Responses In Offspring Research Articles

Environmental stress during the last trimester of gestation in pregnant cows and its effect on offspring growth performance and response to glucose and adrenocorticotropic hormone.

Winter and spring precipitation are predicted to increase in the Midwest region of the United States, causing muddy conditions. In a previous experiment, Angus cows (8 per treatment) were paired based on initial body weight (BW) and one cow from each pair was randomly allocated to either the mud or control treatment. Though cows consumed the same amount of dry matter, cows in the mud treatment weighed 37.4 kg less than cows in the control treatment by day 269 of gestation. The objective of this experiment was to evaluate developmental programming effects of steers born to cows in the mud treatment (MUD; n = 7) or the control treatment (CON; n = 6). Steers were weighed at birth and then weekly from approximately 56 d of age until weaning and were subjected to a glucose tolerance test (GTT) and adrenocorticotropic hormone (ACTH) challenge after weaning. Steers were then placed in the feedlot for an 84-d growing phase and were weighed weekly and 12th rib back fat (BF) and ribeye area (REA) were imaged every 28 d using ultrasonography. Data were analyzed as a randomized complete block design with repeated measurements when appropriate (SAS 9.4). Although there was a 37.4 kg decrease in BW of cows by the end of gestation, there was no evidence of a pen treatment effect on calf birth weight (P = 0.60) or weaning weight (P = 0.99). Additionally, there was no evidence of a pen treatment × day effect for steer BW from birth to weaning (P = 0.67) or growing phase BW (P = 0.60). There was evidence of a treatment × day of growing phase effect (P = 0.02) for BF, such that CON steers had greater BF on day 28 of the growing phase; however, there was no evidence of a treatment × day effect for REA (P = 0.20). Furthermore, there was no evidence of a pen treatment effect for the growing phase average daily gain (P = 0.74), dry matter intake (P = 0.65), gain:feed (P = 0.48), plasma glucose concentration (P = 0.67) or plasma insulin concentration (P = 0.61) in response to the GTT, or plasma cortisol concentration in response to the ACTH challenge (P = 0.51). These results indicate that while mud increased net energy requirements for cows in the MUD treatment, there were no subsequent effects observed for steer BW, gain:feed, or response to glucose and ACTH during the growing phase.

Health behavioral responses to parental myocardial infarction and impact on own risk of disease in the general population.

A family history of coronary heart disease increases one's own risk of experiencing cardiovascular disease and death. An implication of the hereditary nature of the disease is that individuals are provided information about their own risk when a parent is affected, potentially leading them to engage in behaviors that reduce their own risk. In this study, we assessed how a 10-year risk of a cardiovascular event, measured by SCORE, changes for the offspring in response to a parent experiencing a myocardial infarction. We analyzed 19,995 individuals from the general population in the Copenhagen City Heart Study of whom 2,071 had a parent, who suffered from a myocardial infarction during four decades of observation using fixed-effects regressions. Following a parental myocardial infarction, individuals reduced their 10-year risk by 0.16 percentage points constituting a 7.1% reduction of baseline risk. Male participants had the largest change in the risk SCORE following an event of the mother, with a 12.4% reduction from the baseline risk. The degree of response contingent on their own level of risk was found to be the largest for individuals with a 10-year risk between 5% and 10%, who also showed a reduction in systolic blood pressure following paternal myocardial infarction. Parental myocardial infarction was associated with an increased smoking rate in individuals with a baseline risk above 10%, while reductions in risk were seen for individuals with a lower baseline risk. Following a parental event, individuals reduced their 10-year risk with the largest reductions in their own risk, as observed in men and individuals experiencing a maternal event. The response was the largest for individuals with a 10-year risk for myocardial infarction between 5 and 10%.

Effects of Maternal Stress on the Behavioral and HPA Responses of Offspring Exposed to the Predator or Non-Predator Odor in Brandt’s Voles

Effects of Maternal Stress on the Behavioral and HPA Responses of Offspring Exposed to the Predator or Non-Predator Odor in Brandt’s Voles

Methimazole-induced gestational hypothyroidism affects the offspring development and differently impairs the conditioned fear in male and female adulthood rodents.

