Intrauterine growth restriction (IUGR) and fetal exposure to a maternal high-fat diet (HFD) independently increase the risk of developing obesity in adulthood. Excess glucocorticoids increase obesity. We hypothesized that surgically induced IUGR combined with an HFD would increase adiposity and glucocorticoids more than in non-IUGR offspring combined with the same HFD, findings that would persist despite weaning to a regular diet. Non-IUGR (N) and IUGR (I) rat offspring from dams fed either regular rat chow (R) or an HFD (H) were weaned to either a regular rat chow or an HFD. For non-IUGR and IUGR rats, this study design resulted in three diet groups: offspring from dams fed a regular diet and weaned to a regular diet (NRR and IRR), offspring rats from dams fed an HFD and weaned to a regular diet (NHR and IHR) and offspring from dams fed an HFD and weaned to an HFD (NHH and IHH). Magnetic resonance imaging or fasting visceral and subcutaneous adipose tissue collection occurred at postnatal day 60. IHH male rats had greater adiposity than NHH males, findings that were only partly normalized by weaning to a regular chow. IHH male rats had a 10-fold increase in serum corticosterone levels. IHH female rats had increased adiposity and serum triglycerides. We conclude that IUGR combined with an HFD throughout life increased adiposity, glucocorticoids and triglycerides in a sex-specific manner. Our data suggest that one mechanism through which the perinatal environment programs increased adiposity in IHH male rats may be via increased systemic glucocorticoids.

Chorioamnionitis and intrauterine growth retardation (IUGR) are risk factors for cerebral palsy (CP). Common bacteria isolated in chorioamnionitis include group B Streptococcus (GBS) serotypes Ia and III. Little is known about the impact of placental inflammation induced by different bacteria, including different GBS strains. We aimed to test the impact of chorioamnionitis induced by two common GBS serotypes (GBSIa and GBSIII) on growth and neuromotor outcomes in the progeny. Dams were exposed at the end of gestation to either saline, inactivated GBSIa or GBSIII. Inactivated GBS bacteria invaded placentas and triggered a chorioamnionitis featured by massive polymorphonuclear cell infiltrations. Offspring exposed to GBSIII – but not to GBSIa – developed IUGR, persisting beyond adolescent age. Male rats in utero exposed to GBSIII traveled a lower distance in the Open Field test, which was correlating with their level of IUGR. GBSIII-exposed rats presented decreased startle responses to acoustic stimuli beyond adolescent age. GBS-exposed rats displayed a dysmyelinated white matter in the corpus callosum adjacent to thinner primary motor cortices. A decreased density of microglial cells was detected in the mature corpus callosum of GBSIII-exposed males – but not females – which was correlating positively with the primary motor cortex thickness. Altogether, our results demonstrate a causal link between pathogen-induced acute chorioamnionitis and (1) IUGR, (2) serotype- and sex-specific neuromotor impairments and (3) abnormal development of primary motor cortices, dysmyelinated white matter and decreased density of microglial cells.

A challenge for implementing DOHaD-defined health promotion is how to engage the at-risk population. The WHO Health Promoting School (HPS) model has proven success engaging youth and improving health behaviors. Hence, we introduced DOHaD concepts to 151 pupils aged 12–15 years in three HPS programs in rural Uganda, inquired what factors would make DOHaD-related health promotion resonate with them, and discussed how they recommended making learning about DOHaD acceptable to youth. Economic factors were judged the most compelling; with nutrition and responsive care elements next in importance. Suggested approaches included: teach how good health is beneficial, what works and why, and give tools to use to achieve it, and make information positive rather than linked to later harm. Involve youth in making DOHaD learning happen, make being a parent sound interesting, and include issues meaningful to boys. These are the first data from youth charged with addressing their engagement in the DOHaD agenda.

Fortification of margarine with vitamin D was mandatory in Denmark during 1961–1985. The aim of the study was to assess whether gestational and early infancy exposure to margarine fortification was associated with seasonality of birth in Danish type 1 diabetes (T1D) patients. The risks of T1D in Danes born during various exposure periods around margarine fortification termination in 1985 were analyzed. As expected, the T1D hazards in males unexposed to margarine fortification and born in spring were higher than in males born in autumn: relevant hazard ratios (95% confidence intervals) in various exposure groups ranged from 1.74 (1.112/2.708) to 37.43 (1.804/776.558). There were no indications of seasonality of birth in males exposed to fortification, nor in both exposed and unexposed females. The study suggests that early life exposure to low-dose vitamin D from fortified food eliminates seasonality of birth in T1D male patients. Further studies are required to investigate the identified gender differences.

