Chromosome-length genome assembly of Teladorsagia circumcincta - a globally important helminth parasite in livestock.

BACKGROUND: Gastrointestinal (GIT) helminthiasis is a global problem that affects livestock health, especially in small ruminants. One of the major helminth parasites of sheep and goats, Teladorsagia circumcincta, infects the abomasum and causes production losses, reductions in weight gain, diarrhoea and, in some cases, death in young animals. Control strategies have relied heavily on the use of anthelmintic medication but, unfortunately, T. circumcincta has developed resistance, as have many helminths. Vaccination offers a sustainable and practical solution, but there is no commercially available vaccine to prevent Teladorsagiosis. The discovery of new strategies for controlling T. circumcincta, such as novel vaccine targets and drug candidates, would be greatly accelerated by the availability of better quality, chromosome-length, genome assembly because it would allow the identification of key genetic determinants of the pathophysiology of infection and host-parasite interaction. The available draft genome assembly of T. circumcincta (GCA_002352805.1) is highly fragmented and thus impedes large-scale investigations of population and functional genomics. RESULTS: We have constructed a high-quality reference genome, with chromosome-length scaffolds, by purging alternative haplotypes from the existing draft genome assembly and scaffolding the result using chromosome conformation, capture-based, in situ Hi-C technique. The improved (Hi-C) assembly resulted in six chromosome-length scaffolds with length ranging from 66.6 Mbp to 49.6 Mbp, 35% fewer sequences and reduction in size. Substantial improvements were also achieved in both the values for N50 (57.1 Mbp) and L50 (5 Mbp). A higher and comparable level of genome and proteome completeness was achieved for Hi-C assembly on BUSCO parameters. The Hi-C assembly had a greater synteny and number of orthologs with a closely related nematode, Haemonchus contortus. CONCLUSION: This improved genomic resource is suitable as a foundation for the identification of potential targets for vaccine and drug development.

Non-invasive assessment of fecal glucocorticoid and androgen metabolites in the pygmy hippopotamus (Choeropsis liberiensis).

The pygmy hippopotamus (Choeropsis liberiensis) is an endangered species endemic to the Upper Guinea Forest ecosystem in West Africa. We have limited information concerning the species' reproduction and well-being under managed care. We therefore developed non-invasive methods for characterizing gonadal androgen and adrenal hormone profiles in pygmy hippos using fecal samples collected from 12 males and 12 females housed in North American zoological institutions. We aimed to: 1) identify and validate enzyme immunoassays (EIAs) for measuring metabolites of corticosteroids and testosterone in feces; and 2) test whether gonadal activity is correlated with previous breeding history, season or type of housing. For glucocorticoids, several EIAs for measuring metabolites were investigated. A group-specific EIA exhibiting cross-reactivity with 11,17-dioxoandrostane (DOA) metabolites of cortisol most clearly reflected adrenocortical activity in response to pharmocological challenge with adrenocorticotropic hormone (ACTH) in both males and females. However, day-to-day concentrations of this metabolite in the feces of pygmy hippos that did not undergo ACTH challenge were near the detection limits of the assay, making this EIA impractical for assessing glucocorticoid activity in this species. Another group-specific EIA, exhibiting cross-reactivity with 5α-pregnane-3ß,11ß,21-triol-20-one, produced biologically relevant data and evidence of an appropriate response to pharmacological challenge with exogenous ACTH. The testosterone metabolite assay C196 (Arbor Assays, Ann Arbor, Michigan, USA) also produced biologically coherent data: adult males exhibited the highest mean androgen metabolite concentrations (477 ng/g), followed by adult females (259 ng/g) and juvenile males (160 ng/g). Proven breeding males had higher, but not significantly different, mean concentrations (472 ng/g) to unproven males (352 ng/g; P = 0.400). Similarly, adult males housed outdoors year-round in subtropical climates exhibited higher, but not statistically different mean concentrations (554 ng/g) to males in temperate climates that were housed indoors at least part of the year (412 ng/g; P = 0.208). There were, however, significant differences in mean concentrations among seasons for adult males, with higher values in spring (546 ng/g) and summer (542 ng/g) than in autumn (426 ng/g) and winter (388 ng/g, P = 0.003). In conclusion, we identified EIAs for the measurement of fecal metabolites of androgens and glucocorticoids that can be used for further studies to monitor gonadal activity in male pygmy hippos and adrenocortical activity in both sexes. We also identified a seasonal trend in male gonadal activity in this species under managed care in North America. Finally, our findings highlight an important consideration when using non-invasive methods for evaluating fecal cortisol metabolites: ACTH used for pharmacological validation of an EIA does not necessarily equate to biological relevance.

