Maternal Offspring Research Articles

Lactational metformin exposure programs offspring white adipose tissue glucose homeostasis and resilience to metabolic stress in a sex-dependent manner

We previously demonstrated that exposing mouse dams to metformin during gestation results in increased beta-cell mass at birth and increased beta-cell insulin secretion in adult male offspring. Given these favorable changes after a gestational maternal metformin exposure, we wanted to understand the long-term metabolic impact on offspring after exposing dams to metformin during the postnatal window. The newborn period provides a feasible clinical window for intervention and is important for beta-cell proliferation and metabolic tissue development. Using a C57BL/6 model, we administered metformin to dams from the day of birth to postnatal day 21. We monitored maternal health and offspring growth during the lactation window, as well as adult glucose homeostasis through in vivo testing. At necropsy we assessed pancreas and adipocyte morphology using histological and immunofluorescent staining techniques. We found that metformin exposure programmed male and female offspring to be leaner with a higher proportion of small adipocytes in the gonadal white adipose tissue (GWAT). Male, but not female, offspring had an improvement in glucose tolerance as young adults concordant with a mild increase in insulin secretion in response to glucose in vivo. These data demonstrate long-term metabolic programming of offspring associated with maternal exposure to metformin during lactation.

Habitat selection of white-tailed deer fawns and their dams in the Northern Great Plains

Habitat availability can affect important life-history traits such as survival; however, little information exists on how microhabitat characteristics found at parturition sites selected by dams and bed sites selected by their offspring differ from the surrounding area and from each other. Therefore, we assessed how vegetation affected maternal parturition and offspring bed site selection for white-tailed deer (Odocoileus virginianus) in the Northern Great Plains. Dams selected for sites with decreased vegetation height, potentially improving their visibility, which may increase their ability to escape approaching predators. Conversely, there was no variation between vegetative characteristics at neonate bed sites and their associated random sites, indicating grasslands provide adequate concealment for neonates. Dams possess the ability to flee from approaching predators, thus increasing the importance of visibility while giving birth. Conversely, neonates depend on fear bradycardia as their main antipredator defense, so concealment is more important. Our results suggest that vegetation structure is an important characteristic to white-tailed deer as habitat needs vary between adults and neonates.

Lady Beetle Oviposition Site Choices: Maternal Effects on Offspring Performance

Maternal effects can result in adaptive phenotypic responses of offspring that increase their fitness. Several recent studies report a positive relationship between maternal choices and offspring fitness. However, few studies have assessed the associations between aphidophagous lady beetle oviposition site selection, the adequacy of food resources for their offspring, and offspring performance. To clarify these issues, we explored whether aphidophagous lady beetle oviposition site selection can influence offspring performance, thereby reflecting adaptive maternal behavior. To assess the effect of food resources on offspring performance, we fed the larvae of 3 lady beetle species: Cycloneda sanguinea (L.), Harmonia axyridis (Pallas), and Hippodamia convergens (Guerin-Meneville) (all Coleoptera: Coccinellidae), with different types of aphids (Uroleucon and Brevicoryne) (both Hemiptera: Aphididae) then measured development time, survival, adult body mass, brightness, and chromatic coloration of the adult beetles. We found that Ha. axyridis larvae fed Brevicoryne exhibited a higher survival rate than those fed Uroleucon. Also more adults emerged from C. sanguinea larvae fed Uroleucon aphids, and these adults were heavier, shinier, with more chroma, and developed faster than those fed on Brevicoryne. Overall, lady beetles performed better when fed aphids commonly found near their respective oviposition sites. We conclude that aphidophagous lady beetle oviposition site selection reflects adaptive maternal choices associated with an adequate food resource positively affecting offspring fitness. Elucidating the links between lady beetle oviposition site choice and optimal resource for their offspring enhances our understanding of habitat use and co-existence of aphidophagous lady beetle communities in Brazilian agroecosystems. Resumo Os efeitos maternos podem resultar em respostas fenotipicas adaptativas da prole que aumentam sua aptidao. Varios estudos recentes relatam uma relacao positiva entre escolhas maternas e aptidao dos filhos. No entanto, poucos estudos avaliaram as associacoes entre a selecao do local de oviposicao de besouros afidofagos, a adequacao dos recursos alimentares para a prole e o desempenho da prole. Para esclarecer essas questoes, avaliamos se a selecao do local de oviposicao de besouros afidofagos pode influenciar o desempenho da prole, refletindo assim o comportamento materno adaptativo. Para avaliar o efeito dos recursos alimentares no desempenho da prole, alimentamos as larvas de tres especies de besouros: Cycloneda sanguinea (L.), Harmonia axyridis (Pallas), e Hippodamia convergens (Guerin-Meneville) (todos Coleoptera: Coccinellidae), com diferentes tipos de pulgoes (Uroleucon e Brevicoryne) (ambos Hemiptera: Aphididae), medimos o tempo de desenvolvimento, a sobrevivencia, a massa corporal adulta, o brilho e a coloracao cromatica dos besouros adultos. Foi observado que larvas de Ha. axyridis alimentadas com Brevicoryne exibiram uma taxa de sobrevivencia mais alta do que aquelas alimentadas com Uroleucon. Tambem emergiram mais adultos de larvas de C. sanguinea quando alimentadas com pulgoes Uroleucone e esses adultos eram mais pesados, mais brilhantes, com mais croma e se desenvolveram mais rapidamente do que aqueles alimentados com Brevicoryne. No geral, as joaninhas tiveram melhor desempenho quando alimentados com pulgoes comumente encontrados perto de suas respectivas posturas. Concluimos que a selecao do local de oviposicao de besouros afidofagos reflete escolhas maternas adaptativas associadas a um recurso alimentar adequado que afeta positivamente a aptidao da prole. A elucidacao dos vinculos entre a escolha do local de oviposicao do besouro e o recurso ideal para seus filhotes aprimora nossa compreensao do uso do habitat e a coexistencia de comunidades de besouros afidofagos nos agroecossistemas brasileiros. Key Words: Cycloneda sanguinea; Harmonia axyridis; Hippodamia convergens; Uroleucon; Brevicoryne; adaptative maternal behavior View this article in BioOne