Gestational hypothyroidism is a prevalent disorder in pregnant women and also impairs fetal development with relevant outcomes. One of the outcomes of greatest interest has been rodent fear- and anxiety-like behavior. However, the relationship between maternal hypothyroidism and onset of conditioned fear-related responses in offspring remains controversial. Here, we used a well-validated methimazole-induced gestational hypothyroidism to investigate the behavioral consequences in offspring. Dams were treated with methimazole at 0.02% in drinking water up to gestational Day 9. Maternal body weights and maternal behavior were evaluated, and the puppies ware analyzed for weight gain and physical/behavioral development and assigned for the open field and fear conditioning test. Methimazole-induced gestational hypothyroidism induced loss in maternal and litter weight, increases in maternal behavior, and impairs in offspring developmental landmarks in both male and female rodents. Only male offspring enhanced responsiveness to conditioned fear-like behavior in adulthood.

Supplementation of Methyl-Donor Nutrients to a High-Fat, High-Sucrose Diet during Pregnancy and Lactation Normalizes Circulating 25-Dihydroxycholecalciferol Levels and Alleviates Inflammation in Offspring.

A Western-style diet that is high in fat and sucrose has been shown to alter DNA methylation and epigenetically modify genes related to health risk in offspring. Here, we investigated the effect of a methyl-donor nutrient (MS) supplemented to a high-fat, high-sucrose (HFS) diet during pregnancy and lactation on vitamin D (VD) status and inflammatory response in offspring. After mating, 10-week-old female Sprague-Dawley (SD) rats (n = 10/group) were randomly assigned to one of the four dietary groups during pregnancy and lactation: (1) control diet (CON), (2) CON with MS (CON-MS), (3) HFS, and (4) HFS with MS (HFS-MS). Weanling offspring (three weeks old) were euthanized and sacrificed (n = 8-10/sex/group). The remaining offspring (n = 10/sex/group) were randomly assigned to either a CON or an HFS diet for 12 weeks and sacrificed at 15 weeks of age. Our results indicated that prenatal MS supplementation, but not postnatal diet, restored low vitamin D status and suppressed elevation of proinflammatory cytokine induced by maternal HFS in the offspring. Furthermore, both prenatal and postnatal diets modulated the abundance of Lactobacillus spp. and Bacteroides spp. in the offspring, a shift that was independent of vitamin D status. Collectively, our data support a role for MS in restoring the perturbation of VD status and normalizing maternal HFS-induced inflammation in the offspring. Further investigation is warranted to elucidate the methylation status of VD metabolism-related pathways in the offspring, as well as the immunomodulatory role of vitamin D during the progression of obesity.

Maternal obesity and resistance to breast cancer treatments among offspring: Link to gut dysbiosis.

About 50 000 new cases of cancer in the United States are attributed to obesity. The adverse effects of obesity on breast cancer may be most profound when affecting the early development; that is, in the womb of a pregnant obese mother. Maternal obesity has several long-lasting adverse health effects on the offspring, including increasing offspring's breast cancer risk and mortality. Gut microbiota is a player in obesity as well as may impact breast carcinogenesis. Gut microbiota is established early in life and the microbial composition of an infant's gut becomes permanently dysregulated because of maternal obesity. Metabolites from the microbiota, especially short chain fatty acids (SCFAs), play a critical role in mediating the effect of gut bacteria on multiple biological functions, such as immune system, including tumor immune responses. Maternal obesity can pre-program daughter's breast cancer to be more aggressive, less responsive to treatments and consequently more likely to cause breast cancer related death. Maternal obesity may also induce poor response to immune checkpoint inhibitor (ICB) therapy through increased abundance of inflammation associated microbiome and decreased abundance of bacteria that are linked to production of SCFAs. Dietary interventions that increase the abundance of bacteria producing SCFAs potentially reverses offspring's resistance to breast cancer therapy. Since immunotherapies have emerged as highly effective treatments for many cancers, albeit there is an urgent need to enlarge the patient population who will be responsive to these treatments. One of the factors which may cause ICB refractoriness could be maternal obesity, based on its effects on the microbiota markers of ICB therapy response among the offspring. Since about 40% of children are born to obese mothers in the Western societies, it is important to determine if maternal obesity impairs offspring's response to cancer immunotherapies.

