Schwerin Manfred, Kanitz Ellen, Tuchscherer Margret, Brüssow Klaus-Peter, Nürnberg Gerd, Otten Winfried
Research Unit of Molecular Biology, Research Institute for the Biology of Farm Animals Dummerstorf, D-18196 Dummerstorf, Germany.
Theriogenology. 2005 Mar 1;63(4):1220-34. doi: 10.1016/j.theriogenology.2004.06.004.
This study was conducted to examine stress-induced effects on gene expression of specific markers for HPA axis and neuronal activity in fetuses and neonatal pigs. Brain, pituitary gland, and adrenal gland were obtained to determine the mRNA levels for corticotropin-releasing hormone (CRH), CRH receptor 1 (CRHR1), pro-opiomelanocortin (POMC), ACTH receptor (MC2R), c-jun and c-fos. The suitability of these molecular markers was determined in neonatal pigs which were maternally deprived for two hours. It was found that maternal deprivation caused significantly higher transcript levels of c-fos and CRH in brain accompanied by a down-regulation of CRHR1 mRNA and an up-regulation of c-jun in the pituitary gland. To determine the effect of elevated maternal cortisol levels on gene expression of these molecular markers in fetuses, pregnant sows were treated with 100 IU ACTH (Synacthen Depot) s.c. every two days between Day 49 and Day 75 of gestation (normal gestation length 114 days). Animals were killed 48 hours after the last ACTH administration and fetuses of each sow were isolated. The ACTH treatment of sows significantly increased mRNA expression of c-fos but not of CRH in the fetal brain, and significantly decreased MC2R mRNA expression in the adrenal gland. However, HPA axis seems not to be fully developed in Day 77-fetuses because fetal pituitary CRHR1 and POMC mRNA expression was low in most of the fetuses. Although the expression of endocrine regulatory factors was partially incomplete in fetuses at the beginning of the third-trimester, ACTH dependent activation of c-fos mRNA in brain indicates a stress-related increase of neuronal activity. Based on these results it is assumed that prenatal stress in pigs may also have effects on the activity of the HPA axis in the offspring.
本研究旨在探讨应激对胎儿和新生仔猪下丘脑-垂体-肾上腺(HPA)轴特定标志物基因表达及神经元活动的影响。获取脑、垂体和肾上腺,以测定促肾上腺皮质激素释放激素(CRH)、CRH受体1(CRHR1)、阿黑皮素原(POMC)、促肾上腺皮质激素(ACTH)受体(MC2R)、c-jun和c-fos的mRNA水平。在母体剥夺两小时的新生仔猪中确定这些分子标志物的适用性。结果发现,母体剥夺导致脑中c-fos和CRH的转录水平显著升高,同时垂体中CRHR1 mRNA下调,c-jun上调。为了确定母体皮质醇水平升高对胎儿这些分子标志物基因表达的影响,在妊娠第49天至第75天(正常妊娠期为114天)期间,每两天给怀孕母猪皮下注射100 IU促肾上腺皮质激素(长效促皮质素)。在最后一次注射促肾上腺皮质激素48小时后处死动物,并分离每头母猪的胎儿。母猪接受促肾上腺皮质激素治疗显著增加了胎儿脑中c-fos的mRNA表达,但未增加CRH的表达,且显著降低了肾上腺中MC2R mRNA的表达。然而,在妊娠77天的胎儿中,HPA轴似乎尚未完全发育,因为大多数胎儿的垂体CRHR1和POMC mRNA表达较低。尽管在妊娠晚期开始时胎儿体内内分泌调节因子的表达部分不完整,但脑中ACTH依赖的c-fos mRNA激活表明神经元活动与应激相关增加。基于这些结果,推测猪的产前应激也可能对后代的HPA轴活性产生影响。