Fisher R E, Or'Rashid M, Quinton M, AlZahal O, Boermans H J, McBride B W, Karrow N A
1 Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada.
2 Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
J Dev Orig Health Dis. 2014 Jun;5(3):206-13. doi: 10.1017/S2040174414000191.
Adverse uterine environments caused by maternal stress (such as bacterial endotoxin) can alter programming of the fetal hypothalamic-pituitary-adrenal axis (HPAA) rendering offspring susceptible to various adulthood diseases. Thus, protection against this type of stress may be critical for ensuring offspring health. The present study was designed to determine if maternal supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) during pregnancy helps to protect against stress-induced fetal programming. Briefly, 53 ewes were fed a diet supplemented with fishmeal (FM) or soybean meal (SM) from day 100 of gestation (gd100) through lactation. On gd135, half the ewes from each dietary group were challenged with either 1.2 μg/kg Escherichia coli lipopolysaccharide (LPS) endotoxin, or saline as the control. The offspring's cortisol response to weaning stress was assessed 50 days postpartum by measuring serum cortisol concentrations 0, 6 and 24 h post weaning. Twenty-four hours post-weaning, lambs were subjected to an adrenocorticotropic hormone (ACTH) challenge (0.5 μg/kg) and serum cortisol concentrations were measured 0, 0.25, 0.5, 1 and 2 h post injection. At 5.5 months of age, offspring were also challenged with 400 ng/kg of LPS, and serum cortisol concentrations were measured 0, 2, 4 and 6 h post challenge. Interestingly, female offspring born to FM+LPS mothers had a greater cortisol response to weaning and endotoxin challenge compared with the other treatments, while female offspring born to SM+LPS mothers had a faster cortisol response to the ACTH stressor. Additionally, males born to FM+LPS mothers had a greater cortisol response to the ACTH challenge than the other treatments. Overall, FM supplementation during gestation combined with LPS challenge alters HPAA responsiveness of the offspring into adulthood.
母体应激（如细菌内毒素）所导致的不良子宫环境会改变胎儿下丘脑 - 垂体 - 肾上腺轴（HPAA）的编程，使后代易患各种成年疾病。因此，抵御这类应激对于确保后代健康可能至关重要。本研究旨在确定孕期母体补充ω-3多不饱和脂肪酸（n-3 PUFAs）是否有助于抵御应激诱导的胎儿编程。简而言之，从妊娠第100天（gd100）到哺乳期，对53只母羊饲喂添加鱼粉（FM）或豆粕（SM）的日粮。在gd135时，每个日粮组的一半母羊接受1.2μg/kg大肠杆菌脂多糖（LPS）内毒素挑战，另一半接受生理盐水作为对照。产后50天，通过测量断奶后0、6和24小时的血清皮质醇浓度，评估后代对断奶应激的皮质醇反应。断奶后24小时，对羔羊进行促肾上腺皮质激素（ACTH）挑战（0.5μg/kg），并在注射后0、0.25、0.5、1和2小时测量血清皮质醇浓度。在5.5月龄时，后代还接受400 ng/kg LPS挑战，并在挑战后0、2、4和6小时测量血清皮质醇浓度。有趣的是，与其他处理相比，FM + LPS组母羊所生的雌性后代对断奶和内毒素挑战的皮质醇反应更大，而SM + LPS组母羊所生的雌性后代对ACTH应激源的皮质醇反应更快。此外，FM + LPS组母羊所生的雄性后代对ACTH挑战的皮质醇反应比其他处理更大。总体而言，妊娠期补充FM并结合LPS挑战会改变后代成年期HPAA的反应性。