Severe maternal stress alters placental function, resulting in adipose tissue and liver dysfunction in offspring of mice

The developmental origins of health and disease (DOHaD) hypothesis is that future lifestyle diseases in offspring are associated with intrauterine origins in the mother; stress during pregnancy is a risk factor for these diseases in offspring. This study aimed to clarify association of maternal stress with placental dysfunction and offspring development in mice. We applied water stress for 24 h during late pregnancy to explore the metabolic response of offspring to a normal diet (ND) and high-fat diet (HFD). Placental functions were altered by maternal stress, reducing the birth weight of the offspring. In the later life of offspring fed with ND, maternal stress impaired systemic glucose tolerance and altered adipokine secretion in adipose tissue and/or liver. The female offspring of stress-induced dams were light in body weight with lower adipose tissue and smaller adipocytes in both the ND and HFD groups. Abnormal situations, such as dysregulation of plasma glucose levels and fatty liver despite and lower increases in body weight, were observed in the female offspring of stress-induced dams, especially in the HFD-treated group. These findings suggest that long-lasting abnormal conditions and responses to metabolic challenges in maternal stress-induced offspring are linked to placental dysregulation and fetal programming.

Maternal exercise improves epithelial development of fetal intestine by enhancing apelin signaling and oxidative metabolism.

Obesity in pregnancy is currently the leading cause of gestational complications for the mother and fetus worldwide. Maternal obesity (MO), common in western societies, impedes development of intestinal epithelium in the fetuses, which causes disorders in the nutrient absorption and intestine-related immune responses in offspring. Here, using a mouse model of maternal exercise (ME), we found that exercise during pregnancy protects the impairment of fetal intestinal morphometrical formation and epithelial development due to MO. MO decreased villus length and epithelial proliferation markers in E18.5 fetal small intestine, which was increased due to ME. The expression of the epithelial differentiation markers, Lyz1, Muc2, and Tff3, in fetal small intestine was decreased due to MO, but protected by ME. Consistently, the biomarkers related to mitochondrial biogenesis and oxidative metabolism were downregulated in MO fetal small intestine but recovered by ME. Apelin injection to dams partially mirrored the beneficial effects of ME. ME and apelin injection activated AMPK, the downstream target of apelin receptor signaling, which might mediate the improvement of fetal epithelial development and oxidative metabolism. These findings suggest that ME, a highly accessible intervention, is effective in improving fetal intestinal epithelium of obese dams. Apelin-AMPK-mitochondrial biogenesis axis provides amenable therapeutic targets to facilitate fetal intestinal development of obese mothers.

A miRNA derived from the 17/92 cluster is a novel player in programming pulmonary hypertension in response to gestational hypoxia via NADPH oxidases and the mTOR pathway

Abstract Background Gestational hypoxia can lead to intrauterine growth restriction (IUGR) and programming of cardiovascular diseases in adulthood via different, although not completely understood, epigenetic mechanisms. We have previously shown that reactive oxygen species (ROS) derived from NADPH oxidases contribute to hypoxia induced pulmonary hypertension (PH). However, their role in disease programming by gestational hypoxia is not resolved. Purpose We aimed to elucidate the role of NADPH oxidases and redox sensitive miRNAs in the cardiovascular response of adult offspring to transient gestational hypoxia. Methods Wildtype (WT) and nmf333 mice, lacking a functional p22phox dependent NADPH oxidase, were exposed to gestational hypoxia from E10.5 to E11.5. Embryos and adult offspring were analyzed by functional, immunohistochemical and molecular methods including mRNA and miRNA profiling. miRNA mimics or inhibitors were applied in vivo and in vitro using embryoid bodies (EBs). Heart samples from patients with right heart disease associated with congenital heart disease (CHD) were used to validate target miRNA expression. Results Transient gestational hypoxia was sufficient to induce IUGR in embryos and pulmonary hypertension (PH) characterized by right ventricular hypertrophy, increased right ventricular pressure and pulmonary vascular remodeling in adult offspring from WT mice while p22phox-deficient nmf333 mice were protected. Cardiac mRNA and miRNA profiling followed by qPCR validation identified several single miRNAs derived from the 17/92 miRNA cluster as downregulated by gestational hypoxia and NADPH oxidases in embryos and adult offspring hearts. In vitro analyses using EBs validated a single miRNA from this cluster to be sufficient to induce cardiac differentiation in response to hypoxia and p22phox, and target analyses identified the mTOR pathway as dysregulated. Treatment with an inhibitor targeting this miRNA was sufficient to induce PH in adult mice, while treating offspring derived from gestational hypoxia pregnancies with an miRNA mimic prevented the development of PH in the adult and dysregulation of the mTOR pathway. Importantly, expression of this single miRNA from the miRNA 17/92 cluster was negatively correlated to right ventricular pressure in CHD patients. Conclusions In this study, we demonstrate that gestational hypoxia programs PH in adulthood by upregulating NADPH oxidases and downregulating miRNAs derived from the 17/92 cluster subsequently affecting the mTOR pathway. Since dysregulation of a single miRNA from this cluster induced not only PH but was also associated with right ventricular pressure in CHD patients, these findings might open novel options for diagnosis, prevention and treatment of right heart disease. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): DZHK (German Centre for Cardiovascular Research)

