Hyatt Melanie A, Budge Helen, Walker David, Stephenson Terence, Symonds Michael E
Centre for Reproduction and Early Life, Institute of Clinical Research, The University of Nottingham, Nottingham, UK.
Am J Physiol Regul Integr Comp Physiol. 2007 May;292(5):R1934-42. doi: 10.1152/ajpregu.00802.2006. Epub 2007 Jan 4.
The liver is a major metabolic and endocrine organ in growing neonates, but the extent to which its hormone receptor (R) sensitivity is potentially determined by maternal parity and the mother's nutritional environment is unknown. This was therefore investigated by sampling livers from postnatal sheep born to nulliparous or multiparous mothers. Offspring were sampled 1 or 30 days after birth from mothers consuming either 100 or 50% [i.e., nutrient-restricted (NR) group] of total metabolizable energy requirements from 110 days gestation to term ( approximately 147 days). Regardless of maternal diet, offspring of nulliparous mothers were lighter at birth and had smaller livers. By 1 mo of age, they exhibited catch-up growth, an adaptation not seen when mothers were NR, but they retained their lighter livers. At both sampling ages, livers from offspring born to nulliparous mothers exhibited increased mRNA abundance for growth hormone (GH) receptor, IGF-IR, plus hepatocyte growth factor (HGF); and at day 1 only IGF-I, but not IGF-IIR mRNA was decreased. In addition, mRNA for IGF-II, the HGFR, c-Met, and Bax were persistently reduced in these offspring. Effects of parity were largely unaffected by maternal nutrient restriction. Maternal parity therefore has a substantial effect on liver size during postnatal development and its receptor population that is not dependent on maternal diet. First-born offspring appear to exhibit a resetting of the endocrine control of hepatic growth within the HGF and GH-IGF axis, which could have later consequences after their growth has caught up.
肝脏是生长中的新生儿的主要代谢和内分泌器官，但其激素受体（R）敏感性在多大程度上可能由母体产次和母亲的营养环境决定尚不清楚。因此，通过对初产或经产母亲所生的产后绵羊肝脏进行采样来对此进行研究。从妊娠110天到足月（约147天）摄入总可代谢能量需求的100%或50%（即营养限制组）的母亲所生的后代在出生后1天或30天进行采样。无论母体饮食如何，初产母亲的后代出生时体重较轻且肝脏较小。到1月龄时，它们表现出追赶生长，这是母亲营养受限时未见的一种适应，但它们的肝脏仍较轻。在两个采样年龄，初产母亲所生后代的肝脏中生长激素（GH）受体、IGF-IR以及肝细胞生长因子（HGF）的mRNA丰度均增加；仅在出生1天时，IGF-I的mRNA减少，而IGF-IIR的mRNA未减少。此外，这些后代中IGF-II、HGFR、c-Met和Bax的mRNA持续减少。产次的影响在很大程度上不受母体营养限制的影响。因此，母体产次对产后发育期间的肝脏大小及其受体群体有重大影响，且不依赖于母体饮食。头胎后代似乎表现出HGF和GH-IGF轴内肝脏生长的内分泌控制重置，这在其生长追赶后可能会产生后续影响。
