Maternal stress during pregnancy alters circulating small extracellular vesicles and enhances their targeting to the placenta and fetus.

BACKGROUND: Maternal psychological distress during pregnancy can negatively impact fetal development, resulting in long-lasting consequences for the offspring. These effects show a sex bias. The mechanisms whereby prenatal stress induces functional and/or structural changes in the placental-fetal unit remain poorly understood. Maternal circulating small extracellular vesicles (sEVs) are good candidates to act as "stress signals" in mother-to-fetus communication. Using a repetitive restraint-based rat model of prenatal stress, we examined circulating maternal sEVs under stress conditions and tested whether they could target placental-fetal tissues. RESULTS: Our mild chronic maternal stress during pregnancy paradigm induced anhedonic-like behavior in pregnant dams and led to intrauterine growth restriction (IUGR), particularly in male fetuses and placentas. The concentration and cargo of maternal circulating sEVs changed under stress conditions. Specifically, there was a significant reduction in neuron-enriched proteins and a significant increase in astrocyte-enriched proteins in blood-borne sEVs from stressed dams. To study the effect of repetitive restraint stress on the biodistribution of maternal circulating sEVs in the fetoplacental unit, sEVs from pregnant dams exposed to stress or control protocol were labeled with DiR fluorescent die and injected into pregnant females previously exposed to control or stress protocol. Remarkably, maternal circulating sEVs target placental/fetal tissues and, under stress conditions, fetal tissues are more receptive to sEVs. CONCLUSION: Our results suggest that maternal circulating sEVs can act as novel mediators/modulators of mother-to-fetus stress communication. Further studies are needed to identify placental/fetal cellular targets of maternal sEVs and characterize their contribution to stress-induced sex-specific placental and fetal changes.

Maternal stress increases risk of allergic lung inflammation in adult mice.

BACKGROUND: Allergies are increasing worldwide. The presence of atopic diseases in the mother propagates the onset of allergic diseases in the offspring with a considerably stronger penetrance than atopic diseases of the father. Such observation challenges genetic predispositions as the sole cause of allergic diseases. Epidemiological studies suggest that caregiver stress in the perinatal period may predispose offspring to asthma. Only one group has studied the link between prenatal stress and neonatal asthma susceptibility in a murine model. OBJECTIVES: We aimed to study if the neonatal increased risk of developing allergic lung inflammation persists after puberty and if there are sex differences in susceptibility. METHODS: Pregnant BALB/c mice were subjected to a single restraint stress exposure at day 15 of gestation. Pups were separated by gender and subjected to a well-known sub-optimal asthma model after puberty. RESULTS: Adult mice born to stressed dams were more susceptible to developing allergic pulmonary inflammation since an increase in the number of eosinophils in bronchoalveolar lavage (BAL), a greater peribronchial and perivascular infiltrate, a higher proportion of mucus-producing cells, and increased IL-4 and IL-5 levels in BAL were detected compared to control mice. These effects were more profound in females than males. Moreover, only females from stressed dams showed an increase in IgE levels. CONCLUSIONS: Increased litter susceptibility to develop allergic lung inflammation induced by maternal stress persists after puberty and is more potent in females than in male mice.

An examination of behavioural and emotional problems in children exposed prenatally to the 27F Chilean earthquake: findings from the ELPI cohort.

PURPOSE: Associations between prenatal earthquake exposure and children's mental health remain unclear. Moreover, there is a paucity of research using quasi-experimental statistical techniques to diminish potential selection bias. Thus, this study aimed to explore the impact of prenatal exposure to the Chilean earthquake of 2010 on children's behavioural and emotional problems between 1½ and 3 years old using propensity score matching. METHODS: Participants included 1549 families from the Encuesta Longitudinal de la Primera Infancia cohort in Chile. Maternal reports using the Child Behaviour Checklist (CBCL) were used to assess behavioural and emotional problems between 1½ and 3 years old. Information on prenatal earthquake exposure was collected via maternal report. The Kernel matching estimator was used to compare the average treatment effects of children who were exposed to the earthquake compared to those who were not. RESULTS: Five of the seven CBCL outcomes were statistically significant after matching and adjustment for multiple testing, suggesting greater difficulties for exposed children which included emotional reactivity, anxious/depressed, sleep problems, attention problems, and aggression (mean difference of 0.69, 0.87, 0.73, 0.85, 3.51, respectively). The magnitude of the effect was small to medium. CONCLUSION: Findings contribute to the potential causal inferences between prenatal earthquake exposure and increased behavioural and emotional problems in early childhood. Results suggest that in utero experiences may have long-term consequences for infants' well-being, supporting the need for specific interventions in pregnancy after natural disasters.

