of spearmint leaves extract on body weight, liver weight and RTWI of pups in Swiss albino mice. Study Design: Experimental study Place and Duration of Study: Anatomy Department, Shaikh Zayed PGMI, Lahore from 1st March 2014 to 30th June 2014. Methodology: Seven male and 21 female mice were used. After conception female mice were divided into control (A), low dose (B) and high dose (C) experimental groups. There were7 mice in each group. Group A was given distilled water where as group B was given 3g/kg/day and group C were given 6g/kg/day spearmint leaves extract. After 21 days (duration of pregnancy in mice) hysterotomy was done after euthanasia. Three groups of pups were made. These pups were selected randomly and marked as control, low dose and high dose experimental groups (A1, B1 & C1 respectively). Their body weights and liver weights were taken and recorded. Results: Body weight, weight of liver and RTWI of pups in both the experimental groups were decreased significantly with p<0.001 and difference between the experimental groups was also highly significant with p<0.001. Conclusion: The spearmint leaves extract decrease the body weight, weight of liver and RTWI of pups of Swiss Albino mice. Keywords: Spearmint, Garden mint, Herbal tea, Swiss Albino mice, Conception, Body weight, Weight of liver, RTWI

Maternal omega-3 fatty acid deficiency affects fetal thermogenic development and postnatal musculoskeletal growth in mice

Maternal omega-3 (n-3) polyunsaturated fatty acids (PUFAs) deficiency can affect offspring's adiposity and metabolism by modulating lipid and glucose metabolism. However, the impact of n-3 PUFA deficiency on the development of fetal thermogenesis and its consequences is not reported. Using an n-3 PUFA deficient mice, we assessed fetal interscapular brown adipose tissue (iBAT), body fat composition, insulin growth factor-1 (IGF-1), glucose transporters (GLUTs), and expression of lipid storage & metabolic proteins in the offspring. The n-3 PUFA deficiency did not change the pups' calorie intake, organ weight, and body weight. However, the offspring's skeletal growth was altered due to excess fat to lean mass, reduced tibia & femur elongation, dysregulated IGF-1 in the mother and pups (P< .05). Localization of uncoupling protein 1 (UCP1) in iBAT exhibited a reduced expression in the deficient fetus. Further, UCP1, GLUT1, GPR120 were downregulated while FABP3, ADRP, GLUT4 expressions were upregulated in the BAT of the deficient offspring (P< .05). The deficiency decreased endogenous conversion of the n-3 LCPUFAs from their precursors and upregulated SCD1, FASN, and MFSD2A mRNAs in the liver (P< .05). An altered musculoskeletal growth in the offspring is associated with impaired browning of the fetal adipose, dysregulated thermogenesis, growth hormone, and expression of glucose and fatty acid metabolic mediators due to maternal n-3 PUFA deficiency. BAT had higher metabolic sensitivity compared to WAT in n-3 PUFA deficiency. Maternal n-3 PUFA intake may prevent excess adiposity by modulating fetal development of thermogenesis and skeletal growth dynamics in the mice offspring.

Quercetin Supplement to Aspirin Attenuates Lipopolysaccharide-Induced Pre-eclampsia-Like Impairments in Rats Through the NLRP3 Inflammasome.

Aspirin is a common drug for the treatment of pre-eclampsia. We aimed to explore whether quercetin as a supplement to aspirin could enhance the therapeutic outcome in pre-eclampsia rat models. We further aimed to evaluate the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome as a potential pre-eclampsia-related molecular mechanism, which can be affected by quercetin treatment. Rat pre-eclampsia models were established using an intravenous lipopolysaccharide injection after gestation. Rats were treated with aspirin and quercetin at 6-18days after pregnancy. On day 20, blood, fetus, and placenta were harvested. Blood pressure and the level of proteinuria were measured every 4days. Fetal outcomes were analyzed by pup body weight. Serum soluble Fms-like tyrosine kinase-1, PIGF, interleukin-6, and interleukin-10 levels were measured using the enzyme-linked immunosorbent assay. Caspase-1, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and p-caspase-1 levels in the placenta were assessed using western blot or quantitative real-time polymerase chain reaction analyses. Pre-eclampsia rat models showed a pronounced increase in systolic blood pressure and proteinuria after 4days of pregnancy, while aspirin, quercetin, and aspirin/quercetin combinatory treatment significantly attenuated the blood pressure and proteinuria abnormalities. Notably, the aspirin/quercetin combinatory treatment showed the highest efficacy in attenuating pre-eclampsia-like symptoms. Placental caspase-1 and NLRP3 levels also showed the greatest attenuation in pre-eclampsia rats after aspirin/quercetin treatment. Our data suggested that quercetin supplementation to aspirin is more effective in attenuating symptoms of pre-eclampsia and improving pregnancy outcomes compared with quercetin or aspirin alone. Quercetin can ameliorate placental NLRP3 inflammasome activation, which might serve as an underlying mechanism for its therapeutic efficacies in pre-eclampsia.

