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Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Here we explored the developmental impact of gestational chronodisruption (chronic photoperiod shift, CPS) on adult and fetal adrenal biorhythms and function. We found that gestational chronodisruption altered fetal and adult adrenal function, at the molecular, morphological and physiological levels. The differences between control and CPS offspring suggest desynchronization of the adrenal circadian clock and steroidogenic pathway, leading to abnormal stress responses and metabolic adaptation, potentially increasing the risk of developing chronic diseases.Light at night is essential to a 24/7 society, but it has negative consequences on health. Basically, light at night induces an alteration of our biological clocks, known as chronodisruption, with effects even when this occurs during pregnancy. Indeed, an abnormal photoperiod during gestation alters fetal development, inducing long-term effects on the offspring. Accordingly, we carried out a longitudinal study in rats, exploring the impact of gestational chronodisruption on the adrenal biorhythms and function of the offspring. Adult rats (90 days old) gestated under chronic photoperiod shift (CPS) decrease the time spent in the open arm zone of an elevated plus maze to 62% and increase the rearing time to 170%. CPS adults maintained individual daily changes in corticosterone, but their acrophases were distributed from 12.00 h to 06.00 h. CPS offspring maintained clock gene expression and oscillation, nevertheless no daily rhythm was observed in genes involved in the regulation and synthesis of steroids. Consistent with adult adrenal gland being programmed during fetal life, blunted daily rhythms of corticosterone, core clock gene machinery, and steroidogenic genes were observed in CPS fetal adrenal glands. Comparisons of the global transcriptome of CPS versus control fetal adrenal gland revealed that 1078 genes were differentially expressed (641 down-regulated and 437 up-regulated). In silico analysis revealed significant changes in Lipid Metabolism, Small Molecule Biochemistry, Cellular Development and the Inflammatory Response pathway (z score: 48-20). Altogether, the present results demonstrate that gestational chronodisruption changed fetal and adult adrenal function. This could translate to long-term abnormal stress responses and metabolic adaptation, increasing the risk of developing chronic diseases.

Key points Maternal shift work increases the risk of pregnancy complications, although its effects on progeny health after birth are not clear. We evaluated the impact of a simulated shift work protocol for one-third, two-thirds or all of pregnancy on the metabolic health of sheep progeny. Simulated shift work had no effect on growth, body size, body composition or glucose tolerance in pre-pubertal or young adult progeny. Glucose-stimulated insulin secretion was reduced in adult female progeny and insulin sensitivity was increased in adult female singleton progeny. The results of the present study do not support the hypothesis that maternal shift work exposure impairs metabolic health of progeny in altricial species. Abstract Disrupted maternal circadian rhythms, such as those experienced during shift work, are associated with impaired progeny metabolism in rodents. The effects of disrupted maternal circadian rhythms on progeny metabolism have not been assessed in altricial, non-litter bearing species. We therefore assessed postnatal growth from birth to adulthood, as well as body composition, glucose tolerance, insulin secretion and insulin sensitivity, in pre-pubertal and young adult progeny of sheep exposed to control conditions (CON: 10 males, 10 females) or to a simulated shift work (SSW) protocol for the first one-third (SSW0-7: 11 males, 9 females), the first two-thirds (SSW0-14: 8 males, 11 females) or all (SSW0-21: 8 males, 13 females) of pregnancy. Progeny growth did not differ between maternal treatments. In pre-pubertal progeny (12-14 weeks of age), adiposity, glucose tolerance and insulin secretion during an i.v. glucose tolerance test and insulin sensitivity did not differ between maternal treatments. Similarly, in young adult progeny (12-14 months of age), food intake, adiposity and glucose tolerance did not differ between maternal treatments. At this age, however, insulin secretion in response to a glucose bolus was 30% lower in female progeny in the combined SSW groups compared to control females (P = 0.031), and insulin sensitivity of SSW0-21 singleton females was 236% compared to that of CON singleton female progeny (P = 0.025). At least in this model, maternal SSW does not impair progeny metabolic health, with some evidence of greater insulin action in female young adult progeny.

