The role of glucocorticoid and mineralocorticoid receptor DNA methylation in antenatal depression and infant stress regulation.
糖皮质激素和盐皮质激素受体 DNA 甲基化在产前抑郁和婴儿应激调节中的作用。
- 作者列表："Galbally M","Watson SJ","van IJzendoorn M","Saffery R","Ryan J","de Kloet ER","Oberlander TF","Lappas M","Lewis AJ
:Understanding fetal programming pathways that underpin the relationship between maternal and offspring mental health necessitates an exploration of potential role of epigenetic variation in early development. Two genes involved in stress response regulation, the glucocorticoid and mineralocorticoid receptors (NR3C1 and NR3C2) have been a focus in understanding stressful exposures and mental health outcomes. Data were obtained from 236 pregnant women from the Mercy Pregnancy Emotional Wellbeing Study (MPEWS), a selected pregnancy cohort, recruited in early pregnancy. Depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV) and repeated measures of the Edinburgh Postnatal Depression Scale (EPDS). Antidepressant use, stressful events and anxiety symptoms were measured. NR3C1 and NR3C2 DNA methylation was measured in placental and infant buccal samples. Infant cortisol was measured in repeat saliva samples across a task. This study found maternal early pregnancy depressive disorder and symptoms were associated with lower DNA methylation at NR3C2 CpG_24 in placental tissue. There were no significant differences for depression or antidepressant use for DNA methylation of NR3C1. Antenatal depression was associated with lower infant cortisol reactivity at 12 months. DNA methylation in CpG_24 site in NR3C2 in placental samples suppressed the relationship between early maternal depressive symptoms and infant cortisol reactivity. These findings show a relationship between antenatal depression, NR3C2 DNA methylation and infant cortisol response providing support for a specific fetal programming pathway. Further research is required to examine the stability of this epigenetic mark across childhood and long-term mental health outcomes.
: 了解支持母体和后代精神卫生之间关系的胎儿编程途径需要探索表观遗传变异在早期发育中的潜在作用。参与应激反应调节的两个基因，糖皮质激素和盐皮质激素受体 (NR3C1 和 NR3C2) 一直是理解应激暴露和精神卫生结果的焦点。数据来自 Mercy 妊娠情绪健康研究 (MPEWS) 的 236 名孕妇，MPEWS 是一个选定的妊娠队列，在妊娠早期招募。使用 DSM-IV (SCID-IV) 的结构化临床访谈和爱丁堡产后抑郁量表 (EPDS) 的重复测量来测量抑郁。测量抗抑郁药使用、紧张事件和焦虑症状。在胎盘和婴儿颊标本中测定 NR3C1 和 NR3C2 DNA 甲基化。在整个任务中重复唾液样本中测量婴儿皮质醇。本研究发现母体妊娠早期抑郁障碍和症状与胎盘组织 NR3C2 CpG_24 DNA 甲基化降低有关。抑郁症或抗抑郁药使用 NR3C1 DNA 甲基化无显著差异。产前抑郁与 12 个月时婴儿皮质醇反应性较低有关。胎盘样本 NR3C2 中 CpG_24 位点的 DNA 甲基化抑制了早期母亲抑郁症状与婴儿皮质醇反应性之间的关系。这些发现显示了产前抑郁、 NR3C2 DNA 甲基化和婴儿皮质醇反应之间的关系，为特定的胎儿编程途径提供了支持。需要进一步的研究来检查这种表观遗传标记在儿童和长期精神卫生结果中的稳定性。
METHODS::Maternal lifestyle affects both mother health and pregnancy outcome in humans. Several studies have demonstrated that interventions oriented towards reducing stress and anxiety have positive effects on pregnancy complications such as preeclampsia, excessive gestational weight, gestational diabetes and preterm birth. In this work, we showed that the environmental enrichment (EE), defined as a noninvasive and biological significant stimulus of the sensory pathway combined with voluntary physical activity, prevented preterm birth (PTB) rate in a 41% in an inflammatory mouse model induced by the systemic administration of bacterial lipopolysaccharide (LPS). Furthermore, we found that EE modulates maternal metabolism and produces an anti-inflammatory environment that contributes to pregnancy maintenance. In pregnant mice uterus, EE reduces the expression of TLR4 and CD14 (the LPS receptor and its coactivator protein), preventing the LPS-induced increase in PGE2 and PGF2α release and nitric oxide synthase (NOS) activity. In cervical tissue, EE inhibits cervical ripening events, such as PGE2 release, matrix metalloproteinase (MMP)-9 increased activity and neutrophil recruitment, therefore conserving cervical function. It seems that EE exposure could mimic the stress and anxiety-reducing techniques mentioned above, explaining, at least partially, the beneficial effects of having a healthy lifestyle before and during gestation. Furthermore, we propose that designing an EE protocol for humans could be a noninvasive and preventive therapy for pregnancy complications, averting pre-term birth occurrence and dreaded sequelae that are present in the offspring born to soon.
