Estimating short and longer-term exposure of domestic cats to dietary iodine fluctuation.

Hyperthyroidism is a common endocrinopathy of domestic felines. In humans, toxic nodular goitre is pathophysiologically similar to feline hyperthyroidism and can be caused by chronically low or fluctuating dietary iodine intake. The aetiopathogenesis of feline hyperthyroidism is not known, but chronically low or fluctuating dietary iodine intake is likely common. This study assessed habitual iodine intake in domestic cats by: (1) conducting a dietary survey involving 361 owners of 549 cats, (2) analysing iodine content of 119 cat feeds, 38 urine and 64 hair samples and (3) assessing variation in iodine content of eight cat feeds over 4-6 different batches. Owners varied their cats feed regularly, usually on a day-to-day basis and often between wet and dry feeds with differing flavours. The majority (78%; 93 of 119) feeds for cats were within the guideline range for iodine. Of the 22% (n = 26 feeds) that were not compliant, the majority (n = 23) were below the nutritional minimum value with most (n = 16) being dry kibble. Iodine content of feeds did not vary considerably between types of feed or feed packaging, but variation between different batches of the same feed was 14-31%. Hence, urine iodine in cats also varied markedly. Cats being treated for hyperthyroidism had lower hair iodine. In conclusion, a survey assessing how domestic cats are fed, together with an analysis of commercial cat feeds suggests that domestic cats are likely to experience chronically low or fluctuating dietary iodine intake. The latter is supported by wide variation in urine iodine content.

Equine influenza vaccination as reported by horse owners and factors influencing their decision to vaccinate or not.

BACKGROUND: Equine influenza virus is a highly contagious respiratory pathogen that causes pyrexia, anorexia, lethargy and coughing in immunologically naïve horses. Vaccines against equine influenza are available and vaccination is mandatory for horses that participate in affiliated competitions, but this group forms a small proportion of the total horse population. The aims of this study were to: i) identify the equine influenza vaccination rate as reported in 2016 by horse owners in the United Kingdom (UK); ii) examine the demographics of owners and horses which were associated with significantly lower influenza vaccination rates and iii) explore factors that influence horse owners' decisions around influenza vaccine uptake. RESULTS: Responses from 4837 UK horse owners who were responsible for 10,501 horses were analysed. An overall equine influenza vaccination rate of 80% (8385/10501) was reported. Several owner demographic characteristics were associated with significantly lower (p<0.05) reported equine influenza vaccination rates including: some geographical locations, increasing horse owner age, annual household income of less that £15,000 and owning more than one horse. Horse-related features which were associated with significantly lower reported equine influenza vaccination rates included age ranges of <4 years and > 20 years, use as a companion or breeding animal or leaving their home premises either never or at most once a year. The most common reasons cited for failing to vaccinate horses was no competition activity, lack of exposure to influenza and expense of vaccines. In contrast, the most common underlying reasons given by horse owners who vaccinated their horse were protection of the individual horse against disease, veterinary advice and to protect the national herd. Owners of vaccinated horses had less previous experience of an influenza outbreak or adverse reaction to vaccination compared with owners of unvaccinated horses. CONCLUSIONS: This study documented a high rate of equine influenza vaccination as reported by owners in a substantial number of horses in the UK, but this does not reflect the level of protection. Sub-populations of horses which were less likely to be vaccinated and the factors that influence each owner's decision around vaccination of their horses against equine influenza were identified, but may alter following the 2019 European influenza outbreak. This information may nevertheless help veterinary surgeons identify "at-risk" patients and communicate more personalised advice to their horse-owning clients. It may also influence educational campaigns about equine influenza directed to horse owners, which aim to improve uptake of vaccination against this pathogen.

Renal accumulation of prooxidant mineral elements and CKD in domestic cats.

