Developmental Outcomes In Offspring Research Articles

290 Ewe Undernutrition Alters Cotyledon Development and Function

Abstract Undernutrition is common for animals maintained in a range setting, particularly during periods of drought, and during gestation can be detrimental to offspring development. The placenta is a known mediator for maternal-fetal nutrient exchange, and developmental impacts to the placenta during times of nutritional stress contribute to poor offspring outcomes. The objective of this study was to determine the impacts of maternal nutrient restriction on the development and function of placental cotyledons. Targhee ewes were allocated into two dietary treatment groups for the entirety of gestation. The control group (CON; n = 10) was fed to meet 100% of NRC requirements and the nutrient restricted group (NR; n = 11) was fed to meet 60% of NRC requirements, to mimic the nutritional stress experienced by range ewes during drought. At the time of lambing total placental weight, total cotyledon number, and lamb birth weight were recorded. Cotyledons (n = 3 / placenta) were removed from multiple locations, weighed, and processed for RNA-sequencing. Total placental weight, total cotyledon number, and lamb birth weight were not affected by maternal diet restriction (P > 0.05). Average cotyledon weight was greater in the CON group compared with the NR group (P < 0.05). Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathways (KEGG) analyses were performed to identify biological pathways involved in placental function and nutrient transfer. Cotyledons from NR singletons vs CON singletons expressed 470 differentially expressed genes (DEGs; P < 0.05; 187 up-regulated, 283 down-regulated). Gene ontology terms represented by DEGs include hormone activity (P = 0.0003) and antigen processing and presentation (P = 0.0004). KEGG pathways of interest include pyruvate metabolism, estrogen signaling, extracellular matrix receptor interaction, and antigen processing and presentation. There were also 426 DEGs (P < 0.05; 195 up-regulated, 231 down-regulated) in cotyledons of NR twins vs CON twins. Represented GO categories include heme binding (P = 0.003) and oxidoreductase activity (P = 0.03). These data show that prolonged nutrient restriction alters cotyledon development and gene expression indicating modifications in placental function. These changes in placental function likely mediate poor offspring developmental outcomes observed following gestational under nutrition.

Intergenerational transmission of parent adverse childhood experiences to child outcomes: A systematic review and meta-analysis

ObjectiveThe current meta-analytic review provides a comprehensive synthesis of studies examining parent exposure to ACEs and the developmental and mental health outcomes of their children. Participants and settingEligible studies up to August 2021 were identified through comprehensive database searches in PsycINFO, MEDLINE, and Embase. Studies that were included examined the intergenerational effects of parent ACEs on child development (i.e., cognitive, language, motor, social difficulties, and early social-emotional development) or mental health (i.e., internalizing problems, externalizing problems) outcomes. MethodsData were extracted by two coders using a standardized extraction protocol. A multi-level meta-analytic approach was used to derive pooled effect sizes and test for moderators. ResultsA total of 52 studies were included in the meta-analysis. Parent ACEs were positively associated with child mental health problems (r=0.17, 95% CI [0.12, 0.21], p<.001), child externalizing difficulties (r=0.20, 95% CI [0.15, 0.26], p<.001), and child internalizing difficulties (r=0.17, 95% CI [0.11, 0.22], p<.001). There were no significant sociodemographic (i.e., child age, parent age, income level, child sex, or racial/ethnic minority status) or methodological (i.e., study type or quality) moderators of these associations. Preliminary evidence suggests that parent ACEs were not associated with offspring developmental outcomes, such as cognitive or language skills. ConclusionsResults suggest that parent ACEs are associated with some, but not all child outcomes. Additional research focused on the mechanisms of transmission are needed to inform policies and practices related to the intergenerational transmission of ACEs.

Nutrient Supplementation during the Prenatal Period in Substance-Using Mothers: A Narrative Review of the Effects on Offspring Development.