Maternal Low-Protein Diet during Puberty and Adulthood Aggravates Lipid Metabolism of Their Offspring Fed a High-Fat Diet in Mice.

A maternal low-protein (LP) diet during gestation and/or lactation results in metabolic syndrome in their offspring. Here, we investigated the effect of maternal LP diet during puberty and adulthood on the metabolic homeostasis of glucose and lipids in offspring. Female mice were fed with normal-protein (NP) diet or a LP diet for 11 weeks. Male offspring were then fed with a high-fat diet (NP-HFD and LP-HFD groups) or standard chow diet (NP-Chow and LP-Chow groups) for 4 months. Results showed that maternal LP diet during puberty and adulthood did not alter the insulin sensitivity and hepatic lipid homeostasis of their offspring under chow diet, but aggravated insulin resistance, hepatic steatosis, and hypercholesterolemia of offspring in response to a post-weaning HFD. Accordingly, transcriptomics study with offspring’s liver indicated that several genes related to glucose and lipid metabolism, including lipoprotein lipase (Lpl), long-chain acyl-CoA synthetase 1 (Acsl1), Apoprotein A1 (Apoa1), major urinary protein 19 (Mup19), cholesterol 7α hydroxylase (Cyp7a1) and fibroblast growth factor 1 (Fgf1), were changed by maternal LP diet. Taken together, maternal LP diet during puberty and adulthood could disarrange the expression of metabolic genes in the liver of offspring and aggravate insulin resistance and hepatic steatosis in offspring fed a HFD.

The maternal reduced uteroplacental perfusion model of preeclampsia induces sexually dimorphic metabolic responses in rat offspring

BackgroundOffspring born to preeclamptic mothers are prone to obesity, diabetes and hypertension in later life, but still, studies investigating the underlying mechanism are limited. Here, we aimed to investigate the impact of the reduced uteroplacental perfusion (RUPP) rat preeclampsia model on offspring metabolic outcomes.MethodsTimed pregnant Wistar rats underwent RUPP or sham surgeries on day 14 of gestation. Glucometabolic parameters were evaluated on postnatal days (PND), 14 (childhood), and 60 (young adult). In addition, intraperitoneal glucose tolerance test (IPGTT), homeostatic model assessment of insulin resistance (HOMA-IR), immunohistochemical staining for insulin in pancreatic islets, arterial blood pressure and 24-h urine protein (24hUP) excretion were performed at PND60.ResultsMale, but not female, young adult rats (PND60) of RUPP dams exhibited an impaired IPGTT, decreased circulatory insulin and weakened pancreatic insulin immunoreactivity. Compared to the male offspring of the sham group, the body mass of male RUPP offspring significantly caught up after PND42, but it was not sex-specific. RUPP pups also exhibited upregulations in glucagon (only males) and ghrelin (both sexes with a more significant increase in males) during PND14–PND60. However, in sham offspring (both sexes), glucagon levels were downregulated and ghrelin levels unchanged during PND14–PND60. The blood pressure, HOMA-IR and 24hUP values did not alter in RUPP pups.ConclusionsThe overall results suggest that maternal RUPP has negative and sex-specific impacts on insulin, glucagon and ghrelin regulations in offspring and that, as young adults, male RUPP rats may be more prone to develop obesity and diabetes.

