AIMS Perinatal iron deficiency (ID) alters developmental trajectories of offspring, predisposing them to cardiovascular dysfunction in later life. The mechanisms underlying this long-term programming of renal function have not been defined. We hypothesized perinatal ID causes hypertension and alters kidney metabolic function and morphology in a sex-dependent manner in adult offspring. Furthermore, we hypothesized these effects are exacerbated by chronic consumption of a high salt diet. METHODS AND RESULTS Pregnant Sprague Dawley rats were fed either an iron-restricted or replete diet prior to and throughout pregnancy. Adult offspring were fed normal or high salt diets for 6 weeks prior to experimentation at 6 months of age. Blood pressure (BP) was assessed via indwelling catheters in anaesthetized offspring; kidney mitochondrial function was assessed via high-resolution respirometry; reactive oxygen species and nitric oxide were quantified via fluorescence microscopy. Adult males, but not females, exhibited increased systolic BP due to ID (P = 0.01) and high salt intake (P = 0.02). In males, but not in females, medullary mitochondrial content was increased by high salt (P = 0.003), while succinate-dependent respiration was reduced by ID (P < 0.05). The combination of perinatal ID and high salt reduced complex IV activity in the cortex of males (P = 0.01). Perinatal ID increased cytosolic superoxide generation (P < 0.001) concomitant with reduced nitric oxide bioavailability (P < 0.001) in male offspring, while high salt increased mitochondrial superoxide in the medulla (P = 0.04) and cytosolic superoxide within the cortex (P = 0.01). Male offspring exhibited glomerular basement membrane thickening (P < 0.05), increased collagen deposition (P < 0.05), and glomerular hypertrophy (interaction, P = 0.02) due to both perinatal ID and high salt. Female offspring exhibited no alterations in mitochondrial function or morphology due to either high salt or ID. CONCLUSION Perinatal ID causes long-term sex-dependent alterations in renal metabolic function and morphology, potentially contributing to hypertension and increased cardiovascular disease risk.

中文翻译：

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围产期铁缺乏和高盐饮食会导致长期的肾脏线粒体功能障碍和氧化应激。

AIMS围产期铁缺乏症（ID）会改变后代的发育轨迹，使他们在以后的生活中易患心血管功能障碍。尚未确定这种长期编程肾功能的机制。我们假设成年后代的围产期ID会导致高血压并以性别相关的方式改变肾脏的代谢功能和形态。此外，我们假设长期食用高盐饮食会加剧这些影响。方法和结果怀孕的Sprague Dawley大鼠在怀孕前和整个怀孕期间都接受了铁限制饮食或补充饮食。成年后代在6个月大之前进行正常饮食或高盐饮食6周，然后再进行实验。通过留置导管评估麻醉后代的血压（BP）。通过高分辨率呼​​吸测定法评估肾脏线粒体功能；通过荧光显微镜对活性氧和一氧化氮进行定量。成年男性而非女性由于ID（P = 0.01）和高盐摄入（P = 0.02）而表现出收缩压升高。在男性而非女性中，高盐会增加髓质线粒体含量（P = 0.003），而ID会降低琥珀酸依赖性呼吸作用（P <0.05）。围产期ID和高盐的结合降低了男性皮层的复杂IV活性（P = 0.01）。围产期ID增加雄性后代中胞质超氧化物的产生（P <0.001），同时降低一氧化氮的生物利用度（P <0.001），而高盐会增加髓质中线粒体超氧化物（P = 0.04）和皮层中的胞质超氧化物（P = 0.01） ）。由于围生期ID和高盐分，雄性后代表现出肾小球基底膜增厚（P <0.05），胶原蛋白沉积增加（P <0.05）和肾小球肥大（相互作用，P = 0.02）。雌性后代由于高盐或高ID而未显示线粒体功能或形态改变。结论围产期ID会导致肾脏代谢功能和形态的长期性别依赖性改变，可能导致高血压和增加心血管疾病的风险。