Maternal perinatal depression exerts pervasive effects on the developing brain, as evidenced by electroencephalographic (EEG) patterns that differ between children of women who do and do not meet DSM or ICD diagnostic criteria. However, little research has examined if the same EEG pattern of right-frontal alpha asymmetry exists in newborns and thus originates in utero independent of postnatal influences, and if depressive symptoms are associated with this neural signature. Utilizing 125-lead EEG (n=18), this study considered clinician-rated maternal prenatal depressive symptoms in relation to newborn EEG. Maternal depressive symptomatology was associated with greater relative right-frontal alpha asymmetry during quiet sleep. These results suggest that even subclinical levels of maternal depression may influence infant brain development, and further support the role of the prenatal environment in shaping children’s future neurobehavioral trajectories.

Preeclampsia (PE) and gestational hypertension (GH) are pregnancy-specific diseases that occur in around 10% of pregnancies worldwide. Increasing evidence suggests that women whose pregnancies were complicated by PE or GH, and their offspring, are at increased risk of cardiovascular disease (CVD) later in life. We hypothesised that PE and GH would associate with CVD risk factors 8–10 years after the first pregnancy in the mother and child and that differences in cardiovascular risk profile would be seen between 8- and 10-year-old male and female children. This is a follow-up study of the Adelaide SCOPE pregnancy cohort where 1164 nulliparous women and their babies were recruited between 2005 and 2008. Haemodynamic function was assessed using non-invasive USCOMBP+ and USCOM1A devices. Microvascular function was assessed by post-occlusive reactive hyperaemia. Of the 273 mother–child pairs followed up, 38 women had PE and 20 had GH during pregnancy. Augmentation index (Aix) and suprasystolic pulse pressure (ssPP) were increased, whereas measures of microvascular function were decreased in children who were born to PE compared to uncomplicated pregnancies. Female children had decreased Aix and ssPP compared to male children after in utero exposure to PE. Women who developed GH during their first pregnancy had increased systolic, diastolic and mean arterial pressures compared to women who had uncomplicated pregnancy. Our data suggest that GH is associated with increased cardiovascular risk in women 8–10 years after first pregnancy and PE is associated with increased offspring risk at 8–10 years of age, highlighting differences between these two hypertensive disorders of pregnancy.

Diabetes predisposition is determined by pancreatic islet insulin secretion and insulin resistance. We studied female rat offspring exposed to low-protein maternal diet (50% control protein diet) in pregnancy and/or lactation at postnatal days 36, 110 and 450. Rats were fed either control 20% casein diet (C) or restricted diet (R – 10% casein) during pregnancy. After delivery, mothers received either C or R diet until weaning to provide four offspring groups: CC, RR, CR and RC (first letter denoting maternal pregnancy diet and the second lactation diet). Serum glucose, insulin and homeostatic model assessment (HOMA) were measured. Pancreatic islets were isolated and in vitro insulin secretion quantified in low glucose (5 mM) and high glucose (11 mM). Serum glucose, insulin and HOMA were similar in all groups at 36 and 110 postnatal days. HOMA was only higher in RR at 450 postnatal days. Only CC demonstrated differences in glucose sensitivity of β-cells to high and low doses at the three ages studied. At 36 days, RR, CR and RC and at 450 days RR and RC groups did not show glucose-stimulated insulin secretion differences between low and high glucose. Aging-associated glucose-stimulated insulin secretion loss was affected by maternal dietary history, indicating that developmental programming must be considered a major factor in aging-related development of predisposition to later-life dysfunctional insulin metabolism. Female offspring islets’ insulin secretion was higher than previously reported in males.