1245-P: Maternal HbA1c Is Related to Childhood Fat Mass and Only Partially Mediated by Neonatal Fat Mass

Maternal diabetes during pregnancy impacts offspring body composition and has been associated with greater offspring adiposity across the life course. However, the extent to which the relationship between maternal glycemia and offspring adiposity during later life is independent of neonatal adiposity is unclear. In a prospective study of 544 mother-child pairs in the Healthy Start Study, we estimated the total effect of maternal HbA1c on childhood fat mass (FM) %, and the direct effect independent of neonatal FM %. We measured maternal fasting HbA1c at a gestational age of 20-34 weeks, and offspring FM % using air displacement plethysmography at birth and during childhood (age 4-7 y). We used multivariable linear regression with HbA1c tertiles (T1 [reference], T2, T3) as the exposure, neonatal FM % as the mediator, and childhood FM % as the outcome. A counterfactual-based approach was used to estimate total and direct effects, while also accounting for exposure-mediator interaction. Covariates were maternal race, education, gestational weight gain and smoking, and offspring sex and age. The medians (interquartile ranges) of the HbA1c tertiles were T1: 4.80 (3.70, 4.90), T2: 5.05 (5.00, 5.10), and T3: 5.30 (5.20, 6.30). The estimated total effect on child FM % was 1.27 (95% CI: 0.00, 2.54) units higher for T2 vs. T1, and 1.53 (0.23, 2.82) units higher for T3 vs. T1 (P-trend=0.02). After adjusting for pre-pregnancy BMI, the total effect was 1.18 (-0.09, 2.44) and 1.31 (0.00, 2.62) units higher for T2 vs. T1 and T3 vs. T1, respectively (P-trend=0.04). The direct effect after accounting for neonatal FM % was slightly attenuated (T2 vs. T1: 1.14 [-0.11, 2.39], T3 vs. T1: 1.20 [-0.11, 2.51]; P-trend=0.07). Excluding women with gestational diabetes mellitus (n=27) did not substantially impact the results. Our data suggest that maternal glycemia during pregnancy, even within normal levels, may influence childhood adiposity through pathways that are in part mediated by programming of neonatal adiposity. Disclosure E.C. Francis: None. B. Ringham: None. D.H. Glueck: None. W. Perng: None. D. Dabelea: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK076648-10)

Abstract 41: The Effect Of Maternal Weight On Offspring Blood Pressure At 18 Years Of Age: A Causal Natural-effects Mediation Analysis

