To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Low birth weight is associated with increased risk of cardiovascular disease in adulthood. Intrauterine growth restriction (IUGR) hearts have fewer CMs in early postnatal life, which may impair postnatal cardiovascular function and hence, explain increased disease risk, but whether the cardiomyocyte deficit persists to adult life is unknown. We therefore studied the effects of experimentally induced placental restriction (PR) on cardiac outcomes in young adult sheep. Heart size, cardiomyocyte number, nuclearity and size were measured in control (n=5) and PR (n=5) male sheep at 1 year of age. PR lambs were 36% lighter at birth (P=0.007), had 38% faster neonatal relative growth rates (P=0.001) and had 21% lighter heart weights relative to body weight as adults (P=0.024) than control lambs. Cardiomyocyte number, nuclearity and size in the left ventricle did not differ between control and PR adults; hearts of both groups contained cardiomyocytes (CM) with between one and four nuclei. Overall, cardiomyocyte number in the adult left ventricle correlated positively with birth weight but not with adult weight. This study is the first to demonstrate that intrauterine growth directly influences the complement of CM in the adult heart. Cardiomyocyte size was not correlated with cardiomyocyte number or birth weight. Our results suggest that body weight at birth affects lifelong cardiac functional reserve. We hypothesise that decreased cardiomyocyte number of low birth weight individuals may impair their capacity to adapt to additional challenges such as obesity and ageing.
Most individuals whose growth was restricted before birth undergo accelerated or catch-up neonatal growth. This is an independent risk factor for later metabolic disease, but the underlying mechanisms are poorly understood. This study aimed to test the hypothesis that natural and experimentally induced in utero growth restriction increase neonatal appetite and milk intake. Control (CON) and placentally restricted (PR) ewes carrying multiple fetuses delivered naturally at term. Outcomes were compared between CON (n=14) and PR (n=12) progeny and within twin lamb pairs. Lamb milk intake and feeding behaviour and ewe milk composition were determined using a modified weigh-suckle-weigh procedure on days 15 and 23. PR lambs tended to have lower birth weights than CON (−15%, P=0.052). Neonatal growth rates were similar in CON and PR, whilst heavier twins grew faster in absolute but not fractional terms than their co-twins. At day 23, milk protein content was higher in PR than CON ewes (P=0.038). At day 15, PR lambs had fewer suckling bouts than CON lambs and in females light twins had more suckling attempts than their heavier co-twins. Birth weight differences between twins positively predicted differences in milk intakes. Lactational constraint and natural prenatal growth restriction in twins may explain the similar milk intakes in CON and PR. Within twin comparisons support the hypothesis that prenatal constraint increases lamb appetite, although this did not increase milk intake. We suggest that future mechanistic studies of catch-up growth be performed in singletons and be powered to assess effects in each sex.
Epidemiology formed the basis of ‘the Barker hypothesis’, the concept of ‘developmental programming’ and today’s discipline of the Developmental Origins of Health and Disease (DOHaD). Animal experimentation provided proof of the underlying concepts, and continues to generate knowledge of underlying mechanisms. Interventions in humans, based on DOHaD principles, will be informed by experiments in animals. As knowledge in this discipline has accumulated, from studies of humans and other animals, the complexity of interactions between genome, environment and epigenetics, has been revealed. The vast nature of programming stimuli and breadth of effects is becoming known. As a result of our accumulating knowledge we now appreciate the impact of many variables that contribute to programmed outcomes. To guide further animal research in this field, the Australia and New Zealand DOHaD society (ANZ DOHaD) Animals Models of DOHaD Research Working Group convened at the 2nd Annual ANZ DOHaD Congress in Melbourne, Australia in April 2015. This review summarizes the contributions of animal research to the understanding of DOHaD, and makes recommendations for the design and conduct of animal experiments to maximize relevance, reproducibility and translation of knowledge into improving health and well-being.
Intrauterine growth restriction (IUGR) has adverse effects on metabolic health and early life, whereas physical activity is protective against later development of metabolic disease. Relationships between birth weight and physical activity in humans, and effects of IUGR on voluntary activity in rodents, are mixed and few studies have measured physical activity in a free-ranging environment. We hypothesized that induced restriction of placental growth and function (PR) in sheep would decrease spontaneous ambulatory activity (SAA) in free-ranging adolescent and young adult progeny from multi-fetal pregnancies. To test this hypothesis, we used Global Positioning System watches to continuously record SAA between 1800 and 1200 h the following day, twice during a 16-day recording period, in progeny of control (CON, n=5 males, 9 females) and PR pregnancies (n=9 males, 10 females) as adolescents (30 weeks) and as young adults (43 weeks). PR reduced size at birth overall, but not in survivors included in SAA studies. In adolescents, SAA did not differ between treatments and females were more active than males overall and during the day (each P<0.001). In adults, daytime SAA was greater in PR than CON females (P=0.020), with a similar trend in males (P=0.053) and was greater in females than males (P=0.016). Adult SAA was negatively correlated with birth weight in females only. Contrary to our hypothesis, restricted placental function and small size at birth did not reduce progeny SAA. The mechanisms for increased daytime SAA in adult female PR and low birth weight sheep require further investigation.
Intrauterine growth restriction (IUGR) and subsequent neonatal catch-up growth are implicated in the programming of increased appetite, adiposity and cardiometabolic diseases. Guinea pigs provide an alternate small animal model to rodents to investigate mechanisms underlying prenatal programming, being relatively precocial at birth, with smaller litter sizes and undergoing neonatal catch-up growth after IUGR. The current study, therefore, investigated postnatal consequences of spontaneous IUGR due to varying litter size in this species. Size at birth, neonatal, juvenile (post-weaning, 30–60 days) and adolescent (60–90 days) growth, juvenile and adolescent food intake, and body composition of young adults (120 days) were measured in 158 male and female guinea pigs from litter sizes of one to five pups. Compared with singleton pups, birth weight of pups from litters of five was reduced by 38%. Other birth size measures were reduced to lesser degrees with head dimensions being relatively conserved. Pups from larger litters had faster fractional neonatal growth and faster absolute and fractional juvenile growth rates (P<0.005 for all). Relationships of post-weaning growth, feed intakes and adult body composition with size at birth and neonatal growth rate were sex specific, with neonatal growth rates strongly and positively correlated with adiposity in males only. In conclusion, spontaneous IUGR due to large litter sizes in the guinea pig causes many of the programmed sequelae of IUGR reported in other species, including human. This may therefore be a useful model to investigate the mechanisms underpinning perinatal programming of hyperphagia, obesity and longer-term metabolic consequences.
Email your librarian or administrator to recommend adding this to your organisation's collection.