With the increased prevalence of non-communicable disease and availability of medications to treat these and other conditions, a pregnancy free from prescribed medication exposure is rare. Up to 99% of women take at least one medication during pregnancy. These medications can be divided into those used to improve maternal health and wellbeing (e.g., analgesics, antidepressants, antidiabetics, antiasthmatics), and those used to promote the baby's wellbeing in either fetal (e.g., anti-arrhythmics) or postnatal life (e.g., antenatal glucocorticoids). These medications are needed for pre-existing or coincidental illnesses in the mother, maternal conditions induced by the pregnancy itself through to conditions that arise in the fetus or that will be encountered by the newborn. Thus, medications administered to the mother may be used to treat the mother, the fetus or both. Metabolism of medications is regulated by a range of physiological processes that change during pregnancy. Other pathological processes such as placental insufficiency can in turn have both immediate and lifelong adverse health consequences for babies. Individuals born growth restricted are more likely to require medications but may also have an altered ability to metabolise these medications in fetal and postnatal life. This review aims to determine the effect of suboptimal fetal growth on the fetal expression of the drug metabolising enzymes (DMEs) that convert medications into active or inactive metabolites, and the transporters that remove both these medications and their metabolites from the fetal compartment. Refereed/Peer-reviewed

At birth, weight of the neonate is used as a marker of the 9-month journey as a fetus. Those neonates born less than the 10th centile for their gestational age are at risk of being intrauterine growth restricted.However, this depends on their genetic potential for growth and the intrauterine environment in which they grew. Alterations in the supply of oxygen and nutrients to the fetus will decrease fetal growth, but these alterations occur due to a range of causes that are maternal, placental or fetal in nature. Consequently, IUGR neonates are a heterogeneous population. For this reason, it is likely that these neonates will respond differently to interventions compared not only to normally grown fetuses, but also to other neonates that are IUGR but have travelled a different path to get there. Thus, a range of models of IUGR should be studied to determine the effects of IUGR on the development and function of the heart and lung and subsequently the impact of interventions to improve development of these organs. Here we focus on a range of models of IUGR caused by manipulation of the maternal, placental or fetal environment on cardiorespiratory outcomes. Refereed/Peer-reviewed

Key points Chronic hypoxaemia is associated with intrauterine growth restriction (IUGR) and a predisposition to the development of hypertension in adult life. IUGR fetuses exhibit a greater reliance on α-adrenergic activation for blood pressure regulation. The fetal blood pressure response to post-ganglionic blockade is not different between control and IUGR fetuses. The decrease in mean arterial pressure is greater in the IUGR sheep fetus after α-adrenergic receptor blockade at the level of the vasculature and this is inversely related to fetal P O 2 . The increased reliance that the IUGR fetus has on α-adrenergic activation for maintenance of mean arterial pressure is not a result of increased post-ganglionic sympathetic activation. Abstract Intrauterine growth restriction (IUGR) is associated with an increased risk of cardiovascular disease in adult life. Placental restriction (PR) in sheep results in chronic hypoxaemia and early onset IUGR with increased circulating plasma noradrenaline concentrations. These IUGR fetuses exhibit a greater decrease in mean arterial pressure (MAP) during α-adrenergic blockade. We aimed to determine the role of post-ganglionic sympathetic activation with respect to regulating MAP in IUGR fetal sheep. PR was induced by carunclectomy surgery prior to conception. Fetal vascular catheterization was performed at 110-126 days gestational age (GA) (term, 150 days) in nine control and seven PR-IUGR fetuses. The fetal blood pressure response to both a post-ganglionic and an α-adrenergic receptor blocker was assessed at 116-120 days GA and/or 129-131 days GA. The effect of both post ganglionic and α-adrenergic blockade on fetal blood pressure was then compared between control and IUGR fetuses at both GAs. There was no difference in the effect of post-ganglionic blockade on MAP in control and IUGR fetal sheep at either 116-120 days GA or 129-131 days GA. α-adrenergic receptor blockade decreased MAP to the same extent in both control and IUGR fetuses at 116-120 days GA. At 129-131 days GA, the drop in MAP in response to α-adrenergic receptor blockade was greater in IUGR fetuses than controls. There was a significant inverse relationship between the drop in MAP in response to α-adrenergic receptor blockade at both GAs with fetal P O 2 . Thus, the increased dependence on α-adrenergic activation for blood pressure regulation in the chronically hypoxaemic IUGR fetus is not a result of increased post-ganglionic sympathetic activation.