Objectives: Examine the relationship between maternal pre-pregnancy body mass index (BMI) and offspring systolic blood pressure (SBP) at 18 yrs old. Methods: We performed multivariate regression and causal mediation analysis within 3700 mother - offspring pairs from a prospective birth cohort. The main exposure was maternal pre-pregnancy BMI categorized as healthy weight, overweight, or obese according to international criteria. The main outcomes were high-normal BP and hypertension defined as SBP between the 90-95 th centile and >95 th centile for height and sex at 18 years, respectively, as per 2017 AAP guidelines. Analyses were adjusted for social class, pre-eclampsia, sex, and maternal tobacco use during pregnancy. The Canadian Pediatric Endocrine Group R Shiny app was used to obtain age-standardized BMI Z-scores and latent class analysis (LCA) was used to quantify the mediating factor of offspring BMIZ trajectories from 7 to 18 yrs. Results: Before pregnancy 14% of women were overweight and 5% were obese. At 18 yrs, SBP (122 ± 12 vs 118 ±11mmHg, p < 0.001), DBP (67 ± 7 vs 63 ± 6mmHg, p < 0.001) and the odds of elevated BP (aOR: 1.6; 95% CI: 1.1-2.3) and hypertension (aOR: 2.1; 95% CI: 1.4-3.1) were higher in offspring from women that were obese prior to pregnancy compared to those that were normal weight. LCA identified five distinct offspring BMIZ trajectories shown in the figure. SBP (125 ± 12 vs 117 ± 10 mmHg, p < 0.001) and the odds of hypertension (aOR: 3.8; 95% CI: 2.8-5.1) at 18 years were significantly higher in offspring with sustained high BMIZ (teal) compared to sustained low normal BMIZ (green). Casual mediation analysis revealed that maternal BMI directly (OR: 1.14; 95% CI: 1.03-1.25) and indirectly through offspring BMIZ trajectories (OR: 1.12; 95% CI: 1.08-1.15) increased offspring SBP at 18 years of age. Conclusion: Maternal obesity prior to pregnancy is associated with an increased risk of hypertension in offspring at 18 yrs of age, partly mediated by an elevated BMIZ score trajectory throughout childhood and adolescence.

Maternal anemia and offspring failure to thrive – results from a large population-based cohort

Objective To evaluate whether an association exists between maternal anemia and offspring failure to thrive (FTT) during childhood. Methods A population-based cohort analysis was performed, comparing the risk for FTT among children (up to 18 years old) based on maternal hemoglobin (Hb) levels, upon postpartum discharge. Maternal Hb levels were categorized into 3 levels: <9.0 (moderate–severe anemia), 9.0–11.0 (mild anemia), and ≥11.0 g/dL (no anemia). FTT diagnosis was based on hospital records. All singletons born between 1991 and 2014 and discharged alive without congenital malformations were included. A survival curve was constructed to compare the cumulative FTT incidence, and a Weibull parametric survival analysis to assess the independent association between maternal anemia and offspring FTT while controlling for confounders. Results Of the 214,305 included deliveries, 22,071 parturients (10.3%) were discharged with Hb <9.00; 83,932 (39.2%) with Hb between 9.0–11.0; and 108,302 (50.5%) with Hb ≥11.0 g/dL. FTT rates were 1.3% (n = 287), 1.2% (n = 967), and 1.1% (n = 1141) in the same groups, respectively (p = .003). The survival curve demonstrated a significantly higher cumulative incidence of FTT diagnosis in the moderate–severe maternal anemia group (p < .001). In the Weibull analysis, constructed for newborns with appropriate birthweight, both groups of maternal anemia were found to be independently associated with FTT related hospitalizations (mild anemia aHR, 1.1; 95%CI 1.002–1.219; p = .045, moderate-severe anemia aHR, 1.321; 95%CI, 1.141–1.529; p < .001). Conclusion Maternal anemia is independently associated with long-term FTT in offspring, with increasing FTT rates proportional to anemia severity.

Maternal pre-pregnancy body mass index and offspring temperament at 3 months

Introduction: Pre-pregnancy obesity has been linked to emotional and behavioural problems in offspring, though it remains unclear when the presence of these difficulties first emerges.&#x0D; Method: We examined the association between maternal pre-pregnancy body mass index (BMI) and temperament at 3 months of age in the offspring of 16 women residing in Hamilton, Ontario. Infant temperament was measured using the Infant Behaviour Questionnaire Revised, which specifically examined surgency/extraversion, negative affectivity, and orienting/regulation.&#x0D; Results: A statistically significant association was observed between maternal BMI and infant negative affectivity (B=0.05, 95% CI=0.01-0.08), which remained significant after adjusting for confounding variables (B=0.04, 95% CI=0.01-0.08).&#x0D; Conclusion: The current study provides evidence that fetal exposure to high maternal BMI during pregnancy is associated with increased negative affectivity in infants at 3 months of age. The results suggest that the intrauterine environment associated with high maternal BMI may influence temperament at a very early stage in development.