Impact of maternal physical exercise on inflammatory and hypothalamic-pituitary-adrenal axis markers in the brain and lungs of prenatally stressed neonatal mice.

This study aimed to evaluate the effects of maternal exercise on alterations induced by prenatal stress in markers of the inflammatory process and the hypothalamic-pituitary-adrenal axis in the brain and lungs of neonatal mice. Female Balb/c mice were divided into three groups: control, prenatal restraint stress, prenatal restraint stress and physical exercise before and during the gestational period. On day 0 (PND0) and 10 (PND10), mice were euthanized for brain and lung analyses. The gene expression of GR, MR, IL-6, IL-10, and TNF in the brain and lungs and the protein expression of MMP-2 in the lungs were analyzed. Maternal exercise reduced IL-6 and IL-10 gene expression in the brain of PND0 mice. Prenatal stress and maternal exercise decreased GR, MR, IL-6, and TNF gene expression in the lungs of PND0 mice. In the hippocampus of PND10 females, exercise inhibited the effects of prenatal stress on the expression of MR, IL-6, and IL-10. In the lungs of PND10 females, exercise prevented the decrease in GR expression caused by prenatal stress. In the hippocampus and lungs of PND10 males, prenatal stress decreased GR gene expression. Our findings confirm the effects induced by prenatal stress and demonstrate that physical exercise before and during the gestational period may have a protective role on inflammatory changes.

Maternal Stress during Pregnancy in Mice Induces Sex-Dependent Behavioral Alterations in Offspring along with Impaired Serotonin and Kynurenine Pathways of Tryptophan Metabolism.

Maternal stress during pregnancy results in increased risk of developing psychiatric disorders in the offspring including anxiety, depression, schizophrenia, and autism. However, the mechanisms underlying this disease susceptibility remain largely to be determined. In this study, the involvement of the serotonin (5-HT) and kynurenine (KYN) pathways of tryptophan metabolism on the behavioral deficits induced by maternal stress during the late phase of gestation in mice was investigated. Adult offspring born to control or restraint-stressed dams were exposed to the elevated plus-maze and tail suspension tests. Metabolites of the KYN and 5-HT pathways were measured in the hippocampus and brainstem by ultra-performance liquid chromatography tandem mass spectrometry. Female, but not male, prenatally stressed (PNS) offspring displayed a depressive-like phenotype, mainly when in proestrus/diestrus, along with reduced hippocampal 5-HT levels and high 5-HT turnover rate in the hippocampus and brainstem. In contrast, male PNS mice showed enhanced anxiety-like behaviors and higher hippocampal and brainstem quinolinic acid levels compared to male offspring born to nonstressed dams. These results indicate that maternal stress affects the behavior and brain metabolism of tryptophan in the offspring in a sex-dependent manner and suggest that alterations in both the 5-HT and KYN pathways may underlie the emotional dysfunctions observed in individuals exposed to stress during in utero development.

Avaliação comportamental da rata gestante após o transporte nos primeiros dias de gestação e cria

Pregnancy is considered a period of big variation to the maternal organism. Besides, the mother is due to stressing influences from the external environment that might intervene in health and mother-fetal wellbeing. Thus, mating in the experimental facility may avoid stress from handling and transporting pregnancy females, assuring full observation over pre and post gestational periods. However, to obtain pregnancy females can avoid loss of animals that cannot get pregnant and prevent acquiring males. This study aimed to determine if there are behavior changings caused by handling and transporting females obtained already pregnant by observing pre and postnatal periods: gestation, lactation, soundness of neonates and their development after weaning verifying alterations that could cause injury for litter growth. Animals were evaluated through neurobehavior tests and results were compared to those previously obtained in studies whose mating was performed in the experimental animal facility. In the handgrip reflex test, an increase in the experimental group of males and females was observed on the 4th day of observation and a decrease on the 8th day, in females. When comparing postural reflex, results didn’t show significant differences. In the results for negative geotaxia, no significant difference was observed among groups, as well as locomotion movement and general activity. Mother’s body weight during pregnancy didn’t present any significative difference for the experimental group related to control group. These results, put together, cannot allow stating significant influence in transporting females in the first stages of pregnancy in Wistar rats.