Purpose: Ten percent of pregnancies are affected by intrauterine growth restriction (IUGR), and evidence suggests that affected neonates have reduced activity of hepatic cytochrome P450 (CYP) drug metabolising enzymes. Given that almost all pregnant individuals take medications and additional medications are often required during an IUGR pregnancy, we aimed to determine the impact of IUGR on hepatic CYP activity in sheep fetuses and pregnant ewes. Methods: Specific probes were used to determine the impact of IUGR on the activity of several CYP isoenzymes (CYP1A2, CYP2C19, CYP2D6 and CYP3A) in sheep fetuses and pregnant ewes. Probes were administered intravenously to the ewe at 132 days (d) gestation (term 150 d), followed by blood sampling from the maternal and fetal circulation over 24 h. Maternal and fetal liver tissue was collected at 139–140 d gestation, from which microsomes were isolated and incubated with probes. Metabolite and maternal plasma cortisol concentrations were measured using Liquid Chromatography – tandem mass spectrometry (LC-MS/MS). Results: Maternal plasma cortisol concentration and maternal hepatic CYP1A2 and CYP3A activity was significantly higher in IUGR pregnancies. Maternal hepatic CYP activity was higher than fetal hepatic CYP activity for all CYPs tested, and there was minimal CYP1A2 or CYP3A activity in the late gestation fetus when assessed using in vitro methods. Conclusions: The physiological changes to the maternal-placental-fetal unit in an IUGR pregnancy have significant effects on maternal drug metabolism, suggesting changes in medications and/or doses may be required to optimise maternal and fetal health. Refereed/Peer-reviewed

Refereed/Peer-reviewed Introduction: Non-alcoholic fatty liver disease (NAFLD) is characterised by accumulation of triglycerides and cholesterol within the liver and dysregulation of specific hepatic cytochrome P450 (CYPs) activity. CYPs are involved in the metabolism of endogenous and exogenous chemicals. Hepatic CYP activity is dysregulated in human studies and animal models of a Western diet (WD) or low birth weight (LBW) independently, but the additive effects of LBW and postnatal WD consumption are unknown. As such, the aim of this study was to determine the independent and combined effect of birthweight and postnatal diet on hepatic CYP activity in a guinea pig model. Methods: LBW was generated via uterine artery ablation at mid gestation (term = 70 days gestation). Normal birthweight (NBW) and LBW pups were allocated either a control diet (CD) or WD at weaning. After 4 months of dietary intervention, guinea pigs were humanely killed, and liver tissue collected for biochemical and functional hepatic CYP activity analyses. Results: Independent of birthweight, functional activity of CYP3A was significantly reduced in female and male WD compared to CD animals (female, P < 0.0001; male, P = 0.004). Likewise, CYP1A2 activity was significantly reduced in male WD compared to CD animals (P = 0.020) but this same reduction was not observed in females. Conclusion: Diet, but not birthweight, significantly altered hepatic CYP activity in both sexes, and the effect of diet appeared to be greater in males. These findings may have clinical implications for the management of NAFLD and associated co-morbidities between the sexes.

Preclinical imaging studies of fetal hemodynamics require anesthesia to immobilize the animal. This may induce cardiovascular depression and confound measures under investigation. We compared the impact of four anesthetic regimes upon maternal and fetal blood gas and hemodynamics during baseline periods of normoxia, and in response to an acute hypoxic challenge in pregnant sheep. Merino ewes were surgically prepared with maternal and fetal vascular catheters and a fetal femoral artery flow probe at 105–109 days gestation. At 110–120 days gestation, ewes were anesthetized with either isoflurane (1.6%), isoflurane (0.8%) plus ketamine (3.6 mg·kg−1·h−1), ketamine (12.6 mg·kg−1·h−1) plus midazolam (0.78 mg·kg−1·h−1), propofol (30 mg·kg−1·h−1), or remained conscious. Following 60 min of baseline recording, nitrogen was administered directly into the maternal trachea to displace oxygen and induce maternal and thus fetal hypoxemia. During normoxia, maternal PaO2 was ~30 mmHg lower in anesthetized ewes compared to conscious controls, regardless of the type of anesthesia (p .05), but heart rate was 32 ± 8 bpm lower in fetuses from ewes administered isoflurane (p = .044). During maternal hypoxia, fetal MAP increased, and peripheral blood flow decreased in all fetuses except those administered propofol (p, Preclinical imaging studies of fetal haemodynamics require anaesthesia to immobilise the animal. In the presence of isoflurane, isoflurane/ketamine and ketamine/midazolam, but not propofol anaesthesia, maternal and fetal hypoxaemia increased fetal mean arterial pressure and decreased peripheral blood flow. Acute fetal hypoxaemia induced fetal tachycardia regardless of anaesthetic type. These results have implications for the design and interpretation of preclinical imaging studies where anaesthesia is required.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder affecting the reproductive, metabolic and psychological health of women. Clinic-based studies indicate that sleep disturbances and disorders including obstructive sleep apnea and excessive daytime sleepiness occur more frequently among women with PCOS compared to comparison groups without the syndrome. Evidence from the few available population-based studies is supportive. Women with PCOS tend to be overweight/obese, but this only partly accounts for their sleep problems as associations are generally upheld after adjustment for body mass index; sleep problems also occur in women with PCOS of normal weight. There are several, possibly bidirectional, pathways through which PCOS is associated with sleep disturbances. The pathophysiology of PCOS involves hyperandrogenemia, a form of insulin resistance unique to affected women, and possible changes in cortisol and melatonin secretion, arguably reflecting altered hypothalamic–pituitary–adrenal function. Psychological and behavioral pathways are also likely to play a role, as anxiety and depression, smoking, alcohol use and lack of physical activity are also common among women with PCOS, partly in response to the distressing symptoms they experience. The specific impact of sleep disturbances on the health of women with PCOS is not yet clear; however, both PCOS and sleep disturbances are associated with deterioration in cardiometabolic health in the longer term and increased risk of type 2 diabetes. Both immediate quality of life and longer-term health of women with PCOS are likely to benefit from diagnosis and management of sleep disorders as part of interdisciplinary health care. Refereed/Peer-reviewed