Physiology and behaviour of juvenile snowshoe hares at the start of the 10-year cycle

Snowshoe hares, Lepus americanus, are the dominant prey species in the boreal forest and they undergo regular, predator-driven population cycles every 8–11 years. Previous research has found that hare stress physiology is highly sensitive to both within-year (seasonal/litter group) and across-year (cycle phase) variation in predation risk and that maternal–offspring stress profiles are tightly correlated. Thus, both pre- and postnatal environments may interact to shape offspring physiological phenotype. If changes in the function and reactivity of the maternal stress axis are associated with variation in offspring behaviours that increase survival during periods of high predation risk, then the maternal effects on offspring physiology seen previously could represent a mechanistic route of adaptive maternal programming. To examine the relationship between physiology and behaviour in snowshoe hares, we monitored free-ranging adult and juvenile stress hormone levels in the first and second litters of the breeding season and assessed open field exploratory behaviour in weaning-age and independent juveniles in the southwestern Yukon (Canada) during 2013–2015, when predator density was low but increasing. Thus, our study spanned the late low phase (2013) and the early increase phase (2014–2015) of the hare population cycle. We found that increased concentrations of faecal cortisol metabolites (FCMs) were associated with aspects of risk avoidance in weaning-age hares. Juveniles with higher stress hormone levels spent more time under cover and were less active during open field trials, highlighting a potential mechanistic route to allow individuals to sensitively cope with a changing environment. Although average FCM levels of breeding females and juveniles were not correlated with one another and litter-based differences in physiology and behaviour were not present during these low-risk phases of the cycle, the association between stress hormone levels and behaviour sets the stage for adaptive maternal effects on offspring behaviour and survival as the cycle progresses and predation risk intensifies.

Maternal high fat diet programs hypothalamic-pituitary-adrenal function in adult rat offspring

Abstract Maternal environmental factors such as diet have profound effects on offspring development and later health. The hypothalamic-pituitary-adrenal (HPA) axis is an important stress neuroendocrine system that is subject to programming by early life challenges. The present study was further to investigate whether maternal high fat diet (HFD) exposure during rat pregnancy and lactation can alter the HPA axis activity in adult male offspring. We observed that maternal HFD consumption exerted long-term effects on the basal activity of the HPA axis in adult offspring, with increased mean plasma corticosterone levels that result from elevated steroid pulse frequence and pulse amplitude. More importantly, maternal HFD offspring displayed enhanced corticosterone responses to restraint (1 h) and lipopolysaccharide (25 μg/kg, iv) but not insulin-induced hypoglycemia (0.3U/kg, iv) stress, suggesting a stressor-specific effect of maternal diet on the hyperresponsiveness of the HPA axis to stress. Additionally, maternal HFD exposure markedly attenuated the habituation of HPA responses to repeated restraint stress. These findings demonstrate that perinatal HFD exposure has a potent and long-lasting influence on development of neuroendocrine regulatory mechanisms. Maternal HFD consumption significantly increased basal corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus; nevertheless, similar increments in CRF mRNA levels following restraint were observed between maternal HFD offspring and control rats. Furthermore, the medial and central nuclei of amygdala played a pivotal role in maternal HFD-induced sensitization of the HPA response to psychological and systemic stress, respectively, suggesting that different neural pathways may mediate maternal HFD-induced HPA hyperresponsivity to different types of stressors. Take together, the long-term effects of maternal HFD challenge on the central regulation of the HPA axis, therefore, expose the adult offspring to greater HPA function throughout lifespan, in stressor-specific and region-specific manner.

Effect of Maternal High Fructose and Offspring High Fat Intake on Programmed Hypertension in Young Adult: the Role of Nutrient Sensing Signaling in the Brain

There is now substantial epidemiological evidence suggesting the origin of susceptibility for metabolic syndromes (MetS) and associated cardiovascular dysfunctions in adulthood can be traced back to the early life. We have previously demonstrated that maternal high fructose diet (HFD) induces programmed hypertension in adult offspring; however, the cellular and molecular signaling contributing to the developmental programming of adult hypertension is not fully understood. There are a number of nutrient sensing pathways, including silent information regulator transcript (SIRT), AMP‐activated protein kinase (AMPK), and phosphatidylinositol 3‐kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) located in the central nervous system and are responsible for the detection of sugars, amino acids, lipids and the surrogate metabolite level for the maintenance of metabolic homeostasis. Perturbation of these signaling pathways could lead to MetS and the associated cardiovascular complications. This study was designed to investigate the role of these nutrient sensing pathways in the brain on developmental programming of hypertension in offspring to maternal HFD, and the influence of high fat diet (HFatD) in offspring to these nutrient sensing pathways. Female Sprague‐Dawley rats were fed with 60% HFD or normal diet (ND) during gestation and lactation periods. After weaning both HFD and ND offspring were subjected to HFatD or ND from the age of 3 to 12 weeks. Blood pressure was monitored under conscious condition via tail‐cuff method from week 6 to 12. Expression of nutrient sensing signals in the forebrain hypothalamus was examined by Western blot analysis. Tissue oxidative stress was quantified by electron spin resonance spectroscopy. Maternal HFD induced programmed MetS and hypertension that became significant at age of 9 weeks and maintained in young adult at age of 12 weeks. Changes in both metabolic and blood pressure phenotypes were appreciably enhanced in HFD offspring with additional HFatD intake after weaning. Protein expressions of SIRT1, phosphorylated AMPK (p‐AMPK), and p‐Akt in the hypothalamus were downregulated in the HFD offspring, which were further suppressed in offspring fed with HFatD. These molecular changes were associated with tissue oxidative stress in the hypothalamus.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Role of maternal folic acid on implantation of embryos and on maternal body weight &amp; offspring's birth weight