Globally, the availability and formulations for the administration of cannabis are changing with decriminalization or legalization of recreational use in some jurisdictions, and the prescription of cannabis also occurring. These changes are likely to affect the prevalence of use, including by women of childbearing age. The effects of in utero and infant alcohol and tobacco exposure are well-documented, but the outcomes of cannabis exposure are less certain. The content of delta-9-tetrahydrocannabinol (THC), the psychoactive component of cannabis has progressively increased over several decades. This review explores the limited knowledge surrounding the epidemiology of gestational and postnatal cannabis exposure and implications for the mother–placenta–fetus/neonate triad. We examine cannabis’ effects from antenatal and lactation exposure on (a) pregnancy and perinatal outcomes, (b) placental health, and (c) longer term cardiometabolic and neurodevelopmental risks and outcomes. Though definitive outcomes are lacking, gestational cannabis has been associated with increased risk of other substance use during pregnancy; impaired placental blood flow; increased risk of small for gestational age births; and associated complications. Childhood and adolescent outcomes are sparsely assessed, with suggested outcomes including increased risk of depression and attention-deficit hyperactivity disorder. Cardiometabolic implications of gestational cannabis use may include maternal fatty liver, obesity, insulin resistance, and increased risk of gestational diabetes mellitus (GDM), with potential consequences for the fetus. Clinical implications for pediatric practice were explored in a bid to understand any potential risk or impact on child health and development.

We assessed vascular programming in genetically identical monochorionic twin pairs with twin-to-twin transfusion syndrome (TTTS) treated differently in utero by serial amnioreduction or fetal laser arterial photocoagulation. This case–control study re-assessed four twin groups at median 11 years comprising 20 pairs of monochorionic diamniotic twins: nine treated by amnioreduction (TTTS-amnio) and eleven by laser (TTTS-laser) with seven monochorionic and six dichorionic control pairs. Outcome measures were current blood pressure (BP), brachio-radial arterial stiffness derived from pulse wave velocity (PWV), resting microcirculation (Flux) and response to heating and post-occlusive reactive hyperaemia measured using laser Doppler. Potential confounders [PWV and BP at first study, current height, weight, heart rate and twin type (ex-recipient, ex-donor or heavier/lighter of pair)] were accounted for by Mixed Linear Models statistical methodology. PWV dichorionic > monochorionic (P = 0.024); systolic and diastolic BP dichorionic > TTTS-amnio and TTTS-laser (P = 0.004, P = 0.02 and P = 0.005, P = 0.02, respectively). Within-twin pair pattern of PWV discordance was similar in laser treated and dichorionic controls (heavier-born > lighter), opposite to TTTS-amnio and monochorionic controls. Flux monochorionic > dichorionic (P = 0.044) and heavier > lighter-born (P = 0.024). TTTS-laser and dichorionic diamniotic showed greatest hyperaemic responses (dichorionic > TTTS-amnio or monochorionic controls (P = 0.007, P = 0.025). Hyperaemic responses were slower in heavier-born twins (P = 0.005). In summary, monochorionic twins had lower BP, arterial stiffness and increased resting vasodilatation than dichorionic twins implying shared fetal circulation affects vascular development. Vascular responses in laser-TTTS were similar to dichorionic and opposite to TTTS-amnio suggesting a lasting effect of fetal therapy on vascular health.

Lead is one of the environmental pollutants with cardiovascular toxicity. The embryos are particularly sensitive to lead exposure, because it can move through the blood-placental barrier and the blood-brain barrier easily during embryonic development. Cerebral cavernous malformations 3 (CCM3) gene plays an important role in cardiovascular development, mainly affecting cell proliferation, differentiation and apoptosis. In this study, we established a blood vessel development model of mouse embryos in order to imitate human people with CCM3 genes defects and exposing to environment toxin Pb in utero. We would like to determine the interaction of Pb and CCM3 gene on vascular development, and to explore the mechanisms. We found that the yolk sac of CCM3 heterozygous mice embryo showed abnormal morphology at E11.5 after lead treatment comparing with wild type (WT) mice without lead exposure, meanwhile it showed more angiogenesis and vascular remodeling in the hematoxylin and eosin stained sections of the CCM3+/− yolk sac with lead exposure. We also found that the similar effect of Pb and CCM3 gene on mitochondrial DNA (mtDNA) copy number in vivo and in vitro. Mitochondrial morphology and function also changed in primary human umbilical vein endothelial cells after lead exposure. Besides, it was found that the HIF-1α and TFAM which have close relationship with mtDNA biogenesis showed similarly increasing messenger RNA expression in both human and mouse-derived primary cells with lead treated and CCM3 gene knockout. All of the above results indicated that lead and CCM3 might damage endothelial cells through mitochondria pathway and eventually both affected angiogenesis.