Implications • As a model of human pregnancy, research studies in catheterized fetal sheep have made significant contributions to our understanding of both normal and abnormal fetal development. • Owing to the invasive nature of catheterization surgery, effective postoperative analgesia is required. • Decisions regarding appropriate analgesia should consider effectiveness in reducing maternal pain and fetal well-being as well as potential impacts upon fetal physiological parameters under investigation. • The reporting of analgesic regimes in all research studies should comply with the ARRIVE guidelines Refereed/Peer-reviewed

Animal studies demonstrate that circadian rhythm disruption during pregnancy can be deleterious to reproductive capacity and the long-term health of the progeny. Our previous studies in rats have shown that exposure of pregnant dams to an environment that significantly disrupts maternal circadian rhythms programs increased adiposity and poor glucose metabolism in offspring. In this study, we used mice with a ClockΔ19 mutation to determine whether foetal development within a genetically disrupted circadian environment affects pregnancy outcomes and alters the metabolic health of offspring. Ten female ClockΔ19+MEL mutant mice were mated with 10 wildtype males, and 10 wildtype females were mated with 10 ClockΔ19+MEL mutant males. While genetically identical, the heterozygote foetuses were exposed to either a normal (wildtype dams) or disrupted (ClockΔ19+MEL mutant dams) circadian environment during gestation. Pregnancy outcomes including time to mate, gestation length, litter size and birth weight were assessed. One male and one female offspring from each litter were assessed for postnatal growth, body composition, intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test at 3 and 12 months of age. There was no effect of maternal genotype on pregnancy outcomes, with days to plug, gestation length, litter size and perinatal mortality not significantly different between wildtype and ClockΔ19+MEL mutant dams. Similarly, there was no effect of maternal genotype on weight of the offspring at birth or at any stage of postnatal growth. While there was an effect of sex on various tissue weights at 3 and 12 months of age, there were minimal effects of maternal genotype. Relative adrenal weight was significantly reduced (−32%) in offspring from ClockΔ19+MEL mutant dams, whereas gastrocnemius muscle was significantly increased (+16%) at 3 months of age only. Intraperitoneal glucose tolerance tests at 3 months of age revealed female offspring from ClockΔ19+MEL mutant dams had significantly reduced area under the curve following glucose administration (−25%), although no differences were found at 12 months of age. There was no effect of maternal genotype on intraperitoneal insulin tolerance at 3 or 12 months of age for either sex. These results demonstrate that foetal growth within a genetically disrupted circadian environment during gestation has no effect on pregnancy success, and only marginal impacts upon the long-term metabolic health of offspring. These results do not support the hypothesis that circadian rhythm disruption during pregnancy programs poor metabolic homeostasis in offspring. However, when maintained on a 12L:12D photoperiod, the ClockΔ19+MEL mutant dams display relatively normal patterns of activity and melatonin secretion, which may have reduced the impact of the mutation upon foetal metabolic programming. Refereed/Peer-reviewed