Substance use during pregnancy increases the risk for poor developmental outcomes of the offspring, and for substance-dependent mothers, abstaining from substance use during pregnancy is often difficult. Given the addictive nature of many substances, strategies that may mitigate the harmful effects of prenatal substance exposure are important. Prenatal nutrient supplementation is an emerging intervention that may improve developmental outcomes among substance-exposed offspring. We provide a narrative review of the literature on micronutrient and fatty acid supplementation during pregnancies exposed to substance use in relation to offspring developmental outcomes. We first discuss animal models exposed to ethanol during pregnancy with supplementation of choline, zinc, vitamin E, iron, and fatty acids. We follow with human studies of both alcohol- and nicotine-exposed pregnancies with supplementation of choline and vitamin C, respectively. We identified only 26 animal studies on ethanol and 6 human studies on alcohol and nicotine that supplemented nutrients during pregnancy and reported offspring developmental outcomes. There were no studies that examined nutrient supplementation during pregnancies exposed to cannabis, illicit substances, or polysubstance use. Implementations and future directions are discussed.

Maternal and paternal depressive symptoms and parental vocalisation behaviours in infancy: findings from UK-based birth cohort

BackgroundBoth maternal and paternal postnatal depression (PND) are associated with increased risk of less optimal offspring developmental outcomes. Early exposure to differences in maternal and paternal vocalisation behaviours associated with maternal and paternal PND may be important in this relationship. However, little research has captured vocalisation patterns at home without researchers present.ObjectivesThis study sought to examine the associations between maternal and paternal PND and various aspects of parental vocalisation behaviours.MethodsMothers (n = 104) and fathers (n = 34) of six-months old infants from the Avon Longitudinal Study of Parents and Children Generation-2 (ALSPAC-G2) provided video footage of mother- and father-infant interactions filmed at home using the head-worn video cameras (headcams) without the need for researchers to be present. Twenty-five mother-infant and father-infant interactions were coded on multiple aspects of parental and infant vocalisation behaviours using the micro-behavioural observational coding system. Parental (PND) was measured using the Edinburgh Postnatal Depression Scale (EPDS; total score).ResultsFrequencies and duration of vocalisation behaviours were similar in mothers and fathers. However, there was an indication that fathers demonstrated higher frequency and duration of commands, exclamations and ironic/sarcastic tone, and criticisms compared to mothers, while mothers engaged in more teaching compared to fathers. Linear regression models indicated that maternal and paternal PND were not associated with the majority of vocalisation behaviours. However, there were some specific patterns observed, mostly related to the emotional tone of the vocalisations. Higher levels of maternal PND were associated with lower frequency of speech in a neutral tone, frequency and duration of use of humour, and increased duration of speech in a positive tone. Higher levels of paternal PND were associated with higher mean duration of speech, infant-directed speech, higher frequency and duration of laughing, and increased duration of speech using questions and encouragement.ConclusionThese findings extend existing research by investigating the associations between maternal and paternal PND and a wide range of vocalisation behaviours captured and coded using innovative methods and in a more ecologically valid way than previous studies.

Association of maternal personality traits with medication use during pregnancy to appraise unmeasured confounding in long-term pharmacoepidemiological safety studies.

