The effects of heat stress on intrauterine development, reproductive function, and ovarian gene expression of F1 female mice as well as gene expression of F2 embryos†.

Exposure to heat stress (HS) in utero was postulated to trigger an adaptive molecular response that can be transmitted to the next generation. Hence, this study assessed the impact of HS exposure at different stages of the gestational period of mice on the female F1 population and their offspring. Heat stress exposure (41°C and 65% relative humidity-RH) occurred during the first half (FP), the second half (SP), or the entire pregnancy (TP). A control group (C) was maintained in normothermic conditions (25°C, 45% RH) throughout the experiment. Heat stress had a significant negative effect on intrauterine development, mainly when HS exposure occurred in the first half of pregnancy (FP and TP groups). Postnatal growth of FP and TP mice was hindered until 4 weeks of age. The total number of follicles per ovary did not vary (P > 0.05) between the control and HS-exposed groups. Mean numbers of primordial follicles were lower (P < 0.05) in the sexually mature FP than those in SP and TP F1 females. However, the mean number of viable embryos after superovulation was lower (P < 0.05) in TP compared with C group. The expression of genes associated with physiological and cellular response to HS, autophagy, and apoptosis was significantly affected in the ovarian tissue of F1 females and F2 in vivo-derived blastocysts in all HS-exposed groups. In conclusion, exposure to HS during pregnancy compromised somatic development and reproductive parameters as well as altered gene expression profile that was then transmitted to the next generation of mice.

Programming the next generation of prenatal programming of stress research: A review and suggestions for the future of the field.

In this article, I highlight core ideas, empirical findings, and advances in the study of how stress during pregnancy may prenatally program child neurodevelopmental, psychopathological, and health outcomes, emphasizing reviews, metanalyses, and recent contributions of conceptual and empirical work. The article offers a perspective on the history of this area of science, the underrecognized contributions of influential scholars from diverse fields of study, what we know from the evidence to date, the persistent challenges in sorting through what is left to learn, and suggestions for future research. I include sections focused on promoting resilience, pregnancy interventions that demonstrate positive effects across two generations, and the translational implications of the accruing data for practice and policy, highlighting opportunities for integrating across a range of fields and sectors. In the concluding sections, I discuss lessons learned from conducting this work and provide a closing summary of progress and future directions. The goal of this writing was to provide a viewpoint on some ways that emerging intergenerational transmission scholars might responsibly contribute to the future of the field of developmental psychopathology.

Maternal early life and prenatal stress in relation to birth outcomes in Argentinian mothers.

Environmental influences before and during pregnancy significantly impact offspring development. This study investigates open research questions regarding the associations between maternal early life stress (ELS), prenatal psychosocial stress, prenatal hair cortisol (HC), and birth outcomes in Argentinian women. Data on ELS, prenatal life events, HC (two samples representing first and second half of pregnancy), and birth outcomes were collected from middle-class Argentinian women (N = 69) upon delivery. Linear mixed models indicated that HC increased from the first half to the second half of pregnancy with considerable variability in the starting values and slopes between individuals. Mothers who experienced more ELS, were taller, or more educated, tended to show lower increases in HC. Older age was positively related to HC increases. Our data did not suggest an interaction between ELS and prenatal life events in relation to HC. We found that the change in HC was most likely negatively associated with birth weight. Our data are most compatible with either a weak or the absence of an association between ELS or prenatal life events and absolute values of HC. Mothers with stronger increases in hair cortisol tended to have newborns with slightly lower birth weight. Hence, ELS and birthweight may either have been related to changes in cortisol exposure during pregnancy or to factors that influence accumulation or retention of cortisol in hair.

Negative emotionality as a candidate mediating mechanism linking prenatal maternal mood problems and offspring internalizing behaviour.

Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother-infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament.

Parental sensitivity modifies the associations between maternal prenatal stress exposure, autonomic nervous system functioning and infant temperament in a diverse, low-income sample.