A gestação é considerada um período de grandes variações no organismo materno. Além disso, a mãe está sujeita às influências estressantes provindas do ambiente externo que podem interferir na saúde e no bem-estar materno-fetal. Assim, o acasalamento feito no próprio biotério de experimentação pode evitar o estresse da manipulação e do transporte da fêmea gestante, garantindo o acompanhamento total do período pré e pós-gestacional. Porém, adquirir fêmeas prenhes pode evitar perdas decorrentes de animais que não conseguem emprenhar e evitar a solicitação de machos. Este estudo buscou determinar se existem alterações comportamentais causadas pela manipulação e transporte em fêmeas adquiridas prenhez a partir do acompanhamento dos períodos pré e pós-natal: gestação, lactação, sanidade dos neonatos e seu desenvolvimento após o desmame para verificação de alterações que possam causar prejuízo no desenvolvimento dos filhotes. Os animais foram avaliados através da realização de testes neurocomportamentais e comparados a resultados obtidos anteriormente em estudos cujo acasalamento fora feito no próprio biotério de experimentação. No teste de reflexo de preensão palmar foi observado um aumento no tempo de realização no grupo experimental em machos e fêmeas no PN4 e diminuição no PN8 em fêmeas. Na comparação dos grupos no reflexo postural os resultados não demonstraram diferença significativa. Os resultados da geotaxia negativa, na comparação dos grupos, não evidenciou nenhuma diferença significativa, tampouco houve diferenças significativas para movimentos de locomoção e na atividade geral. O peso das mães durante o tempo de gestação não apresentou nenhuma diferença significativa do grupo experimental em relação ao grupo controle. Estes resultados, avaliados em conjunto, não nos permitem afirmar que houve uma influência significativa do transporte das fêmeas no estágio inicial da gestação de ratas Wistar.

Anatomía del cuerpo calloso en ratas sometidas a estrés prenatal crónico / Anatomy of corpus callosum in rats submitted to chronic prenatal stress

RESUMEN: El cuerpo calloso (CC), es la mayor comisura de sustancia blanca del encéfalo de los mamíferos placentados, constituida por numerosos haces de fibras transversales que conectan áreas corticales de ambos hemisferios cerebrales. Por otro lado, el estrés se define como una respuesta general del organismo ante demandas externas o internas, inicialmente amenazantes, que consiste en movilizar recursos fisiológicos y psicológicos para poderlas afrontar. Dada la importancia del cuerpo calloso en las conexiones cortico-corticales, el objetivo del presente estudio, fue evaluar el efecto en ratas, de un estrés prenatal crónico por inmovilización, sobre la anatomía macroscópica del CC. Se utilizaron seis ratas preñadas de la cepa Wistar de 250 g, de las cuales tres fueron sometidas, a partir del octavo día postconcepción, a una restricción de movimiento por diez días (2h/día). Posteriormente, las madres prosiguieron su gestación, parto y lactancia. Al nacimiento, las camadas fueron ajustadas a seis crías machos por madre (n=36), destetadas a los 21 días y sacrificadas a los 45-52 días de edad. Los encéfalos fueron seccionados a través de la cisura interhemisférica y ambos hemisferios fotografiados por su cara medial. Las imágenes fueron digitalizadas y analizadas mediante el programa Scion Image®, para la medición del área total, parciales (tercio anterior, medio, posterior y quinto posterior) y perímetro callosal. Es así como, el estrés prenatal por inmovilización, afectó significativamente (p<0,01), la morfología macroscópica del cuerpo calloso. Evidenciándose una disminución del área total, áreas parciales y perímetro callosal, en los animales sometidos a restricción prenatal. Estableciendo una relación directa entre número de axones y área callosal e inversa entre diámetro y densidad axonal; lo observado podría tener incidencia en la transferencia interhemisférica.

