PDF(Pubmed)
Abstract：
Intrauterine growth restriction (IUGR) occurs both in humans and domestic species. It has a particularly high incidence in pigs, and is a leading cause of neonatal morbidity and mortality as well as impaired postnatal growth. A key feature of IUGR is impaired muscle development, resulting in decreased meat quality. Understanding the developmental origins of IUGR, particularly at the molecular level, is important for developing effective strategies to mitigate its economic impact on the pig industry and animal welfare. The aim of this study was to characterise transcriptional profiles in the muscle of growth restricted pig foetuses at different gestational days (GD; gestational length ~ 115 days), focusing on selected genes (related to development, tissue injury and metabolism) that were previously identified as dysregulated in muscle of GD90 fetuses. Muscle samples were collected from the lightest foetus (L) and the sex-matched foetus with weight closest to the litter average (AW) from each of 22 Landrace x Large White litters corresponding to GD45 (n = 6), GD60 (n = 8) or GD90 (n = 8), followed by analyses, using RT-PCR and protein immunohistochemistry, of selected gene targets. Expression of the developmental genes, MYOD, RET and ACTN3 were markedly lower, whereas MSTN expression was higher, in the muscle of L relative to AW littermates beginning on GD45. Levels of all tissue injury-associated transcripts analysed (F5, PLG, KNG1, SELL, CCL16) were increased in L muscle on GD60 and, most prominently, on GD90. Among genes involved in metabolic regulation, KLB was expressed at higher levels in L than AW littermates beginning on GD60, whereas both IGFBP1 and AHSG were higher in L littermates on GD90 but only in males. Furthermore, the expression of genes specifically involved in lipid, hexose sugar or iron metabolism increased or, in the case of UCP3, decreased in L littermates on GD60 (UCP3, APOB, ALDOB) or GD90 (PNPLA3, TF), albeit in the case of ALDOB this only involved females. In conclusion, marked dysregulation of genes with critical roles in development in L foetuses can be observed from GD45, whereas for a majority of transcripts associated with tissue injury and metabolism differences between L and AW foetuses were apparent by GD60 or only at GD90, thus identifying different developmental windows for different types of adaptive responses to IUGR in the muscle of porcine foetuses.
摘要：
宫内生长受限(IUGR)发生在人类和家养物种中。它在猪中的发病率特别高，是新生儿发病和死亡以及产后生长受损的主要原因。IUGR的一个关键特征是肌肉发育受损，导致肉质下降。了解IUGR的发育起源，特别是在分子水平上，对于制定有效的战略以减轻其对养猪业和动物福利的经济影响非常重要。这项研究的目的是表征不同孕日（GD;妊娠长度〜115天）生长受限的猪胎儿肌肉中的转录谱，专注于选定的基因(与发育有关，组织损伤和代谢）先前被鉴定为GD90胎儿肌肉失调。从最轻的胎儿（L）和性别匹配的胎儿中收集肌肉样本，这些胎儿的体重最接近22个长白x大白窝中的每一个的平均窝（AW），对应于GD45（n=6），GD60(n=8)或GD90(n=8)，接下来是分析，使用RT-PCR和蛋白质免疫组织化学，选择的基因目标。发育基因的表达，MYOD,RET和ACTN3明显较低，而MSTN表达更高，从GD45开始，相对于AW同窝的L肌肉。分析的所有组织损伤相关转录本的水平(F5，PLG，KNG1，出售，CCL16）在GD60和L肌肉中增加，最突出的是,GD90在参与代谢调节的基因中，从GD60开始，L中的KLB表达水平高于AW同窝，而IGFBP1和AHSG在GD90的L同窝中均较高，但仅在雄性中。此外，特别涉及脂质的基因的表达，己糖或铁代谢增加或，在UCP3的情况下，GD60的L同窝减少(UCP3，APOB，ALDOB）或GD90（PNPLA3，TF），尽管在ALDOB的情况下，这只涉及女性。总之,从GD45可以观察到在L胎儿发育中具有关键作用的基因的明显失调，而对于与组织损伤和代谢相关的大多数转录本，L和AW胎儿之间的差异在GD60或仅在GD90时很明显，因此鉴定了不同的发育窗口猪胎儿肌肉中对IUGR的不同类型的适应性反应。