Introduction There has been a much debate on the role of pre-/periconceptional and prenatal folic acid (FA) supplements for the long-term health of their offspring. Maternal deficiency of FA or excess of FA would likely to affect the developing fetus at critical stages of development to cause long-lasting health consequences in their offspring. The present study aimed to know the effect of folic acid supplementation and folic acid absence diet during pregnancy on the number of implantation, endometrial changes at the implantation site and on maternal body weight & offspring's birth weight. Material & Methods Thirty-Six Wistar strained female rats were approved for experimental use by the Institutional Animal Ethical Committee. Rats were randomly divided into two groups with 18 rats in each group. Further, each group has been divided into three sets with 6 rats in each. The control set was fed a normal diet, the second set was fed a diet containing no FA. 1% Succinyl sulfathiazole was added to the diet with no FA content to reduce/ inhibit the gut flora responsible for the synthesis of FA in their body. The third set was given diet with an excess of FA (40mg/kg body weight/day). Rats were given respective diet for 4 weeks before mating, continued throughout their pregnancy and 5 weeks after the delivery of pups (weening period). All female rats were paired with males of their own strain overnight at room temperature (25°C). To check whether they mated or not, the vaginal smear was taken in the early morning and stained with methylene blue and confirmed the presence of sperm plug under microscopy. On confirmation of sperm plug, the gestational day was termed as day 1 (GD1). Rats have remained in their cage and diets until they were sacrificed during gestation from day GD6-GD9. Rats were remained in their cage and with their respective diets until they delivered the pups. Delivered pups were counted for each rat and gross malformation in each pup was noted. Immediately after the delivery, all the pups born to each rat were weighed individually in the digital weighing machine. Results Average number of pups born to pregnant dams fed with FA supplementation, FA absent diet, and in normal diet was found to be 8,8, and 9 respectively. Regarding the birth weight of pups born to pregnant dams fed with FA supplementation the average weight was found to be 6.01-5.09 gm, with evidence diet it was 5.51-5.08 gm, and least weight was observed in pups born with FA absent diet (4.74-3.31 gm). Pair-wise comparison was done to correlate the significant association between the different groups. It showed significant difference when compared with pups born to FA supplementation diet to pups born to FA absent diet. Also, significant differences were noted when compared pups born to FA absent diet mother with pups born to FA supplementation and with pups born to normal diet. Conclusion Our study provides clear evidence that FA is essential in successful implantation by providing favorable receptive environment to receive the implantation-competent blastocyst for a successful pregnancy. Birth weight of pups born to pregnant dams fed with FA supplementation was found to be significantly increased when compared to those with the diet with normal amount of FA, and least weight wasobserved in pups born with FA absent diet. As the fetal birth weight is the best predictor of pregnancy outcome as the growth restriction has been associated with high morbidity and mortality. FA supplementation is essential during the period of pregnancy to prevent untoward effects on pregnancy-related complications in mother and to prevent birth defects in fetuses. Further research from longitudinal studies is warranted to confirm these results before its recommendation to the public health.

Prenatal maternal antidepressants, anxiety, and depression and offspring DNA methylation: epigenome-wide associations at birth and persistence into early childhood

BackgroundMaternal mood disorders and their treatment during pregnancy may have effects on the offspring epigenome. We aim to evaluate associations of maternal prenatal antidepressant use, anxiety, and depression with cord blood DNA methylation across the genome at birth and test for persistence of associations in early and mid-childhood blood DNA.MethodsA discovery phase was conducted in Project Viva, a prospective pre-birth cohort study with external replication in an independent cohort, the Generation R Study. In Project Viva, pregnant women were recruited between 1999 and 2002 in Eastern Massachusetts, USA. In the Generation R Study, pregnant women were recruited between 2002 and 2006 in Rotterdam, the Netherlands. In Project Viva, 479 infants had data on maternal antidepressant use, anxiety, depression, and cord blood DNA methylation, 120 children had DNA methylation measured in early childhood (~ 3 years), and 460 in mid-childhood (~ 7 years). In the Generation R Study, 999 infants had data on maternal antidepressants and cord blood DNA methylation. The prenatal antidepressant prescription was obtained from medical records. At-mid pregnancy, symptoms of anxiety and depression were assessed with the Pregnancy-Related Anxiety Scale and the Edinburgh Postnatal Depression Scale in Project Viva and with the Brief Symptom Inventory in the Generation R Study. Genome-wide DNA methylation was measured using the Infinium HumanMethylation450 BeadChip in both cohorts.ResultsIn Project Viva, 2.9% (14/479) pregnant women were prescribed antidepressants, 9.0% (40/445) experienced high pregnancy-related anxiety, and 8.2% (33/402) reported symptoms consistent with depression. Newborns exposed to antidepressants in pregnancy had 7.2% lower DNA methylation (95% CI, − 10.4, − 4.1; P = 1.03 × 10−8) at cg22159528 located in the gene body of ZNF575, and this association replicated in the Generation R Study (β = − 2.5%; 95% CI − 4.2, − 0.7; P = 0.006). In Project Viva, the association persisted in early (β = − 6.2%; 95% CI − 10.7, − 1.6) but not mid-childhood. We observed cohort-specific associations for maternal anxiety and depression in Project Viva that did not replicate.ConclusionsThe ZNF575 gene is involved in transcriptional regulation but specific functions are largely unknown. Given the widespread use of antidepressants in pregnancy, as well as the effects of exposure to anxiety and depression, implications of potential fetal epigenetic programming by these risk factors and their impacts on development merit further investigation.