SUMMARY: The Corpus Callosum (CC) is the largest white matter commissure in the brain of placental mammals, consisting of numerous transverse fiber bundles that connect cortical areas of both cerebral hemispheres. On the other hand, stress is defined as a general response of the organism to external or internal demands, initially threatening, which consists of mobilizing physiological and psychological resources to be able to face them. Given the importance of CC in cortico-cortical connections, the aim of the present study, was to evaluate the effect of chronic pre-natal immobilization stress on the macroscopic anatomy of CC in rats. Six 250g pregnant rats of the Wistar strain were used, of which three were subjected, starting on the eighth post-conception day, to movement restriction for ten days (2h/day). Subsequently, the mothers continued their gestation, delivery and lactation. At birth, litters were adjusted to six male offspring per mother (n=36), which were weaned at 21 days and slaughtered at 45-52 days of age. The brains were fixed, and later sectioned through the interhemispheric fissure and both hemispheres photographed by their medial aspect. The images were digitized and analyzed using the Scion Image® program, for the measurement of the total area, partial area (ante- rior, middle and posterior thirds, as well as posterior fifth) and callosal perimeter. Thus, prenatal stress due to immobilization significantly affected (p<0.01), the macroscopic morphology of the CC. Evidence shows a decrease in the total area, partial areas and callosal perimeter in the animals subjected to prenatal restraint, as compared to normal animals. Establishing a direct relationship between number of axons and callosal area and an inverse relationship between diameter and axonal density, what was observed may have an impact on interhemispheric transfer.

Prenatal stress promotes insulin resistance without inflammation or obesity in C57BL/6J male mice.

During gestation, stress exposure increases the risk of developing cognitive and physiological alterations in either the long or short term. Among them, metabolic alterations have been described. Adipose tissue is responsible for the secretion of several factors involved in controlling body weight and energy expenditure, the regulation of insulin sensitivity, and the development of inflammation, among others. Moreover, the liver regulates glucose homeostasis and lipid metabolism, playing an essential role in developing insulin resistance. In this work, we analyzed if prenatal stress leads to alterations in metabolism and the relationship between these alterations and gene expression in the adipose tissue and the liver. Prenatal stress-exposed animals developed disturbances in the glucose and insulin response curve, showing in both tests higher glycemia than the control group. However, they did not exhibit increased body weight. At the same time, in the adipose tissue, we observed an increase in mRNA expression of Leptin and Resistin and a decrease in Adiponectin. In the liver, we observed a lower mRNA expression of several genes involved in glucose metabolism and fatty acid oxidation, such as Sirt1, Pgc1α, Pparα, among others. In both tissues, we observed a lower expression of inflammatory genes. These results suggest that prenatal stress exposure produces insulin resistance at both physiological and molecular levels without pro-inflammatory signaling or obesity.

Prenatally stress-exposed male rats present lower theta prefrontal activity during attention behaviors to receptive females.

Prenatal stress affects brain functionality and sexual behavior. The medial prefrontal cortex (mPFC) participates in the integration and processing of sexual stimuli. Electroencephalographic (EEG) theta activity has been associated with attention as well as rewarding and sexually motivated states. Considering that the induction of sexual motivation requires attention to, and the adequate processing of, sexual stimuli, this study aimed to evaluate the effects of exposure to stress during the prenatal period on EEG activity in the mPFC during nose pokes in adulthood, actions which are indicators of attention to a receptive female. Eighteen sexually experienced male rats were used, nine stressed prenatally by immobilization during days 14-21 of gestation (stress-exposed group). The other nine formed the control group. All rats were implanted bilaterally in the mPFC (specifically in prelimbic areas) and were allowed one intromission with a receptive female to induce a sexually motivated state before the experimental session. During this session, both nose pokes and non-contact erections in the male rats were evaluated in the presence of an inaccessible receptive female. EEGs were recorded only during nose pokes. The stress-exposed group presented lower nose poke duration, fewer non-contact erections, and lower relative power of the theta band (4-7 Hz) in both prefrontal areas. Considering that the prevalence of this band is associated with attention and motivational processes, these data confirm the deleterious effect of prenatal stress on attention and sexual activation to sexually relevant stimuli in male rats during adulthood.

Lay summariesPrenatal stress diminishes attention and activation behaviors in receptive females.Prenatal stress decreases prefrontal activation in the presence of receptive females.Prenatal stress decreases prefrontal theta rhythms in male rats.