Felids have a high incidence of chronic kidney disease (CKD), for which the most common renal lesion is chronic interstitial nephritis (CIN). CIN can be induced by tissue oxidative stress, which is determined by the cellular balance of pro- and anti-oxidant metabolites. Fish-flavoured foods are more often fed to cats than dogs, and such foods tend to have higher arsenic content. Arsenic is a pro-oxidant metallic element. We propose that renal accumulation of pro-oxidant elements such as arsenic and depletion of anti-oxidant elements such as zinc, underpin the high incidence of CIN in domestic cats. Total arsenic and other redox-reactive metal elements were measured in kidneys (after acid-digestion) and urine (both by inductively-coupled plasma-mass spectrometry) of domestic cats (kidneys, n = 56; urine, n = 21), domestic dogs (kidneys, n = 54; urine, n = 28) and non-domesticated Scottish Wildcats (kidneys, n = 17). Renal lesions were graded by severity of CIN. In our randomly sampled population, CIN was more prevalent in domestic cat versus domestic dog (51%, n = 32 of 62 cats; 15%, 11 of 70 dogs were positive for CIN, respectively). CIN was absent from all Scottish wildcats. Tissue and urinary (corrected for creatinine) arsenic content was higher in domestic cats, relative to domestic dogs and wildcats. Urine arsenic was higher in domestic cats and dogs with CIN. Arsenobetaine, an organic and relatively harmless species of arsenic, was the primary form of arsenic found in pet foods. In summary, the kidneys of domestic cats appear to have greater levels of pro-oxidant trace elements, as compared to dogs and wildcats. Since there was no difference in renal arsenic levels in cats with or without CIN, renal arsenic accumulation does not appear a primary driver of excess CIN in cats. Given clear differences in renal handling of pro vs. anti-oxidant minerals between cats and dogs, further in vivo balance studies are warranted. These may then inform species-specific guidelines for trace element incorporation into commercial diets.

Ultrasonographic-based predictive factors influencing successful return to racing after superficial digital flexor tendon injuries in flat racehorses: A retrospective cohort study in 469 Thoroughbred racehorses in Hong Kong.

BACKGROUND: Superficial digital flexor tendon (SDFT) injury is an important health and welfare concern in racehorses. It is generally diagnosed with ultrasonography, but predictive ultrasonographic features have not been reported. OBJECTIVES: To determine ultrasonographic features of forelimb SDFT injury at initial presentation in Thoroughbred racehorses that could predict a successful return to racing (completing ≥5 races). STUDY DESIGN: Retrospective cohort study. METHODS: Digitised ultrasonographic images of 469 horses with forelimb SDFT injuries from the Hong Kong Jockey Club (2003-2014) were evaluated, using a previously validated ultrasonographic scoring system. Six ultrasonographic parameters were evaluated (type and extent of the injury, location, echogenicity, cross-sectional area and longitudinal fibre pattern of the maximal injury zone [MIZ]), as well as horse signalment, retirement date and number of races before and after injury. Data were analysed by generalised linear regression with significance at P<0.05. RESULTS: Cases were divided into two groups: 1) For cases of SDFT tendonitis with core lesions, cross-sectional area at the MIZ was the most significant factor determining a successful return to racing (P = 0.03). If the lesion was <50% of the total cross-sectional area, horses had 29-35% probability of successfully racing again, but if it was ≥50% this decreased to 11-16%. 2) For cases of SDFT tendonitis without a core lesion, longitudinal fibre pattern at the MIZ best predicted a successful return to racing (P = 0.002); if the affected longitudinal fibre pattern was <75% of the total, horses had 49-99% probability of successfully return to racing, but if it was ≥75% this decreased to 14%. MAIN LIMITATIONS: Prognostic information may not be applicable to other breeds/disciplines. CONCLUSIONS: This is the first study to describe ultrasonographic features of forelimb SDFT injuries at initial presentation that were predictive of successful return to racing. The outcomes will assist with early, evidence-based decisions on prognosis in Thoroughbred racehorses.

Mineral analysis of complete dog and cat foods in the UK and compliance with European guidelines.

