Epigenetics and transgenerational inheritance in domesticated farm animals

Epigenetics provides a molecular mechanism of inheritance that is not solely dependent on DNA sequence and that can account for non-Mendelian inheritance patterns. Epigenetic changes underlie many normal developmental processes, and can lead to disease development as well. While epigenetic effects have been studied in well-characterized rodent models, less research has been done using agriculturally important domestic animal species. This review will present the results of current epigenetic research using farm animal models (cattle, pigs, sheep and chickens). Much of the work has focused on the epigenetic effects that environmental exposures to toxicants, nutrients and infectious agents has on either the exposed animals themselves or on their direct offspring. Only one porcine study examined epigenetic transgenerational effects; namely the effect diet micronutrients fed to male pigs has on liver DNA methylation and muscle mass in grand-offspring (F2 generation). Healthy viable offspring are very important in the farm and husbandry industry and epigenetic differences can be associated with production traits. Therefore further epigenetic research into domestic animal health and how exposure to toxicants or nutritional changes affects future generations is imperative.     

Research Progress on Relationship between Nutrition and Epigenetic Modification

Epigenetics is a branch of genetics to study the gene expression of heritable changes when nucleotide sequence has no change.Although classical genetics theory deems that genetic DNA sequence can dominate parental gene to their offspring,growing evidence suggests that environmental factors such as nutrition play an important role in modifying genetic expression.Nutrition can affect epigenetics by DNA methylation,histone modification and microRNA (miRNA).More and more researches prove that nutrition (especially early-life nutrition) is very important to keep the body healthy.The author mainly focused on the research progress about the relationship between nutrition and epigenetic modification and its mechanism,including animal or human chronically expose on the feed condition of protein and energy deficiency,high fat,overfeeding and some especial nutrients to provide reference for the further study.     

营养与表观遗传修饰关系的研究进展

表观遗传学是在DNA碱基序列不变的前提下引起的基因表达或细胞表观型变化的一种遗传现象。经典遗传学理论认为DNA序列的遗传能够主导亲代基因传递给后代,但越来越多的证据表明营养等环境因素对基因表达具有重要的修饰作用,如营养因素可通过DNA甲基化、组蛋白修饰和microRNA(miRNA)调控等作用来影响表观遗传,且营养素对机体健康的保持有着非常重要的作用(尤其是生命早期的营养)。作者就动物或人长期暴露在蛋白质缺乏、能量不足、高脂和采食过度等营养不平衡日粮条件下,以及一些特殊的营养素作用条件下,其表观遗传修饰的变化及作用机制方面的最新研究进展进行综述,旨在为后续的深入研究提供参考。     

Board-invited review: intrauterine growth retardation: implications for the animal sciences

Intrauterine growth retardation (IUGR), defined as impaired growth and development of the mammalian embryo/fetus or its organs during pregnancy, is a major concern in domestic animal production. Fetal growth restriction reduces neonatal survival, has a permanent stunting effect on postnatal growth and the efficiency of feed/forage utilization in offspring, negatively affects whole body composition and meat quality, and impairs long-term health and athletic performance. Knowledge of the underlying mechanisms has important implications for the prevention of IUGR and is crucial for enhancing the efficiency of livestock production and animal health. Fetal growth within the uterus is a complex biological event influenced by genetic, epigenetic, and environmental factors, as well as maternal maturity. These factors impact on the size and functional capacity of the placenta, uteroplacental blood flows, transfer of nutrients and oxygen from mother to fetus, conceptus nutrient availability, the endocrine milieu, and metabolic pathways. Alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, metabolism, and postnatal growth of the offspring. Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenic factor) and polyamines (key regulators of DNA and protein synthesis) may provide a unified explanation for the etiology of IUGR in response to maternal undernutrition and overnutrition. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the role of maternal nutrition on fetal programming and genomic imprinting. Innovative interdisciplinary research in the areas of nutrition, reproductive physiology, and vascular biology will play an important role in designing the next generation of nutrient-balanced gestation diets and developing new tools for livestock management that will enhance the efficiency of animal production and improve animal well being.     

