The longitudinal and intergenerational effects of childhood maltreatment on cumulative stress biomarkers

Medientyp: E-Book; Hochschulschrift

Titel: The longitudinal and intergenerational effects of childhood maltreatment on cumulative stress biomarkers

Beteiligte: Mavioğlu, Rezan Nehir [Verfasser:in]

Körperschaft: Universität Ulm

Erschienen: Ulm, 2024

Umfang: 1 Online-Ressource

Sprache: Englisch

DOI: 10.18725/OPARU-53658

Identifikator:

Schlagwörter: Adverse childhood experiences ; Child abuse ; Stress, Psychological ; Mitochondria ; DNA methylation ; Telomere shortening ; Epigenomics ; Kindesmisshandlung ; Kind ; Psychisches Trauma ; Epigenetik ; Mitochondrium ; DNS-Methyltransferase ; Telomer ; Hochschulschrift

Entstehung:

Hochschulschrift: Dissertation, Universität Ulm, 2024

Anmerkungen:

Beschreibung: Childhood maltreatment (CM), a form of chronic early life stress, has been associated with poor physical and mental health in an individual as well as their offspring through its impact on stress response systems. Dysregulation of the stress response systems through CM might lead to alterations in certain cumulative stress biomarkers, which can predict long term health outcomes. Changes in DNA methylation (DNAm) induced by CM can alter gene expression in all physiological systems and determine long-term trajectories. Additionally, CM can contribute to an accelerated profile of biological aging through its effects on TL. However, the underlying mechanisms regarding CM-related alterations in DNAm and TL, and intergenerational effects of maternal CM on these biomarkers are unclear. Furthermore, CM-related regulation of TL can differ depending on the metabolic state, but has not been studied in the postpartum period, which is characterized as a rapidly resolved catabolic state. The main objective of this thesis was to investigate the effects of CM history on DNAm and TL in a sample of postpartum mothers and their newborns, both cross-sectionally, longitudinally, and intergenerationally. This objective was achieved in three studies. The Childhood Trauma Questionnaire was used to create groups of mothers with and without CM. Peripheral blood mononuclear cells were isolated from maternal venous blood, and umbilical cord mononuclear cells were isolated from newborn cord blood. The first study investigated the effect of varying levels of CM on the DNAm of DNA methyltransferase 1 (DNMT1), a crucial enzyme in the DNAm machinery, in immune and buccal cells of mother-newborn dyads. The DNAm was evaluated using mass spectrometry on immune cell DNA from mothers 1-week postpartum (n = 117) and their newborns (n = 113), as well as buccal cell DNA from 68 mother-newborn dyads. Mothers with CM history exhibited lower mean DNAm of DNMT1 in immune cells compared to mothers who have not experienced CM. The influence of CM status on maternal DNMT1 gene expression was only observed when moderate or severe CM was reported. There was no association between buccal cell DNAm and CM status. Maternal history of CM was not linked to any changes in DNMT1 mean DNAm in any of the cell types studied in newborns. The study concludes that changes in DNMT1 DNAm associated with CM may indicate allostatic load and have physiological relevance, particularly in individuals with more severe CM experiences. This could result in an activated DNA methylation machinery that may affect stress response genes. The second study investigated immune cell TL in mother-newborn dyads, depending on CM history. First part of this study assessed the longitudinal effects of CM on mothers’ TL during the first year after giving birth, specifically at 1 week (n = 175), 3 months (n = 140), and 1 year postpartum (n = 106). TL was measured from peripheral blood mononuclear cells by quantitative polymerase chain reaction. The results indicated, for the first time, a postpartum recovery of TL within 3 months, and preservation of TL from 3 months to 1 year. A time x CM interaction showed that women with a CM history had shorter TL compared to women without a CM history only at 1 year postpartum, but not earlier. Postpartum TL dynamics were explained with the regulation of telomere maintenance with changing metabolic and inflammatory state, that were further explored in the next study. The second part of this study investigated the intergenerational influence of maternal history of CM on newborn TL (n = 132). There was no significant influence of total maternal CM history on newborn TL. However, maternal history of childhood sexual abuse was found to be a predictor of shorter newborn rTL, after controlling for newborn sex, maternal age, and duration of cell cryopreservation. Although pregnancy complications were not associated with newborn TL in this cohort, maternal history of childhood sexual abuse-associated fetal programming of TL might be possible through other mechanisms such as prenatal stress and inflammation. The final study explored the telomere – mitochondria dynamics in immune cells of postpartum women and their newborns during different energetic states, such as parturition, CM history, and growth. Mitochondrial variables consisted of mitochondrial bioenergetics parameters, which were measured with high resolution respirometry, and mitochondrial DNA copy number and proportion of variant (damaged) mitochondrial DNA, which were measured by quantitative polymerase chain reaction. In the first week postpartum which is characterized by more inflammation and a higher energetic demand, TL was found to be shorter with decreased efficiency of mitochondrial energy production. One year later in basal conditions, these mitochondria – TL associations were present only in women with a history of CM. In newborns, TL decreased as basal routine and ATP production-related respiration increased. Mitochondrial DNA copy number was associated with TL regardless of energetic state, both in mothers and newborns. Overall, our results indicate that telomere – mitochondria dynamics are plastic and might be regulated depending on the body’s energetic requirements.

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