Internal Medicine Department, School of Medicine, State University of Campinas, São Paulo, Brazil.
PLoS One. 2019 Apr 29;14(4):e0210454. doi: 10.1371/journal.pone.0210454. eCollection 2019.
Gestational protein restriction was associated with low birth weight, hypertension and higher prevalence of cardiac disorders in adults. Several mechanisms, including epigenetics, could be related with the cardiovascular phenotype on protein-restricted offspring. Thus, we investigated the morphological cardiac effects of gestational protein restriction and left ventricle miRNAs and target genes expression pattern in both 12-day and 16-week old gestational protein-restricted male offspring. Pregnant Wistar rats were allocated into two groups, according to protein supply during pregnancy: NP (normal protein diet- 17%) or LP (low protein diet-6%). Dams on the gestational protein-restricted diet had lower body weight gain and higher food intake. Gestational protein-restricted offspring had low birth weight, followed by rapidly body weight recovery, hypertension, and increased myocytes cross-sectional area and collagen fraction at 16-week old age. At 12-days old, miR-184, miR-192, miR-376c, miR-380-3p, miR-380-5p, miR-451, and miR-582-3p had increased expression, and miR-547 and miR-743a had decreased expression in the gestational protein-restricted left ventricle. At 16-week old, let-7b, miR-125a-3p, miR-142-3p, miR-182 and miR-188-5p had increased expression and let-7g, miR-107, miR-127, miR-181a, miR-181c, miR-184, miR-324-5p, miR-383, miR-423-5p and miR-484 had decreased expression in gestational protein-restricted left ventricle. Target predicted gene expression analysis showed higher expression of Dnmt3a, Oxct1, Rictor and Trps1 and lower expression of Bbs1 and Calml3 in 12-day old protein-restricted offspring. 16-week old protein-restricted offspring had higher expression of Adrbk1, Bbs1, Dnmt3a, Gpr22, Inppl1, and Oxct1 genes. In conclusion, gestational protein restriction was related to offspring low birth weight, increased systolic blood pressure and morphological heart alterations that could be related to early heart miRNA expression changes that perpetuate into adulthood and which are associated with the regulation of essential genes involved in cardiovascular development, heart morphology, function, and metabolism.
妊娠期蛋白质限制与低出生体重、高血压和成年人中心脏疾病的患病率较高有关。包括表观遗传学在内的几种机制可能与蛋白质限制后代的心血管表型有关。因此，我们研究了妊娠期蛋白质限制对心脏的形态学影响，以及在 12 天和 16 周龄的妊娠期蛋白质限制雄性后代的左心室 miRNA 和靶基因表达模式。根据妊娠期间的蛋白质供应，将怀孕的 Wistar 大鼠分为两组：NP（正常蛋白质饮食-17%）或 LP（低蛋白质饮食-6%）。妊娠期蛋白质限制饮食的母鼠体重增加减少，食物摄入量增加。妊娠期蛋白质限制的后代出生体重较低，随后体重迅速恢复，16 周龄时出现高血压和心肌横截面积增加以及胶原分数增加。在 12 天龄时，miR-184、miR-192、miR-376c、miR-380-3p、miR-380-5p、miR-451 和 miR-582-3p 的表达增加，miR-547 和 miR-743a 的表达减少在妊娠期蛋白质限制的左心室。在 16 周龄时，let-7b、miR-125a-3p、miR-142-3p、miR-182 和 miR-188-5p 的表达增加，let-7g、miR-107、miR-127、miR-181a、miR-181c、miR-184、miR-324-5p、miR-383、miR-423-5p 和 miR-484 的表达减少在妊娠期蛋白质限制的左心室。靶基因预测表达分析显示，12 天龄蛋白质限制后代的 Dnmt3a、Oxct1、Rictor 和 Trps1 表达增加，Bbs1 和 Calml3 表达减少。16 周龄蛋白质限制后代的 Adrbk1、Bbs1、Dnmt3a、Gpr22、Inppl1 和 Oxct1 基因表达增加。综上所述，妊娠期蛋白质限制与后代出生体重低、收缩压升高以及形态学心脏改变有关，这些改变可能与早期心脏 miRNA 表达变化有关，这些变化持续到成年，并与心血管发育、心脏形态、功能和代谢相关的关键基因的调节有关。