Inclusive inheritance for residual feed intake in pigs and rabbits

Non-genetic information (epigenetic, microbiota, behaviour) that results in different phenotypes in animals can be transmitted from one generation to the next and thus is potentially involved in the inheritance of traits. However, in livestock species, animals are selected based on genetic inheritance only. The objective of the present study was to determine whether non-genetic inherited effects play a role in the inheritance of residual feed intake (RFI) in two species: pigs and rabbits. If so, the path coefficients of the information transmitted from sire and dam to offspring would differ from the expected transmission factor of 0.5 that occurs if inherited information is of genetic origin only. Two pigs (pig1, pig2) and two rabbits (rabbit1, rabbit2) datasets were used in this study (1,603, 3,901, 5,213 and 4,584 records, respectively). The test of the path coefficients to 0.5 was performed for each dataset using likelihood ratio tests (null model: transmissibility model with both path coefficients equal to 0.5, full model: unconstrained transmissibility model). The path coefficients differed significantly from 0.5 for one of the pig datasets (pig2). Although not significant, we observed, as a general trend, that sire path coefficients of transmission were lower than dam path coefficients in three of the datasets (0.46 vs 0.53 for pig1, 0.39 vs 0.44 for pig2 and 0.38 vs 0.50 for rabbit1). These results suggest that phenomena other than genetic sources of inheritance explain the phenotypic resemblance between relatives for RFI, with a higher transmission from the dam's side than from the sire's side.     

小型猪动物模型在医学领域中的研究应用

猪在解剖学和生理学等方面与人极其相似。小型猪作为实验动物模型应用于医学研究领域,其优点是:体型小,饲料消耗低,管理操作方便,特别是经过人工培育的各品系小型猪能够配合试验,应激小,基因纯合度较高,成为理想的动物模型。作者综述了小型猪的国内外品种、品系,及其作为动物模型在心血管系统领域、消化系统领域、皮肤整形领域、外科领域、器官移植领域、口腔系统领域的研究与应用。     

Differences in susceptibility to Haemophilus parasuis infection in pigs

In animal breeding programs, deoxyribonucleic acid (DNA) markers can be used to identify sires that are less susceptible to disease. These DNA markers are typically discovered in populations that display differences in susceptibility. To find those differences, it was hypothesized that sires influence their offspring responses to infection with H. parasuis. To identify differences in susceptibility, colostrum-deprived pigs derived from 6 sires were inoculated with a virulent strain of H. parasuis serovar 5. Pigs were infected at 21-d of age and euthanized 1, 2, or 3 days post-infection. Rectal temperatures, bacterial detection, clinical signs, and lesions were measured by comparing disease susceptibility in the offspring from each sire. The effect of the sire on the severity of disease in the offspring was statistically analyzed using to a 2-way ANOVA with sire and test day as fixed effects. Significant differences among sires were found for lesions, rectal temperatures from days 0-1 and 0-2 (P < 0.05) and marginal effects for clinical signs (P = 0.08). On average, the offspring of sire H94 was the most susceptible to challenge. Responses to infection were categorized to determine the clinical responses and analyzed by Chi square. Overall, 10% of all pigs infected were fully resistant to H. parasuis infection. Boar H94 didn't produce any fully resistant offspring. Differences in susceptibility to H. parasuis were observed, and the results support the hypothesis that sires influence their offspring's response to infection. Tissues from this population could be used to identify DNA markers for genetic selection of sires that produce offspring more resistant to H. parasuis infection.     