Prenatal Exposure to Famine and Risk for Development of Psychopathology in Adulthood: A Meta-Analysis.

Prenatal famine, resulting in intrauterine malnutrition, impacts offspring psychopathology later in adulthood. In addition, the specific impact of intrauterine malnutrition of different psychopathology differs by the timing of the exposure. Using a meta-analysis, the current study assessed the specific risk of developing affective, psychotic, and personality disorders. Studies were identified using PubMed and PsycINFO. Studies met the following criteria for inclusion in the analysis: availability in peer-reviewed English journals, use of human subjects, prenatal exposure to famine, and psychopathology in adulthood defined by diagnostic criteria as an outcome. Fixed effect relative risks (RRs) were calculated for affective, psychotic, and personality domains. Furthermore, timing of exposure was assessed as an effect modifier in our analysis, defined by the index trimester at the height of famine. Our meta-analysis found that adults exposed in utero during the 1st trimester were at a significant increased risk of psychotic disorders (RR=1.46, 95% CI=1.08, 1.97, p=0.014), and personality disorders (RR=2.31, 95% CI=1.36, 3.92, p=0.002). Those exposed during the 2nd trimester were at a significant increased risk of affective disorders (RR=1.45, 95% CI=1.22, 1.72, p<0.0001), and psychotic disorders (RR=1.46, 95% CI=1.13, 1.89, p=0.004). Similarly, those exposed in the 3rd trimester were at a significant increased risk of affective disorders (RR=1.33, 95% CI=1.13, 1.57, p=0.0001), and psychotic disorders RR=1.47, 95% CI=1.10, 1.97, p=0.010). Our findings suggest that there is differential risk across the different domains of psychopathology by trimester of exposures. This meta-analysis underscores the need for further investigation into the mechanisms underlying prenatal maternal nutrition and offspring psychopathology where magnitude of elevated risk differs by the exposure timing during pregnancy.

The origins of genomic imprinting in mammals.

Genomic imprinting is a process that causes genes to be expressed according to their parental origin. Imprinting appears to have evolved gradually in two of the three mammalian subclasses, with no imprinted genes yet identified in prototheria and only six found to be imprinted in marsupials to date. By interrogating the genomes of eutherian suborders, we determine that imprinting evolved at the majority of eutherian specific genes before the eutherian radiation. Theories considering the evolution of imprinting often relate to resource allocation and recently consider maternal-offspring interactions more generally, which, in marsupials, places a greater emphasis on lactation. In eutherians, the imprint memory is retained at least in part by zinc finger protein 57 (ZFP57), a Kruppel associated box (KRAB) zinc finger protein that binds specifically to methylated imprinting control regions. Some imprints are less dependent on ZFP57invivo and it may be no coincidence that these are the imprints that are found in marsupials. Because marsupials lack ZFP57, this suggests another more ancestral protein evolved to regulate imprints in non-eutherian subclasses, and contributes to imprinting control in eutherians. Hence, understanding the mechanisms acting at imprinting control regions across mammals has the potential to provide valuable insights into our understanding of the origins and evolution of genomic imprinting.