Elevated levels of organochlorines (OC) have been reported in Inuit populations in the Arctic. We hypothesized that prenatal exposure to a Canadian Arctic OC mixture adversely affects male reproductive function and health with age. Sprague–Dawley female rats (F0) were gavaged with an environmentally relevant concentration of an Arctic OC mixture or corn oil (Control) during mating with untreated males until parturition (F1 litters). After postnatal day (PND) 90, the weights of the OC F1 males differed dramatically relative to Controls (P<0.05; n=10) and they exhibited respiratory distress. Except for possible thinning of the alveolar barrier, histological observation of the lungs revealed no apparent pathology to explain the respiratory distress. At PND 365, OC F1 males had reduced relative reproductive organ weights and lower sperm quality than Controls (P<0.05). At PND 90, OC F1 males were subfertile (P<0.05), but were infertile at PND 365. In conclusion, environmentally relevant prenatal OC exposure reduced reproductive function and health in aging male rats, providing new insight into the effects of early-life exposures to these contaminants.

Prenatal hormones have been proposed as key factors impacting child development as well as long-term health and disease. Digit ratio (the ratio of the lengths of the second to fourth digits; 2D:4D) has been proposed as a sexually dimorphic, noninvasive marker of prenatal androgen exposure that can be reliably measured in children and adults. To date, few longitudinal pregnancy cohort studies have examined childhood digit ratio in relation to other relevant measures including prenatal hormones and androgen-sensitive outcomes. To augment the current literature on this topic, we measured right-hand digit ratio in 4-year-old children participating in The Infant Development and the Environment Study, a multicenter longitudinal cohort study that has been following mother–child dyads since the first trimester of pregnancy (n = 321). We assessed sex differences in digit ratio and fit multivariable linear regression models to examine digit ratio in relation to: (1) child sex; (2) maternal sex steroid hormone concentrations in early pregnancy; (3) newborn anogenital distance, another proposed measure of sensitivity to prenatal androgens; and (4) gender-typical play behavior as measured by the Preschool Activities Inventory (PSAI) at age 4. We observed no sex difference in digit ratio; the mean 2D:4D was 0.97 ± 0.05 mm in both sexes. Furthermore, digit ratio was not associated with maternal sex steroid concentrations in early pregnancy, anogenital distance in either sex, or PSAI scores in either sex in covariate-adjusted models. In conclusion, we observed no evidence that early childhood digit ratio was associated with child sex or hormone-sensitive measures in this cohort.

Evidence from animal models indicates that exposure to an obesogenic or hyperglycemic intrauterine environment adversely impacts offspring kidney development and renal function. However, evidence from human studies has not been evaluated systematically. Therefore, the aim of this systematic review was to synthesize current research in humans that has examined the relationship between gestational obesity and/or diabetes and offspring kidney structure and function. Systematic electronic database searches were conducted of five relevant databases (CINAHL, Cochrane, EMBASE, MEDLINE and Scopus). Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed, and articles screened by two independent reviewers generated nine eligible papers for inclusion. Six studies were assessed as being of ‘neutral’ quality, two of ‘negative’ and one ‘positive’ quality. Observational studies suggest that offspring exposed to a hyperglycemic intrauterine environment are more likely to display markers of renal dysfunction and are at higher risk of end-stage renal disease. There was limited and inconsistent evidence for a link between exposure to an obesogenic intrauterine environment and offspring renal outcomes. Offspring renal outcome measures across studies were diverse, with a large variation in offspring age at follow-up, limiting comparability across studies. The collective current body of evidence suggests that intrauterine exposure to maternal obesity and/or diabetes adversely impacts renal programming in offspring, with an increased risk of kidney disease in adulthood. Further high-quality, longitudinal, prospective cohort studies that measure indicators of offspring renal development and function, including fetal kidney volume and albuminuria, at standardized follow-up time points, are warranted.

Adverse uterine environments caused by maternal stress (such as bacterial endotoxin) can alter programming of the fetal hypothalamic–pituitary–adrenal axis (HPAA) rendering offspring susceptible to various adulthood diseases. Thus, protection against this type of stress may be critical for ensuring offspring health. The present study was designed to determine if maternal supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) during pregnancy helps to protect against stress-induced fetal programming. Briefly, 53 ewes were fed a diet supplemented with fishmeal (FM) or soybean meal (SM) from day 100 of gestation (gd100) through lactation. On gd135, half the ewes from each dietary group were challenged with either 1.2 μg/kg Escherichia coli lipopolysaccharide (LPS) endotoxin, or saline as the control. The offspring’s cortisol response to weaning stress was assessed 50 days postpartum by measuring serum cortisol concentrations 0, 6 and 24 h post weaning. Twenty-four hours post-weaning, lambs were subjected to an adrenocorticotropic hormone (ACTH) challenge (0.5 μg/kg) and serum cortisol concentrations were measured 0, 0.25, 0.5, 1 and 2 h post injection. At 5.5 months of age, offspring were also challenged with 400 ng/kg of LPS, and serum cortisol concentrations were measured 0, 2, 4 and 6 h post challenge. Interestingly, female offspring born to FM+LPS mothers had a greater cortisol response to weaning and endotoxin challenge compared with the other treatments, while female offspring born to SM+LPS mothers had a faster cortisol response to the ACTH stressor. Additionally, males born to FM+LPS mothers had a greater cortisol response to the ACTH challenge than the other treatments. Overall, FM supplementation during gestation combined with LPS challenge alters HPAA responsiveness of the offspring into adulthood.

