Subclinical inflammation during third trimester of pregnancy was not associated with markers of the metabolic syndrome in young adult offspring.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files.Growing evidence indicates that the metabolic syndrome (MS) is rooted in adverse exposures during fetal life. The aim of this study was to assess the possible associations between biomarkers of inflammation during third trimester of pregnancy and markers of MS in adult offspring.High-sensitive C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleuki-6 (IL-6) were measured in serum samples obtained in gestational week 30. Offspring were clinically examined at age 20 years. Analyses based on 439 mother-offspring dyads were adjusted for maternal smoking during pregnancy, height, prepregnancy body mass index (BMI), education, and offspring's sex. Offspring MS markers included waist circumference, BMI, blood pressure, HOMA insulin resistance, and plasma levels of fasting glucose, triglycerides, cholesterol fractions, insulin, and leptin.The median level was 2.8 (interquartile range = 3.3) µg/ml for CRP, for TNF-α: 5.7 (3.2) pg/ml, for IL-1β: 0.5 (0.4) pg/ml, and for IL-6: 1.1 (0.7) pg/ml. Concentrations were not significantly associated with MS markers in the offspring. The results remained essentially unchanged after correction for potential confounding.Markers for subclinical inflammation in third trimester in healthy women were not associated with components of MS in their adult offspring

Increases in maternal depressive symptoms during pregnancy and infant cortisol reactivity: Mediation by placental corticotropin-releasing hormone.

BackgroundMaternal depressive symptoms in pregnancy may affect offspring health through prenatal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The biological mechanisms that explain the associations between maternal prenatal depressive symptoms and offspring HPA axis regulation are not yet clear. This pre-registered investigation examines whether patterns of maternal depressive symptoms in pregnancy are associated with infant cortisol reactivity and whether this association is mediated by changes in placental corticotropin-releasing hormone (pCRH).MethodA sample of 174 pregnant women completed assessments in early, mid, and late pregnancy that included standardized measures of depressive symptoms and blood samples for pCRH. Infant cortisol reactivity was assessed at 1 and 6 months of age.ResultsGreater increases in maternal depressive symptoms in pregnancy were associated with higher cortisol infant cortisol reactivity at 1 and 6 months. Greater increases in maternal depressive symptoms in pregnancy were associated with greater increases in pCRH from early to late pregnancy which in turn were associated with higher infant cortisol reactivity.ConclusionsIncreases in maternal depressive symptoms and pCRH over pregnancy may contribute to higher infant cortisol reactivity. These findings help to elucidate the prenatal biopsychosocial processes contributing to offspring HPA axis regulation early in development

Pregnancy-specific anxiety and gestational length: The mediating role of diurnal cortisol indices

BackgroundPreterm birth or shorter gestation is a common adverse pregnancy outcome. Pregnancy-specific anxiety is robustly associated with risk for shorter gestation. Hypothalamic-pituitary-adrenal (HPA) dysregulation, indicated by diurnal cortisol index variability [slope, area-under-the-curve (AUC) or cortisol awakening response (CAR)], could mediate associations between pregnancy-specific anxiety and shorter gestation. The purpose of this study was to explore whether diurnal cortisol index variability mediates associations between pregnancy-specific anxiety and gestational length.MethodsA sample of 149 women from the Healthy Babies Before Birth study reported pregnancy-specific anxiety in early pregnancy. Saliva samples were taken at three times during pregnancy, for two days each, at wake, 30 min post wake, noon, and evening. Diurnal cortisol indices were calculated using standard approaches. Pregnancy cortisol index variability was calculated across pregnancy timepoints. Gestational length was derived from medical charts. Covariates were sociodemographics, parity and obstetric risk. Mediation models were tested using SPSS PROCESS.ResultsThere was a significant indirect effect of pregnancy-specific anxiety on gestational length via CAR variability, b(SE)= -0.102(0.057), .95CI [- 0.227,- 0.008]. Higher pregnancy-specific anxiety was associated with lower CAR variability, b(SE)= -0.019(0.008), p = .022, and lower CAR variability was associated with shorter gestation, b(SE)= 5.29(2.64), p = .047. Neither AUC or slope variability mediated associations between pregnancy-specific anxiety and gestational length.ConclusionLower CAR variability during pregnancy mediated the association between higher pregnancy-specific anxiety and shorter gestational length. Pregnancy-specific anxiety could dysregulate HPA axis activity, as indicated by lower CAR variability, demonstrating the importance of the HPA axis system in regulating pregnancy outcomes

Epigenetic age and pregnancy outcomes: GrimAge acceleration is associated with shorter gestational length and lower birthweight

