He Guo-Qian, Dai Yi-Ling, Huang Zhuo, Ling Feng, Li Ping
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, P.R. China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, P.R. China.
PLoS One. 2025 Jun 5;20(6):e0312221. doi: 10.1371/journal.pone.0312221. eCollection 2025.
Infants born with intrauterine growth restriction (IUGR) followed by postnatal rapid catch-up growth are prone to develop metabolic diseases later in life. However, its effects and underlying molecular mechanisms remain unclear. Male offspring from mothers fed a low-protein diet (maternal diet, 8% protein) were randomly assigned to one of the following groups: normal diet (RC group) and low-protein diet (RR group). Offspring were fed a normal-protein diet (maternal diet, 20% protein, control group). In our study, at birth, approximately 93.33% of the offspring fats from mothers fed a low-protein diet were born with IUGR. Following weaning, all IUGR groups showed catch-up growth. The RC groups showed accelerated and early postnatal catch-up growth and regained the same weight as the controls from 3 to 9 months. At 9 months of age, the RC group animals had shorter telomere length (TL) than the Control and RR groups and also showed higher oxidative stress levels and lipid levels. Furthermore, compared to the control group, there was increased mitochondrial translocation of telomerase reverse transcriptase (TERT) under conditions of elevated oxidative stress in the RC group. There was no significant difference in mtDNA content between the RC and control groups. Moreover, at 9 months of age, only in the RC group were liver and pancreas Sirt3 expression levels higher than in the Control and RR groups. These data indicate that IUGR with early and rapid catch-up growth is exposed to chronic oxidative stress and subsequently affects TL and TERT translocations. Chronic oxidative stress may promote the translocation of TERT from the nucleus to mitochondria and protect tissues from oxidative stress damage.
出生时患有宫内生长受限(IUGR)且出生后快速追赶生长的婴儿在日后生活中容易患代谢性疾病。然而,其影响和潜在分子机制仍不清楚。将喂食低蛋白饮食(母体饮食,8%蛋白质)的母亲所生的雄性后代随机分为以下组:正常饮食组(RC组)和低蛋白饮食组(RR组)。后代喂食正常蛋白饮食(母体饮食,20%蛋白质,对照组)。在我们的研究中,出生时,喂食低蛋白饮食的母亲所生的后代中约93.33%患有IUGR。断奶后,所有IUGR组均出现追赶生长。RC组出生后早期出现加速追赶生长,并在3至9个月时恢复到与对照组相同的体重。在9个月大时,RC组动物的端粒长度(TL)比对照组和RR组短,并且氧化应激水平和脂质水平也更高。此外,与对照组相比,在氧化应激升高的条件下,RC组端粒酶逆转录酶(TERT)的线粒体易位增加。RC组和对照组之间的线粒体DNA含量没有显著差异。此外,在9个月大时,仅RC组肝脏和胰腺中的Sirt3表达水平高于对照组和RR组。这些数据表明,伴有早期快速追赶生长的IUGR会受到慢性氧化应激的影响,随后影响TL和TERT易位。慢性氧化应激可能促进TERT从细胞核向线粒体的易位,并保护组织免受氧化应激损伤。