Low birth weight female piglets show altered intestinal development, gene expression, and epigenetic changes at key developmental loci
Low birth weight female piglets show altered intestinal development, gene expression, and epigenetic changes at key developmental loci
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DOI：
10.1096/fj.202002587r
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发表时间：
2021-04-01
期刊：
影响因子：
4.8
通讯作者：
Van Ginneken, Chris
中科院分区：
文献类型：
--
作者：
Ayuso, Miriam;Irwin, Rachelle;Van Ginneken, Chris
肠道发育在低出生体重（LBW）猪中受到损害，对它们的生长，健康和恢复力产生负面影响。我们通过比较LBW与正常出生体重（NBW）雌性仔猪肠道形态、基因表达和甲基化的变化，研究了在新生儿和幼年LBW雌性仔猪中观察到的肠道成熟改变的分子机制。在0小时、8小时、10天和8周龄时，共处死16对LBW/NBW同胞对。对胃肠道进行称重、测量，并对小肠取样进行组织形态学、基因表达和甲基化分析。在LBW雌性仔猪中观察到肠道发育受损，绒毛较短，隐窝较浅。肠道发育标志物（ALPI和OLFM）的表达在出生后迅速达到高峰，但在LBW母猪仔猪。LBW中参与营养消化（ANPEP和SI）和屏障功能（OCLN和CLDN 4）的基因的较低表达，以及它们的肠绒毛和隐窝发育延迟，可以帮助解释LBW雌性仔猪的健康和生长潜力受损。在LBW中观察到的肠道发育关键调节因子（OLFM 4和FZD 5）的甲基化变化表明BW对肠道基因表达，发育和功能的长期影响。因此，在IPEC-J2细胞中诱导的实验性去甲基化导致肠基因（MGA、DPP 4和GLUT 2）的表达增加。总体而言，我们已经确定了一些对肠道发育至关重要的基因的转录或表观遗传标记的改变，这可能导致LBW雌性仔猪短期和长期无法茁壮成长。
Intestinal development is compromised in low birth weight (LBW) pigs, negatively impacting their growth, health, and resilience. We investigated the molecular mechanisms of the altered intestinal maturation observed in neonatal and juvenile LBW female piglets by comparing the changes in intestinal morphology, gene expression, and methylation in LBW versus normal birth weight (NBW) female piglets. A total of 16 LBW/NBW sibling pairs were sacrificed at 0 hours, 8 hours, 10 days, and 8 weeks of age. The gastrointestinal tract was weighed, measured, and the small intestine was sampled for histomorphology, gene expression, and methylation analyses. Impaired intestinal development, with shorter villi and shallower crypts, was observed in LBW female piglets. The expression of intestinal development markers (ALPI and OLFM) rapidly peaked after birth in NBW but not in LBW female piglets. The lower expression of genes involved in nutrient digestion (ANPEP and SI) and barrier function (OCLN and CLDN4) in LBW, together with their delayed development of intestinal villi and crypts could help to explain the compromised health and growth potential of LBW female piglets. The changes in methylation observed in LBW in key regulators of intestinal development (OLFM4 and FZD5) suggest long-term effects of BW on intestinal gene expression, development, and function. Accordingly, experimental demethylation induced in IPEC-J2 cells led to increased expression of intestinal genes (MGA, DPP4, and GLUT2). Overall, we have identified the alterations in transcription or epigenetic marking at a number of genes critical to intestinal development, which may contribute to both the short- and long-term failure of LBW female piglets to thrive.