Maternal personality is a possible confounder on the association between prenatal medication exposure and long-term developmental outcomes in offspring, but it is often unmeasured. This study aimed to (i) estimate the association between five maternal personality traits and prenatal use of acetaminophen (including extended use), opioid analgesics, antidepressants, benzodiazepines/z-hypnotics, and antipsychotics; (ii) evaluate, using an applied example, whether unmeasured confounding by maternal neuroticism would make the association between prenatal antidepressant-child ADHD null, using the E-value framework. We used data from 8,879 pregnant women and recent mothers who participated in the Multinational Medication Use in Pregnancy Study, a web-based cross-sectional study performed within the period from 1-Oct-2011 to 29-Feb-2012 in Europe, North America and Australia. Medication use in pregnancy was self-reported by the women. Personality was assessed with the Big Five Inventory, capturing the dimensions of neuroticism, extraversion, openness, agreeableness, and conscientiousness. Adjusted logistic regression analyses were conducted for each trait-medication pair, using the survey weighting. There was a strong association between having high neuroticism and prenatal use of antidepressants (Odds Ratio (OR): 5.63, 95% Confidence Interval (CI): 3.96-8.01), benzodiazepines/z-hypnotics (OR: 6.66, 95% CI: 4.05-10.95), and analgesic opioids (OR: 2.24, 95% CI: 1.41-3.56), but not with antipsychotics. Among women with mental illness, this association attenuated for benzodiazepines/z-hypnotics, but decreased to the null for antidepressants. High neuroticism (OR: 1.31, 95% CI: 1.08-1.59) and high openness (OR: 0.77, 95% CI: 0.64-0.93) were associated with extended use of acetaminophen. The E-value for the Hazard Ratio 1.93 in the applied example was 3.27. If the example study was conducted using a population comparison group, high maternal neuroticism could have explained away the association antidepressant-ADHD. Because the example study included only women with a mental illness, this risk of bias was assessed as minimal. Various personality dispositions in the mother are associated, with a different degree, to prenatal use of medication. The strength of these association can aid researchers in evaluating the influence of uncontrolled confounding by maternal personality in long-term safety studies in pregnancy, using the E-value. This assessment should always be performed in addition to a rigorous study design using approaches to triangulate the evidence.

Maternal depressive symptom trajectories from preconception through postpartum: Associations with offspring developmental outcomes in early childhood

BackgroundTwo theoretical frameworks, the cumulative stress and match-mismatch model, propose that patterns of maternal depressive symptoms over early periods of offspring development predict outcomes in opposing ways. Studies have yet to test these theories across the preconception, prenatal, and early postnatal period. Study 1 identified trajectories of maternal depressive symptoms from preconception to postpartum. Study 2 examined associations of these trajectories with offspring developmental outcomes in early childhood. MethodsIn Study 1, women (n = 362) enrolled in a longitudinal study were assessed prior to conception and through a subsequent pregnancy and postpartum. In Study 2, a subsample of 125 mother-child pairs completed home visits in early childhood. Mothers reported on child temperament at age 4. Children completed assessments of executive function at age 5. ResultsFour trajectories of maternal depressive symptoms were identified: low-stable, increasing, decreasing, persistent. In controlled analyses, children of women with decreasing symptoms were lower in maternal ratings of effortful control at age four (β = −0.24, p = .003). Children of women with increasing symptoms scored lower on an inhibitory control task at age five (β = −0.35, p = .001). ConclusionsChanges in maternal depressive symptoms, but not stable symptoms, were associated with lower maternal ratings of effortful control and poorer performance on an inhibitory control task. Results are consistent with the match-mismatch model. Assessment of preconception depressive symptoms in women and changes in symptoms may be beneficial for early intervention for women and children.

Psychosocial Impact of COVID-19: Health Impact and Clinical Findings

Besides its high mortality rates, COVID-19 disease has dramatic psychosocial and psychological effects worldwide. There are significant reports of mental issues, panic attacks, anxiety, depression, and financial difficulties, and the effects continue to persist months after recovery [1]. The disease itself multipliedgic by many other problems like post-traumatic stress disorder, depression, change in behaviors. All these have a significant impact on their lives [1]. It also has adverse effects on pregnancy. COVID-19 has affected the mother as well as the child’s health. There are many panic and anxiety issues. Many deaths were not even reported. Coronavirus pandemic has led to many health and mental illnesses. Many lockdowns led to financial difficulties and problems in the present and future.&#x0D; Long-term neuropsychiatric effects may be caused by more than only the massive psychological trauma suffered during the outbreak.&#x0D; Poor developmental outcomes in offspring have been associated with prenatal psychological distress, including abnormalities in brain development 4, 7, and worse socio-emotional and cognitive development.&#x0D; This article tends to define the psychosocial (psychosocial remove) impact of COVID-19 on students, health workers, pregnant women, how their lives and mental health are affected worldwide. COVID-19 affected the workplace. Stress throughout pregnancy and early life has been linked to cancer lately. It has affected many lives in agricultural areas, economic-financial losses. Current reports put forward feasible passing on vertical coronavirus, although longitudinal studies offspring are needed. The paternal infection on the offspring and generational upshot can be contemplated.