Mineral content of complete pet food is regulated to ensure health of the companion animal population. Analysis of adherence to these regulatory guidelines has not been conducted. Here, mineral composition of complete wet (n = 97) and dry (n = 80) canine and feline pet food sold in the UK was measured to assess compliance with EU guidelines. A majority of foods complied with ≥8 of 11 guidelines (99% and 83% for dry and wet food, respectively), but many failed to provide nutritional minimum (e.g. Cu, 20% of wet food) or exceeded nutritional maximum (e.g. Se, 76% of wet food). Only 6% (6/97) of wet and 38% (30/80) of dry food were fully compliant. Some foods (20-30% of all analysed) had mineral imbalance, such as not having the recommended ratio of Ca:P (between 1:1 to 2:1). Foods with high fish content had high levels of undesirable metal elements such as arsenic. This study highlights broad non-compliance of a range of popular pet foods sold in the UK with EU guidelines (94% and 61% of wet and dry foods, respectively). If fed exclusively and over an extended period, a number of these pet foods could impact the general health of companion animals.

Radiographic assessment of the skeletons of Dolly and other clones finds no abnormal osteoarthritis.

Our recent report detailing the health status of cloned sheep concluded that the animals had aged normally. This is in stark contrast to reports on Dolly (first animal cloned from adult cells) whose diagnoses of osteoarthritis (OA) at 5½ years of age led to considerable scientific concern and media debate over the possibility of early-onset age-related diseases in cloned animals. Our study included four 8-year old ewes derived from the cell line that gave rise to Dolly, yet none of our aged sheep showed clinical signs of OA, and they had radiographic evidence of only mild or, in one case, moderate OA. Given that the only formal record of OA in Dolly is a brief mention of a single joint in a conference abstract, this led us to question whether the original concerns about Dolly's OA were justified. As none of the original clinical or radiographic records were preserved, we undertook radiographic examination of the skeletons of Dolly and her contemporary clones. We report a prevalence and distribution of radiographic-OA similar to that observed in naturally conceived sheep, and our healthy aged cloned sheep. We conclude that the original concerns that cloning had caused early-onset OA in Dolly were unfounded.

Seroepidemiology of Toxoplasma gondii infection in patients with liver disease in eastern China.

The role of the protozoan parasite Toxoplasma gondii in the pathogenesis of liver disease has recently gained much interest. The aim of this study was to determine the prevalence and risk factors associated with T. gondii infection in patients with liver disease from three cities in Shandong and Henan provinces, China. A case-control study was conducted from December 2014 to November 2015 and included 1142 patients with liver disease and 1142 healthy controls. Serum samples were collected from all individuals and were examined with enzyme-linked immunosorbent assay for the presence of anti-T. gondii IgG and IgM antibodies. Information on the demographics, clinical, and lifestyle characteristics of the participants was collected from the medical records and by the use of a questionnaire. The prevalence of anti-T. gondii IgG was 19·7% in patients with liver disease compared with 12·17% in the controls. Only 13 patients had anti-T. gondii IgM antibodies compared with 12 control individuals (1·14% vs. 1·05%, respectively). The highest seroprevalence was detected in patients with liver cancer (22·13%), followed by hepatitis patients (20·86%), liver cirrhosis patients (20·42%), and steatosis patients (20%). Multivariate logistic regression analysis indicated that consumption of raw meat (odds ratio (OR) = 1·32; 95% confidence interval (CI) 1·01-1·71; P = 0·03) and source of drinking water from wells (OR = 1·56; 95% CI 1·08-2·27; P = 0·01) were independent risk factors for T. gondii infection in liver disease patients. These findings indicate that T. gondii infection is more likely to be present in patients with liver disease. Therefore, efforts should be directed toward health education of populations at high risk of T. gondii infection and measures should be taken to protect vulnerable patients with liver disease.

Mineral status in canine medial coronoid process disease: a cohort study using analysis of hair by mass spectrometry.

