Department of Physiology, Shanxi Medical University, Taiyuan, People's Republic of China.
Antioxid Redox Signal. 2012 Sep 1;17(5):733-43. doi: 10.1089/ars.2011.4365. Epub 2012 Mar 13.
Abnormal fetal and early postnatal growth is closely associated with adult-onset metabolic syndrome (MetS). However, the underlying etiological factors remain complex. The presence of the autoantibody against the angiotensin II type 1 receptor (AT1-Ab), a known risk factor for pre-eclampsia, may create a suboptimal intrauterine fetal environment. The current study investigated whether middle-aged offspring of AT1-Ab-positive mothers were prone to metabolic disorder development.
The AT1-Abs was detected in placental trophoblastic cells, capillary endothelium, and milk of pregnant rats actively immunized with the second extracellular loop of the AT1 receptor. AT1-Abs in newborn rats induced vasoconstriction, increased intracellular-free Ca(2+) in vitro, and was undetectable 7 weeks later. Immunized group offspring exhibited increased weight variability and insulin resistance at 40 weeks of age under a normal diet, evidenced by elevated fasting serum insulin and homeostasis model assessment score compared with the vehicle control. To further observe metabolic alterations, the offspring were given a high-sugar diet (containing 20% sucrose) 40-48 weeks postnatally. The fasting plasma glucose in immunized group offspring was markedly increased. Concomitantly, these offspring manifested increased visceral adipose tissue, increased fatty liver, increased triglycerides, decreased high-density lipoprotein cholesterol, and decreased adiponectin levels, indicative of MetS.
AT1-Abs could be transferred from mother to offspring via the placenta and milk. Moreover, offspring of an AT1-Ab-positive mother were more vulnerable to MetS development in middle age.
AT1-Ab-positivity of mothers during pregnancy is a previously unrecognized "silent" risk factor for MetS development in their offspring.
胎儿和新生儿早期生长异常与成人代谢综合征（MetS）密切相关。然而，潜在的病因仍然很复杂。抗血管紧张素 II 型 1 型受体（AT1-Ab）自身抗体的存在，已知是子痫前期的一个危险因素，可能会导致宫内胎儿环境不佳。本研究旨在探讨 AT1-Ab 阳性母亲的中年后代是否容易发生代谢紊乱。
用 AT1 受体第二细胞外环主动免疫的怀孕大鼠胎盘滋养层细胞、毛细血管内皮细胞和乳汁中可检测到 AT1-Abs。新生大鼠的 AT1-Abs 诱导血管收缩，增加体外细胞内游离钙，7 周后检测不到。在正常饮食下，免疫组后代 40 周时体重变化和胰岛素抵抗增加，表现为空腹血清胰岛素和稳态模型评估评分升高，与载体对照组相比。为了进一步观察代谢变化，在产后 40-48 周，给后代喂食高糖饮食（含 20%蔗糖）。免疫组后代的空腹血糖明显升高。同时，这些后代表现出内脏脂肪组织增加、脂肪肝增加、甘油三酯增加、高密度脂蛋白胆固醇降低、脂联素水平降低，提示代谢综合征。
AT1-Ab 可通过胎盘和乳汁从母亲传递给后代。此外，AT1-Ab 阳性母亲的后代在中年更容易发生 MetS。
母亲在怀孕期间的 AT1-Ab 阳性是其后代代谢综合征发展的一个以前未被认识的“沉默”危险因素。