Evidence suggests that adversity experienced during fetal development may shape infant physiologic functioning and temperament. Parental sensitivity is associated with child stress regulation and may act as a buffer against risk for intergenerational health effects of pre- or postnatal adversity. Building upon prior evidence in a racially and ethnically diverse sample of infants (M infant age = 6.5 months) and women of low socioeconomic status, this study examined whether coded parenting sensitivity moderated the association between an objective measure of prenatal stress exposures (Stressful Life Events (SLE)) and infant parasympathetic (respiratory sinus arrhythmia; RSA) or sympathetic (pre-ejection period; PEP) nervous system functioning assessed during administration of the Still-Face-Paradigm (SFP) (n = 66), as well as maternal report of temperament (n = 154). Results showed that parental sensitivity moderated the associations between prenatal stress exposures and infant RSA reactivity, RSA recovery, PEP recovery, and temperamental negativity. Findings indicate that greater parental sensitivity is associated with lower infant autonomic nervous system reactivity and greater recovery from challenge. Results support the hypothesis that parental sensitivity buffers infants from the risk of prenatal stress exposure associations with offspring cross-system physiologic reactivity and regulation, potentially shaping trajectories of health and development and promoting resilience.

Impact of angiotensin II receptor antagonism on the sex-selective dysregulation of cardiovascular function induced by in utero dexamethasone exposure.

In utero exposure to glucocorticoids in late gestation programs changes in cardiovascular function. The objective of this study was to determine the degree to which angiotensin II mediates sex-biased changes in autonomic function as well as basal and stress-responsive cardiovascular function following in utero glucocorticoid exposure. Pregnant rats were administered the synthetic glucocorticoid dexamethasone (Dex; 0.4 mg/kg/day sc) or vehicle on gestation days 18-21. Mean arterial pressure, heart rate, and heart rate variability (HRV) were measured via radiotelemetry in freely moving, conscious adult rats. To evaluate the impact of stress, rats were placed in a restraint tube for 20 min. In a separate cohort of rats, restraint stress was performed before and after chronic treatment with the angiotensin type 1 receptor antagonist, losartan (30 mg/kg/day ip). Frequency domain analysis of HRV was evaluated, and data were integrated into low-frequency (LF, 0.20-0.75 Hz) and high-frequency (HF, 0.75-2.00 Hz) bands. Prenatal Dex resulted in an exaggerated pressor and heart rate response to restraint in female offspring that was attenuated by prior losartan treatment. HF power was higher in vehicle-exposed female rats compared with Dex females. Following losartan, HF power was equivalent between female vehicle and Dex-exposed rats. In utero exposure to Dex produced female-biased alterations in stress-responsive cardiovascular function, which may be indicative of a reduction in parasympathetic activity. Moreover, these findings suggest this autonomic dysregulation may be mediated, in part, by long-term changes in renin-angiotensin signaling.NEW & NOTEWORTHY Our findings reveal the involvement of angiotensin II on sex-selective cardiovascular function and autonomic changes in adult offspring exposed to dexamethasone during the last 4 days of gestation. We show that angiotensin II receptor blockade reverses the exaggerated pressor and heart rate response to acute restraint stress and the autonomic dysregulation observed in female, but not male, offspring exposed to dexamethasone in utero.

Effect of prenatal glucocorticoids and thyroid hormones on developmental plasticity of mitochondrial aerobic metabolism, growth and survival: an experimental test in wild great tits.

Developmental plasticity is partly mediated by transgenerational effects, including those mediated by the maternal endocrine system. Glucocorticoid and thyroid hormones may play central roles in developmental programming through their action on metabolism and growth. However, the mechanisms by which they affect growth and development remain understudied. One hypothesis is that maternal hormones directly affect the production and availability of energy-carrying molecules (e.g. ATP) by their action on mitochondrial function. To test this hypothesis, we experimentally increased glucocorticoid and thyroid hormones in wild great tit eggs (Parus major) to investigate their impact on offspring mitochondrial aerobic metabolism (measured in blood cells), and subsequent growth and survival. We show that prenatal glucocorticoid supplementation affected offspring cellular aerobic metabolism by decreasing mitochondrial density, maximal mitochondrial respiration and oxidative phosphorylation, while increasing the proportion of the maximum capacity being used under endogenous conditions. Prenatal glucocorticoid supplementation only had mild effects on offspring body mass, size and condition during the rearing period, but led to a sex-specific (females only) decrease in body mass a few months after fledging. Contrary to our expectations, thyroid hormone supplementation did not affect offspring growth or mitochondrial metabolism. Recapture probability as juveniles or adults was not significantly affected by prenatal hormonal treatment. Our results demonstrate that prenatal glucocorticoids can affect post-natal mitochondrial density and aerobic metabolism. The weak effects on growth and apparent survival suggest that nestlings were mostly able to compensate for the transient decrease in mitochondrial aerobic metabolism induced by prenatal glucocorticoids.