Early-Life Stress Reprograms Stress-Coping Abilities in Male and Female Juvenile Rats.

Prenatal stress (PS) is a major risk factor for the development of emotional disorders in adulthood that may be mediated by an altered hypothalamic-pituitary-adrenal axis response to stress. Although the early onset of stress-related disorders is recognized as a major public health problem, to date, there are relatively few studies that have examined the incidence of early-life stressors in younger individuals. In this study, we assessed PS impact on the stress-coping response of juvenile offspring in behavioral tests and in the induced molecular changes in the hippocampus. Furthermore, we assessed if pregnancy stress could be driving changes in patterns of maternal behavior during early lactation. We found that PS modified stress-coping abilities of both sex offspring. In the hippocampus, PS increased the expression of bdnf-IV and crfr1 and induced sex difference changes on glucocorticoids and BDNF mRNA receptor levels. PS changed the hippocampal epigenetic landscape mainly in male offspring. Stress during pregnancy enhanced pup-directed behavior of stressed dams. Our study indicates that exposure to PS, in addition to enhanced maternal behavior, induces dynamic neurobehavioral variations at juvenile ages of the offspring that should be considered adaptive or maladaptive, depending on the characteristics of the confronting environment. Our present results highlight the importance to further explore risk factors that appear early in life that will be important to allow timely prevention strategies to later vulnerability to stress-related disorders.

Performance of urine, blood, and integrated metal biomarkers in relation to birth outcomes in a mixture setting.

BACKGROUND: Studies on the health effects of metal mixtures typically utilize biomarkers measured in a single biological medium, such as blood or urine. However, the ability to evaluate mixture effects are limited by the uncertainty whether a unified medium can fully capture exposure for each metal. Therefore, it is important to compare and assess metal mixtures measured in different media in epidemiology studies. OBJECTIVES: The aim of this study was to examine the mixture predictive performance of urine and blood metal biomarkers and integrated multi-media biomarkers in association with birth outcomes. METHODS: In our analysis of 847 women from the Puerto Rico PROTECT Cohort, we measured 10 essential and non-essential metals in repeated and paired samples of urine and blood during pregnancy. For each metal, we integrated exposure estimates from paired urine and blood biomarkers into multi-media biomarkers (MMBs), using intraclass-correlation coefficient (ICC) and weighted quantile sum (WQS) approaches. Using Ridge regressions, four separate Environmental risk scores (ERSs) for metals in urine, blood, MMBICC, and MMBWQS were computed as a weighted sum of the 10 metal concentrations. We then examined associations between urine, blood, and multi-media biomarker ERSs and birth outcomes using linear and logistic regressions, adjusting for maternal age, maternal education, pre-pregnancy body mass index (BMI), and second-hand smoke exposure. The performance of each ERS was evaluated with continuous and tertile estimates and 95% confidence intervals of the odds ratio of preterm birth using area under the curve (AUC). RESULTS: Pb was the most important contributor of blood ERS as well as the two integrated multi-media biomarker ERSs. Individuals with high ERS (3rd tertile) showed increased odds of preterm birth compared to individuals with low ERS (1st tertile), with 2.8-fold (95% CI, 1.49 to 5.40) for urine (specific gravity corrected); 3.2- fold (95% CI, 1.68 to 6.25) for blood; 3.9-fold (95% CI, 1.72 to 8.66) for multi-media biomarkers composed using ICC; and 5.2-fold (95% CI, 2.34 to 11.42) for multi-media biomarkers composed using WQS. The four ERSs had comparable predictive performances (AUC ranging from 0.64 to 0.68) when urine is examined with specific gravity corrected concentrations. CONCLUSIONS: Within a practical metal panel, measuring metals in either urine or blood may be an equally good approach to evaluate the metals as a mixture. Applications in practical study design require validation of these methods with other cohorts, larger panels of metals and within the context of other adverse health effects of interest.

Epigenetics: A Missing Link Between Early Life Stress and Depression.