Telegony,the Sire Effect and non‐Mendelian Inheritance Mediated by Spermatozoa: A Historical Overview and Modern Mechanistic Speculations

Telegony is the belief that the sire first mated to a female will have an influence upon some of that female’s later offspring by another male. Although the reality of telegony was acknowledged by such authorities as Darwin, Spencer, Romanes and many experienced breeders, it has been met with scepticism because of Weismann’s unfavourable comments and negative results obtained in several test experiments. In this article, alleged cases of telegony are provided. A search of the literature of cell biology and biochemistry reveals several plausible mechanisms that may form the basis for telegony. These involve the penetration of spermatozoa into the somatic tissues of the female genital tract, the incorporation of the DNA released by spermatozoa into maternal somatic cells, the presence of foetal DNA in maternal blood, as well as sperm RNA‐mediated non‐Mendelian inheritance of epigenetic changes.     

表观遗传调控机制在犬肿瘤中的研究进展

犬肿瘤性疾病是兽医临床上常发的一种疾病，其发病率较高，是造成世界范围内犬死亡的重要原因之一，由于其病理学分类、自发性、基因和信号通路等方面与人类肿瘤有相似之处，可作为人类肿瘤的研究模型。表观遗传是基于DNA序列没有发生改变的情况下所致基因功能和表达水平发生了可遗传的变化，主要通过基因转录或翻译过程的调控，影响其功能和特性。表观遗传改变主要包括DNA甲基化水平改变、组蛋白修饰、染色质重塑和非编码RNA调控等。DNA异常甲基化在犬的多种肿瘤中均有研究，包括犬白血病、淋巴瘤及黑色素瘤等，且犬与人类肿瘤的DNA异常甲基化模式相似。在肿瘤中组蛋白各种修饰酶表达失调，是抗肿瘤药物开发分子靶点研究的主要焦点，但目前在犬肿瘤中的研究较少。非编码RNA中microRNA与lncRNA是目前的研究热点，已有较多研究致力于开发针对非编码RNA的靶向研究药物，但目前在兽医领域应用较少。作者主要综述了犬肿瘤疾病的流行病学、DNA甲基化、组蛋白修饰、非编码RNA等表观遗传学变化在犬肿瘤中的研究进展，揭示表观遗传异常与犬肿瘤发生发展的关系，以期为开发犬肿瘤性疾病诊断、靶向治疗及预后的特异性标志物提供参考依据。     

Domestic animal models for biomedical research

Experimental animals in biomedical research provide insights into disease mechanisms and models for determining the efficacy and safety of new therapies and for discovery of corresponding biomarkers. Although mouse and rat models are most widely used, observations in these species cannot always be faithfully extrapolated to human patients. Thus, a number of domestic species are additionally used in specific disease areas. This review summarizes the most important applications of domestic animal models and emphasizes the new possibilities genetic tailoring of disease models, specifically in pigs, provides.     

抑制素及其对动物生殖机能的影响

抑制素是一种水溶性多肽激素,对动物生殖活动有重要的调控作用,是内源性FSH分泌的调节剂之一,抑制素抗原免疫可以有效的提高雌性动物的排卵率,对雄性动物生殖功能也有重要的作用,这些也正是家畜繁殖力的基础。随着免疫学的发展和免疫技术的进步,抑制素必将大规模用于畜牧生产,比如可制成多胎疫苗以提高家畜的产仔数。因此,研究抑制素对动物生殖机能的影响,对于提高动物的生殖潜力以及对人类计划生育的研究,都具有重要的理论价值和应用前景。     

Commercially available rabbit anti-human polyclonal antisera as a useful tool for immune system studies in veterinary species

We have used selected rabbit anti-human polyclonal antibodies as an example of useful and easily available tools for studies on immune system structure and development in important veterinary species, many of which also represent animal models in biomedicine. The cocktail of anti-human Igkappa-FITC/anti-Iglambda-RPE F(ab')(2) fragments was used for two-colour and, in combination with the cross-reactive anti-CD79alpha monoclonal antibody HM-57, for three-colour flow cytometry of canine, feline, bovine and porcine peripheral B-cells. A possible application of such immunoreagents in studies on primary B-cell differentiation has been suggested in pigs; the same approach can be used in other species of interest. Rabbit anti-human lactoferrin-FITC F(ab')(2) fragment was used for visualizing neutrophils in dogs, pigs and cattle and an application for two-colour immunophenotyping of canine granulocyte subsets has been designed. Affinity isolated rabbit anti-human CD3 and anti-human TdT have been shown to represent a ready-to-use tool for in situ studies on primary T-lymphopoiesis in pigs with possible extensions both to the B-lineage development in pigs and other animal models. Altogether, our study show that carefully selected polyclonal antibodies available on the market may possess broad cross-reactivity with important applications in veterinary research.     