In several species, developmental skeletal diseases involving abnormal endochondral ossification have been associated with imbalanced mineral intake. Hair analysis reflects long-term mineral status. To determine the mineral content of hair from dogs with or without medial coronoid process disease (MCPD). Dogs with MCPD have a different profile of minerals known to influence metalloenzymes involved in endochondral ossification. After cleansing, chelation and acid digestion of hair samples (n=79 in total: control dogs, n=70 v MCPD, n=9), mineral profile (7 major and 25 trace elements) was determined by inductively coupled plasma-mass spectrometry. Dogs were of similar age (control, 4.05 [1.85-7.70] v MCPD, 4.30 [3.25-6.53] median (IQR) years; P=0.78) and gender (control, n=43/27 v MCPD, n=4/5 males/females). 28/70 (40 per cent) of control and 8/9 (88 per cent) of MCPD dogs were neutered, respectively. Hair from dogs with MCPD contained significantly lower amounts (µg/g/DM) of copper, sulphur and zinc (all at P<0.001). Age, sex and neutered status had no effect on hair mineral status. Based on hair analysis, a role for mineral imbalance including copper, sulphur and zinc in the aetiopathogenesis of canine MCPD is suggested. Hair mineral analysis may prove useful as a biomarker for susceptible puppies.

Epigenetics and developmental programming of welfare and production traits in farm animals.

The concept that postnatal health and development can be influenced by events that occur in utero originated from epidemiological studies in humans supported by numerous mechanistic (including epigenetic) studies in a variety of model species. Referred to as the 'developmental origins of health and disease' or 'DOHaD' hypothesis, the primary focus of large-animal studies until quite recently had been biomedical. Attention has since turned towards traits of commercial importance in farm animals. Herein we review the evidence that prenatal risk factors, including suboptimal parental nutrition, gestational stress, exposure to environmental chemicals and advanced breeding technologies, can determine traits such as postnatal growth, feed efficiency, milk yield, carcass composition, animal welfare and reproductive potential. We consider the role of epigenetic and cytoplasmic mechanisms of inheritance, and discuss implications for livestock production and future research endeavours. We conclude that although the concept is proven for several traits, issues relating to effect size, and hence commercial importance, remain. Studies have also invariably been conducted under controlled experimental conditions, frequently assessing single risk factors, thereby limiting their translational value for livestock production. We propose concerted international research efforts that consider multiple, concurrent stressors to better represent effects of contemporary animal production systems.

Healthy ageing of cloned sheep.

The health of cloned animals generated by somatic-cell nuclear transfer (SCNT) has been of concern since its inception; however, there are no detailed assessments of late-onset, non-communicable diseases. Here we report that SCNT has no obvious detrimental long-term health effects in a cohort of 13 cloned sheep. We perform musculoskeletal assessments, metabolic tests and blood pressure measurements in 13 aged (7-9 years old) cloned sheep, including four derived from the cell line that gave rise to Dolly. We also perform radiological examinations of all main joints, including the knees, the joint most affected by osteoarthritis in Dolly, and compare all health parameters to groups of 5-and 6-year-old sheep, and published reference ranges. Despite their advanced age, these clones are euglycaemic, insulin sensitive and normotensive. Importantly, we observe no clinical signs of degenerative joint disease apart from mild, or in one case moderate, osteoarthritis in some animals. Our study is the first to assess the long-term health outcomes of SCNT in large animals.

Ministry of Health Clinical Practice Guidelines: Diabetes Mellitus.

The Ministry of Health (MOH) have updated the clinical practice guidelines on Diabetes Mellitus to provide doctors and patients in Singapore with evidence-based treatment for diabetes mellitus. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Diabetes Mellitus, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Paraganglioma with acute hyperamylasaemia masquerading as acute pancreatitis.

Phaeochromocytomas are rare catecholamine-producing tumours. Although classically described to present with headache, diaphoresis and palpitations, they also present in unusual ways; hyperamylasaemia is one such rare presentation. We describe a man with an extra-adrenal phaeochromocytoma (paraganglioma) presenting with diaphoresis, abdominal pain and multi-organ failure. He had hyperamylasaemia of 1,087 (normal range [NR] 44-161) U/L, which mimicked acute severe pancreatitis. Serum lipase and radiographic imaging of the pancreas appeared normal, and the serial amylase levels normalised over six days upon stabilisation of his condition. 24-hour urinary metanephrines of 10,406 (NR 400-1,500) nmol/day suggested a catecholamine-secreting tumour, and metaiodobenzylguanine scintigraphy confirmed this. We postulate that amylase (of the salivary isotype) is released by hypoxic tissues when high catecholamine levels cause vasoconstriction and that fluctuating hypotension decreases organ perfusion. This case highlights the need for awareness of rare presentations of phaeochromocytomas and encourages physicians to rethink the diagnosis when investigations are inconsistent.

