Master Jordanna S, Zimanyi Monika A, Yin Kom V, Moritz Karen M, Gallo Linda A, Tran Melanie, Wlodek Mary E, Black Mary J
Department of Physiology, The University of Melbourne, Parkville, Vic., Australia.
Clin Exp Pharmacol Physiol. 2014 Nov;41(11):884-90. doi: 10.1111/1440-1681.12303.
Epidemiological studies have shown an association between low birthweight and adult disease development with transmission to subsequent generations. The aim of the present study was to examine the effect of intrauterine growth restriction in rats, induced by uteroplacental insufficiency, on cardiac structure, number, size, nuclearity, and adult blood pressure in first (F1) and second (F2) generation male offspring. Uteroplacental insufficiency or sham surgery was induced in F0 Wistar-Kyoto pregnant rats in late gestation giving rise to F1 restricted and control offspring, respectively. F1 control and restricted females were mated with normal males, resulting in F2 control and restricted offspring, respectively. F1 restricted male offspring were significantly lighter at birth (P < 0.05), but there were no differences in birthweight of F2 offspring. Left ventricular weights and volumes were significantly increased (P < 0.05) in F1 and F2 restricted offspring at day 35. Left ventricular cardiomyocyte number was not different in F1 and F2 restricted offspring. At 6 months-of-age, F1 and F2 restricted offspring had elevated blood pressure (8-15 mmHg, P < 0.05). Our findings demonstrate the emergence of left ventricular hypertrophy and hypertension, with no change in cardiomyocyte number, in F1 restricted male offspring, and this was transmitted to the F2 offspring. The findings support transgenerational programming effects.
流行病学研究表明，低出生体重与成人疾病发展以及向后代的传递之间存在关联。本研究的目的是研究子宫胎盘功能不全诱导的大鼠子宫内生长受限对第一代（F1）和第二代（F2）雄性后代心脏结构、数量、大小、核型和成年血压的影响。在妊娠晚期，对F0代Wistar-Kyoto孕鼠进行子宫胎盘功能不全或假手术，分别产生F1代受限和对照后代。F1代对照和受限雌性与正常雄性交配，分别产生F2代对照和受限后代。F1代受限雄性后代出生时体重显著较轻（P<0.05），但F2代后代的出生体重没有差异。在第35天时，F1代和F2代受限后代的左心室重量和容积显著增加（P<0.05）。F1代和F2代受限后代的左心室心肌细胞数量没有差异。在6个月大时，F1代和F2代受限后代的血压升高（8-15 mmHg，P<0.05）。我们的研究结果表明，F1代受限雄性后代出现左心室肥厚和高血压，心肌细胞数量无变化，且这种情况传递给了F2代后代。这些发现支持了跨代编程效应。