Prenatal nicotine exposure (PNE) is a risk factor for developing an addiction to nicotine at a later stage in life. Understanding the neurobiological changes in reward related circuitry induced by exposure to nicotine prenatally is vital if we are to combat the heightened addiction liability in these vulnerable individuals. The laterodorsal tegmental nucleus (LDT), which is comprised of cholinergic, GABAergic and glutamatergic neurons, is importantly involved in reward mediation via demonstrated excitatory projections to dopamine-containing ventral tegmental neurons. PNE could lead to alterations in LDT neurons that would be expected to alter responses to later-life nicotine exposure. To examine this issue, we monitored nicotine-induced responses of LDT neurons in brain slices of PNE and drug naive mice using calcium imaging and whole-cell patch clamping. Nicotine was found to induce rises in calcium in a smaller proportion of LDT cells in PNE mice aged 7–15 days and smaller rises in calcium in PNE animals from postnatal ages 11–21 days when compared with age-matched control animals. While inward currents induced by nicotine were not found to be different, nicotine did induce larger amplitude excitatory postsynaptic currents in PNE animals in the oldest age group when compared with amplitudes induced in similar-aged control animals. Immunohistochemically identified cholinergic LDT cells from PNE animals exhibited slower spike rise and decay slopes, which likely contributed to the wider action potential observed. Further, PNE was associated with a more negative action potential afterhyperpolarization in cholinergic cells. Interestingly, the changes found in these parameters in animals exposed prenatally to nicotine were age related, in that they were not apparent in animals from the oldest age group examined. Taken together, our data suggest that PNE induces changes in cholinergic LDT cells that would be expected to alter cellular excitability. As the changes are age related, these PNE-associated alterations could contribute differentially across ontogeny to nicotine-mediated reward and may contribute to the particular susceptibility of in utero nicotine exposed individuals to addict to nicotine upon nicotine exposure in the juvenile period.

Adverse pregnancy outcomes including prematurity and low birth weight (LBW) have been associated with life-long chronic disease risk for the infant. Stress during pregnancy increases the risk of adverse pregnancy outcomes. Many studies have reported the incidence of adverse pregnancy outcomes in Indigenous populations and a smaller number of studies have measured rates of stress and depression in these populations. This study sought to examine the potential association between stress during pregnancy and the rate of adverse pregnancy outcomes in Australian Indigenous women residing in rural and remote communities in New South Wales. This study found a higher rate of post-traumatic stress disorder, depression and anxiety symptoms during pregnancy than the general population. There was also a higher incidence of prematurity and LBW deliveries. Unfortunately, missing post-traumatic stress disorder and depressive symptomatology data impeded the examination of associations of interest. This was largely due to the highly sensitive nature of the issues under investigation, and the need to ensure adequate levels of trust between Indigenous women and research staff before disclosure and recording of sensitive research data. We were unable to demonstrate a significant association between the level of stress and the incidence of adverse pregnancy outcomes at this stage. We recommend this longitudinal study continue until complete data sets are available. Future research in this area should ensure prioritization of building trust in participants and overestimating sample size to ensure no undue pressure is placed upon an already stressed participant.