Suboptimal maternal nutrition, during early fetal liver development, promotes lipid accumulation in the liver of obese offspring.

Maternal nutrition during the period of early organ development can modulate the offspring's ability to metabolise excess fat as young adults when exposed to an obesogenic environment. This study examined the hypothesis that exposing offspring to nutrient restriction coincident with early hepatogenesis would result in endocrine and metabolic adaptations that subsequently lead to increased ectopic lipid accumulation within the liver. Pregnant sheep were fed either 50 or 100% of total metabolisable energy requirements from 30 to 80 days gestation and 100% thereafter. At weaning, offspring were made obese, and at ~1 year of age livers were sampled. Lipid infiltration and molecular indices of gluconeogenesis, lipid metabolism and mitochondrial function were measured. Although hepatic triglyceride accumulation was not affected by obesity per se, it was nearly doubled in obese offspring born to nutrient-restricted mothers. This adaptation was accompanied by elevated gene expression for peroxisome proliferator-activated receptor γ (PPARG) and its co-activator PGC1α, which may be indicative of changes in the rate of hepatic fatty acid oxidation. In contrast, maternal diet had no influence on the stimulatory effect of obesity on gene expression for a range of proteins involved in glucose metabolism and energy balance including glucokinase, glucocorticoid receptors and uncoupling protein 2. Similarly, although gene expressions for the insulin and IGF1 receptors were suppressed by obesity they were not influenced by the prenatal nutritional environment. In conclusion, excess hepatic lipid accumulation with juvenile obesity is promoted by suboptimal nutrition coincident with early development of the fetal liver.

Dietary regulation of developmental programming in ruminants: epigenetic modifications in the germline.

Ruminants have been utilised extensively to investigate the developmental origins of health and disease, with the sheep serving as the model species of choice to complement dietary studies in the rat and mouse. Surprisingly few studies, however, have investigated delayed effects of maternal undernutrition during pregnancy on adult offspring health and a consistent phenotype, together with underlying mechanistic pathways, has not emerged. Nevertheless, when broad consideration is given to all studies with ruminants it is apparent that interventions that are initiated very early in gestation, and/or prior to conception, lead to greater effects on adult physiology than those that are specifically targeted to late gestation. Effects induced following dietary interventions at the earliest stages of mammalian development have been shown to arise as a consequence of alterations to key epigenetic processes that occur in germ cells and pluripotent embryonic cells. Currently, our understanding of epigenetic programming in the germline is greatest for the mouse, and is considered in detail in this article together with what is known in ruminants. This species imbalance, however, looks set to change as fully annotated genomic maps are developed for domesticated large animal species, and with the advent of 'next-generation' DNA sequencing technologies that have the power to globally map the epigenome at single-base-pair resolution. These developments would help to address such issues as sexually dimorphic epigenetic alterations to DNA methylation that have been found to arise following dietary restrictions during the peri-conceptional period, the effects of paternal nutritional status on epigenetic programming through the germline, and transgenerational studies where, in future, greater emphasis in domesticated ruminants should be placed on traits of agricultural importance.

Influence of prenatal nutrition and obesity on tissue specific fat mass and obesity-associated (FTO) gene expression.