METHODS:PROBLEM:We aimed to investigate the main causes of recurrent miscarriage (RM) in patients with losses after spontaneous gestation (SG) and after in vitro fertilization (IVF). METHOD OF STUDY:A prospective case-control study was conducted. The eligible patients were women who had experienced two or more consecutive abortions after less than 12 weeks gestation, two consecutive losses after SG or two consecutive losses after IVF. All patients were subjected to the following evaluations: karyotyping of the aborted material, alloimmune and autoimmune marker testing, and acquired and hereditary thrombophilia marker testing. RESULTS:In total, 58 patients were eligible: 32 patients with RM after SG and 26 patients with RM after IVF. The factors associated with RM were genetic (29%), immune (14%), thrombophilic (21%), and thrombophilic and immune (24%), and only 12% of the cases were idiopathic. Comparing the two study groups (SG and IVF), all studied factors were similar, except for a higher ANA positivity observed in the SG group (SG 30.4% versus IVF 5.3%, OR 8.6 (CI 1.1 - 21.1, P 0.048). CONCLUSIONS:Our study identified the possibly factors associated with recurrent miscarriage in 86% of the cases, and these factors appear to be similar in patients with recurrent miscarriage after spontaneous gestation and IVF. This study demonstrates that IVF with PGT-A with euploid embryo transfer could reduce abortions by up to 29%, but other factors needs to be investigated even in patients undergoing in vitro fertilization.
METHODS:OBJECTIVES:To evaluate the impact of pre-operative Music Therapy (MT) on pain in first-trimester abortion under local anaesthesia (ALA). DESIGN:Randomised controlled trial comparing patients undergoing a first-trimester ALA with or without a pre-operative MT session. SETTING:University hospital of Angers from November 2016 to August 2017. POPULATION:Patients who underwent first-trimester abortion under ALA. METHODS:Patients allocated to MT group underwent a pre-operative 20 minutes session of MT. MAIN OUTCOME MEASURES:Pain was assessed using a visual analogue scale (VAS) just before the procedure, during the procedure, at the end of the procedure and upon returning to the ward. RESULTS:159 patients were randomised (80 in MT group, and 79 in the control group). 2 patients were excluded from the control group and 6 from the MT group. Therefore, 77 patients were analysed in the control group and 74 in the MT group. The intensity of pain were similar in both the MT group and the Control group just before the procedure (VAS: 4.0±2.9 vs. 3.6±2.5, p=0.78), during the procedure (VAS: 5.3±2.5 vs. 4.9±2.9, p=0.78), at the end of the procedure (VAS: 2.7±2.4 vs. 2.6±2.4, p=0.43) and upon returning to the ward (VAS:1.8±2.0 vs. 1.5±2.0, p=0.84). The difference in pain between entering the department and returning to the room after the procedure was similar between the MT and Control groups (0.3±2.5 vs. 0.3±2.4 VAS levels difference; p=0.92). CONCLUSION:Music therapy session before an ALA procedure resulted in no improvement in patient perception of pain during a first-trimester abortion.