Evaluvation of the Lactogenic activity of Erythrina indica Lam. leaves

Erythrina indica Lam. is used as a galactagogue in folklore medicine. But no report is available to validate its herbal galactagogue activity in literature. So, this in vivo study was designed to assess the galactagogue activity of juice of Erythrina indica tender leaves. The milk production was assessed by parameters including the milk yield, weight gain of mother ratsand pups during the experimental period, serum cortisol and prolactin level, glycogen and protein content of mammary gland also were measured and compared with experimental group and respective control group. To estimate the milk yield, the weights of the pups were taken before and after 60 min of drug administration. On oral administration of the Erythrina indica tender leaf juice, milk yield and prolactin level were statistically significant. The other parameters like body weight of mother and pups, glycogen, and protein level were also found to be clinically significant and statistically not significant and the cortisol level is not significantly decreased. This study proves the galactagogue activity of Erythrina indica, by increasing the milk yield, and serum prolactin level in the lactating rats.

Aloe vera protects against fluoride-induced teratogenic effects during pre- and postnatal development in mice.

Pregnancy and feto-gestational toxicities on exposure to fluoride and its possible amelioration on co-administration with aloe vera were studied in pregnant Swiss albino mice. Once the confirmed pregnancy was tested, animals were equally divided into four groups as follows: group I was given no treatment and served as control, and groups II and III were administered with 100 and 300ppm sodium fluoride, respectively, while group IV was co- administered aloe vera (300mg/kg bw) along with sodium fluoride (300ppm) daily for 14days prior to gestation and continued till the 18th day of gestation. Animals were sacrificed on the 19th day of gestation for prenatal observations. Maternal body weight, the gravid uterine weight, number of corpora lutea in both the ovaries, number of implantations and resorptions, number of live (mature and immature) fetuses, and number of dead fetuses were examined in each dam. The treatment continued in another set of animals till the completion of the weaning period to observe postnatal changes due to test substances on the mother and pups. Sodium fluoride-treated animals showed morphometric and skeletal changes which were more pronounced in the high-dose group showing significantly decreased body weight gain in pregnant mothers and dead/immature fetuses. Morphometric changes included open eyelids, limb defects, wrinkles on the whole body, anophthalmia, pulmonary edema, enlarged esophagus, and decreased body weight of fetuses and pups. Alizarin-prepared skeletal structures of fetuses of such female mice showed delayed ossification or bending in the number of bones of skull, thoracic, and limb regions. However, concomitant exposure to sodium fluoride and aloe vera in treated animals led to a marked improvement in all the prenatal and postnatal variables. The study suggests that sodium fluoride at high concentrations may be teratogenic while co-administration of aloe vera during fluoride exposure might be beneficial in reducing these toxic effects. The use of aloe vera as a preventive agent or as a complimentary agent is thus recommended following fluoride exposure through the oral route.

Developmental toxicity of Nafion byproduct 2 (NBP2) in the Sprague-Dawley rat with comparisons to hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) and perfluorooctane sulfonate (PFOS).