Prenatal Hypoxia Affects Foetal Cardiovascular Regulatory Mechanisms in a Sex- and Circadian-Dependent Manner: A Review.

Prenatal hypoxia during the prenatal period can interfere with the developmental trajectory and lead to developing hypertension in adulthood. Prenatal hypoxia is often associated with intrauterine growth restriction that interferes with metabolism and can lead to multilevel changes. Therefore, we analysed the effects of prenatal hypoxia predominantly not associated with intrauterine growth restriction using publications up to September 2021. We focused on: (1) The response of cardiovascular regulatory mechanisms, such as the chemoreflex, adenosine, nitric oxide, and angiotensin II on prenatal hypoxia. (2) The role of the placenta in causing and attenuating the effects of hypoxia. (3) Environmental conditions and the mother's health contribution to the development of prenatal hypoxia. (4) The sex-dependent effects of prenatal hypoxia on cardiovascular regulatory mechanisms and the connection between hypoxia-inducible factors and circadian variability. We identified that the possible relationship between the effects of prenatal hypoxia on the cardiovascular regulatory mechanism may vary depending on circadian variability and phase of the days. In summary, even short-term prenatal hypoxia significantly affects cardiovascular regulatory mechanisms and programs hypertension in adulthood, while prenatal programming effects are not only dependent on the critical period, and sensitivity can change within circadian oscillations.

Maternal Interleukin-6 Hampers Hippocampal Neurogenesis in Adult Rat Offspring in a Sex-Dependent Manner.

Maternal immune activation (MIA) during pregnancy leads to long-lasting effects on brain development and function. Several lines of evidence suggest that the maternal inflammatory cytokine interleukin (IL)-6 plays a crucial role in the long-lasting effects of MIA on adult offspring. IL-6 is naturally produced during pregnancy in the absence of any underlying immune activation. The objective of this study was to assess whether this naturally occurring IL-6 has long-lasting effects on brain plasticity and function. Therefore, pregnant rats were given either an IL-6-neutralizing antibody (IL-6Ab) or vehicle during the third week of pregnancy. Newly born (doublecortin) and mature neurons (NeuN) were monitored in the hippocampus of adult male and female offspring. Prenatal IL-6Ab led to an enhanced number of newly born and mature neurons in the dentate gyrus of the hippocampus of male but not female adult offspring. This enhanced neurogenesis was associated with an increased propensity in memory acquisition in male offspring. Blunting the naturally occurring IL-6 during pregnancy did not have a significant long-lasting impact on astrocyte cell density (GFAP), or on anxiety-like behavior as assessed with elevated plus maze and open field tests. Taken together, these data suggest that maternal IL-6 contributes, at least in part, to the programming of the brain's development in a sex-dependent manner.

Maternally derived hormones, neurosteroids and the development of behaviour.

In a wide range of taxa, there is evidence that mothers adaptively shape the development of offspring behaviour by exposing them to steroids. These maternal effects have major implications for fitness because, by shaping early development, they can permanently alter how offspring interact with their environment. However, theory on parent-offspring conflict and recent physiological studies showing that embryos rapidly metabolize maternal steroids have placed doubt on the adaptive significance of these hormone-mediated maternal effects. Reconciling these disparate perspectives requires a mechanistic understanding of the pathways by which maternal steroids can influence neural development. Here, we highlight recent advances in developmental neurobiology and psychiatric pharmacology to show that maternal steroid metabolites can have direct neuro-modulatory effects potentially shaping the development of neural circuitry underlying ecologically relevant behavioural traits. The recognition that maternal steroids can act through a neurosteroid pathway has critical implications for our understanding of the ecology and evolution of steroid-based maternal effects. Overall, compared to the classic view, a neurosteroid mechanism may reduce the evolutionary lability of hormone-mediated maternal effects owing to increased pleiotropic constraints and frequently influence long-term behavioural phenotypes in offspring.

Maternal Stress During Pregnancy Predicts Infant Infectious and Noninfectious Illness.