Contribution of the Immune Response in the Ileum to the Development of Diarrhoea caused by Helminth Infection: Studies with the Sheep Model.

Gastrointestinal helminths are a global health issue, for humans as well as domestic animals. Most studies focus on the tissues that are infected with the parasite, but here we studied the ileum, a tissue that is rarely infected by helminths. We tested whether inflammation in the ileum contributes to the development and severity of diarrhoea, by comparing sheep that are susceptible (n = 4) or resistant (n = 4) to the disease. We analyzed the ileum transcriptome using RNASeq sequencing approach and various bioinformatics tools including FastQC, STAR, featureCounts, DESeq2, DAVID, clusterProfiler, Cytoscape (ClusterONE) and EnrichR. We identified 243 differentially expressed genes (DEGs), of which 118 were up-regulated and 125 were down-regulated DEGs in the diarrhoea-susceptible animals compared to the diarrhoea-resistant animals. The resulting DEGs were functionally enriched for biological processes, pathways and gene set enrichment analysis. The up-regulated DEGs suggested that an inflammatory immune response was coupled with genes involved in 'Th2 immune response' and 'anti-inflammatory response'. The down-regulated DEGs were related to ion transport, muscle contraction and pathways preventing inflammation. We conclude that i) susceptibility to helminth-induced diarrhoea involves an inflammatory response at a non-infectious site; ii) down-regulation of pathways preventing inflammation can contribute to the severity of diarrhoea; and iii) genes involved in anti-inflammatory responses can reduce the inflammation and diarrhoea.

Maternal undernutrition during pregnancy and lactation increases transcription factors, ETV5 and GDNF, and alters regulation of apoptosis and heat shock proteins in the testis of adult offspring in the rat.

We tested whether changes in Sertoli cell transcription factors and germ cell heat shock proteins (HSPs) are linked to the effects of maternal undernutrition on male offspring fertility. Rats were fed ad libitum with a standard diet (CONTROL) throughout pregnancy and lactation or with 50% of CONTROL intake throughout pregnancy (UNP) or lactation (UNL) or both periods (UNPL). After postnatal Day 21, 10 male pups per group were fed a standard diet ad libitum until postnatal Day 160 when testes were processed for histological, mRNA and immunohistochemical analyses. Compared with CONTROL: caspase-3 was increased in UNP and UNPL (P=0.001); Bax was increased in UNL (P=0.002); Bcl-2 (P<0.0001) was increased in all underfed groups; glial cell line-derived neurotrophic factor (P=0.002) was increased in UNP and UNL; E twenty-six transformation variant gene 5 and HSP70 were increased, and HSP90 was diminished in all underfed groups (P<0.0001). It appears that maternal undernutrition during pregnancy and lactation disrupts the balance between proliferation and apoptosis in germ cells, increasing germ cell production and perhaps exceeding the support capacity of the Sertoli cells. Moreover, fertility could be further compromised by changes in meiosis and spermiogenesis mediated by germ cell HSP90 and HSP70.

The ovarian follicle of ruminants: the path from conceptus to adult.

This review resulted from an international workshop and presents a consensus view of critical advances over the past decade in our understanding of follicle function in ruminants. The major concepts covered include: (1) the value of major genes; (2) the dynamics of fetal ovarian development and its sensitivity to nutritional and environmental influences; (3) the concept of an ovarian follicle reserve, aligned with the rise of anti-Müllerian hormone as a controller of ovarian processes; (4) renewed recognition of the diverse and important roles of theca cells; (5) the importance of follicular fluid as a microenvironment that determines oocyte quality; (6) the 'adipokinome' as a key concept linking metabolic inputs with follicle development; and (7) the contribution of follicle development to the success of conception. These concepts are important because, in sheep and cattle, ovulation rate is tightly regulated and, as the primary determinant of litter size, it is a major component of reproductive efficiency and therefore productivity. Nowadays, reproductive efficiency is also a target for improving the 'methane efficiency' of livestock enterprises, increasing the need to understand the processes of ovarian development and folliculogenesis, while avoiding detrimental trade-offs as greater performance is sought.

Amino Acids in the Nutrition and Production of Sheep and Goats.