Exposure to early life stress (ELS) represents a major risk factor for the development of psychiatric disorders, including depression. The susceptibility associated with ELS may result from persistent changes in gene transcription, which can occur through epigenetic mechanisms, such as DNA methylation, histone modifications, and microRNA expression. Animal models and reports in humans described that negative stimuli can alter the neurodevelopment of an individual, affecting their behavior and cognitive development. It is currently hypothesized that levels of environmental adversity in this early developmental period are able to shape the experience-dependent maturation of stress-regulating pathways leading to long-lasting alterations in stress responsivity during adulthood. Here, we review key findings from animal and clinical studies examining the effects of prenatal and postnatal environment in shaping development of the neuroendocrine regulation of stress and the role of epigenetic mechanisms in the predisposition of depression.

Psychosocial status modifies the effect of maternal blood metal and metalloid concentrations on birth outcomes.

BACKGROUND: Metal exposure and psychosocial stress in pregnancy have each been associated with adverse birth outcomes, including preterm birth and low birth weight, but no study has examined the potential interaction between them. OBJECTIVES: We examined the modifying effect of psychosocial stress on the association between metals and birth outcomes among pregnant women in Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) birth cohort study. METHODS: In our analysis of 682 women from the PROTECT study, we measured 16 essential and non-essential metals in blood samples at two time points. We administered questionnaires to collect information on depression, perceived stress, social support, and life experience during pregnancy. Using K-means clustering, we categorized pregnant women into one of two groups: "good" and "poor" psychosocial status. We then evaluated whether the effect of blood metals (geometric average) on adverse birth outcomes (gestational age, preterm birth [overall and spontaneous], birth weight z-score, small for gestation [SGA], large for gestation [LGA]) vary between two clusters of women, adjusting for maternal age, maternal education, pre-pregnancy body mass index (BMI), and second-hand smoke exposure. RESULTS: Blood manganese (Mn) was associated with an increased odds ratio (OR) of overall preterm birth (OR/interquartile range [IQR] = 2.76, 95% confidence interval [CI] = 1.25, 6.12) and spontaneous preterm birth (OR/IQR: 3.68, 95% CI: 1.20, 6.57) only among women with "poor" psychosocial status. The association between copper (Cu) and SGA was also statistically significant only among women having "poor" psychosocial status (OR/IQR: 2.81, 95% CI: 1.20, 6.57). We also observed associations between nickel (Ni) and preterm birth and SGA that were modified by psychosocial status during pregnancy. CONCLUSIONS: Presence of "poor" psychosocial status intensified the adverse associations between Mn and preterm birth, Cu and SGA, and protective effects of Ni on preterm. This provides evidence that prenatal psychosocial stress may modify vulnerability to metal exposure.

Influence of prenatal stress on metabolic abnormalities induced by postnatal intake of a high-fat diet in BALB/c mice.

Prenatal insults during fetal development result in increased likelihood of developing chronic disease. Obesity, the biggest risk factor for the development of metabolic disease, is affected by several genetic and environmental factors. High-fat diet (HFD) consumption is usually linked with the development of obesity. The main goal of this study was to analyze the impact of the exposure to a HFD in prenatally stressed animals. For this purpose, we subjected pregnant BALB/c mice to restraint stress for 2 h a day between gestational day (GD) 14 and GD 21. Prenatally stressed and control offspring of both sexes were postnatally exposed to a HFD for 24 weeks. We found that prenatal stress (PS) per se produced disturbances in males such as increased total blood cholesterol and triglycerides, with a decrease in mRNA expression of sirtuin-1. When these animals were fed a HFD, we observed a rise in glucose and insulin levels and an increase in visceral adipose tissue gene expression of leptin, resistin, and interleukin-1 beta. Although females proved to be more resilient to PS consequences, when they were fed a HFD, they showed significant metabolic impairment. In addition to the changes observed in males, females also presented an increase in body weight and adiposity and a rise in cholesterol levels.

Prenatal Maternal Objective and Subjective Stress Exposures and Rapid Infant Weight Gain.