Prenatal cannabis use disorders and offspring primary and secondary educational outcomes.

Cannabis use is increasing among women of reproductive age, warranting a greater understanding of the impact of prenatal cannabis use on offspring developmental outcomes. We tested for a potential relationship between prenatal cannabis use disorders (CUD) and offspring educational outcomes across primary and secondary school. Data were drawn from the New South Wales (NSW) Perinatal Data Collection, which included all live births in the Australian state of NSW between January 2003 and December 2005. These were linked with the NSW Admitted Patient Data collection for mothers and offspring, and the NSW National Assessment Program-Literacy and Numeracy (NAPLAN). New South Wales, Australia. A total of 189 558 offspring who completed the NAPLAN in grades 3, 5 and 7 (resulting in 568 674 examination periods). The exposure variable was ICD-10 cannabis use disorders (CUD=F13.0-F13.9). The study included five outcome variables measured at three time-points as not meeting the minimum national standards for: (i) numeracy, (ii) reading, (iii) spelling, (iv) writing and (v) grammar and punctuation. In unadjusted analyses, prenatal CUD was associated with an increased risk for not meeting the national minimum standard of all outcomes [odds ratios (OR) ranging from 3.42 (95% confidence interval (CI)=2.94, 3.99) to 4.17 (95% CI=3.55, 4.91)], with no evidence for an interaction across time. However, the associations attenuated greatly after exact matching by covariates, with reading and numeracy no longer associated with prenatal CUD, while the increased risk of the other outcomes ranged from OR=1.31 (95% CI=1.09, 1.57) to OR=1.40 (95% CI=1.17, 1.68). Socio-economic status appears to confound the association between prenatal cannabis use disorder and poor educational performance in offspring.

Histone H3 lysine 4 trimethylation in sperm is transmitted to the embryo and associated with diet-induced phenotypes in the offspring.

A father's lifestyle impacts offspring health; yet, the underlying molecular mechanisms remain elusive. We hypothesized that a diet that changes methyl donor availability will alter the sperm and embryo epigenomes to impact embryonic gene expression and development. Here, we demonstrate that a folate-deficient (FD) dietalters histone H3 lysine 4 trimethylation (H3K4me3) in sperm at developmental genes and putative enhancers. A subset of H3K4me3 alterations in sperm are retained in the pre-implantation embryo and associated with deregulated embryonic gene expression. Using a genetic mouse model in which sires have pre-existing altered H3K4me2/3 in sperm, we show that a FD diet exacerbates alterations in sperm H3K4me3 and embryonic gene expression, leading to an increase in developmental defect severity. These findings imply that paternal H3K4me3 is transmitted to the embryo and influences gene expression and development. It further suggests that epigenetic errors can accumulate in sperm to worsen offspring developmental outcomes.

Prenatal maternal psychological distress and fetal developmental trajectories: associations with infant temperament.

Associations between prenatal maternal psychological distress and offspring developmental outcomes are well documented, yet relatively little research has examined links between maternal distress and development in utero, prior to postpartum influences. Fetal heart rate (FHR) parameters are established indices of central and autonomic nervous system maturation and function which demonstrate continuity with postnatal outcomes. This prospective, longitudinal study of 149 maternal-fetal pairs evaluated associations between prenatal maternal distress, FHR parameters, and dimensions of infant temperament. Women reported their symptoms of psychological distress at five prenatal visits, and FHR monitoring was conducted at the last three visits. Maternal report of infant temperament was collected at 3 and 6 months of age. Exposure to elevated prenatal maternal psychological distress was associated with higher late-gestation resting mean FHR (FHRM) among female but not male fetuses. Higher late-gestation FHRM was associated with lower infant orienting/regulation and with higher infant negative affectivity, and these associations did not differ by infant sex. A path analysis identified higher FHRM as one pathway by which elevated prenatal maternal distress was associated with lower orienting/regulation among female infants. Findings suggest that, for females, elevated maternal distress alters fetal development, with implications for postnatal function. Results also support the notion that, for both sexes, individual differences in regulation emerge prenatally and are maintained into infancy. Collectively, these findings underscore the utility of direct assessment of development in utero when examining if prenatal experiences are carried forward into postnatal life.