Research status on maternal pesticide exposure and offspring's risk of congenital heart disease

We are interpreting the effects of maternal pesticide exposure during pregnancy on the heart development of offspring. Based on literature review till October 2018, 43 studies were included and three types of pesticide exposure (pesticides, herbicides and fungicides) were focused on. Our result show that maternal pesticide exposure during pregnancy could lead to an increased risk of congenital cardiovascular abnormalities in offsprings. Moreover, it is found that different types of pesticide exposure are associated with different subtypes of congenital heart disease. Generally and relatively, the evidence is consistent and strong for the following relationships: the associations of insecticide exposure with atrial septal defect, pulmonary valve stenosis and ventricular septal defects; the associations of herbicide exposure with transposition of the great arteries and ventricular septal defects; and the associations of bactericide exposure with hypoplastric left heart syndrome and aortic coarctation. Key words: Maternal exposure; Pesticides; Toxic actions; Heart defects, congenital; Fetus

Limonium homoploid and heteroploid intra‐ and interspecific crosses unveil seed anomalies and neopolyploidy related to sexual and/or apomictic reproduction

AbstractApomixis is a form of asexual reproduction that consists in cloning through seeds. In Limonium (Plumbaginaceae) species present a pollen–stigma dimorphism linked to a sporophytic self‐incompatibility system associated with sexual and/or apomictic reproductive modes. Previous work in other genera suggests that the emergence of apomixis is associated with hybridization and/or polyploidy. In this study, our goal was to test the ability of diploid and tetraploid species to hybridize and to evaluate the variate outcomes from these crosses. To achieve this, sexual diploid (L. nydeggeri, L. ovalifolium) and facultative apomict tetraploid (L. binervosum, L. dodartii) plants from cultivated material, previously cytogenetically and reproductively characterized, were used for experimental intra‐ and interspecific crosses. Genome sizes, ploidy levels and morphology were examined in the resulting progenies. Results showed a high production of viable seeds in particular in plants from tetraploid × diploid (heteroploid) crosses. In these crosses, some seedlings exhibited pleiocotyly (tricotyl, tetracotyl), while others showed polyembryony. In both homoploid (diploid × diploid) and heteroploid (tetraploid × diploid) crosses, most of the offspring plants were morphologically and in their ploidy similar to the female receiver, although some morphological abnormalities were found. Molecular progeny tests using the nrDNA ITS1‐ITS2 sequence demonstrated an astounding range of diploid offspring plants originated from diploid × diploid crosses that were either genetically similar or distinct from parental plants. Although in intraspecific crosses most of the resulting progeny was diploid, one triploid plant was formed. Moreover, in homoploid interspecific crosses, neopolyploids (two tetraploid plants) were produced. Progeny plants from heteroploid crosses always showed nrDNA ITS1‐ITS2 sequences identical to the parental plant used as female receiver. In conclusion, diploid homoploid crosses presented genetically diverse offspring arising from sexual reproduction. By contrast, heteroploid crosses generated clonal, maternal (apomictic) offspring.

Dietary Approaches to Stop Hypertension Diet and Activity to Limit Gestational Weight: Maternal Offspring Metabolics Family Intervention Trial, a Technology Enhanced Randomized Trial

Technology-enhanced antenatal diet and lifestyle intervention could prevent excess gestational weight gain and benefit mother and child. A randomized clinical trial. Overweight and obese ethnically diverse pregnant women in Chicago, Illinois, were enrolled between October 2012 and December 2015, with antenatal data collection completed by July 2016. Analysis was completed June 2017. Participants were randomized when their fetus was gestational age 16 weeks to dietitian-led Dietary Approaches to Stop Hypertension diet and physical activity coaching that was received as three individual and six group counseling sessions by phone and webinar. A commercially available smartphone application was used for self-monitoring diet and physical activity. Telephone, text message prompts, and e-mail reminders encouraged adherence and website viewing. Usual-care, "web-watcher" participants were e-mailed biweekly newsletters and publicly available maternity website links. The primary outcome was gestational weight gain measured at baseline, 24 weeks, and 35.0-36.6 weeks. Secondary outcomes included weekly rate of gestational weight gain, newborn anthropometrics, maternal diet quality, physical activity, and blood pressure. Among 281 participants randomized (n=140 in intervention, n=141 in usual care, BMI 25 to <40, and age range 18-40 years), 37% were non-white and 274 completed antenatal data collection (n=139 in the intervention group and n=135 in the usual-care group). Gestational weight gain differed significantly by intervention group (difference, 1.7kg, p=0.01) and rate of weight gain was 0.4 (SD=0.2) vs 0.5 (SD=0.2) kg/week. No significant differences were noted in birth weight, percentage body fat, or adverse pregnancy outcomes, but more cesarean sections (55 [40%] vs 37 [27%]) occurred among the intervention group. Technology-enhanced Dietary Approaches to Stop Hypertension diet and lifestyle intervention resulted in significantly less total gestational weight gain over 35 weeks with no adverse infant outcomes. Nutrient quality improved without an adverse impact on rate of prematurity. Increased cesarean delivery requires further exploration. The National Academy of Medicine goals were not achieved by the majority of participants. Obesity prevention preconception is needed. This study is registered at www.clinicaltrials.gov NCT01631747.