Nafion byproduct 2 (NBP2) is a polyfluoroalkyl ether sulfonic acid that was recently detected in surface water, drinking water, and human serum samples from monitoring studies in North Carolina, USA. We orally exposed pregnant Sprague-Dawley rats to NBP2 from gestation day (GD) 14-18 (0.1-30mg/kg/d), GD17-21, and GD8 to postnatal day (PND) 2 (0.3-30mg/kg/d) to characterize maternal, fetal, and postnatal effects. GD14-18 exposures were also conducted with perfluorooctane sulfonate (PFOS) for comparison to NBP2, as well as data previously published for hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX). NBP2 produced stillbirth (30mg/kg), reduced pup survival shortly after birth (10mg/kg), and reduced pup body weight (10mg/kg). Histopathological evaluation identified reduced glycogen stores in newborn pup livers and hepatocyte hypertrophy in maternal livers at≥10mg/kg. Exposure to NBP2 from GD14-18 reduced maternal serum total T3 and cholesterol concentrations (30mg/kg). Maternal, fetal, and neonatal liver gene expression was investigated using RT-qPCR pathway arrays, while maternal and fetal livers were also analyzed using TempO-Seq transcriptomic profiling. Overall, there was limited alteration of genes in maternal or F1 livers from NBP2 exposure with significant changes mostly occurring in the top dose group (30mg/kg) associated with lipid and carbohydrate metabolism. Metabolomic profiling indicated elevated maternal bile acids for NBP2, but not HFPO-DA or PFOS, while all three reduced 3-indolepropionic acid. Maternal and fetal serum and liver NBP2 concentrations were similar to PFOS, but ∼10-30-fold greater than HFPO-DA concentrations at a given maternal oral dose. NBP2 is a developmental toxicant in the rat, producing neonatal mortality, reduced pup body weight, reduced pup liver glycogen, reduced maternal thyroid hormones, and altered maternal and offspring lipid and carbohydrate metabolism similar to other studied PFAS, with oral toxicity for pup loss that is slightly less potent than PFOS but more potent than HFPO-DA.

Effect of Fenugreek Seeds in Maternal Diet on Some Features of Newborn Pups in Albino Mice

Introduction: Fenugreek seeds have got interest of researchers for their positive effects on laboratory animals and human being, including their effects on reproductive system. The present study aimed to investigate the effects of 5% raw fenugreek seed and its boiled aqueous extract containing diet on adult female mice, for 2 weeks before mating, to evaluate fertility, and some features of newborn pups. Materials and Methods: A total of 90 adult female mice randomly and equally were divided into three groups. Group I: Control, Group II: Female mice treated with 5% raw fenugreek seed containing diet, and Group III: Female mice treated with boiled aqueous extract of 5% fenugreek seed containing diet. The animals were treated daily for 2 weeks before mating. Some of them were mated with normal males, while the others were used for uterus study. The following parameters were evaluated: Fertility of adult female mice; body weight (BW); uterus weight; uterus sections; litter size; sex ratio; live and dead pups; and pup BW. Results: There was non-significant change in litter size and sex ratio; live and dead pups; adult female BW; and uterus weight. While wet and dry weight of pups, were significantly increased. Histological sections in uterus showed multilayering in endometrial glands of both the experimental groups. No differences were observed between fenugreek treated groups. Conclusion: Both forms of fenugreek seed (raw and aqueous extract) induced significant increase in pup weight; possibly are due to multilayering in endometrial glands of uterus.

TAMARINDUS INDICA IMPROVED GROWTH RETARDATION ASSOCIATED WITH PRENATAL ETHANOL EXPOSURE IN WISTAR RAT NEONATES

Background: Complications associated with alcoholism such as enduring growth retardation, especially during pregnancy, are serious health issues calling for lots of attention. Objectives: The study evaluated the effect of Tamarindus indica during prenatal ethanol (ET) exposure on pregnancy outcome and morphometric features of Wistar rat pups. Methodology: Twenty-four (24) pregnant timed Wistar rats were randomly assigned into 6 groups (n=4); Group A received 2 ml (distilled water), Groups B and C were administered 200 mg/kg ethanol extract of Tamarindus indica pulp (EETI), and 300 mg/kg of Vitamin E respectively, Group D received 30%v/v (2 mg/kg) of ET, Group E received 30%v/v (2 mg/kg) of ET + 200 mg/kg EETI, while Group F was administered 30%v/v (2 mg/kg) of ET + 300 mg/kg of Vitamin E. All administrations were via the oral route and lasted for 7 days from prenatal day 7 to 14. On postnatal day (PoND) zero, physical observations were made and the total number of littered pups was counted. Morphometric studies involved the measurements of the crown-rump length (CRL), fore-limb length (FL), hind-limb length (HL), tail length (TL), and body weight (BW) of pups were made using digital vernier caliper and analytical balance. Result: Prenatal ET exposure interfered with the pregnancy outcome, CRL, FL, HL, TL, and BW measurement; while treatment with EETI and vitamin E was associated with marked improvement. Conclusion: The administration of EETI during prenatal ethanol exposure was associated with significant improvements CRL, FL, HL, TL, and BW pups. Therefore, more attention should be given to the important medicinal plant that could possibly reduce pregnancy complications associated with prenatal ethanol exposure.