OBJECTIVES: To examine the association between prenatal stress and infant physical health in the first year of life within an understudied, racially and ethnically diverse, highly stressed community sample. We expected that greater stress exposure would predict higher rates of infant illness. STUDY DESIGN: Low-income, racially/ethnically diverse, overweight women with low medical risk pregnancies were recruited (2011-2014) during pregnancy. Pregnancy Stressful Life Events were assessed retrospectively (mean, 11.88 months postpartum). Perceived stress was assessed twice during pregnancy (at a mean of 17.4 weeks and again at a mean of 25.6 weeks) and at 6 months postpartum. Women with live births (n = 202) were invited; 162 consented to the offspring study. Medical records from pediatric clinics and emergency departments for 148 infants were abstracted for counts of total infectious illnesses, total noninfectious illness, and diversity of illnesses over the first year of life. RESULTS: The final analytic sample included 109 women (mean age, 28.08 years) and their infants. In covariate-adjusted negative binomial models, maternal perceptions of stress across pregnancy were positively associated with infant illness. Each 1-point increase in average stress was associated with a 38% increase in incidence of infant infections (Incidence rate ratio, 1.38; 95% CI, 1.01-1.88; P < .05), a 73% increase in noninfectious illness (IRR, 1.73; 95% CI, 1.34-2.23; P < .05), and a 53% increase in illness diversity (IRR, 1.53; 95% CI, 1.25, 1.88; P < .01); effect sizes were larger for perceived stress later in pregnancy. Stressful life events count and postnatal stress were not uniquely associated with illness. CONCLUSIONS: In line with recommendations from the American Academy of Pediatrics to screen for maternal perinatal depression, screening and support for stress reduction during pregnancy may benefit both maternal and child health.

Nutritional and weight status of Indian mother-child dyads experienced by a natural disaster.

Natural disasters have detrimental effects not only on local infrastructure in an affected population but may also have an impact on the human biological condition, particularly during critical periods of life. This study aimed to assess the nutritional and weight status of women and their children who had experienced cyclone Aila prenatally and postnatally in comparison with a non-affected neighbouring group. The study sample involved N = 597 dyads consisting of mothers and their prepubertal children prenatally or postnatally (during infancy) exposed to a natural disaster and a control group from a neighbouring region (West Bengal, India). The analysed anthropometric indices involved body mass index (BMI) and mid-upper arm circumference (MUAC). Moreover, several socioeconomic characteristics were collected (mother's and father's education, family size and family income). Analyses revealed that the group factor (Aila-exposed or non-exposed groups) had the highest impact on both children's and their mothers' BMI and MUAC (p < 0.001) in comparison with socioeconomic variables. Surprisingly, both mothers and their children revealed deteriorated nutritional and relative weight status several years after the occurrence of cyclone Aila, which is in opposition to the results obtained in developed countries, where prenatal maternal stress caused by the natural disaster led to the subsequent higher risk of excessive weight in affected children.

Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder.

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men.

Maternal Pregnancy Diet Quality Is Directly Associated with Autonomic Nervous System Function in 6-Month-Old Offspring.

BACKGROUND: Many pregnant women are consuming diets of poor overall quality. Although many studies have linked poor prenatal diet quality to an increased risk of specific diseases in offspring, it is not known if exposure to poor prenatal diet affects core neurophysiological regulatory systems in offspring known to lie upstream of multiple diseases. OBJECTIVE: We aimed to examine the association between prenatal diet quality and autonomic nervous system (ANS) function in infants at 6 mo of age. METHODS: Data from 400 women (aged >18 y, with uncomplicated pregnancies) and their infants participating in the Maternal-Infant Research on Environmental Chemicals-Infant Development cohort were used to investigate links between prenatal diet quality and infant ANS function at 6 mo of age. Prenatal diet quality was assessed using the Healthy Eating Index (2010), calculated from a validated FFQ completed by women during the first trimester. Infant ANS function was measured using 2 assessments of heart rate variability (HRV) including root mean square of successive differences (RMSSD) and SD of N-N intervals (SDNN). Associations were analyzed before and after adjustment for socioeconomic status, maternal depression symptoms, maternal cardiometabolic dysfunction, breastfeeding, and prenatal smoking. RESULTS: Poorer prenatal diet quality was associated with lower infant HRV assessed using RMSSD (B: 0.07; 95% CI: 0.01, 0.13; R2 = 0.013) and SDNN (B: 0.18; 95% CI: 0.02, 0.35; R2 = 0.011). These associations remained significant after adjustment for confounding variables [RMSSD: B: 0.09; 95% CI: 0.003, 0.18; squared semipartial correlation (sp2) = 0.14 and SDNN B: 0.24; 95% CI: 0.0, 0.49; sp2 = 0.13]. CONCLUSIONS: In a large cohort study, poorer prenatal diet quality was associated with lower offspring HRV, a marker of decreased capacity of the ANS to respond adaptively to challenge. Therefore, poor prenatal diet may play a significant role in the programming of multiple organ systems and could increase general susceptibility to disease in offspring.