DNA甲基化在动物遗传育种中的研究进展

DNA甲基化作为表观遗传学修饰方法之一,对基因的表达发挥重要的调控作用。随着众多DNA甲基化检测技术(如高通量检测技术)的迅速发展对DNA甲基化的生物信息学研究已经变成了一个非常活跃的热点。在动物遗传育种方面,由于DNA甲基化程度的改变,可能影响众多性状相关基因的表达量,因此改变动物的各种性状。所以目前已有相关研究开始探索DNA甲基化在动物遗传育种上的具体作用。     

牧草表观遗传学研究进展

表观遗传是指在DNA序列不变的情况下基因表达发生变化的现象。表观遗传现象与外界环境条件的变化紧密相关,它参与植物的生长发育、胁迫响应、衰老死亡等重要生命过程并在其中起到了关键作用。表观遗传学作为一门新兴学科在近20年间得到了快速发展,成为当前动植物和医学领域的研究热点。目前植物表观遗传学的相关研究主要集中在DNA甲基化、组蛋白修饰、RNA甲基化、染色质重塑和非编码RNA修饰等方面,并取得了许多重要成果。然而,相对于模式植物拟南芥和其他主要作物而言,牧草的表观遗传学研究仍处于起步阶段。因此,开展牧草表观遗传学研究对我国草牧业的可持续发展具有重要意义。本研究对表观遗传学的概念、研究方法、研究内容(包括DNA甲基化、组蛋白修饰、RNA甲基化、染色质重塑和非编码RNA修饰等)及牧草表观遗传学相关研究进行了全面总结和综述,并对表观遗传在草牧业中的发展前景进行了展望。     

Cell Biology Symposium: Zinc finger nucleases to create custom-designed modifications in the swine (Sus scrofa) genome

Engineered zinc finger nucleases (ZFN) are rapidly gaining popularity as a means to enhance the rate and specificity of DNA modifications in plant and animal cells. Repair-mediated gene modification by ZFN is driven by introducing DNA double-strand breaks via a nonspecific nuclease domain linked to a sequence-specific zinc finger nucleotide recognition domain. This review examines the use of ZFN to produce genetically modified swine and the potential of this technology for the future. By combining conventional gene targeting methods with somatic cell nuclear transfer, several genetically modified pig models have been produced. These conventional techniques are inefficient in mammalian somatic cells and provide little control over the site specificity and rate of exogenous DNA integration. The use of engineered ZFN that bind and cleave genomic DNA at specific loci can enhance targeting efficiencies by orders of magnitude. Recent publication of the first genetic modification in pigs by combining ZFN technology with somatic cell nuclear transfer has opened the door to genome targeting with a precision that was not previously possible in a large animal model. Since that time, model pigs with selective knockout of endogenous genes have been produced. This review will examine the use of ZFN to generate these pig models and the potential of ZFN to accelerate the production of genetically modified pigs of agricultural and biomedical importance. Current methods of ZFN design, important considerations for their safe and effective use in modification of the swine genome, and future innovative applications of this technology in pigs will be discussed.     

Impacts of prenatal nutrition on animal production and performance: a focus on growth and metabolic and endocrine function in sheep

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.     

