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1. Glucocorticoid receptor sensitivity in early pregnancy in an African American cohort

   https://doi.org/10.1111/aji.13252  

   Clarke, Lasha S. ; Corwin, Elizabeth J. ; Dunlop, Anne L. ; Hankus, Allison ; Bradner, Joshua M. ; Paul, Sudeshna ; Jiao, Yunshen ; Smith, Alicia K. ; Patrushev, Nikolay ; Mulle, Jennifer G. ; et al ( May 2020 , American Journal of Reproductive Immunology)

   Disruption in homeostatic feedback loops between inflammatory mediators and the hypothalamic‐pituitary‐adrenal (HPA) axis is a key mechanism linking chronic stress to inflammation and adverse health outcomes, including those occurring during pregnancy. In particular, alterations in glucocorticoid sensitivity may occur as a result of chronic stress, including that due to racial discrimination, and may be implicated in the persistent adverse maternal and infant health outcomes experienced by African Americans. While there are a few large‐scale studies in human pregnancy that measure both cytokines and HPA axis hormones, to our knowledge, none directly measure glucocorticoid sensitivity at the cellular level, especially in an African American population.

   We measured the full range of the dexamethasone (DEX) dose‐response suppression of TNF‐α in first‐trimester blood samples from 408 African American women and estimated leukocyte cell type contribution to the production of TNF‐α.

   The mean (SD) DEX level needed to inhibit TNF‐α production by 50% (ie, DEX IC₅₀) was 9.8 (5.8) nmol/L. Monocytes appeared to be the main driver of Uninhibited TNF‐α production, but monocyte counts explained only 14% of the variation. Monocyte counts were only weakly correlated with the DEX IC₅₀(r = −.11,P < .05). Moreover, there was no statistically significant correlation between the DEX IC₅₀and circulating pro‐inflammatory (CRP, IL‐6, IFN‐γ) or anti‐inflammatory (IL‐10) mediators (P > .05).

   These findings challenge some prior assumptions and position this comprehensive study of glucocorticoid sensitivity as an important anchor point in the growing recognition of interindividual variation in maternal HPA axis regulation and inflammatory responses.

    

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2. Old friends and friendly fire: Pregnancy, hookworm infection, and anemia among tropical horticulturalists

   https://doi.org/10.1002/ajhb.23337  

   Anderson, Amy S. ; Trumble, Benjamin C. ; Hové, Carmen ; Kraft, Thomas S. ; Kaplan, Hillard ; Gurven, Michael ; Blackwell, Aaron D. ( October 2019 , American Journal of Human Biology)

   Despite public health concerns about hookworm infection in pregnancy, little is known about immune profiles associated with hookworm (Necator americanusandAncylostoma duodenale) infection during pregnancy. Fetal tolerance requirements may constrain maternal immune response to hookworm, thereby increasing susceptibility to new infections or increasing hemoglobin loss. To explore this possibility, we study systemic immune response and hemoglobin levels in a natural fertility population with endemic helminthic infection.

   We used Bayesian multilevel models to analyze mixed longitudinal data on hemoglobin, hookworm infection, reproductive state, eosinophils, and erythrocyte sedimentation rate (ESR) to examine the effects of pregnancy and hookworm infection on nonspecific inflammation, cellular parasite response, and hemoglobin among 612 Tsimane women aged 15‐45 (1016 observations).

   Pregnancy is associated with lower eosinophil counts and lower eosinophil response to hookworm, particularly during the second and third trimesters. Both hookworm and pregnancy are associated with higher ESR, with evidence for an interaction between the two causing further increases in the first trimester. Pregnancy is moderately associated with higher odds of hookworm infection (OR: 1.23, 95% CI: 0.83 to 1.83). Pregnancy and hookworm both decrease hemoglobin and may interact to accentuate this effect in the first‐trimester of pregnancy (Interaction: β: −0.30 g/dL; CI: −0.870 to 0.24).

   Our findings are consistent with a possible trade‐off between hookworm immunity and successful pregnancy, and with the suggestion that hookworm and pregnancy may have synergistic effects, particularly in the first trimester.

    

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3. High‐resolution epigenomic liquid biopsy for noninvasive phenotyping in pregnancy

   https://doi.org/10.1002/pd.5833  

   Chu, Tianjiao ; Shaw, Patricia ; McClain, Lora ; Simhan, Hyagriv ; Peters, David ( October 2020 , Prenatal Diagnosis)

   We explored the potential of genome‐wide epigenomic liquid biopsy for the comprehensive analysis of cell‐free DNA (cfDNA) methylation signatures in maternal plasma in early gestation.

   We used solution phase hybridization for targeted region capture of bisulfite‐converted DNA obtained from plasma of pregnant women in early gestation and nonpregnant female controls.