In sheep and goats, amino acid nutrition is essential for the maintenance of health and productivity. In this review, we analysed literature, mostly from the past two decades, focusing on assessment of amino acid requirements, especially on the balance of amino acid profiles between ruminal microbial protein and animal production protein (foetal growth, body weight gain, milk and wool). Our aim was to identify amino acids that might limit genetic potential for production. We propose that much attention should be paid to amino acid nutrition of individuals with greater abilities to produce meat, milk or wool, or to nourish large litters. Moreover, research is warranted to identify interactions among amino acids, particularly these amino acids that can send positive and negative signals at the same time.

Mobility of Japanese quail spermatozoa and its relationship to egg fertility.

Sperm mobility (SM) appears to be primary determinant of fertility in chicken and turkey. The aims of this study were to extend the concept to the Japanese quail by developing an assay to quantify SM, explaining the basis of SM using motility properties measured by CASA, and exploring the relationship between SM and egg fertility. The study was carried out in three stages: i) males (n = 20) and females (n = 20) were mated individually; ii) ejaculates were collected from 20 males, and SM was measured; iii) males (n = 20) and females (n = 20) were mated individually. In Stages I and III, data were collected for egg fertility, SpermOPVL and HolesIPVL . In Stage II, SM assay was developed and assay conditions were defined: effect of sperm numbers on absorbance in Accudenz solution; effect of Accudenz concentration on sperm motility and mobility; effect of quail proctodeal gland foam extract and incubation temperature on SM at 37 and 41°C. The recorded absorbance of sperm movement was dependent on sperm numbers in the sperm suspension overlaying the Accudenz (p < .001). At 41°C, SM, progressively motile sperm, VCL, VSL and VAP were negatively affected by Accudenz concentration (p < .05). The effect of foam on SM and motility depended on an interaction between the concentration of foam extract and incubating temperature. Males were categorized into low, average and high SM phenotypes. These categories differed significantly (p < .001), but sperm motility and SM were not related to egg fertility. In conclusion, SM assay can be used to identify mobility phenotypes, but the poor relationship between SM and egg fertility indicates a need for further studies on interaction between the concentration of foam extract, incubating temperature, and in vivo sperm movement and egg fertilization success.

Seventy years of progestagen treatments for management of the sheep oestrous cycle: where we are and where we should go.

Management of the ovine oestrous cycle is mainly based on the use of exogenous hormones to mimic or enhance (progesterone and its analogues) or manipulate (prostaglandin F2α and its analogues) the activity of the corpus luteum, combined with the application of other hormones mimicking the pituitary secretion of gonadotrophins (e.g. equine chorionic gonadotrophin). These protocols have been applied without major change for decades but, now, there are two reasons to reconsider them: (1) our greatly improved knowledge of the dynamics of ovarian physiology, following the application of transrectal ultrasonography, indicates that modification of the protocols may improve fertility yields and (2) increasing concerns about animal health and welfare, food safety and the environmental impact of the treatments, as evidenced by public opinion and therefore market forces. Here, we offer an overview of these issues, introduce an updated protocol and suggest ways for future improvements to the protocols.

Age-related declines in ejaculate quality and sperm kinematics vary among strains of Japanese Quail (Coturnix japonica).

For successful breeding programs, it is important to quantify the useful period of a male's reproductive life and it is often done simply by measurement of semen quality. This information is lacking for Japanese quail so we tested whether there is a decline in ejaculate quality and sperm kinematics with age, and whether the decline varies among strains. Nine males (n = 9) from each of 5 strains (A, B, C, D and E) were subjected to 4 semen collections (n = 16 per male) at 8, 16, 26 and 36 weeks of age. Ejaculate volume, sperm concentration and total sperm per ejaculate were measured, and sperm kinematics were analysed using a Sperm Class Analyser (SCA® ). There was a significant effect of age for ejaculate volume, total sperm per ejaculate and per cent medium sperm. The effect of the interaction between age and strain was significant for percent progressive motile sperm, percent rapid sperm, velocity curvilinear, velocity straight line, velocity average path, linearity, straightness and beat cross frequency. Ejaculate volume peaked at Week 26 in all strains, while peak values for sperm concentration and total sperm per ejaculate were observed at Week 16 for most strains. There were declines in percent motile sperm, progressive motile sperm and rapid sperm, and in velocity curvilinear velocity, velocity straight line and velocity average path, by Week 16 for most strains. Linearity declined by Week 26 in some strains, and all strains showed a significant decline in beat cross frequency by that age. In conclusion, the ability of CASA to detect age-related changes in sperm kinematics makes it a valuable tool for identifying the best males and thus improving quail flock fertility. It is essential that breeders understand that age affects both sperm production and sperm kinematics, and that the changes vary with strain.