OBJECTIVES: To evaluate the associations between 3 prenatal stress exposures and rapid infant weight gain. STUDY DESIGN: Participants were 162 maternal-child dyads drawn from a nonrandomized controlled trial evaluating a prenatal intervention for reducing women's stress and excessive gestational weight gain and subsequent longitudinal observational study of offspring outcomes. Participants were predominantly low-income and racial or ethnic minorities, and mothers were overweight or obese prepregnancy. Primary exposures were objective stress exposures (number of stressful life events) and subjective distress (maternal perceived stress and depressive symptoms) during pregnancy. The primary outcome was rapid infant weight gain from birth to 6 months, assessed via birth records and in-person anthropometry measurements. RESULTS: In total, 28% of the sample (N = 40) met criteria for rapid infant weight gain. In adjusted models, exposure to prenatal stressful life events was associated with increased odds of rapid infant weight gain (OR 1.40, 95% CI 1.07-1.83, P = .014). Neither prenatal perceived stress (OR 0.47, 95% CI 0.16-1.37, P = .17) nor depressive symptoms (OR 0.89, 95% CI 0.76-1.03, P = .13) were significantly associated with rapid infant weight gain. CONCLUSIONS: Each additional stressful life event a woman experienced during pregnancy was associated with 40% greater odds of rapid infant weight gain. Future research should evaluate whether prenatal interventions that focus on reducing exposure to stressful events prevent rapid infant weight gain.

Prenatal stress up-regulated hippocampal glucocorticoid receptor expression in female adult rat offspring / Estrés prenatal expresión del receptor de glucocorticoides del hipocampo regulado por aumento en crías de ratas hembras adultas

Accumulating evidence from preclinical and clinical studies indicates prenatal exposure to stress or excess glucocorticoids can affect offspring brain. Glucocorticoid receptor (GR) is an important target of glucocorticoid. Therefore the aim of the present study was to investigate the expression of GR in prenatally stressed adult offspring and the relationship between GR expression and behavior in offspring. Pregnant rats received restraint stress during the last week of pregnancy. Hippocampal glucocorticoid receptor expression levels in the offspring were detected on postnatal 60 (P60).Cognition function was also detected. It shows significantly lower hippocampal GR expression was observed in female prenatally stressed offspring compared with their controls at P60. Corresponding to the expression of GR, female prenatally stressed offspring exhibited poorer spatial learning and memory abilities in the Barnes maze than control, This suggests that cognitive impairment in prenatally stressed rat offspring attribute lower hippocampal GR expression.

La evidencia acumulada de estudios preclínicos y clínicos indica que la exposición prenatal al estrés, o el exceso de glucocorticoides puede afectar el desarrollo cerebral de las crías. El receptor de glucocorticoides (RG) es un objetivo importante de los glucocorticoides. Por lo tanto, el objetivo del presente estudio fue investigar la expresión de RG en crías adultas estresadas durante el período prenatal y la relación entre la expresión de RG y el comportamiento de las crías. Las ratas preñadas recibieron niveles de estrés restringido, durante la última semana de embarazo. Se determinaron niveles de expresión del receptor de glucocorticoides del hipocampo y niveles de función cognitiva en las crías. En comparación con el grupo control se observó una expresión de RG en el hipocampo, significativamente menor en las crías estresadas prenatalmente, en comparación con los controles en P60. En referencia a la expresión de RG, las crías estresadas prenatalmente exhibieron habilidades de memoria y aprendizaje espacial menores, en el laberinto de Barnes que el grupo control. Esto sugiere que el deterioro cognitivo en crías de ratas estresadas prenatalmente muestran una menor expresión de RG en el hipocampo.

Prenatal restraint stress impairs recognition memory in adult male and female offspring.

OBJECTIVE: Accumulating evidence from preclinical and clinical studies indicates that prenatal exposure to stress impairs the development of the offspring brain and facilitates the emergence of mental illness. This study aims to describe the impact of prenatal restraint stress on cognition and exploration to an unfamiliar environment at adulthood in an outbred strain of mice. METHODS: Late pregnant mice were exposed to restraint stress and adult offspring (60 days of age) behaviours were assessed in the object recognition task and open field test. FINDINGS: Prenatal stress (PNS) impaired new object recognition in male and female mice. Importantly, the learning deficits in female PNS mice were linked to their estrous cycle. Actually, PNS females in metestrus/diestrus but not in proestrus/estrus phases displayed recognition deficits compared to controls. Concerning locomotion in an unfamiliar environment, male but not female PNS mice displayed significant increase, but showed no differences in the distance travelled within the centre zone of the arena. CONCLUSION: Present findings support the view that maternal restraint-stress during late pregnancy impairs recognition memory in both male and female offspring, and in females, this cognitive deficit is dependent on the estrous cycle phase. Ultimately, these data reinforce that PNS is an aetiological component of psychiatric disorders associated with memory deficits.