This study was aimed to investigate associations between birth weight and multiple adiposity indicators in youth, and to examine potential mediating effects by biological maturation. This was a school-based study involving 981 Brazilian adolescents aged between 10 and 17 years. Birth weight was reported retrospectively by mothers. Maturation was estimated by age of peak height velocity. Adiposity indicators included body mass index (BMI), waist circumference and percent body fat estimated from triceps and subscapular skinfolds. Multilevel mediation analyses were performed using the Sobel test, adjusted for chronological age, gestational age, cardiorespiratory fitness and socio-economic status. Except for body fat in girls, biological maturation partly or fully mediated (P<0.05) positive relationships between birth weight with all other obesity indicators in both sexes with their respective values of indirect effects with 95% confidence intervals: BMI [boys: 0.44 (0.06–0.82); girls: 0.38 (0.13–0.64)], waist circumference [boys: 1.14 (0.22–2.05); girls: 0.87 (0.26–1.48)] and body fat [boys: 0.60 (0.13–1.07)]. To conclude, birth weight is associated with elevated obesity risk in adolescence and biological maturation seems to at least partly mediate this relationship.

There is evidence that epigenetic changes occur early in breast carcinogenesis. We hypothesized that early-life exposures associated with breast cancer would be associated with epigenetic alterations in breast tumors. In particular, we examined DNA methylation patterns in breast tumors in association with several early-life exposures in a population-based case–control study. Promoter methylation of E-cadherin, p16 and RAR-β2 genes was assessed in archived tumor blocks from 803 cases with real-time methylation-specific PCR. Unconditional logistic regression was used for case–case comparisons of those with and without promoter methylation. We found no differences in the prevalence of DNA methylation of the individual genes by age at menarche, age at first live birth and weight at age 20. In case–case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E-cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ⩽2.5 v. 2.6–2.9 kg); higher adult height with RAR-β2 methylation (OR = 3.34, 95% CI, 1.19–9.39, for ⩾1.65 v. <1.60 m); and not having been breastfed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. Being other than first in the birth order was inversely associated with likelihood of ⩾1 of the three genes being methylated for premenopausal breast cancers, but positively associated with methylation in postmenopausal women. These results suggest that there may be alterations in methylation associated with early-life exposures that persist into adulthood and affect breast cancer risk.

Environmental enteropathy (EE) is a syndrome of altered small intestine structure and function hypothesized to be common among individuals lacking access to improved water and sanitation. There are plausible biological mechanisms, both inflammatory and non-inflammatory, by which EE may alter the cardiometabolic profile. Here, we test the hypothesis that EE is associated with the cardiometabolic profile among young children living in an environment of intense enteropathogen exposure. In total, 156 children participating in the Peruvian cohort of a multicenter study on childhood infectious diseases, growth and development were contacted at 3–5 years of age. The urinary lactulose:mannitol ratio, and plasma antibody to endotoxin core were determined in order to assess intestinal permeability and bacterial translocation. Blood pressure, anthropometry, fasting plasma glucose, insulin, and cholesterol and apolipoprotein profiles were also assessed. Extant cohort data were also used to relate biomarkers of EE during the first 18 months of life to early child cardiometabolic profile. Lower intestinal surface area, as assessed by percent mannitol excretion, was associated with lower apolipoprotein-AI and lower high-density lipoprotein concentrations. Lower intestinal surface area was also associated with greater blood pressure. Inflammation at 7 months of age was associated with higher blood pressure in later childhood. This study supports the potential for a relationship between EE and the cardiometabolic profile.

Monosodium l-glutamate (MSG)-induced obesity is a useful model for non-alcoholic fatty liver disease (NAFLD) studies. However, there is limited data on its initiation and progression. Thus, this study aimed to characterize the onset of metabolic and histopathological features of NAFLD and its progression to non-alcoholic steatohepatitis (NASH) in this model. To perform this study, Swiss mice pups were neonatally injected with MSG (4 g/kg/day, s.c.) or equiosmolar saline and followed up to 60, 120 or 180 days old. At each age, blood, liver, as well as periepididymal and retroperitoneal fat pads were collected for morphometric, biochemical and histological analyses, the later according to NAFLD activity score. MSG mice presented hypertriglyceridemia and central obesity at all ages, but peripheral insulin-resistance was verified only in 120- and 180-day-old mice. Hepatic total fat and triglycerides content were higher in MSG mice at all ages. Accordingly, histopathological analysis showed that 60-day-old MSG mice had microvesicular steatosis with occasional ballooning, which evolved into NASH from 120 days old. Retroperitoneal fat accumulation was the only variable to independently correlate with NAFLD activity total score upon multivariate analysis (R2=71.45%). There were no differences in IL-6 and TNF-α serum levels among groups. Overall, this study shows that NAFLD is a precocious outcome in MSG-obese mice, whereas the period comprised between 60 and 120 days old seems to be a crucial metabolic window for comprehending pathophysiological events involved in NAFLD-to-NASH progression in this model.