Patterns of preoptic-hypothalamic neuronal activation and LH secretion in female sheep following the introduction and withdrawal of novel males.

The neuroendocrine response of female sheep to a novel male involves neural activation in the hypothalamus. However, if males are removed, the gonadotrophic signal declines, so the neural activity is likely to change. We examined Fos-immunoreactive (IR) cells in hypothalamic tissues from seasonally anovulatory female sheep exposed to males for 2 or 6h, or for 2h followed by 4h isolation from males. Control females were killed in the absence of male exposure. Male introduction increased LH secretion in all females; male removal was associated with a reduction only in mean and basal LH concentrations. Females exposed to males for 2h had more Fos-IR cells in the arcuate nucleus (ARC), ventromedial nucleus of the hypothalamus (VMH) and organum vasculosum of the lamina terminalis (OVLT) than control females. Fos-IR cells in the preoptic area (POA) were only greater than in control females after 6h exposure to a male. Removal of males decreased the number of Fos-IR cells in the ARC, VMH and OVLT, but not in the POA. Thus, hypothalamic neural activation and LH secretion in female sheep are stimulated by males and decline after male removal. However, activation in the POA persists after removal and may explain the incomplete decline in the LH response.

Pre-pubertal growth, muscle and fat accumulation in male and female sheep-Relationships with metabolic hormone concentrations, timing of puberty and reproductive outcomes.

Metabolic homeostasis is aligned with changes in growth and body composition, through processes mediated by circulating metabolites and metabolic hormones, and is eventually linked to reproductive success. In the present study with sheep, we determined the relationships among phenotypic and genotypic rates of growth, muscle and fat accumulation, and the circulating concentrations of metabolic and tested for relationships with the timing of puberty and subsequent reproductive outcomes. We used 64 females and 62 males with known phenotypic values for depth of eye muscle (EMD) and fat (FAT) and known Australian Sheep Breeding Values at post-weaning age for live weight (PWT), depth of eye muscle (PEMD) and depth of fat (PFAT). Blood plasma sampled every 20 min for 8 hr via was assayed for growth hormone (GH), insulin-like growth factor I (IGF-I), insulin, leptin, ghrelin, follistatin, glucose and non-esterified fatty acids (NEFA). In males, PWT was positively related to the concentrations of GH, follistatin and glucose, whereas FAT and PFAT were positively related to IGF-I concentrations (p < .01). Testosterone concentration was negatively related to muscle variables (p < .001) and to PFAT (p < .05). In females, the only significant relationship detected was the positive link between EMD and insulin concentrations (p < .05). Reproductive variables were only measured in females. Live weight at first oestrus was related positively to insulin concentration and negatively to GH concentration (p < .05). No other relationships with reproductive variables were significant. The relationships that were detected suggest subtle differences between the sexes in the way their metabolic homeostasis responds to changes in the rates of growth, and muscle and fat accumulation, perhaps due to interference by testosterone in the males.

Phyto-oestrogens affect fertilisation and embryo development in vitro in sheep.

Phyto-oestrogens such as isoflavones are natural compounds that can profoundly affect reproductive function. In the present study, we tested whether including isoflavone compounds (genistein, biochanin A, formononetin) in the maturation medium would affect the outcomes for ovine oocytes in vitro. Each isoflavone compound was evaluated at five concentrations (0, 2.5, 5, 10, 25µgmL-1) and the entire protocol was repeated four times. Cumulus-oocyte complexes were randomly allocated to the treatments, then fertilised and cultured in vitro. Compared with control (0µgmL-1), the lower concentrations of isoflavone (2.5, 5 and 10µgmL-1) had no detectable effect on the rates of cleavage or embryo development, or on embryo total cell counts (TCC). However, the highest concentration (25µgmL-1) of all three isoflavones exerted a variety of effects (P<0.05): genistein decreased cleavage rate, blastocyst rate and blastocyst efficiency (blastocysts produced per 100 oocytes); biochanin A decreased cleavage rate and blastocyst efficiency; and formononetin decreased blastocyst rate and blastocyst efficiency. Biochanin A (25µgmL-1) reduced embryo TCC specifically at the hatched blastocyst stage (P<0.05). We conclude that the presence of isoflavones at 25µgmL-1 during IVM decreases the cleavage rate and inhibits blastocyst hatching.

