Khanal Prabhat, Nielsen Mette Olaf
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 3, 1st floor, DK-1870 Frederiksberg C, Denmark.
Current address: Department of Nutrition, Faculty of Medicine, Transgenic Animal and Lipid Storage, Norwegian Transgenic Centre (NTS), University of Oslo, Oslo, Norway.
J Anim Sci Biotechnol. 2017 Sep 1;8:75. doi: 10.1186/s40104-017-0205-1. eCollection 2017.
The concept of foetal programming (FP) originated from human epidemiological studies, where foetal life nutrition was linked to health and disease status later in life. Since the proposal of this phenomenon, it has been evaluated in various animal models to gain further insights into the mechanisms underlying the foetal origins of health and disease in humans. In FP research, the sheep has been quite extensively used as a model for humans. In this paper we will review findings mainly from our Copenhagen sheep model, on the implications of late gestation malnutrition for growth, development, and metabolic and endocrine functions later in life, and discuss how these implications may depend on the diet fed to the animal in early postnatal life. Our results have indicated that negative implications of foetal malnutrition, both as a result of overnutrition and, particularly, late gestation undernutrition, can impair a wide range of endocrine functions regulating growth and presumably also reproductive traits. These implications are not readily observable early in postnatal life, but are increasingly manifested as the animal approaches adulthood. No intervention or cure is known that can reverse this programming in postnatal life. Our findings suggest that close to normal growth and slaughter results can be obtained at least until puberty in animals which have undergone adverse programming in foetal life, but manifestation of programming effects becomes increasingly evident in adult animals. Due to the risk of transfer of the adverse programming effects to future generations, it is therefore recommended that animals that are suspected to have undergone adverse FP are not used for reproduction. Unfortunately, no reliable biomarkers have as yet been identified that allow accurate identification of adversely programmed offspring at birth, except for very low or high birth weights, and, in pigs, characteristic changes in head shape (dolphin head). Future efforts should be therefore dedicated to identify reliable biomarkers and evaluate their effectiveness for alleviation/reversal of the adverse programming in postnatal life. Our sheep studies have shown that the adverse impacts of an extreme, high-fat diet in early postnatal life, but not prenatal undernutrition, can be largely reversed by dietary correction later in life. Thus, birth (at term) appears to be a critical set point for permanent programming in animals born precocial, such as sheep. Appropriate attention to the nutrition of the late pregnant dam should therefore be a priority in animal production systems.
胎儿编程（FP）的概念源于人类流行病学研究，其中胎儿期营养与生命后期的健康和疾病状况相关联。自这一现象被提出以来，人们已在各种动物模型中对其进行评估，以更深入地了解人类健康和疾病的胎儿起源背后的机制。在胎儿编程研究中，绵羊已被广泛用作人类模型。在本文中，我们将主要回顾来自我们哥本哈根绵羊模型的研究结果，探讨妊娠后期营养不良对生命后期生长、发育、代谢和内分泌功能的影响，并讨论这些影响如何可能取决于出生后早期给动物投喂的饲料。我们的结果表明，胎儿营养不良的负面影响，无论是由于营养过剩，特别是妊娠后期营养不足，都可能损害广泛的调节生长以及可能还有生殖性状的内分泌功能。这些影响在出生后早期不易观察到，但随着动物接近成年期会越来越明显地表现出来。目前还没有已知的干预措施或疗法可以在出生后逆转这种编程。我们的研究结果表明，至少在青春期前，在胎儿期经历过不良编程的动物可以获得接近正常的生长和屠宰结果，但编程效应在成年动物中越来越明显。由于不良编程效应有传递给后代的风险，因此建议怀疑经历过不良胎儿编程的动物不用于繁殖。不幸的是，除了极低或极高的出生体重，以及在猪中头部形状的特征性变化（海豚头）外，尚未鉴定出可靠的生物标志物来在出生时准确识别受到不良编程的后代。因此，未来的努力应致力于鉴定可靠的生物标志物，并评估它们在减轻/逆转出生后不良编程方面的有效性。我们的绵羊研究表明，出生后早期极端高脂肪饮食的不利影响，而不是产前营养不足，在生命后期通过饮食纠正可以在很大程度上得到逆转。因此，足月出生似乎是早产动物（如绵羊）永久性编程的关键设定点。因此，在动物生产系统中，应优先适当关注妊娠后期母羊的营养。