Some Teratogenic Outcomes in Rats Exposed to Zinc Chloride Pre and Post Pregnancy

The aim of present study was to evaluate the possibility of teratogenicity in rats when exposed to zinc chloride (ZnCl2) pre and post pregnancy. To achieve this goal, a total of 40 mature Albino Wistar female rats were divided equally into four groups as follows: T1, dosed 0.7 mg/day ZnCl2 for two months before mating and till to the day 5th of pregnancy, the females of this group were mated with males dosed 0.7 mg/day ZnCl2 for two weeks before mating; T2, dosed 0.7 mg/day ZnCl2 for two months before mating and till to the day 16th of pregnancy and then were mated with control males (not exposed to any level of ZnCl2); T3, dosed 0.7mg/day ZnCl2 for two months before mating and till the end of pregnancy and were mated with control males; Control, dosed with water free from ZnCl2 along the period of experiment and were mated with control males. At the end of each pregnancy phase, results revealed that alpha fetoprotein serum levels were significantly (P&lt;0.05) higher in all treatment groups compared to the control group, and the most prominent increase was observed in the T3 group. All treatment groups showed a significant (P&lt;0.05) decrease in gestation, viability, and lactation indices when compared to the control group, with the T3 group showing the most significant decrease. Additionally, on days 1, 4, 7, 14, and 21 of lactation period, there was a significant (P&lt;0.05) decrease in mean pup body weights in treated groups compared to the control group, with T3 group having the most prominent body weight decrease. The findings of this study revealed that ZnCl2 at a daily dose of 0.7 mg may cause teratogenic defects in rats at various stages of pregnancy, particularly at the third stage. As high-risk groups, pregnant women and children should use Zn supplementation carefully, whether as a food additive or for self-medication. Simultaneously, evaluating effect of low-dose Zn supplementation over a longer duration is required.

Intergenerational effects of a paternal Western diet during adolescence on offspring gut microbiota, stress reactivity, and social behavior.

The global consumption of highly processed, calorie-dense foods has contributed to an epidemic of overweight and obesity, along with negative consequences for metabolic dysfunction and disease susceptibility. As it becomes apparent that overweight and obesity have ripple effects through generations, understanding of the processes involved is required, in both maternal and paternal epigenetic inheritance. We focused on the patrilineal effects of a Western-style high-fat (21%) and high-sugar (34%) diet (WD) compared to control diet (CD) during adolescence and investigated F0 and F1 mice for physiological and behavioral changes. F0 males (fathers) showed increased body weight, impaired glycemic control, and decreased attractiveness to females. Paternal WD caused significant phenotypic changes in F1 offspring, including higher body weights of pups, increased Actinobacteria abundance in the gut microbiota (ascertained using 16S microbiome profiling), a food preference for WD pellets, increased male dominance and attractiveness to females, as well as decreased behavioral despair. These results collectively demonstrate the long-term intergenerational effects of a Western-style diet during paternal adolescence. The behavioral and physiological alterations in F1 offspring provide evidence of adaptive paternal programming via epigenetic inheritance. These findings have important implications for understanding paternally mediated intergenerational inheritance, and its relevance to offspring health and disease susceptibility.

Postnatal weaning to different diets leads to different reproductive phenotypes in female offspring following perinatal exposure to high levels of dietary advanced glycation end products

To examine, following perinatal exposure to a diet high in advanced glycation end products (AGEs), whether the use of standard AGE-free mouse chow during the postweaning period alters metabolism and reproduction differently than exposure to a diet low in AGEs. Experimental animal study. University-based research laboratory. Female CD1 mice. Seven-week-old mice were placed on a diet either low or high in AGEs perinatally, before mating and then during pregnancy and lactation. All offspring were weaned onto an AGE-free normal chow. Growth curve, liver and abdominal fat weight, insulin and glucose tolerance tests, vaginal opening, estrous cyclicity, and serum levels of antimüllerian hormone, leptin, and adiponectin were assessed. Ovarian histologic examination for follicular count and gene expression was also performed. Compared with the mice exposed to a diet low in AGEs, the mice exposed to a diet high in AGEs showed lower body weight in pups, lower liver weight, delayed vaginal opening, higher serum antimüllerian hormone levels, lower primordial and secondary follicle pools, and higher ovarian Fshr messenger RNA levels. Following weaning, perinatal AGEs can target puberty onset and folliculogenesis differently to standard mouse chow.