   Targeted sequencing of ~80.5 Mb of the plasma methylome generated an average read depth across all 17 plasma samples of ~42x. We used these data to explore the pregnancy‐specific characteristics of cfDNA methylation in plasma and found that pregnancy resulted in clearly detectable global alterations in DNA methylation patterns that were influenced by genomic location. We analyzed similar, previously published, data from first‐trimester maternal leukocyte populations and gestational age–matched chorionic villus (CV) and confirmed that tissue‐specific DNA methylation signatures in these samples had a significant influence on global and gene‐specific methylation in the plasma of pregnant women.

   We describe an approach for targeted epigenomic liquid biopsy in pregnancy and discuss our findings in the context of noninvasive prenatal testing with respect to phenotypic pregnancy monitoring and the early detection of complex gestational phenotypes such as preeclampsia and preterm birth.

    

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4. DNA methylation age at birth and childhood: performance of epigenetic clocks and characteristics associated with epigenetic age acceleration in the Project Viva cohort

   https://doi.org/10.1186/s13148-023-01480-2  

   Bozack, Anne K. ; Rifas-Shiman, Sheryl L. ; Gold, Diane R. ; Laubach, Zachary M. ; Perng, Wei ; Hivert, Marie-France ; Cardenas, Andres ( December 2023 , Clinical Epigenetics)

   Epigenetic age acceleration (EAA) and epigenetic gestational age acceleration (EGAA) are biomarkers of physiological development and may be affected by the perinatal environment. The aim of this study was to evaluate performance of epigenetic clocks and to identify biological and sociodemographic correlates of EGAA and EAA at birth and in childhood. In the Project Viva pre-birth cohort, DNA methylation was measured in nucleated cells in cord blood (leukocytes and nucleated red blood cells, N = 485) and leukocytes in early (N = 120, median age = 3.2 years) and mid-childhood (N = 460, median age = 7.7 years). We calculated epigenetic gestational age (EGA; Bohlin and Knight clocks) and epigenetic age (EA; Horvath and skin & blood clocks), and respective measures of EGAA and EAA. We evaluated the performance of clocks relative to chronological age using correlations and median absolute error. We tested for associations of maternal-child characteristics with EGAA and EAA using mutually adjusted linear models controlling for estimated cell type proportions. We also tested associations of Horvath EA at birth with childhood EAA.

   Bohlin EGA was strongly correlated with chronological gestational age (Bohlin EGAr = 0.82,p < 0.001). Horvath and skin & blood EA were weakly correlated with gestational age, but moderately correlated with chronological age in childhood (r = 0.45–0.65). Maternal smoking during pregnancy was associated with higher skin & blood EAA at birth [B(95% CI) = 1.17 weeks (− 0.09, 2.42)] and in early childhood [0.34 years (0.03, 0.64)]. Female newborns and children had lower Bohlin EGAA [− 0.17 weeks (− 0.30, − 0.04)] and Horvath EAA at birth [B(95% CI) = − 2.88 weeks (− 4.41, − 1.35)] and in childhood [early childhood: − 0.3 years (− 0.60, 0.01); mid-childhood: − 0.48 years (− 0.77, − 0.18)] than males. When comparing self-reported Asian, Black, Hispanic, and more than one race or other racial/ethnic groups to White, we identified significant differences in EGAA and EAA at birth and in mid-childhood, but associations varied across clocks. Horvath EA at birth was positively associated with childhood Horvath and skin & blood EAA.

   Maternal smoking during pregnancy and child sex were associated with EGAA and EAA at multiple timepoints. Further research may provide insight into the relationship between perinatal factors, pediatric epigenetic aging, and health and development across the lifespan.

    

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5. Contexts and consequences of takeovers in hamadryas baboons: Female parity, reproductive state, and observational evidence of pregnancy loss

   https://doi.org/10.1002/ajp.22649  

   Amann, Alexis L. ; Pines, Mathew ; Swedell, Larissa ( April 2017 , American Journal of Primatology)

   The evolutionary consequences of sexual selection and sexual conflict are epitomized in the hamadryas baboon, a species characterized by strong sexual dimorphism and intense male–male competition. Hamadryas males coerce individual females into reproductively exclusive one‐male units via aggressive takeovers, and infants involved in such takeovers are at least four times more likely to be killed (or otherwise die) after takeovers compared to other times. Here we examine female reproductive state before and after takeovers to further investigate the determinants of takeovers and their impact on female reproduction. Our data set consists of 162 takeovers over a period of 20 years in a population of wild hamadryas baboons at Filoha, Ethiopia. Results show that, in contrast to their polygynandrous relatives, hamadryas males show no bias with regard to female reproductive state at the time of the takeover, but are more likely to take over nulliparous compared to multiparous females. In addition, these results reinforce previous findings demonstrating the high likelihood of infant loss after hamadryas takeovers and suggest that females may use an additional strategy of pregnancy termination to curtail investment in offspring that are very likely to die anyway. Thus, hamadryas males may target females with high future reproductive value and hamadryas females may employ counterstrategies to help mitigate the effects of sexual coercion and infanticide on their own fitness.

    

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