Department of Biomedical & Clinical Sciences (BKV), BKH/Obstetrics & Gynaecology, Faculty of Medicine and Health Sciences, Linköping University, SE-58185 Linköping, Sweden.
Department of Medicine and Optometry, Faculty of Health and Life Sciences, Linnaeus University, Hus Vita, 43157 Kalmar, Sweden.
Genes (Basel). 2020 Jul 31;11(8):869. doi: 10.3390/genes11080869.
Anxiety, chronical stress, and depression during pregnancy are considered to affect the offspring, presumably through placental dysregulation. We have studied the term placentae of pregnancies clinically monitored with the Beck's Anxiety Inventory (BAI) and Edinburgh Postnatal Depression Scale (EPDS). A cutoff threshold for BAI/EPDS of 10 classed patients into an Index group (>10, = 23) and a Control group (<10, = 23). Cortisol concentrations in hair (HCC) were periodically monitored throughout pregnancy and delivery. Expression differences of main glucocorticoid pathway genes, i.e., corticotropin-releasing hormone (CRH), 11β-hydroxysteroid dehydrogenase (HSD11B2), glucocorticoid receptor (NR3C1), as well as other key stress biomarkers (Arginine Vasopressin, AVP and O-GlcNAc transferase, OGT) were explored in medial placentae using real-time qPCR and Western blotting. Moreover, gene expression changes were considered for their association with HCC, offspring, gender, and birthweight. A significant dysregulation of gene expression for CRH, AVP, and HSD11B2 genes was seen in the Index group, compared to controls, while OGT and NR3C1 expression remained similar between groups. Placental gene expression of the stress-modulating enzyme 11β-hydroxysteroid dehydrogenase (HSD11B2) was related to both hair cortisol levels (Rho = 0.54; < 0.01) and the sex of the newborn in pregnancies perceived as stressful (Index, < 0.05). Gene expression of CRH correlated with both AVP (Rho = 0.79; < 0.001) and HSD11B2 (Rho = 0.45; < 0.03), and also between AVP with both HSD11B2 (Rho = 0.6; < 0.005) and NR3C1 (Rho = 0.56; < 0.03) in the Control group but not in the Index group; suggesting a possible loss of interaction in the mechanisms of action of these genes under stress circumstances during pregnancy.
怀孕期间的焦虑、慢性压力和抑郁被认为会影响后代，可能是通过胎盘失调。我们研究了临床监测贝克焦虑量表（BAI）和爱丁堡产后抑郁量表（EPDS）的足月胎盘。BAI/EPDS 截断值为 10 分，将患者分为指数组（>10，=23）和对照组（<10，=23）。整个孕期和分娩期定期监测头发（HCC）中的皮质醇浓度。使用实时 qPCR 和 Western blot 研究了主要糖皮质激素途径基因（促肾上腺皮质释放激素（CRH）、11β-羟类固醇脱氢酶（HSD11B2）、糖皮质激素受体（NR3C1））以及其他关键应激生物标志物（精氨酸加压素，AVP 和 O-GlcNAc 转移酶，OGT）在中间胎盘中的表达差异。此外，还考虑了基因表达变化与 HCC、后代、性别和出生体重的关系。与对照组相比，指数组的 CRH、AVP 和 HSD11B2 基因表达明显失调，而 OGT 和 NR3C1 表达在两组之间相似。应激调节酶 11β-羟类固醇脱氢酶（HSD11B2）的胎盘基因表达与头发皮质醇水平（Rho=0.54；<0.01）和被认为有压力的妊娠中新生儿的性别（指数，<0.05）相关。CRH 基因表达与 AVP（Rho=0.79；<0.001）和 HSD11B2（Rho=0.45；<0.03）相关，AVP 与 HSD11B2（Rho=0.6；<0.005）和 NR3C1（Rho=0.56；<0.03）相关在对照组中，但在指数组中没有；这表明在妊娠期间的应激情况下，这些基因的作用机制可能存在交互作用的丧失。
