Gnanalingham M G, Mostyn A, Dandrea J, Yakubu D P, Symonds M E, Stephenson T
Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, UK.
J Physiol. 2005 May 15;565(Pt 1):159-69. doi: 10.1113/jphysiol.2005.083246. Epub 2005 Mar 17.
This study investigated the developmental and nutritional programming of uncoupling protein-2 (UCP2), glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) mRNA in the sheep lung from the time of uterine attachment to 6 months of age. The effect of maternal nutrient restriction on lung development was determined in early to mid gestation (i.e. 28-80 days gestation, period of maximal placental growth, and embryonic and pseudoglandular stages of fetal lung development) and late gestation (i.e. 110-147 days gestation, period of maximal fetal growth, and canalicular and saccular stages of fetal lung development). Fetal lungs were sampled at 80 and 140 days (term approximately 148 days) gestation, and sheep lungs at 1, 7, 30 days and 6 months. GR and 11betaHSD1 mRNA were maximal at 140 days gestation, whereas UCP2 mRNA peaked at 1 day of age and then declined with postnatal age. Maternal nutrient restriction in both early-to-mid and late gestation had no effect on lung weight, but increased UCP2, GR and 11betaHSD1 mRNA abundance at every sampling age. These findings suggest that the developmental ontogeny of UCP2 mRNA in the ovine lung is under local glucocorticoid hormone action and that maternal nutrient restriction has long-term consequences for UCP2 and GR mRNA abundance in the lung irrespective of its timing.
本研究调查了从子宫着床到6月龄绵羊肺中解偶联蛋白2(UCP2)、糖皮质激素受体(GR)和11β-羟基类固醇脱氢酶1型(11βHSD1)mRNA的发育和营养编程。在妊娠早期至中期(即妊娠28 - 80天,胎盘生长最快的时期,以及胎儿肺发育的胚胎期和假腺期)和妊娠晚期(即妊娠110 - 147天,胎儿生长最快的时期,以及胎儿肺发育的小管期和囊状期)确定母体营养限制对肺发育的影响。在妊娠80天和140天(足月约148天)采集胎儿肺样本,在出生后1天、7天、30天和6个月采集绵羊肺样本。GR和11βHSD1 mRNA在妊娠140天时最高,而UCP2 mRNA在出生1天时达到峰值,随后随出生后年龄下降。妊娠早期至中期和晚期的母体营养限制对肺重量没有影响,但在每个采样年龄均增加了UCP2、GR和11βHSD1 mRNA丰度。这些发现表明,绵羊肺中UCP2 mRNA的发育个体发生受局部糖皮质激素作用的影响,并且母体营养限制对肺中UCP2和GR mRNA丰度具有长期影响,而与限制发生的时间无关。