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The in utero environment is inherently rhythmic, with the fetus subjected to circadian changes in temperature, substrates, and various maternal hormones. Meanwhile, the fetus is developing an endogenous circadian timing system, preparing for life in an external environment where light, food availability, and other environmental factors change predictably and repeatedly every 24 h. In humans, there are many situations that can disrupt circadian rhythms, including shift work, international travel, insomnias, and circadian rhythm disorders (e.g., advanced/delayed sleep phase disorder), with a growing consensus that this chronodisruption can have deleterious consequences for an individual’s health and well-being. However, the impact of chronodisruption during pregnancy on the health of both the mother and fetus is not well understood. In this review, we outline circadian timing system ontogeny in mammals and examine emerging research from animal models demonstrating long-term negative implications for progeny health following maternal chronodisruption during pregnancy. Refereed/Peer-reviewed

The Robinson Research Institute of the University of Adelaide convened a multidisciplinary group of n = 33 clinicians, researchers and representatives of government organisations on the 2 October 2014 for a workshop entitled “Promoting fertility and healthy conception. How do we generate greater reproductive health awareness?” The key aim of the workshop was to assess the body of knowledge that informs clinical practice and government policy, and to identify questions and additional information needed by health practitioners and government representatives working in the field of reproductive health and to frame future research and policy. The workshop identified topics that fell mostly into three categories: lifestyle-related, societal and biological factors. The lifestyle topics included nutrition and diet, exercise, obesity, shift work and other factors deemed to be modifiable at the level of the individual. The societal topics included discussions of matters that are structural, and resistant to change by individuals, including specific ethical issues, social disadvantage, government and educational policies. The biological factors are intrinsic physical states of the individual, and included many factors where there is a dense body of scientific knowledge which may not be readily accessible in less academic language. This workshop thus provided an opportunity to identify further actions that could be undertaken tomeet the needs of diverse organisations and groups of professionals with an interest in human fertility. Since so many factors in our social and biological environment can impact fertility and preconception health, it is imperative to involve many disciplines or levels of government or societal organisations that have not traditionally been involved in this area. Refereed/Peer-reviewed

This review summarizes the evidence concerning effects of night shift work on women's reproductive health, specifically difficulty in conceiving and miscarriage. We distinguish between fixed night shift and rotating night shift, as the population subgroups exposed, the social and biological mechanisms, and the magnitude of effects are likely to differ; of note, women working fixed night shift are known to have high tolerance for this schedule. We identified two relevant systematic reviews with meta-analyses and five additional studies. Night shift work may give rise to menstrual cycle disturbances, but effect sizes are imprecise. Endometriosis may be elevated in night shift workers, but evidence is only preliminary. Adequate data are lacking to assess associations between night shift work and infertility or time to pregnancy. The weight of evidence begins to point to working at night, whether in fixed or rotating shifts, as a risk factor for miscarriage. There are many methodological problems with this literature, with substantial variation in the definitions of night shift and schedule types making comparisons between studies difficult and pooling across studies questionable. Nevertheless, there appears to be grounds for caution and counselling where women have concerns about night shift work and their reproductive health. Refereed/Peer-reviewed

Adult ewes (n = 7) underwent 3 weeks of a control 12 h light-12 h dark photoperiod, followed by 4 weeks of rapidly alternating photoperiods (RAPs) whereby the time of light exposure was reversed twice each week. Measures of central (melatonin secretion and core body temperature) and peripheral rhythmicity (clock and metabolic gene expression in skeletal muscle) were obtained over 24 h in both conditions. Metabolic homeostasis was assessed by glucose tolerance tests and 24 h glucose and insulin profiles. Melatonin and core body temperature rhythms resynchronized within 2 days of the last photoperiod shift. High-amplitude Bmal1, Clock, Nr1d1, Cry2 and Per3 mRNA rhythms were apparent in skeletal muscle, which were phase advanced by up to 3.5 h at 2 days after the last phase shift, whereas Per1 expression was downregulated at this time. Pparα, Pgc1α and Nampt mRNA were constitutively expressed in both conditions. Nocturnal glucose concentrations were reduced following chronic phase shifts (zeitgeber time 0, -5.5%; zeitgeber time 12, -2.9%; and zeitgeber time 16, -5.7%), whereas plasma insulin, glucose tolerance and glucose-stimulated insulin secretion were not altered. These results demonstrate that clock gene expression within ovine skeletal muscle oscillates over 24 h and responds to changing photoperiods. However, metabolic genes which link circadian and metabolic clocks in rodents were arrhythmic in sheep. Differences may be due to the ruminant versus monogastric digestive organization in each species. Together, these results demonstrate that despite disruptions to central and peripheral rhythmicity following exposure to rapidly alternating photoperiods, there was minimal impact on glucose homeostasis in the sheep. Refereed/Peer-reviewed