Developmental programming of shyness: A longitudinal, prospective study across four decades.

Although shyness is a ubiquitous phenomenon with early developmental origins, little research has examined the influence of prenatal exposures on the developmental trajectory of shyness. Here, we examined trajectories of shyness from childhood to adulthood in three groups (N = 254), with varying degrees of prenatal adversity as indicated by the number of stressful exposures: extremely low birth weight (ELBW; <1000 g) survivors prenatally exposed to exogenous corticosteroids (ELBW+S, n = 56); ELBW survivors not prenatally exposed to exogenous corticosteroids (ELBW+NS, n = 56); and normal birth weight (NBW, n = 142) controls. Multilevel modeling revealed that the ELBW+S individuals exhibited the highest levels of childhood shyness, which remained stable into adulthood. The ELBW+NS and NBW controls had comparably low levels of childhood shyness; however, the ELBW+NS individuals experienced patterns of increasing shyness, while NBW controls displayed decreases in shyness into adulthood. We speculate that individuals exposed to multiple prenatal stressors (i.e., ELBW+S) may be developmentally programmed to be more sensitive to detecting social threat, with one manifestation being early developing, stable shyness, while increasing shyness among ELBW+NS individuals may reflect a later developing shyness influenced by postnatal context. We discuss the implications of these findings for understanding the developmental origins and developmental course of human shyness from childhood through adulthood.

Pregnancy as a period of risk, adaptation, and resilience for mothers and infants.

The pregnancy period represents a unique window of opportunity to identify risks to both the fetus and mother and to deter the intergenerational transmission of adversity and mental health problems. Although the maternal-fetal dyad is especially vulnerable to the effects of stress during pregnancy, less is known about how the dyad is also receptive to salutary, resilience-promoting influences. The present review adopts life span and intergenerational perspectives to review four key areas of research. The first part describes how pregnancy is a sensitive period for both the mother and fetus. In the second part, the focus is on antecedents of maternal prenatal risks pertaining to prenatal stress response systems and mental health. The third part then turns to elucidating how these alterations in prenatal stress physiology and mental health problems may affect infant and child outcomes. The fourth part underscores how pregnancy is also a time of heightened fetal receptivity to maternal and environmental signals, with profound implications for adaptation. This section also reviews empirical evidence of promotive and protective factors that buffer the mother and fetus from developmental and adaptational problems and covers a sample of rigorous evidence-based prenatal interventions that prevent maladaptation in the maternal-fetal dyad before babies are born. Finally, recommendations elaborate on how to further strengthen understanding of pregnancy as a period of multilevel risk and resilience, enhance comprehensive prenatal screening, and expand on prenatal interventions to promote maternal-fetal adaptation before birth.

Malnutrition and depression in pregnancy and associations with child behaviour and cognitive function: a review of recent evidence on unique and joint effects 1.

Accumulating studies suggest that prenatal experiences can shape a child's neurodevelopment. Malnutrition and depression occur in pregnancy relatively often and may affect child neurodevelopment independently as well as synergistically. We aimed to provide an overview of recent studies that have examined malnutrition and (or) depression in pregnancy and associations with child behavioural problems and cognitive function. We conducted a literature search in PubMed, using the following main search terms: "depression", "nutrition", "BMI", "pregnancy", "offspring", "cognition", and "behaviour". We included studies in human populations published from 2013 onwards. The literature search yielded 1531 articles, of which 55 were included in the current review. We presented the evidence on the associations between prenatal markers of nutritional status and (or) depression and child behaviour and (or) cognitive function. We additionally discussed interventions and mechanisms. Both malnutrition and depression in pregnancy are associated with increased externalizing behavioural problems and attentional deficits, and to some extent with poorer cognitive function in the child, but the evidence is not conclusive. Studies on synergistic effects of both factors on child behaviour and cognitive function are still scarce, and more research is needed. Potential shared mechanisms include the hypothalamic-pituitary-adrenal axis, the immune system, epigenetics, and oxidative stress.