406 Maternal nutrition during early gestation: Impacts on developmental outcomes

Abstract Changes in maternal nutrition that represent inadequacies or excesses in nutrient supply have been implicated in altered fetal development as well as offspring outcomes and have been termed fetal or developmental programming. Research in the area of developmental programming of livestock has greatly increased during the last two decades. For ruminants, most research efforts in developmental programming have focused on nutritional perturbations during the last two-thirds of gestation. Unfortunately, research investigating changes to maternal nutrient supply during early gestation or even periconceptually has been limited. The objectives of this invited review are to provide a summary of our current understanding of the impacts of inappropriate maternal nutrition during early gestation on embryo-fetal and offspring developmental outcomes. Nutrient supply to the conceptus varies during the time of early placental and conceptus development, and uterine glandular secretions, often called uterine milk or uterine histotroph, are major suppliers of nutrients during this time. Nutrients in histotroph are essential to conceptus development, and histotroph nutrient concentrations may be responsive to maternal nutrient supply. As the placenta develops and becomes fully functional, fetal nutrient supply becomes dependent on placental function. Research investigating changes in total maternal nutrient supply, even during early gestation, has clearly demonstrated impacts on offspring outcomes. Investigations into supply of specific nutrients and development outcomes have increased rapidly in recent years with results demonstrating that in some cases, even small changes in supply can have consequences on offspring development. Underlying mechanisms of developmental programming are associated with epigenetic events partially driven by methyl donors and cofactors. Emerging knowledge associated with the influence of periconceptual, fetal, and neonatal nutrition on offspring development, postnatal health, function, and productivity is creating opportunities for enhanced livestock production through strategic nutrient supplementation.

Maternal periconceptual nutrition, early pregnancy, and developmental outcomes in beef cattle.

The focus of this review is maternal nutrition during the periconceptual period and offspring developmental outcomes in beef cattle, with an emphasis on the first 50 d of gestation, which represents the embryonic period. Animal agriculture in general, and specifically the beef cattle industry, currently faces immense challenges. The world needs to significantly increase its output of animal food products by 2050 and beyond to meet the food security and agricultural sustainability needs of the rapidly growing human population. Consequently, efficient and sustainable approaches to livestock production are essential. Maternal nutritional status is a major factor that leads to developmental programming of offspring outcomes. Developmental programming refers to the influence of pre-and postnatal factors, such as inappropriate maternal nutrition, that affect growth and development and result in long-term consequences for health and productivity of the offspring. In this review, we discuss recent studies in which we and others have addressed the questions, "Is development programmed periconceptually?" and, if so, "Does it matter practically to the offspring in production settings?" The reviewed studies have demonstrated that the periconceptual period is important not only for pregnancy establishment but also may be a critical period during which fetal, placental, and potentially postnatal development and function are programmed. The evidence for fetal and placental programming during the periconceptual period is strong and implies that research efforts to mitigate the negative and foster the positive benefits of developmental programming need to include robust investigative efforts during the periconceptual period to better understand the implications for life-long health and productivity.

