Department of Midwifery, Biruni University, Faculty of Health Sciences, Istanbul, Türkiye.
Department of Physiotherapy and Rehabilitation-Faculty of Health Sciences, Biomedical Technologies Application and Research Center, Sakarya University of Applied Sciences, Sakarya, Türkiye.
Birth Defects Res. 2023 Sep 1;115(15):1398-1410. doi: 10.1002/bdr2.2205. Epub 2023 Jul 5.
Prenatal stress is a significant risk factor affecting pregnant women and fetal health. In the present study, we aimed to investigate the effect of immobility stress at different periods of pregnancy on oxidative stress, inflammation, placental apoptosis and intrauterine growth retardation in rats.
Fifty adult virgin female Wistar albino rats were used. Pregnant rats were exposed to 6 h/day immobilization stress in a wire cage at different stages of pregnancy. Groups I and II (Day 1-10 stress group) were sacrificed on the 10th day of pregnancy, and Group III, Group IV (10-19th-day stress group), and Group V (1-19th-day stress group) were sacrificed on the 19th day of pregnancy. Inflammatory cytokines, including interleukin-6 (IL-6) and interleukin-10 (IL-10), serum corticotropin-releasing hormone (CRH), and corticosterone levels were measured by enzyme-linked immunosorbent assay. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels in the placenta were spectrophotometrically measured. Histopathological analyses of the placenta were evaluated by hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α) and caspase-3 immunoreactivity in placenta tissues were determined by the indirect immunohistochemical method. Placental apoptosis was determined by the TUNEL staining method.
We found that the immobility stress during pregnancy significantly increased serum corticosterone levels. Our results showed that the immobility stress diminished the number and weight of fetuses in rats compared to the non-stress group. The immobility stress caused significant histopathological changes in the connection zone and labyrinth zone and increased placental TNF-α and caspase-3 immunoreactivity and placental apoptosis. In addition, immobility stress significantly increased the levels of pro-inflammatory IL-6 and MDA and caused a significant decrease in the levels of antioxidant enzymes such as SOD, CAT, and anti-inflammatory IL-10.
Our data suggest that immobility stress causes intrauterine growth retardation by activating the hypothalamic-pituitary-adrenal axis and deteriorating placental histomorphology and deregulating inflammatory and oxidative processes.
产前应激是影响孕妇和胎儿健康的一个重要危险因素。本研究旨在探讨孕期不同时期的不动应激对大鼠氧化应激、炎症、胎盘细胞凋亡和宫内生长迟缓的影响。
使用 50 只成年雌性 Wistar 白化大鼠。将妊娠大鼠置于铁丝笼中，每天接受 6 小时的固定应激，在妊娠的不同阶段进行。第 I 组和第 II 组（第 1-10 天应激组）于妊娠第 10 天处死，第 III 组、第 IV 组（第 10-19 天应激组）及第 V 组（第 1-19 天应激组）于妊娠第 19 天处死。采用酶联免疫吸附试验测定血清中白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、促肾上腺皮质激素释放激素（CRH）和皮质酮水平。采用分光光度法测定胎盘丙二醛（MDA）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）水平。采用苏木精-伊红染色法对胎盘组织进行组织病理学分析。采用间接免疫组化法测定胎盘组织中肿瘤坏死因子-α（TNF-α）和半胱氨酸天冬氨酸蛋白酶-3（caspase-3）的免疫反应性。采用 TUNEL 染色法检测胎盘细胞凋亡。
我们发现，孕期的固定应激显著增加了血清皮质酮水平。与非应激组相比，固定应激降低了大鼠的胎仔数量和体重。固定应激导致胎盘连接区和迷路区的组织形态学发生显著变化，并增加了胎盘 TNF-α和 caspase-3 的免疫反应性以及胎盘细胞凋亡。此外，固定应激显著增加了促炎因子 IL-6 和 MDA 的水平，并导致抗氧化酶如 SOD、CAT 和抗炎因子 IL-10 的水平显著降低。
我们的数据表明，固定应激通过激活下丘脑-垂体-肾上腺轴，恶化胎盘组织形态学，并扰乱炎症和氧化过程，导致宫内生长迟缓。