Disrupting maternal circadian rhythms through exposure to chronic phase shifts of the photoperiod has lifelong consequences for the metabolic homeostasis of the fetus, such that offspring develop increased adiposity, hyperinsulinaemia and poor glucose and insulin tolerance. In an attempt to determine the mechanisms by which these poor metabolic outcomes arise, we investigated the impact of chronic phase shifts (CPS) on maternal and fetal hormonal, metabolic and circadian rhythms. We assessed weight gain and food consumption of dams exposed to either CPS or control lighting conditions throughout gestation. At day 20, dams were assessed for plasma hormone and metabolite concentrations and glucose and insulin tolerance. Additionally, the expression of a range of circadian and metabolic genes was assessed in maternal, placental and fetal tissue. Control and CPS dams consumed the same amount of food, yet CPS dams gained 70% less weight during the first week of gestation. At day 20, CPS dams had reduced retroperitoneal fat pad weight (-15%), and time-of-day dependent decreases in liver weight, whereas fetal and placental weight was not affected. Melatonin secretion was not altered, yet the timing of corticosterone, leptin, glucose, insulin, free fatty acids, triglycerides and cholesterol concentrations were profoundly disrupted. The expression of gluconeogenic and circadian clock genes in maternal and fetal liver became either arrhythmic or were in antiphase to the controls. These results demonstrate that disruptions of the photoperiod can severely disrupt normal circadian profiles of plasma hormones and metabolites, as well as gene expression in maternal and fetal tissues. Disruptions in the timing of food consumption and the downstream metabolic processes required to utilise that food, may lead to reduced efficiency of growth such that maternal weight gain is reduced during early embryonic development. It is these perturbations that may contribute to the programming of poor metabolic homeostasis in the offspring. Refereed/Peer-reviewed

Circadian rhythms impact on a wide range of physiological systems and this impact extends to fertility, such that disruptions to timing systems can impact upon reproductive capacity. This is highlighted most obviously in mutant mouse models whereby deletion or mutation of single genes results not only in disrupted circadian rhythmicity, but also compromised male and female reproductive function. In this review, we discuss the presence of circadian clocks in female and male reproductive tissues and the role these clocks play in the generation of oestrus cycles, ovulation, sperm generation, implantation and the maintenance of pregnancy. Given the increased incidence of shiftwork and international travel which disrupt circadian rhythmicity, and the increasing prevalence of reproductive technologies whereby early embryo development occurs without external time cues, it is important for us to consider the role of circadian rhythms in fertility. Refereed/Peer-reviewed

Shift work during pregnancy is associated with an increased risk for preterm birth and low birth weight. However, the impact upon the long term health of the children is currently unknown. In this study, we used an animal model to determine the consequences of maternal shift work exposure on the health of the adult offspring. Pregnant rats were exposed to chronic phase shifts (CPS) in their photoperiod every 3-4 days throughout gestation and the first week after birth. Adult offspring were assessed for a range of metabolic, endocrine, circadian and neurobehavioural parameters. At 3 months of age, male pups exposed to the CPS schedule in utero had increased adiposity (+29%) and hyperleptinaemia (+99% at 0700h). By 12 months of age, both male and female rats displayed hyperleptinaemia (+26% and +41% respectively) and hyperinsulinaemia (+110% and +83% respectively). 12 month old female CPS rats displayed poor glucose tolerance (+18%) and increased insulin secretion (+29%) in response to an intraperitoneal glucose tolerance test. In CPS males the glucose response was unaltered, but the insulin response was reduced by 35%. The glucose response to an insulin tolerance test was decreased by 21% in CPS females but unaltered in males. Disruption of circadian rhythmicity during gestation resulted in gender dependent metabolic consequences for the adult offspring. These results highlight the need for a thorough analysis of shift work exposure in utero on the health of the adult offspring in humans. Refereed/Peer-reviewed