Intergenerational effects of ocean acidification on reproductive traits of an estuarine copepod

Copepods are an important part of the marine food web because of their high biomass productivity and nutrient turnover rate compared to other zooplankton in the marine ecosystem. Despite their great ecological role in the ocean, there is only limited information available on the consequences of ocean acidification (OA) induced by the future increase in CO2 on the planet. More specifically, there is almost no information about the impact of OA on the European copepod Calanipeda aquaedulcis Kritschagin, 1873. Therefore, the present investigation hypothesized that OA would not produce negative multigenerational effects on the survival and reproductive performance of this copepod species. Here we assessed, the multigenerational (F1 and F2) effect of OA on eight important reproductive traits (maturity, prosome length, fertility, egg release, hatching success, survival rate, reproductive performance, and the total number of adults per generation). For this study, C. aquaedulcis were collected from the Guadalquivir River (southwest of Spain) and were exposed to four different pH gradients (pH 8.1 as control and pH 7.5, 7.0, 6.5 as acidified conditions) to mimic the future seawater acidification scenarios. The survival rate from nauplius to adult, C. aquaedulcis was significantly reduced by pHs and across generations. Besides, results also indicated that there were marked effects on fertility, reflected by a significantly lower number of eggs per female in each generation. Similarly, hatching success also showed a decreasing pattern towards low pH, and importantly, F1 females had lower hatching success than F0 females. While a beneficial parental effect was detected in the offspring in response to OA, it was insufficient to offset the negative effects caused by it. The findings presented here appear to have ecological significance, as decreasing the reproductive performance of copepods may have a negative impact on the marine food web, as ichthyofaunal feeding and growth are heavily reliant on this component of the food web.

Differential DNA methylation in Pacific oyster reproductive tissue in response to ocean acidification

BackgroundThere is a need to investigate mechanisms of phenotypic plasticity in marine invertebrates as negative effects of climate change, like ocean acidification, are experienced by coastal ecosystems. Environmentally-induced changes to the methylome may regulate gene expression, but methylome responses can be species- and tissue-specific. Tissue-specificity has implications for gonad tissue, as gonad-specific methylation patterns may be inherited by offspring. We used the Pacific oyster (Crassostrea gigas) — a model for understanding pH impacts on bivalve molecular physiology due to its genomic resources and importance in global aquaculture— to assess how low pH could impact the gonad methylome. Oysters were exposed to either low pH (7.31 ± 0.02) or ambient pH (7.82 ± 0.02) conditions for 7 weeks. Whole genome bisulfite sequencing was used to identify methylated regions in female oyster gonad samples. C- > T single nucleotide polymorphisms were identified and removed to ensure accurate methylation characterization.ResultsAnalysis of gonad methylomes revealed a total of 1284 differentially methylated loci (DML) found primarily in genes, with several genes containing multiple DML. Gene ontologies for genes containing DML were involved in development and stress response, suggesting methylation may promote gonad growth homeostasis in low pH conditions. Additionally, several of these genes were associated with cytoskeletal structure regulation, metabolism, and protein ubiquitination — commonly-observed responses to ocean acidification. Comparison of these DML with other Crassostrea spp. exposed to ocean acidification demonstrates that similar pathways, but not identical genes, are impacted by methylation.ConclusionsOur work suggests DNA methylation may have a regulatory role in gonad and larval development, which would shape adult and offspring responses to low pH stress. Combined with existing molluscan methylome research, our work further supports the need for tissue- and species-specific studies to understand the potential regulatory role of DNA methylation.

Comparison of dipsogenic responses of adult rat offspring as a function of different perinatal programming models

The perinatal environment interacts with the genotype of the developing organism resulting in a unique phenotype through a developmental or perinatal programming phenomenon. However, it remains unclear how this phenomenon differentially affects particular targets expressing specific drinking responses depending on the perinatal conditions. The main goal of the present study was to compare the dipsogenic responses induced by different thirst models as a function of two perinatal manipulation models, defined by the maternal free access to hypertonic sodium solution and a partial aortic ligation (PAL-W/Na) or a sham-ligation (Sham-W/Na). The programmed adult offspring of both perinatal manipulated models responded similarly when was challenged by overnight water dehydration or after a sodium depletion showing a reduced water intake in comparison to the non-programmed animals. However, when animals were evaluated after a body sodium overload, only adult Sham-W/Na offspring showed drinking differences compared to PAL and control offspring. By analyzing the central neurobiological substrates involved, a significant increase in the number of Fos + cells was found after sodium depletion in the subfornical organ of both programmed groups and an increase in the number of Fos + cells in the dorsal raphe nucleus was only observed in adult depleted PAL-W/Na. Our results suggest that perinatal programming is a phenomenon that differentially affects particular targets which induce specific dipsogenic responses depending on matching between perinatal programming conditions and the osmotic challenge in the latter environment. Probably, each programmed-drinking phenotype has a particular set point to elicit specific repertoires of mechanisms to reestablish fluid balance.