Maternal exposure to mixtures of dienestrol, linuron and flutamide. Part II: Endocrine-related gene expression assessment on male offspring rat testes

Exposure to endocrine-disrupting compounds (EDCs) during pregnancy and early development can lead to adverse developmental outcomes in offspring. One of the endpoints of concern is feminization. The present study aimed to investigate for any possible correlations with endocrine sensitive parameters in the testes of male rat offspring following dam exposure to three EDCs by assessing the expression of endocrine-related genes. Dienestrol (DIES) [0.37–6.25 μg/kg bw/day], linuron (LIN) [1.5–50 mg/kg bw/day], flutamide (FLU) [3.5–50 mg/kg bw/day] as well as their binary mixtures were administered to sexually mature female rats from gestation day (GD) 6 until postnatal day (PND) 21. Gene expression analysis of Star, Cyp11a1, Cyp17a1, Hsd3b2, Pgr and Insl3 was performed by RT-qPCR. Administration of the anti-androgen FLU alone significantly upregulated Cyp11a1 and Cyp17a1 gene expression while administration of LIN and DIES alone did not alter significantly gene expression. The effects of the binary mixtures on gene expression were not as marked as those seen after single compound administrations. Deregulation of Cyp17a1 in rat pup testis, following administration of FLU alone or in mixtures to dams, was significantly correlated with the observed feminization endpoints in male pups.

Specific domains of early parenting, their heritability and differential association with adolescent behavioural and emotional disorders and academic achievement

Variations in parenting across large populations have rarely been described. It also remains unclear which specific domains of parenting are important for which specific offspring developmental outcomes. This study describes different domains of early parenting behaviours and their genetic heritability, then determines the extent to which specific domains of parenting are associated with later offspring outcomes. Parenting behaviours (birth to 3 years) were extracted from self-reported questionnaires administered to 12,358 mothers from the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children and modelled as a latent factor using Confirmatory Factor Analysis. Genetic heritability and correlations between parenting factors were estimated using genome-wide complex trait analysis. Three parenting factors were derived: parental enjoyment, conflictual relationships and stimulation; all showed low genetic heritability. There was no evidence of association between parental enjoyment and offspring behavioural disorders and depressed mood. Stimulation was associated with better English grades (standardised β = 0.195, p < 0.001) and enjoyment was negatively associated with English grades (β = − 0.244, p =  < 0.001). Conflictual relationships were associated with higher risk of offspring behavioural disorders (β = 0.228, p = 0.010) and depressed mood (β = 0.077, p = 0.005). Higher enjoyment reduced the association between conflict and behavioural problems (interaction term β = 0.113, p < 0.001). We found evidence for predictive specificity of early parenting domains for offspring outcomes in adolescence. Early stimulation, unlike enjoyment, promoted later educational achievement. Conflictual relationships were associated with greater risk of behavioural problems, buffered by increased enjoyment. These findings hold implications for parenting interventions, guiding their focus according to the specificity of parenting domains and their long-term outcomes in children.

Pregnancy anxiety in expectant mothers predicts offspring negative affect: The moderating role of acculturation

BackgroundPregnancy anxiety predicts adverse developmental outcomes in offspring from infancy through late childhood, but studies have not examined associations with outcomes in early childhood, nor clarified ethnic or cultural variations in these processes. Aims(1) To examine differences in pregnancy anxiety and related concerns between non-Hispanic White women, Latina women who prefer to speak in English, and Latinas who prefer Spanish; (2) To test prospective associations between pregnancy anxiety and child negative affect and moderation by ethnicity and language preference, used as a proxy for acculturation. Study design and methodsThis longitudinal study included 95 women (40 Non-Hispanic Whites, 31 Spanish-preference Latinas, and 24 English-preference Latinas). Language preference was provided at study entry. Pregnancy anxiety was assessed in the second and third trimesters of pregnancy with two standardized measures. Mothers reported child negative affect at age 4. ResultsSpanish-preference Latinas had significantly more pregnancy-related anxiety about their health and safety in childbirth and concerning the medical system compared to English-preference Latinas and non-Hispanic White women. Adjusting for covariates, pregnancy anxiety in the second trimester, though not the third trimester, predicted significantly higher child negative affect in the full sample. A significant moderation effect indicated that the association was strongest among the lower acculturated Latinas, i.e., those who preferred Spanish. ConclusionThese results document higher risk for offspring associated with pregnancy anxiety in the second trimester especially among less acculturated Latina women, and suggest the need for culturally-sensitive screening tools and interventions to improve outcomes for Latina mothers and their children.