Intergenerational transmission of maternal care deficiency and offspring development delay induced by perinatal protein malnutrition

Objectives: Early life represents a sensitive and critical period for an individual. Nutrition plays a crucial role in the maturation and functional development of the central nervous system. Inadequate nutrition before birth and during the postnatal life can seriously interfere with brain development and lead to behavioral and neurological disorders such as learning disabilities and psychiatric diseases. In addition, the quality of mother–infant interactions represents an important adaptive pathway that prepares offspring for the conditions of life. In this work, we asked if protein malnutrition alters maternal care and offspring development and if these phenotypes can be transmitted to next generation.Methods: Female mice were fed with a normal or hypoproteic diet during pregnancy and lactation. Nurturing behaviors, i.e. arched, blanket and passive nursing, and liking and grooming of the pups, were evaluated from postnatal day 1 (PD1) to postnatal day 7 (PD7). The same protocol was employed to evaluate maternal behavior for filial generation 1 (F1) and filial generation 2 (F2) dams. Offspring development was evaluated for F1, F2, and F3 generations. Developmental landmarks and neurological reflexes were assessed from PD8 until complete development of the landmark or acquisition of the reflex.Results: Our results show that malnourished dams provide a lesser and more fragmented maternal care than their normally fed counterparts. This altered maternal behavior as well as the delay in the physical and neurological development observed in the offspring from malnourished mothers was transmitted up to two generations at least.Conclusion: These results highlight the harmful effects of protein malnutrition even for generations that are not directly exposed to this environmental adversity.

Establishment and Comparison of Juvenile Female Mouse Models of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.

Experimental research has successfully established an adult offspring animal model of nonalcoholic fatty liver disease (NAFLD), but the female offspring model of NAFLD in young age has not been well characterized yet. The aim of this study was to present a direct comparison of the maternal versus postweaning female juvenile NAFLD and nonalcoholic steatohepatitis (NASH) animal models. Four different female mouse models were established and compared using different high-fat diet feeding (HF) strategies in maternal mice and their offspring. The models were non-HF maternal mice and HF offspring with high-high fat (C/HHF), non-HF maternal mice and HF offspring with low-high fat (C/LHF), HF maternal mice and offspring both with high-high fat (HHF/HHF), and HF maternal mice and offspring both with low-high fat (LHF/LHF). A female control group (C/C) was also established. The offspring mice were raised to the age of 8 weeks and then euthanized. Blood glucose levels, lipid profiles, liver function, and triglycerides/total cholesterol contents were examined. Hepatic morphology and superoxide anion levels were evaluated. The nicotinamide-adenine dinucleotide phosphate activity and related regulatory subunits protein expression in the liver tissue were also determined. Our data demonstrated that offspring fat intake contributed to the successful establishment of NAFLD and maternal-offspring fat intake contributed to the successful establishment of NASH in juvenile female mice. Offspring high-fat exposure might be associated with the development of NAFLD and maternal high-fat exposure might be associated with the development of NASH in juvenile female offspring. Higher calories from a fat diet program (both in maternal and offspring) are more prone to inducing liver injury in offspring. In addition, the combination of the aforementioned two factors could aggravate this process. Moreover, oxidative stress was prominent in the juvenile female mouse model of NAFLD/NASH, and the mechanism might be related to the activation of liver NADPH oxidase.

The Influence of LPS-Induced Maternal Inflammation on Postnatal Collagen-Induced Arthritis.

Maternal health and nutritional status influence offspring health and the diseases that may develop in them. The effects of maternal inflammation on offspring from the perspective of the inflammatory response and immune changes are not fully understood. We hypothesized that maternal inflammation modulates immune and metabolic functions, affecting the pathophysiology of inflammatory diseases in offspring. This study investigated whether maternal inflammation affects the onset of collagen-induced arthritis (CIA), a murine model of human rheumatoid arthritis. Female DBA/1J mice received a single intraperitoneal injection of lipopolysaccharide (LPS) 5days before conception. Male offspring of LPS-treated dams were placed in the maternal LPS group (MLG). To induce CIA, type II collagen (CII) was emulsified with Freund's complete adjuvant and injected twice into each mouse, at 13 and 16weeks. The offspring were sacrificed at 26weeks to analyze immunological and metabolic parameters. The degree of joint swelling at an early stage of CIA was lower in the MLG than in the control group. From histological analysis, the severity of joint destruction (severity of arthritis score) and CII-specific IgG titer were significantly lower in the MLG. However, at 26weeks, serum interleukin (IL)-6 levels, an index of CIA disease activity, were significantly higher in the MLG. Moreover, serum leptin levels were lower in the MLG, and a negative correlation between leptin and serum IL-6 was observed. In conclusion, maternal inflammation does not merely suppress inflammation; it may delay CIA in offspring. The analysis of inflammatory cytokines and leptin concentrations at 26weeks suggests that the pathophysiology of arthritis was worsening. This study also suggests that maternal inflammation modulates postnatal inflammatory response patterns in offspring.