The recent discovery of an association between body composition, energy intake and the fat mass and obesity-associated (FTO) gene represents a promising new therapeutic target in obesity prevention. In a well, pre-established large animal model, we investigated the regulation of FTO gene expression under conditions either leading to obesity or increased risk of obesity related disorders: i) a sedentary 'Western' lifestyle and ii) prenatal exposure to nutrient restriction. Pregnant sheep were either fed to fully meet their nutritional requirements throughout gestation or 50% of this amount from early-to-mid gestation. Following weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. A significant positive relationship between placental FTO gene expression and fetal weight was found at 110 days gestation. In both the newborn and adult offspring, the hypothalamus was the major site of FTO gene expression. Hypothalamic FTO gene expression was upregulated by obesity and was further increased by prenatal nutrient restriction. Importantly, we found a strong negative relationship between the hypothalamic FTO gene expression and food intake in lean animals only that may imply FTO as a novel controller of energy intake. In contrast, FTO gene expression in the heart was downregulated in obese offspring born to nutrient restricted mothers. In addition, FTO gene expression was unaffected by obesity or prenatal diet in insulin-dependent tissues, where it changed with age possibly reflecting adaptations in cellular energetic activity. These findings extend information gained from human epidemiology and provide new insights into the regulation of in vivo energy metabolism to prevent obesity.

Effect of the early-life nutritional environment on fecundity and fertility of mammals.

The early-life developmental environment is instrumental in shaping our overall adult health and well-being. Early-life diet and endocrine exposure may independently, or in concert with our genetic constitution, induce a pathophysiological process that amplifies with age and leads to premature morbidity and mortality. Recently, this has become known as 'programming' but is akin to 'maternal effects' described for many years in the biological sciences and is defined as any influence that acts during critical developmental windows to induce long-term changes in the organisms' phenotype. To date, such delayed maternal effects have largely been characterized in terms of susceptibility to cardiovascular or metabolic disease. Here, we review evidence from experimental animal species, non-human primates and man for an effect of the early-life nutritional environment on adult fecundity and fertility. In addition, using a database of pedigree sheep, we also specifically test the hypothesis that being born small for gestational age with or without post-natal growth acceleration directly programmes fertility. We conclude that there is a lack of compelling evidence to suggest pre-natal undernutrition may directly reduce adult fecundity and fertility, but may exert some effects secondarily via an increased incidence of 'metabolic syndrome'. Possible effects of being born relatively large on subsequent fecundity and fertility warrant further investigation.

Effect of maternal nutrient restriction from early to midgestation on cardiac function and metabolism after adolescent-onset obesity.

Maternal nutrient restriction (NR) from early to midgestation has marked effects on endocrine sensitivity and organ function of the resulting offspring. We hypothesized that early NR may reset the expression profile of genes central to myocardial energy metabolism, influencing ectopic lipid deposition and cardiac function in the obese adult offspring. NR offspring were exposed to an "obesogenic" environment, and their cardiac function and molecular indexes of myocardial energy metabolism were assessed to explore the hypothesis that an obese individual's risk of heart disease may be modified after maternal NR. Pregnant sheep were fed 100% (control) or 50% (NR) energy requirement from days 30 to 80 of gestation and 100% energy requirement thereafter. At weaning, offspring were exposed to an obesogenic environment or remained lean. At approximately 1 yr of age, the hemodynamic response of these offspring to hypotension, together with left ventricular expression profiles of fatty acid-binding protein 3 (FABP3), peroxisome proliferator-activated receptor-gamma (PPARgamma) and its coactivator (PGC)-1alpha, acetyl-CoA carboxylase (ACC), AMP-activated protein kinase (AMPK)-alpha(2), and voltage-dependent anion channel 1 (VDAC1), was determined. Obesity produced left ventricular hypertrophy in all animals, with increased ectopic (myocardial) lipid in NR offspring. Obesity per se significantly reduced myocardial transcript expression of PGC-1alpha, AMPKalpha(2), VDAC1, and ACC and increased expression of PPARgamma and FABP3. However, although NR animals were similarly obese, their transcript expression of ACC, PPARgamma, and FABP3 was similar to that of lean animals, indicating altered cardiac energy metabolism. Indeed, blunted tachycardia and an amplified inotropic response to hypotension characterized cardiac function in obese NR offspring. The results suggest that maternal NR during early organogenesis can precipitate an altered myocardial response to hypotension and increased myocardial lipid deposition in the adult offspring after adolescent-onset obesity, potentially rendering these individuals more at risk of early heart failure as they age.