Prenatal concentrations of perfluoroalkyl substances and bone health in British girls at age 17.

PFAS are used to make protective coatings on common household products. Prenatal exposures have been associated with developmental outcomes in offspring. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the association between prenatal concentrations of PFAS and bone health in girls at 17years of age and whether body composition can explain any associations. We measured concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) in maternal serum samples collected during pregnancy. We obtained bone health outcomes in the girls, such as bone mineral density, bone mineral content, bone area, and area-adjusted bone mineral content from whole-body dual-energy X-ray absorptiometry (DXA) scans. We used multivariable linear regression to explore associations between each PFAS and each bone health outcome with adjustment for important confounders such as girls' age at clinic visit, maternal education, and gestational age at sample collection. We also controlled for girls' height and lean mass to explore the role body composition had on observed associations. Prenatal PFOS, PFOA, PFHxS, and PFNA concentrations were associated with inverse effects on bone size and mass after adjusting for important confounders. Conversely, PFNA was positively associated with area-adjusted bone mineral content. However, most significant associations attenuated after additional controlling for height and lean mass. Prenatal concentrations of some PFAS may be associated with reduced bone mass and size in adolescent girls, although it is not clear whether these associations are driven by body size.

Timing of prenatal exposure to trauma and altered placental expressions of hypothalamic-pituitary-adrenal axis genes and genes driving neurodevelopment.

Prenatal maternal stress increases the risk for negative developmental outcomes in offspring; however, the underlying biological mechanisms remain largely unexplored. In the present study, alterations in placental gene expression associated with maternal stress were examined to clarify the potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating foetal hypothalamic-pituitary-adrenal axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy. Objective prenatal traumatic stress was defined as whether mothers were exposed to Superstorm Sandy during pregnancy. Among the 275 mother-infant dyads, 181 dyads were delivered before Superstorm Sandy (ie, Control), 66 dyads were exposed to Superstorm Sandy during the first trimester (ie, Early Exposure) and 28 were exposed to Superstorm Sandy during the second or third trimester (ie, Mid-Late Exposure). Across all trimesters, expression of HSD11B2, MAOA, ZNF507 and DYRK1A was down-regulated among those exposed to Superstorm Sandy during pregnancy. Furthermore, trimester-specific differences were also observed: exposure during early gestation was associated with down-regulation of HSD11B1 and MAOB and up-regulation of CRHBP; exposure during mid-late gestation was associated with up-regulation of SRD5A3. The findings of the present study suggest that placental gene expression may be altered in response to traumatic stress exposure during pregnancy, and the susceptibility of these genes is dependent on the time of the exposure during pregnancy. Further studies should aim to clarify the biological mechanisms that underlie trimester-specific exposure by evaluating the differential impact on offspring neurodevelopment later in childhood.

Maternal and nourishment factors interact to influence offspring developmental trajectories in social wasps.

The social and nutritional environments during early development have the potential to affect offspring traits, but the mechanisms and molecular underpinnings of these effects remain elusive. We used Polistes fuscatus paper wasps to dissect how maternally controlled factors (vibrational signals and nourishment) interact to induce different caste developmental trajectories in female offspring, leading to worker or reproductive (gyne) traits. We established a set of caste phenotype biomarkers in P. fuscatus females, finding that gyne-destined individuals had high expression of three caste-related genes hypothesized to have roles in diapause and mitochondrial metabolism. We then experimentally manipulated maternal vibrational signals (via artificial 'antennal drumming') and nourishment levels (via restricted foraging). We found that these caste-related biomarker genes were responsive to drumming, nourishment level or their interaction. Our results provide a striking example of the potent influence of maternal and nutritional effects in influencing transcriptional activity and developmental outcomes in offspring.

Associations Between the KIAA0319 Dyslexia Susceptibility Gene Variants, Antenatal Maternal Stress, and Reading Ability in a Longitudinal Birth Cohort.