Light condition experienced by parent plants influences the response of offspring to light via both parental effects and soil legacy effects

Abstract Environmental conditions experienced by parent plants can influence offspring performance through parental effects induced by DNA methylation. The offspring can also be influenced by environmental conditions experienced by their parents via soil legacy effects due to plant‐mediated changes in the composition of soil microbes. These two effects are likely to act simultaneously, but empirical evidence for combined effects is limited. We conducted a two‐phase experiment with five genotypes of a clonal plant Hydrocotyle vulgaris. In the first phase, we grew parent plants of each genotype under two light conditions (ambient vs. shade) and two DNA demethylation treatments [treated with water vs. 5‐azacytidine (5‐azaC)]. We then collected soils and clonal offspring for each genotype from each of these four treatments and measured soil (a)biotic properties. In the second phase, we grew the offspring from each of the four treatments in the four different soils, under the two light conditions. When grown under ambient light condition and in soil from ambient parents, offspring produced by ambient parents grew larger than offspring produced by shaded parents when the parents were treated with water. This difference was smaller when the parents were treated with 5‐azaC, and disappeared when the offspring were grown in soil from shaded parents. The growth difference was also observed when the offspring were grown under shaded condition and in soil from shaded parents. However, this difference was greater when the parents were treated with 5‐azaC, and disappeared when the offspring were grown in soil from ambient parents. Moreover, offspring growth was associated with fungal composition and total phosphorus of the soil in which the parents had grown. Our results show, for the first time, that light condition experienced by parents can influence offspring responses to light through both parental effects and soil legacies. The parental effects were mediated by changes in DNA methylation and the soil legacies were due to plant‐mediated changes in a combination of soil biotic and abiotic properties. These impacts may eventually influence the ecological and evolutionary trajectories of clonal plant populations. Read the free Plain Language Summary for this article on the Journal blog.

Alterations in Essential Fatty Acids, Immunoglobulins (IgA, IgG, and IgM), and Enteric Methane Emission in Primiparous Sows Fed Hemp Seed Oil and Their Offspring Response.

This study shows the effects of dietary hemp seed oil on the milk composition, blood immunoglobulins (Ig), and enteric methane (E-CH4) production of primiparous sows, and their offspring's response at three time points. A bifactorial experiment was conducted for 21 days (d) on 18 primiparous sows (195 ± 3 days old). The sows were fed two diets: (i) a control diet (SO) based on soybean oil (1.6%), with an 18.82 n-6:n-3 polyunsaturated fatty acids (PUFA) ratio; (ii) an experimental diet (HO) based on hemp seed oil (1.6%), with a 9.14 n-6:n-3 PUFA ratio. The milk contained an elevated level of linoleic acids (LA), n-3 FA, and especially alpha-linolenic acids (ALA), while the n-6:n-3 ratio declined using hemp oil. The Ig concentration was higher in colostrum than in milk. In the first few hours, the IgG in the plasma of piglets was more than double that of maternal plasma IgG (+2.39 times). A period effect (p < 0.0001) for IgG concentration in the plasma of piglets was recorded (40% at 10 d, respectively 73% lower at 21 d than 12 h after parturition). However, the sow diet did not affect Ig (p > 0.05). The frequency of diarrhoea declined after about 7 d. The value of the rate of diarrhoea was 6.2% lower in the PHO group. We found a 4.5% decline in E-CH4 in the HO group. Applying multiple linear regression, feed intake, n-6:n-3 ratio, ALA, and lean meat were potential indicators in estimating E-CH4. In conclusion, sow dietary hemp seed oil increased lean meat %, milk EFA, and milk IgM. Significant changes in the other dependent variables of interest (body weight, plasma Igs in sows and offspring, E-CH4 production) were not recorded. There was reduced diarrhoea which shows that EFA could play a therapeutic role in the incidence of diarrhoea and in lowering of E-CH4 emission in sows and progeny. All dependent variables were significantly altered at different time points, except for fat concentration in milk and sow plasma IgG.