Physical exercise during pregnancy minimizes PTZ-induced behavioral manifestations in prenatally stressed offspring.

Stress during gestation has been shown to affect susceptibility and intensity of seizures in offspring. Environmental stimuli, such as maternal physical exercise, have shown to be beneficial for brain development. Although studies have demonstrated the deleterious influence of stress during pregnancy on seizure manifestation in offspring, very little is known on how to minimize these effects. This study verified whether physical exercise during the pregnancy associated with prenatal stress minimizes seizure susceptibility in offspring at the beginning of postnatal development. Pregnant rats and male pups were divided into the following groups: control, stress, stress/forced exercise, and stress/voluntary exercise. Behavioral manifestations were analyzed after injection of pentylenetetrazol (PTZ; 45 and 60 mg/kg) at ages P15 and P25. Increased behavioral manifestations and seizure severity was observed in the stress group compared with the control group at both ages. At the dose of 45 mg/kg, offspring of stressed mothers who performed both physical exercise models showed an increase in latency for the first manifestation and decrease in the seizures severity at both ages compared with the mothers groups who were only stressed. Prenatal restraint stress potentiated PTZ-induced seizure behavior, and both forced and voluntary exercise during gestation attenuates the negative effects of PTZ-induced offspring.

Sham-Chewing in Sows Is Associated With Decreased Fear Responses in Their Offspring.

We hypothesized that sham-chewing expressed by the dam during gestation affects fetus programming. The goal of this study was to assess the effects of maternal sham-chewing on offspring welfare indicators, such as behavior and physiology. Sows that exhibited consistent sham-chewing on at least two of 6 days of observation (N = 7) were compared with sows that had never performed sham-chewing (non-sham-chewing sows; N = 4) during these 6 days. Salivary samples from sows and piglets were collected and cortisol concentrations were analyzed to assess the hypothalamic pituitary adrenal (HPA) axis activity as cortisol is a physiological indicator of welfare. Moreover, placental tissue was collected, right after farrowing, to assess cortisol and cortisone concentration. Piglet behavior and fear tests were performed after weaning (one couple per sow). In the fear tests, data was collected in an open field test to determine the states of fear indicators. Non-sham-chewing sows had lower concentrations of cortisol on days 91 and 92 of gestation in the morning. In addition to this, placental cortisol was higher among sham-chewing sows than non-sham-chewing sows. In the open field test, piglets born from non-sham-chewing sows demonstrated more latency to move in the arena and less activity, indicating more fear. Based on our data, we concluded that the expression of maternal sham-chewing is related to less fear in their offspring. Although stereotypies have been studied, attention has not been devoted to the effects of the prenatal period in considering a fetal reprogramming approach.

Mother-infant dyadic dysregulation and postpartum depressive symptoms in low-income Mexican-origin women.

The current study evaluated a mechanistic pathway by which prenatal stress increases the risk of postpartum depressive (PPD) symptoms via observed dyadic emotional, behavioral, and attentional dysregulation and associated cortisol responses during mother-infant interactions. METHODS: Participants included 322 low-income Mexican American mother-infant dyads. Depressive symptoms, economic hardship, and negative life events were assessed at a prenatal visit. Dysregulation in dyadic (mother-infant) interactions and cortisol responses to mother-infant interaction were evaluated at 12 weeks after the birth. Twenty-four weeks after the birth, PPD symptoms were predicted from prenatal stress (negative life events and economic hardship) and prenatal depressive symptoms, mediated through dyadic dysregulation and maternal and infant cortisol responses. RESULTS: More negative life events in the prenatal period predicted more dyadic dysregulation at 12 weeks postpartum. Dyadic dysregulation and economic hardship predicted elevated 12-week infant cortisol total response and reactivity, and higher total infant cortisol response predicted higher maternal PPD symptoms at 24 weeks. Maternal cortisol response was not associated with dyadic dysregulation, either form of prenatal stress, or PPD symptoms. CONCLUSION: The results indicate the salience of early psychosocial processes and mother-infant relationship challenges for subsequent maternal affective well-being.