The association of prenatal growth with metabolic syndrome (MS) components and insulin resistance (IR) in children has not been studied in Chile and most developing countries. Some associations found in developed countries are controversial. A retrospective cohort study was designed linking present information on MS components and IR in children with register-based information on birth weight (BW), birth length (BL) and gestational age (GA). Examinations included anthropometry and blood pressure (BP), as well as self-report of pubertal status. A fasting blood sample was taken to determine lipids, glucose, insulin and homeostasis model assessment (HOMA)-IR was calculated. The study cohort of 2152 children was on average 11.4 ± 1.0 years old. The prevalence of MS, IR and overweight were 7.6%, 24.5% and 34%, respectively. Elevated BP was negatively associated with dichotomized risk categories of the perinatal factors studied (BW, BL and GA). Contingency tables showed that high waist circumference (WC) and elevated BP had a U-shaped association with various categories of BW and BL, respectively. Stepwise linear regressions selected: (a) WC as inversely associated to GA and directly associated to BW, (b) BP as inversely associated to GA and (c) HOMA-IR as inversely associated to BL. Non-optimal prenatal growth seems to predispose to high WC, elevated BP and IR in school-age children, supporting the early life origin of several non-communicable diseases. Those associations were rather weak as estimated by the slopes of the regressions and probably reduced by their U-shaped nature; they would reasonably become stronger with a longer follow-up.

Foetal growth restriction impairs skeletal muscle development and adult muscle mitochondrial biogenesis. We hypothesized that key genes involved in muscle development and mitochondrial biogenesis would be altered following uteroplacental insufficiency in rat pups, and improving postnatal nutrition by cross-fostering would ameliorate these deficits. Bilateral uterine vessel ligation (Restricted) or sham (Control) surgery was performed on day 18 of gestation. Males and females were investigated at day 20 of gestation (E20), 1 (PN1), 7 (PN7) and 35 (PN35) days postnatally. A separate cohort of Control and Restricted pups were cross-fostered onto a different Control or Restricted mother and examined at PN7. In both sexes, peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), cytochrome c oxidase subunits 3 and 4 (COX III and IV) and myogenic regulatory factor 4 expression increased from late gestation to postnatal life, whereas mitochondrial transcription factor A, myogenic differentiation 1 (MyoD), myogenin and insulin-like growth factor I (IGF-I) decreased. Foetal growth restriction increased MyoD mRNA in females at PN7, whereas in males IGF-I mRNA was higher at E20 and PN1. Cross-fostering Restricted pups onto a Control mother significantly increased COX III mRNA in males and COX IV mRNA in both sexes above controls with little effect on other genes. Developmental age appears to be a major factor regulating skeletal muscle mitochondrial and developmental genes, with growth restriction and cross-fostering having only subtle effects. It therefore appears that reductions in adult mitochondrial biogenesis markers likely develop after weaning.

Longitudinal maternal mental health data are needed from high HIV prevalence settings. The Siyakhula Cohort (SC) is a population-based cohort of HIV-positive and negative mothers (n=1506) with HIV-negative children (n=1536) from rural South Africa. SC includes 767 HIV-negative mothers; 465 HIV-positive in pregnancy; 272 HIV-positive since pregnancy (n=2 missing HIV status). A subgroup (n=890) participated in a non-randomized breastfeeding intervention [Vertical Transmission Study (VTS)]; the remaining (n=616) were resident in the same area and received antenatal care at the time of the VTS, but were not part of the VTS, instead receiving the standard of care Prevention of Mother-to-Child Transmission (PMTCT) Programme. In secondary analysis we investigated the prevalence of, and factors associated with, psychological morbidity amongst mothers who were still the primary caregiver of the child (1265 out of 1506) at follow-up (7–11 years post-birth). We measured maternal depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder Scale-7) and parenting stress (Parenting Stress Index-36), using standardized cut-offs and algorithms. In total, 75 (5.9%) mothers met criteria for depression, 37 (2.9%) anxiety and 134 (10.6%) parenting stress. Using complete case logistic regression (n=1206 out of 1265 mothers) as compared to being HIV-negative, testing HIV-positive in pregnancy doubled odds of depression [adjusted odd ratios (aOR)=1.96 [1.0–3.7] P=0.039]. Parenting stress was positively associated with acquisition of HIV after pregnancy (aOR=3.11 [1.9–5.2] P<0.001) and exposure to household crime (aOR=2.02 [1.3–3.2] P=0.003); negatively associated with higher maternal education (aOR=0.29 [0.1–0.8] P=0.014), maternal employment (aOR=0.55 [0.3–0.9] P=0.024). Compared with the standard of care PMTCT, VTS mothers had reduced odds of parenting stress (aOR=0.61 [0.4–0.9] P=0.016). Integrating parental support into mostly bio-medical treatment programmes, during and beyond pregnancy, is important.