Pestiviruses in wild animals

Pestiviruses are not strictly host-species specific and can infect not only domestic but also wild animals. The most important pestivirus, CSFV, infects domestic pigs and wild boars, which may cause a major problem for successful CSFV eradication programmes. Mainly BVDV specific antibodies have been reported in captive and free-living animals. Virus has been isolated from some of these animal species, but since BVDV can contaminate cell cultures and foetal calf serum, early reports of BVDV isolation have to be considered with caution. Genetic typing of early pestivirus isolates from wild species revealed that the majority were BVDV-1. Of the pestiviruses identified so far three species (CSFV, BVDV-1, giraffe pestivirus) and three genotypes (BDV-2, BDV-4, pronghorn) appear to circulate in wildlife animal populations. The potential for pestiviruses to spread between farm animals and free-living animals is discussed as are epidemiological and technical problems, and the future direction of research.     

DNA甲基化与肿瘤研究进展

对肿瘤研究的不断深入,发现除了基因突变之外,表观遗传改变也与肿瘤的发生发展密切相关。肿瘤表观遗传的改变以DNA的异常甲基化为主。DNA的异常甲基化几乎存在于任何类型的人类肿瘤中,包括皮肤恶性肿瘤。DNA甲基化是指在DNA甲基化酶的作用下,以S-腺苷酸-L-甲硫氨酸为甲基供体,将甲基转移到特定碱基上的过程。基因的正常功能除了依赖于正常结构外,还依赖于正常的甲基化状态。DNA的异常甲基化在肿瘤发生中起重要作用。     

表观遗传修饰在骨骼肌细胞增殖分化过程中的研究进展

骨骼肌是肌肉的主要构成部分，骨骼肌细胞发生增殖和分化的过程都是肌肉发育的基础，直接影响着家养动物的产肉性能。研究发现表观遗传修饰作用对骨骼肌细胞增殖分化具有重要的调控作用，表明该遗传修饰作用对家养动物肌肉发育具有重大的意义。作者从DNA甲基化对骨骼肌细胞增殖分化影响、组蛋白乙酰化所含因子调控基因选择表达作用、非编码RNA调控和染色体重塑作用所起的影响等方面分别介绍了表观遗传在骨骼肌细胞增殖分化过程中的研究进展，简述了不同修饰方式和不同作用因子对骨骼肌增殖和分化两个过程的影响。同时也回顾了前人在研究骨骼肌增殖分化过程所用到的方法和手段，进而分析了表观调控作用因子在骨骼肌生长过程中所起到的作用。旨在进一步阐述表观遗传修饰在骨骼肌增殖和分化过程中所起到的重要作用，增强对骨骼肌增殖分化调控过程的了解，为和动物生产实际相结合提供参考途径，同时也为骨骼肌生长发育等分子调控提供更多参考素材。     

Research Progress of Epigenetics Modification in the Process of Skeletal Muscle Cell Proliferation and Differentiation

Skeletal muscle is the most abundant tissue and the main component of muscle in animals.The process of skeletal muscle cell's proliferation and differentiation is the basis of muscle development and it's directly affects the meat production performance of domestic animals.It has been found that epigenetic modification plays an important role in regulating the proliferation and differentiation of skeletal muscle cells.In this study,the effects of epigenetics on skeletal muscle in terms of the effects of DNA methylation on the proliferation and differentiation of skeletal muscle cells,the selection and expression of factors regulated by histone acetylation,the regulation of non-coding RNA,and the effects of chromosome remodeling.Research progress in the process of muscle cell proliferation and differentiation,briefly describes the effects of different modification methods and factors on the two processes of skeletal muscle proliferation and differentiation.At the same time,the methods and means used by predecessor in the study of skeletal muscle proliferation and differentiation were reviewed,and then the role of apparent regulatory factors in skeletal muscle growth was analyzed.The purpose was to further explain the important role of epigenetic modification in the proliferation and differentiation of skeletal muscle,enhanced the understanding of the regulation of skeletal muscle proliferation and differentiation,provided a reference path for integration with animal production,and also provided skeletal muscle.Molecular regulation of such as growth and development provided more reference materials.