Perfluorooctane sulfonic acid (PFOS) exposure during pregnancy increases blood pressure and impairs vascular relaxation mechanisms in the adult offspring.
Perfluorooctane sulfonic acid (PFOS) exposure during pregnancy increases blood pressure and impairs vascular relaxation mechanisms in the adult offspring.
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DOI：
10.1016/j.reprotox.2020.09.008
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Kumar S
中科院分区：
文献类型：
--
作者：
Dangudubiyyam SV;Mishra JS;Zhao H;Kumar S
全氟辛烷磺酸（PFOS）是一种持久性环境因子。我们研究了怀孕期间接触全氟辛烷磺酸是否会改变雄性和雌性后代的血压，以及这是否与血管机制的性别特异性变化有关。从妊娠第4天至分娩期间，通过饮用水（50 μg/ml）给药全氟辛烷磺酸。全氟辛烷磺酸暴露降低了母鼠增重，但没有显著改变母鼠的采食量和饮水量。全氟辛烷磺酸母亲所生的雄性和雌性幼崽的体重分别小29%和27%。雄性全氟辛烷磺酸后代在成年后仍然较小，但雌性全氟辛烷磺酸后代表现出追赶性生长。与对照组相比，全氟辛烷磺酸男性和女性在12周龄和16周龄时的血压升高幅度相似。在全氟辛烷磺酸中，男性和女性的肠系膜动脉对乙酰胆碱的松弛程度都有所降低，但女性的降低程度更大。对硝普钠的松弛在全氟辛烷磺酸女性中减少，但在全氟辛烷磺酸男性中不受影响。PFOS男性血管eNOS表达无变化，但phospho(Ser1177)-eNOS表达降低。在PFOS女性中，eNOS和phospho(Ser1177)-eNOS的总表达均降低。综上所述，产前全氟辛烷磺酸暴露(1)仅在女性中导致低出生体重，随后出现追赶性生长(2)在男性和女性中导致相似程度的高血压；(2)降低雄性血管内皮依赖性舒张，抑制雌性血管内皮依赖性舒张和非依赖性舒张。内皮功能障碍与男性eNOS活性降低和女性eNOS表达和活性降低有关。
Perfluorooctanesulfonate (PFOS) is a persistent environmental agent. We examined whether PFOS exposure during pregnancy alters blood pressure in male and female offspring, and if this is related to sex-specific changes in vascular mechanisms. PFOS was administered through drinking water (50 μg/ml) to pregnant Sprague-Dawley rats from gestational day 4 until delivery. PFOS-exposure decreased maternal weight gain but did not significantly alter feed and water intake in dams. The male and female pups born to PFOS mothers were smaller in weight by 29% and 27%, respectively. The male PFOS offspring remained smaller through adulthood, but the female PFOS offspring exhibited catch-up growth. The blood pressure at 12 and 16 weeks of age was elevated at similar magnitude in PFOS males and females than controls. Mesenteric arterial relaxation to acetylcholine was reduced in both PFOS males and females, but the extent of decrease was greater in females. Relaxation to sodium-nitroprusside was reduced in PFOS females but unaffected in PFOS males. Vascular eNOS expression was not changed, but phospho(Ser1177)-eNOS was decreased in PFOS males. In PFOS females, both total eNOS and phospho(Ser1177)-eNOS expression were reduced. In conclusion, PFOS exposure during prenatal life (1) caused low birth weight followed by catch-up growth only in females (2) lead to hypertension of similar magnitude in both males and females; (2) decreased endothelium-dependent vascular relaxation in males but suppressed both endothelium-dependent and -independent relaxation in females. The endothelial dysfunction is associated with reduced activity of eNOS in males and decreased expression and activity of eNOS in females.
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