Diniz Fabiola, Edgington-Giordano Francesca, Ngo Nguyen Yen Nhi, Caspi Gal, El-Dahr Samir S, Tortelote Giovane G
Section of Pediatric Nephrology, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
Heliyon. 2024 Oct 18;10(20):e39552. doi: 10.1016/j.heliyon.2024.e39552. eCollection 2024 Oct 30.
Parental nutritional status is crucial in shaping offspring's kidney development. However, the association between a protein-restrictive diet and its intergenerational impact on kidney development remains unclear.
We conducted multigenerational morphometric measurements to investigate the effects of parental protein deprivation on offspring kidney development across four generations. F0 mice were divided into two groups and fed a normal protein diet (NPD) or a low-protein diet (LPD) for three weeks before mating and continued these diets throughout gestation and lactation. Body weight (BW), kidney weight (KW), KW/BW ratio, nephron counts, and blood pressure were assessed in F1 pups. To examine paternal effects, we bred CD1 females on an NPD with males on an LPD. BW, KW, KW/BW, and nephron counts were measured at P20. To measure the transgenerational effect of parental LPD on kidney development, F1 offspring (from parents on LPD) were fed NPD upon weaning. These F1 offspring were bred at 6 weeks of age to produce F2, F3 and F4 generations. Kidney metrics were evaluated across generations.
The average body weight of P0 pups from parents on NPD was 1.61g, while pups from parental LPD weighed an average of 0.869g, a decrease of 54 % (p = 6.9e-11, Wilcoxon test). F1 from parental LPD have significantly smaller kidneys than the control, with an average combined kidney weight of 0.0082g versus 0.0129g, a 37 % decrease (p = 3.2e-02, Wilcoxon test). P20 BW and KW remained low in LPD offspring. These effects persisted for 4 generations (F1 to F4) with an average glomerular count reduction of roughly 20 %. F3 and F4 showed wider variability in glomerular counts but were not statistically significant compared to controls.
Both maternal and paternal LPD significantly affected offspring nephron endowment. Our study underscores the complex nature of nutritional transgenerational effects on kidney development, emphasizing the importance of both maternal and paternal dietary impacts on kidney development and the developmental origin of adult disease.
父母的营养状况对后代肾脏发育至关重要。然而，蛋白质限制饮食与其对肾脏发育的代际影响之间的关联仍不清楚。
我们进行了多代形态测量，以研究亲代蛋白质缺乏对四代后代肾脏发育的影响。F0小鼠分为两组，在交配前3周分别喂食正常蛋白质饮食（NPD）或低蛋白饮食（LPD），并在整个妊娠期和哺乳期持续这些饮食。对F1幼崽评估体重（BW）、肾脏重量（KW）、KW/BW比值、肾单位计数和血压。为了研究父系影响，我们将食用NPD的CD1雌性小鼠与食用LPD的雄性小鼠进行交配。在出生后20天（P20）测量BW、KW、KW/BW和肾单位计数。为了测量亲代LPD对肾脏发育的跨代影响，将F1后代（来自食用LPD的父母）断奶后喂食NPD。这些F1后代在6周龄时进行繁殖，产生F2、F3和F4代。对各代的肾脏指标进行评估。
来自食用NPD亲代的P0幼崽平均体重为1.61g，而来自食用LPD亲代的幼崽平均体重为0.869g，下降了54%（p = 6.9e-11，Wilcoxon检验）。来自食用LPD亲代的F1幼崽的肾脏明显小于对照组，平均总肾脏重量为0.0082g，而对照组为0.0129g，下降了37%（p = 3.2e-02，Wilcoxon检验）。LPD后代在P20时的BW和KW仍然较低。这些影响持续了4代（F1至F4），平均肾小球计数减少了约20%。F3和F4在肾小球计数上表现出更大的变异性，但与对照组相比无统计学意义。
母体和父体的LPD均显著影响后代的肾单位数量。我们的研究强调了营养跨代效应在肾脏发育方面的复杂性，强调了母体和父体饮食对肾脏发育以及成人疾病发育起源的重要性。
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