Functional changes in mRNA expression and alternative pre-mRNA splicing associated with the effects of nutrition on apoptosis and spermatogenesis in the adult testis.

BACKGROUND: The effects of nutrition on testis mass in the sexually mature male have long been known, however, the cellular and molecular processes of the testis response to nutrition was not fully understood. METHODS: We tested whether the defects in spermatogenesis and increases in germ cell apoptosis in the testis that are induced by under-nutrition are associated with changes in mRNA expression and pre-mRNA alternative splicing using groups of 8 male sheep fed for a 10% increase or 10% decrease in body mass over 65 days. RESULTS: We identified 2,243 mRNAs, including TP53 and Claudin 11, that were differentially expressed in testis from underfed and well-fed sheep (FDR < 0.1), and found that their expression changed in parallel with variations in germ cell numbers, testis size, and spermatogenesis. Furthermore, pairs of 269 mRNAs and 48 miRNAs were identified on the basis of target prediction. The regulatory effect of miRNAs on mRNA expression, in combination with functional analysis, suggests that these miRNAs are involved in abnormal reproductive morphology, apoptosis and male infertility. Nutrition did not affect the total number of alternative splicing events, but affected 206 alternative splicing events. A total of 159 genes, including CREM, SPATA6, and DDX4, were differentially spliced between dietary treatments, with functions related to RNA splicing and spermatogenesis. In addition, three gene modules were positively correlated with spermatogenesis-related phenotypic traits and negatively related to apoptosis-related phenotypic traits. Among these gene modules, seven (CFLAR, PTPRC, F2R, MAP3K1, EPHA7, APP, BCAP31) were also differentially expressed between nutritional treatments, indicating their potential as markers of spermatogenesis or apoptosis. CONCLUSIONS: Our findings on significant changes in mRNAs and pre-mRNA alternative splicing under-nutrition suggest that they may partly explain the disruption of spermatogenesis and the increase germ cell apoptosis. However, more research is required to verify their causal effects in regulating spermatogenesis and germ cell apoptosis.

Cellular and molecular responses of adult testis to changes in nutrition: novel insights from the sheep model.

This review explores the cellular and molecular mechanisms that regulate spermatogenesis in the post-pubertal testis that is regressing in response to mild undernutrition, using the sexually mature male sheep as a model. Testis regression leads to reductions in daily sperm production and in the quality of ejaculated spermatozoa (poorer movement, DNA damage). There is also a reduction in spermatogenic efficiency that appears to be caused, at least partially, by increases in germ cell apoptosis. Sertoli cell number does not change with testis regression, although about 1% of Sertoli cells do appear to retain proliferative ability after puberty. On the other hand, Sertoli cell function is disrupted during testis regression, as evidenced by a disorganization of tight junctions and indications that cell differentiation and maturation are reversed. Disrupted Sertoli cell function can explain, at least partially, the increase in germ cell apoptosis and any decrease in the rate of spermatogenesis, the two major contributors to spermatogenic efficiency. These outcomes seem to be mediated by changes in two RNA-based processes: (i) the expression of small non-coding RNAs that are involved in the regulation of Sertoli cell function, spermatogenesis and germ cell apoptosis and (ii) alternative pre-mRNA splicing that affects the regulation of spermatogenesis but does not appear to affect germ cell apoptosis, at least during testis progression induced by undernutrition in the male sheep. These research outcomes can be extended to other animal models and are relevant to issues in human male fertility.

Gene polymorphisms associated with temperament.

When individuals are exposed to stressful environmental challenges, the response varies widely in one or more of three components: psychology, behavior and physiology. This variability among individuals can be defined as temperament. In recent years, an increasing large body of evidence suggests that the dimensions of temperament, as well as personality, psychological disorders and behavioral traits, are influenced by genetic factors, and much of the variation appears to involve variation in genes or gene polymorphisms in the hypothalamic-pituitary-adrenocortical (HPA) axis and the behavior-controlling neurotransmitter networks. Here, we review our current understanding of the probabilistic impact of a number of candidate gene polymorphisms that control temperament, psychological disorders and behavioral traits in animals and human, including the gene polymorphisms related to corticotrophin-releasing hormone (CRH) production and adrenal cortisol production involved in the HPA axis, and a large number of gene polymorphisms in the dopaminergic and serotonergic neurotransmitter networks. It will very likely to assist in diagnosis and treatment of human relevant disorders, and provide useful contributions to our understanding of evolution, welfare and conservation, for animals in the wild and in production systems. Additionally, investigations of gene-gene and gene-environment complex interactions in humans and animals need further clear illustration.