BackgroundAdvanced biological aging, as measured by epigenetic aging indices, is associated with early mortality and morbidity. Associations between maternal epigenetic aging indices in pregnancy and pregnancy outcomes, namely gestational length and birthweight, have not been assessed. The purpose of this study was to examine whether epigenetic age during pregnancy was associated with gestational length and birthweight.ResultsThe sample consisted of 77 women from the Los Angeles, CA, area enrolled in the Healthy Babies Before Birth study. Whole blood samples for DNA methylation assay were obtained during the second trimester (15.6 ± 2.15 weeks gestation). Epigenetic age indices GrimAge acceleration (GrimAgeAccel), DNAm PAI-1, DNAm ADM, and DNAm cystatin C were calculated. Gestational length and birthweight were obtained from medical chart review. Covariates were maternal sociodemographic variables, gestational age at blood sample collection, and pre-pregnancy body mass index. In separate covariate-adjusted linear regression models, higher early second trimester GrimAgeAccel, b(SE) = - .171 (.056), p = .004; DNAm PAI-1, b(SE) = - 1.95 × 10-4 (8.5 × 10-5), p = .004; DNAm ADM, b(SE) = - .033 (.011), p = .003; and DNAm cystatin C, b(SE) = 2.10 × 10-5 (8.0 × 10-5), p = .012, were each associated with shorter gestational length. Higher GrimAgeAccel, b(SE) = - 75.2 (19.7), p < .001; DNAm PAI-1, b(SE) = - .079(.031), p = .013; DNAm ADM, b(SE) = - 13.8 (3.87), p = .001; and DNAm cystatin C, b(SE) = - .010 (.003), p = .001, were also associated with lower birthweight, independent of gestational length.DiscussionHigher maternal prenatal GrimAgeAccel, DNAm PAI-1, DNAm ADM, and DNAm cystatin C were associated with shorter gestational length and lower birthweight. These findings suggest that biological age, as measured by these epigenetic indices, could indicate risk for adverse pregnancy outcomes

Maternal Early Life Adversity and Infant Stress Regulation: Intergenerational Associations and Mediation by Maternal Prenatal Mental Health

Early life adversity is a potent risk factor for poor mental health outcomes across the lifespan, including offspring vulnerability to psychopathology. Developmentally, the prenatal period is a sensitive window in which maternal early life experiences may influence offspring outcomes and demarcates a time when expectant mothers and offspring are more susceptible to stressful and salutary influences. This prenatal plasticity constituted the focus of the current study where we tested the association of maternal early life adversity with infant stress regulation through maternal prenatal internalizing symptoms and moderation by prenatal social support. Mother-infant dyads (n = 162) were followed prospectively and mothers completed assessments of social support and depressive and anxiety symptoms across pregnancy. Infants completed standardized stress paradigms at one month and six months. There were several key findings. First, maternal prenatal depressive symptoms significantly mediated predictions of infant cortisol reactivity to the heel stick at one month from maternal early life adversity: specifically, maternal early life adversity positively predicted depressive symptoms in pregnancy, which in turn predicted dampened infant cortisol reactivity. Second, prenatal social support did not significantly moderate predictions of depressive or anxiety symptoms in pregnancy from maternal early life adversity nor did it alter the associations of maternal depressive or anxiety symptoms with infant stress regulation. These results suggest that maternal prenatal mental health is a key mechanism by which maternal early life adverse experiences affect offspring risk for psychopathology. We discuss potential clinical and health implications of dysregulated infant cortisol reactivity with respect to lifespan development

Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort Study

To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming.; We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N?=?78,017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0-18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10(-3); B, 14.33; CI, 10.12-18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth.; Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress

Increased male reproductive success in Ts65Dn “Down syndrome” mice

The Ts65Dn mouse is trisomic for orthologs of about half the genes on Hsa21. A number of phenotypes in these trisomic mice parallel those in humans with trisomy 21 (Down syndrome), including cognitive deficits due to hippocampal malfunction that are sufficiently similar to human that “therapies” developed in Ts65Dn mice are making their way to human clinical trials. However, the impact of the model is limited by availability. Ts65Dn cannot be completely inbred and males are generally considered to be sterile. Females have few, small litters and they exhibit poor care of offspring, frequently abandoning entire litters. Here we report identification and selective breeding of rare fertile males from two working colonies of Ts65Dn mice. Trisomic offspring can be propagated by natural matings or by in vitro fertilization (IVF) to produce large cohorts of closely related siblings. The use of a robust euploid strain as recipients of fertilized embryos in IVF or as the female in natural matings greatly improves husbandry. Extra zygotes cultured to the blastocyst stage were used to create trisomic and euploid embryonic stem (ES) cells from littermates. We developed parameters for cryopreserving sperm from Ts65Dn males and used it to produce trisomic offspring by IVF. Use of cryopreserved sperm provides additional flexibility in the choice of oocyte donors from different genetic backgrounds, facilitating rapid production of complex crosses. This approach greatly increases the power of this important trisomic model to interrogate modifying effects of trisomic or disomic genes that contribute to trisomic phenotypes

Galantamine improves olfactory learning in the Ts65Dn mouse model of Down syndrome

Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities

Psychosocial Stress, Cortisol Levels, and Maintenance of Vaginal Health

Stress stimuli are ubiquitous and women do not enjoy any exemptions. The physiologic “fight-or-flight” response may be deleterious to the female lower genital tract microbiome if the stress stimuli persist for longer than necessary. Persistent exposure to psychosocial stress and stimulation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic-adrenal-medullary (SAM) axes, and associated hormones are risk factors for several infections including genitourinary tract infections. Though this could be due to a dysregulated immune response, a cortisol-induced inhibition of vaginal glycogen deposition may be involved especially in the instance of vaginal infection. The estrogen-related increased vaginal glycogen and epithelial maturation are required for the maintenance of a healthy vaginal ecosystem (eubiosis). The ability of cortisol to disrupt this process as indicated in animal models is important in the pathogenesis of vaginal dysbiosis and the subsequent development of infection and inflammation. This phenomenon may be more crucial in pregnancy where a healthy Lactobacillus-dominated vaginal microbiota is sacrosanct, and there is local production of more corticotropin-releasing hormone (CRH) from the decidua, fetal membranes and placenta. To highlight the relationship between the stress hormone cortisol and the vaginal microbiomial architecture and function, the potential role of cortisol in the maintenance of vaginal health is examined