Maternal stress during pregnancy has been associated with detrimental cognitive developmental outcomes in offspring. This study investigated whether antenatal maternal perceived stress and variants of the rs12193738 and rs2179515 polymorphisms on the KIAA0319 gene interact to affect reading ability and full-scale IQ (FSIQ) in members of the longitudinal Auckland Birthweight Collaborative study. Antenatal maternal stress was measured at birth, and reading ability was assessed at ages 7 and 16. Reading data were available for 500 participants at age 7 and 479 participants at age 16. FSIQ was measured at ages 7 and 11. At age 11, DNA samples were collected. Analyses of covariance revealed that individuals with the TT genotype of the rs12193738 polymorphism exposed to high maternal stress during pregnancy possessed significantly poorer reading ability (as measured by Woodcock-Johnson Word Identification standard scores) during adolescence compared with TT carriers exposed to low maternal stress. TT carriers of the rs12193738 SNP also obtained lower IQ scores at age 7 than C allele carriers. These findings suggest that the KIAA0319 gene is associated with both reading ability and general cognition, but in different ways. The effect on IQ appears to occur earlier in development and is transient, whereas the effect of reading ability occurs later and is moderated by antenatal maternal stress. Copyright © 2016 John Wiley & Sons, Ltd.

Determining Effects of Maternal Methyl Donor Nutrient Deficiency and DNA Sequence Differences on Methylation Potential and Offspring Developmental Outcomes

Methyl donor nutrients folate, choline, betaine, methionine, and vitamin B12 play a critical role in epigenetic modifications. These nutrients and their metabolites carry methyl groups required for generating S‐adenosylmethionine (SAM), the major methyl group contributor for DNA and histone methylation. Here, we assess the role of maternal dietary methyl donor deficiency with and without antibiotic (succinyl sulfathiozole, 1% SS) in determining methylation potential and offspring developmental outcomes. We also assess the role of cis‐acting DNA sequences in determining DNA methylation outcomes in response to methyl donor deficiency using mouse lines carrying mutations at the growth‐regulating H19/Igf2 imprinted domain compared to wild type C57BL/6J (B6) mice. Mice were treated with four diet groups (1) Methyl Sufficient (MS), (2) MS+1%SS, (3) Methyl Deficient (MD) and (4) MD+1%SS for 5 weeks before pregnancy and throughout gestation. We observed a significant decrease in the plasma folate levels of mice within the MD group compared to MS in the presence or absence of 1% SS. However, 1% SS alone did not cause significant reduction in plasma folate levels in mice fed the MS diet. Average liver SAM levels were significantly lower in MD groups compared with MS diet group only in the presence of the antibiotic. Liver SAH levels and SAM/SAH ratios remained relatively constant across the 4 different diet groups. Despite the significant reduction in maternal plasma folate levels, dietary methyl deficiency alone did not affect average litter size or male to female ratios. However, addition of antibiotic (1% SS) in the respective diets led to a significant decline in average litter size and litter success. Both methyl sufficient diets had a larger percentage of litter surviving till weaning as compared to the methyl deficient diets. Effects of the methyl depleted diet alone had insignificant effects on development while the presence of the antibiotic (1% SS) in the diet significantly altered pup body weight at postnatal day 5 (PND5) and PND21. Adult (8 wk) body weights were seemingly unaffected while testes weight mirrored body weight even after correction. Interestingly, dietary effects on body weight were inversely affected when mutant lines were compared to wild‐type lines. In conclusion, a maternal methyl donor deficient diet likely leads to a decrease in methylation potential due to lower plasma folate and liver SAM levels. Phenotypic outcomes are influenced by an aggregate effect of dietary deficiency, antibiotic treatment and maternal genotype. Studies are ongoing to determine the effect of methyl donor deficiency on epigenetic reprogramming and gene expression at imprinted loci across the genome. These effects will be further characterized to determine whether there is an additional role of 1% SS in the diet and whether genetic changes in cis influences susceptibility to epigenetic outcomes.