Maternal Metabolic Complications in Pregnancy and Offspring Behavior Problems at 2 Years of Age.

Objectives Prenatal maternal metabolic problems such as pre-pregnancy adiposity, excess gestational weight gain, and gestational diabetes mellitus (GDM) are associated with an increased risk of psychopathology in offspring. We examined whether these exposures were linked to symptoms of emotional and behavioral problems in offspring at 2 years of age, or if associations were due to confounding variables. Methods Data from 815 mother-child pairs enrolled at the Edmonton site of the Canadian Healthy Infant Longitudinal Development cohort were used to examine associations between gestational metabolic complications and scores on the externalizing and internalizing scales of the Child Behavior Checklist (CBCL-1½ to 5) at age two. Associations between maternal metabolic complications and offspring psychopathology were assessed before and after adjustment for gestational diet, socioeconomic status (SES), postpartum depression (PPD), prenatal smoking and breastfeeding. Results Pre-pregnancy body mass index and GDM, but not gestational weight gain, predicted more offspring externalizing and internalizing problems. However, after adjustment for confounding variables, these associations were no longer statistically significant. Post-hoc analyses revealed that gestational diet accounted for unique variance in both externalizing (semi-partial rdiet = - 0.20, p < 0.001) and internalizing (semi-partial rdiet = - 0.16, p = 0.01) problems. PPD and SES also accounted for a similar amount of variance for both externalizing (semi-partial rPPD = 0.17, p < 0.001; rses = - 0.11, p = 0.03) and internalizing problems (semi-partial rPPD = 0.21, p < 0.001; rses = - 0.14, p = 0.004). Conclusions for Practice Since the confounding effect of gestational diet persisted after adjustment for, and was similar in magnitude to, SES and PPD, future research should consider the impact of unhealthy prenatal diets on offspring neurodevelopment.

Sex differences in frequencies of dermatoglyphic patterns by individual fingers.

Background: The size of sex differences in dermatoglyphic features and their inter-population differences remains a subject of debate. Combining fingers in traditional dermatoglyphic methodology and omitting finger-specific variations might be a cause for uncertainty.Aim: To compare sex differences in whorl frequencies between fingers.Subjects and methods: Using meta-analytical methods, the authors studied sex differences in frequencies of whorls (log Odd Ratios) for each finger separately, including their heterogeneities (between-samples variance). The dataset of 204 population samples was extracted from published dermatoglyphic studies.Results: Aggregated effects of sex differences were significant in all fingers, except for the left 1st finger. Sex differences were higher in the right hand and increased from radial to ulnar fingers. Apart from the right 1st and 3rd fingers, heterogeneities were small and literally zero in the right 4th finger.Conclusion: Higher sex differences in ulnar fingers and the lack of interpopulation differences all over the world in the 4th finger might be caused by a stronger influence of genetic and/or hormonal factors on dermatoglyphic development of the ulnar side of the hand. It is suggested that future studies, when applying dermatoglyphic traits as markers of prenatal environment, use traits by individual fingers or their relationships within the hand.

Gonadotropin-Releasing Hormone in Regulation of Thymic Development in Rats: Profile of Thymic Cytokines.

An increasing body of recent experimental data confirms the impact of neurohormones on fetal development and function of different body systems. The synthesis of many neurohormones starts in fetal tissues before the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal systems are formed, and their high levels are detected in the bloodstream. Here, we studied the role of gonadotropin-releasing hormone (GnRH) in rat thymus development and tried to reveal possible mechanisms underlying the GnRH effects in early development. Western blotting and reverse transcription-polymerase chain reaction allowed us to identify receptor for GnRH in the fetal thymus with peak expression on embryonic days 17-18 (ED17-18). Blocking the receptors in utero on ED17 by a GnRH antagonist suppressed the concanavalin A-induced proliferative response of T cells in adults. GnRH (10-7 M) increased mRNA expression of interleukin (IL)-4, IL-10, IL-1ß, interferon γ (IFNγ), and tumor necrosis factor α (TNFα) in the thymus of 18-day fetuses after an ex vivo culture for 24 h. The increased mRNA levels of the cytokines in the thymus were accompanied by increased numbers of CD4+ T helpers. Overall, the data obtained confirm the regulatory or morphogenetic effect of GnRH on fetal thymus development mediated by synthesis of thymic cytokines.