Effects of paternal high-fat diet and maternal rearing environment on the gut microbiota and behavior

Exposing a male rat to an obesogenic high-fat diet (HFD) influences attractiveness to potential female mates, the subsequent interaction of female mates with infant offspring, and the development of stress-related behavioral and neural responses in offspring. To examine the stomach and fecal microbiome’s potential roles, fecal samples from 44 offspring and stomach samples from offspring and their fathers were collected and bacterial community composition was studied by 16 small subunit ribosomal RNA (16S rRNA) gene sequencing. Paternal diet (control, high-fat), maternal housing conditions (standard or semi-naturalistic housing), and maternal care (quality of nursing and other maternal behaviors) affected the within-subjects alpha-diversity of the offspring stomach and fecal microbiomes. We provide evidence from beta-diversity analyses that paternal diet and maternal behavior induced community-wide shifts to the adult offspring gut microbiome. Additionally, we show that paternal HFD significantly altered the adult offspring Firmicutes to Bacteroidetes ratio, an indicator of obesogenic potential in the gut microbiome. Additional machine-learning analyses indicated that microbial species driving these differences converged on Bifidobacterium pseudolongum. These results suggest that differences in early-life care induced by paternal diet and maternal care significantly influence the microbiota composition of offspring through the microbiota-gut-brain axis, having implications for adult stress reactivity.

Distinct behavior in early life stress dams predicts heterogeneity in future stress response in offspring over lifespan

IntroductionExposure to early life stress (ELS) strongly predicts prevalent, impairing, and costly psychiatric illness throughout life including mental disorders. The reason, some individuals are more vulnerable to ELS whereas others remain resilient, is poorly understood. There is a need for better understanding of early biological changes triggered by ELS with responsibility to negative outcomes in health.ObjectivesWe stratify animals after ELS according to corticosterone levels. [1] Re-challenging the animals to a second stressor, chronic social defeat (CSD) [2], in adulthood was performed to understand individual trajectories depending on corticosterone exposure during early adverse conditions.MethodsWe performed ELS as previously reported [1]. Behavior of mothers was observed during ELS. Correlation between level of corticosterone and behavior observed in dams. ELS animals were exposed to a second stress in adulthood. A battery of tests for different behavioral domains was performed. Behavioral analyses was combined with assessment of litter HPA system reactivity and observed behavior in dams.ResultsStress dams where significantly higher in number of sorties over whole observation period, time dams spent outside the nest differed. We could correlate the number of sorties on p3 with corticosterone plasma level at p9. Control dams spent significantly more time outside in 9pm recordings than stress animals. We could show reduced interaction with social juvenile targets in sociability test for CSD mice. Light dark transition was significantly higher for control mice compared to CSD but lower for control vs ELS animals.ConclusionsBehavior in dams during ELS correlates with chronic stress coping mechanisms in offspring’s adulthood.DisclosureNo significant relationships.

Brief exposures to conspecific-derived alarm substance are sufficient to induce paternal intergenerational effects in zebrafish

Paternal intergenerational effects, whereby the father’s environment influences the phenotype of the offspring via molecular (e.g. epigenetic) changes to the sperm, comprise an area of active research in multiple biological contexts. Spermatogenesis is a critical window of sensitivity to environmental changes, such that males at full sexual maturity can acquire, incorporate, and transmit environmental information in spermatozoa. The degree of sensitivity is less clear, and as such previous experimental studies have typically relied on prolonged exposure regimes encapsulating the entire period of spermatogenesis. Here we exposed adult male zebrafish to a model stressor (conspecific-derived alarm substance, AS) in two 20-min episodes timed either shortly before or during the onset of spermatogenesis. There was no clear effect of paternal stress on a behavioural stress response in larval offspring but clear reductions in anxiety-like behaviour in juvenile offspring. Our findings suggest that prolonged exposures may not be required for the induction of measurable intergenerational responses in this popular vertebrate model.

Microbial antigen in human milk: a natural vaccine?

Microbial antigen in human milk: a natural vaccine?