A retrospective analysis of mortality in captive pygmy hippopotamus (Choeropsis liberiensis) from 1912 to 2014.

The pygmy hippopotamus (Choeropsis liberiensis) is an IUCN Red List Endangered species (CITES Appendix II) that has been housed in zoological collections since 1912. As wild populations continue to decline throughout the species' range, successful ex situ breeding and management, including an understanding of morbidity and mortality, are of utmost importance. This study is the first comprehensive review of mortality data from the captive population since 1982 and significantly expands on previous analyses. We solicited necropsy reports from 129/187 zoological institutions worldwide that currently or previously held pygmy hippos and received data for 404 animals (177 ♂, 220 ♀, 7 undermined sex), representing 43% of pygmy hippos that have died in captivity. Mortality in neonates was primarily due to perinatal causes (51.8%-stillbirth, failure to thrive, weakness, poor suckling reflex, maternal neglect) or parent-inflicted trauma (28%). Common causes of mortality in adult and geriatric animals included cardiovascular disease (16%), degenerative musculoskeletal conditions (10%), obstructive gastrointestinal disease (9%), and renal insufficiency (13%), sometimes associated with advanced polycystic kidney disease (PKD). Although not the direct cause of mortality, a number of adult and geriatric pygmy hippos were also overweight to obese. Infectious causes of mortality in included leptospirosis and encephalomyocarditis virus, the latter usually presenting as acute death due to cardiovascular demise. This comprehensive overview presents a useful guide for recommendations in preventative veterinary care and for improved husbandry and management of pygmy hippos in captivity. Zoo Biol. 35:556-569, 2016. © 2016 Wiley Periodicals, Inc.

Nutrition affects Sertoli cell function but not Sertoli cell numbers in sexually mature male sheep.

We tested whether the reversible effects of nutrition on spermatogenesis in sexually mature sheep were mediated by Sertoli cells. Rams were fed with diets designed to achieve a 10% increase (High), no change (Maintenance) or a 10% decrease (Low) in body mass after 65 days. At the end of treatment, testes were lighter in the Low than the High group (PP<0.05) in the expression of seven Sertoli cell-specific genes. Under-nutrition appeared to reverse cellular differentiation leading to disruption of tight-junction morphology. In conclusion, in sexually mature sheep, reversible reductions in testis mass and spermatogenesis caused by under-nutrition were associated with impairment of basic aspects of Sertoli cell function but not with changes in the number of Sertoli cells.

An Australasian perspective on the role of reproductive technologies in world food production.

Industries based on small ruminants are major contributors to world food supply but, in extensive grazing systems, reproductive technology is not directly relevant to most enterprises. More important is the need to respond to demand in high-profit export markets for products that are 'clean, green and ethical' (CGE). This combination of issues led to the concept of CGE management of reproduction that is based on scientific evidence but does not require complex technology. Nutrition is the major challenge because we are limited primarily to the grazing of forages and pastures, but responding to this challenge opens up opportunities-new forages can supply energy and protein whilst improving animal health and welfare, and reducing carbon emissions. A second major factor is the need for accurate coordination of nutritional inputs with reproductive events to ensure that the metabolic signals are appropriate. To control of the timing of reproduction, we need to move beyond simply managing the presence of the male and seek more precision. Our ultimate CGE package is thus based on manipulation of male socio-sexual signals as well as nutrition, in combination with greater use of ultrasound and birth-site management to prevent neonatal mortality. Finally, genetics is critical in the development of the CGE package.It would be difficult to incorporate the entire package in one hit-adaptations are needed to cover variations in genotype and the geographical and socio-economic environment, and some concepts need research and development. Therefore, we have suggested staged introduction of the elements of the package.CGE management can be simple and cost-effective, and improve productivity whilst safeguarding the future of the industries in society and the marketplace. Reproductive technology might not be used by many farmers but it will be an essential tool for realizing the vision because it underpins the acceleration of genetic progress in otherwise tardy grazing industries. Finally, we suggest that the socio-economic drivers and the scientific principles of CGE management are also applicable to smallholders in developing economies.