Maternal nutrient restriction between early and midgestation and its impact upon appetite regulation after juvenile obesity.

The impact of maternal nutrient restriction during early-to-midgestation, a period coinciding with early fetal brain development, on appetite regulation and energy balance in the offspring after juvenile obesity was examined. Pregnant sheep were either fed to meet fully their nutritional requirements throughout gestation or 50% of this amount between 30 and 80 d gestation. After weaning, offspring were either made obese through exposure to a sedentary obesogenic environment or remained lean. Maternal nutrient restriction had no effect on birth weight or subsequent growth. At 1 wk of age, only, gene expression for neuropeptide Y in the hypothalamus was reduced in nutrient-restricted offspring. By 1 yr of age, all O animals had increased plasma leptin, nonesterified fatty acids, and insulin, with the latter effect amplified in NR offspring. Fasting plasma glucose, triglycerides, and cortisol were unaffected by obesity. The entrained reduction in physical activity that led to obesity persisted when all animals were maintained within individual pens. However, NRO offspring exhibited reduced daily food intake and were, therefore, no longer in positive "energy balance." This adaptation was accompanied by elevated hypothalamic gene expression for the melanocortin-4 and insulin receptors, AMP-activated kinase, and acetyl coenzyme A carboxylase alpha. In conclusion, nutrient restriction specifically targeted over the period of early fetal brain development contributes to a profoundly different adaptation in energy balance after juvenile obesity. The extent to which this adaptive response may benefit the offspring or result in an exacerbated risk of type 2 diabetes remains to be established.

Developmental programming of reproduction and fertility: what is the evidence?

The concept of the foetal/developmental origins of adult disease has been around for ~20 years and from the original epidemiological studies in human populations much more evidence has accumulated from the many studies in animal models. The majority of these have focused upon the role of early dietary intake before conception, through gestation and/or lactation and subsequent interactions with the postnatal environment, e.g. dietary and physical activity exposures. Whilst a number of theoretical models have been proposed to place the experimental data into a biological context, the underlying phenomena remain the same; developmental deficits (of single (micro) nutrients) during critical or sensitive periods of tissue growth alter the developmental pathway to ultimately constrain later functional capacity when the individual is adult. Ageing, without exception, exacerbates any programmed sequelae. Thus, adult phenotypes that have been relatively easy to characterise (e.g. blood pressure, insulin sensitivity, body fat mass) have received most attention in the literature. To date, relatively few studies have considered the effect of differential early environmental exposures on reproductive function and fecundity in predominantly mono-ovular species such as the sheep, cow and human. The available evidence suggests that prenatal insults, undernutrition for example, have little effect on lifetime reproductive capacity despite subtle effects on the hypothalamic-pituitary-gonadal axis and gonadal progenitor cell complement. The postnatal environment is clearly important, however, since neonatal/adolescent growth acceleration (itself not independent from prenatal experience) has been shown to significantly influence fecundity in farm animals. The present paper will expand these interesting areas of investigation and review the available evidence regarding developmental programming of reproduction and fertility. However, it appears there is little strong evidence to indicate that offspring fertility and reproductive senescence in the human and in farm animal species are overtly affected by prenatal nutrient exposure. Nevertheless, it is clear that the developing gonad is sensitive to its immediate environment but more detailed investigation is required to specifically test the long-term consequences of nutritional perturbations during pregnancy on adult reproductive well-being.

Fetal mechanisms that lead to later hypertension.

Extensive epidemiological and experimental evidence suggests the nutritional environment in which a developing conceptus is exposed is a major factor determining later cardiovascular disease. In this review a consideration of the extent to which altered maternal/fetal nutritional environments may predispose toward later anomalies in blood pressure control and hypertension will be undertaken. In particular, a focus will be on potentially novel mechanistic pathways through which early-mid gestational undernutrition may impact upon fetal/adult adipocyte, renal and brain function, that act to increase the risk of later hypertension developing. Within the review we shall also present an opinion on the differing animal models that are currently employed to address developmental programming and introduce a conceptual framework that synthesises current available evidence.