The rising rate of childhood overweight follows the increase in maternal obesity, since perinatal events impact offspring in a diversity of metabolic disorders. Despite many studies that have linked dietary consumption, overnutrition, or maternal obesity as the mediators of fetal metabolic programming, there are gaps regarding the knowledge about the contribution of different maternal phenotypes to the development of metabolic disturbances in offspring. This study aimed to investigate whether maternal high-fat diet (HFD) consumption without the development of the obese phenotype would protect offspring from metabolic disturbances. Female mice were fed standard chow diet or a HFD for 4 weeks before mating. HFD females were classified into obesity-resistant (OR) or obesity-prone (OP), according to weight gain. OP females presented with higher adiposity, fasting serum glucose and insulin, cholesterol and non-esterified fatty acid (NEFA). Newborn offspring from OP dams showed higher serum glucose and insulin and alteration in hepatic gene expression that may have contributed to the rise in hepatic fat content and decline of glycogen levels in the liver. Despite offspring from OR and OP females having showed similar growth after the day of delivery, offspring from OP females had higher caloric intake, fasting glucose, serum triglycerides and altered hepatic gene expression, as well as glucose and pyruvate intolerance and lower insulin sensitivity at d28 compared with offspring from OR females. Maternal pre-pregnancy serum glucose, insulin, and NEFA positively correlated with serum glucose and fat liver content and negatively correlated with hepatic glycogen in offspring. In conclusion, our results show that maternal resistance to diet-induced obesity partially protects offspring from early metabolic disturbances.

The identification of early-life determinants of overweight is crucial to start early prevention. As weight gain accelerates between 2 and 6 years, we studied the association between diet quality in children aged 3 years and the change in BMI and overweight incidence in the following 7 years. From the Dutch GECKO Drenthe birth cohort, 1001 children born in 2006 or 2007 with complete data on diet (food frequency questionnaire at the age of 3 years) and growth at the age of 3 and 10 years were included. Diet quality was estimated with the evidence-based Lifelines Diet Score (LLDS). Measured height and weight at the age of 3 and 10 years were used to calculate BMI z-scores standardized for age and sex. The associations of the LLDS (in quintiles) with BMI-z change and overweight incidence were studied with linear and logistic regression analyses. Overweight prevalence in the total study population increased from 8.3% at the age of 3 years to 16.7% at the age of 10 years. The increase in overweight prevalence ranged from 14.7% in Q1 to 3.5% in Q5. Children with a better diet quality (higher quintiles of LLDS) increased significantly less in BMI-z (confounder adjusted βLLDS = −0.064 (−0.101; −0.026)). Children with a poor diet quality at the age of 3 years had a considerably higher risk for overweight at the age of 10 years (confounder adjusted OR for Q1 vs. Q5 was 2.86 (95% CI 1.34–6.13). These results show the importance of diet in healthy development in the early life following the first 1000 days when new habits for a mature diet composed of food groups with lifelong importance are developed, providing a relevant window for overweight prevention early in life.

Rapid infant growth increases the risk for adult obesity. The gut microbiome is associated with early weight status; however, no study has examined how interactions between microbial and host ribonucleic acid (RNA) expression influence infant growth. We hypothesized that dynamics in infant stool micro-ribonucleic acids (miRNAs) would be associated with both microbial activity and infant growth via putative metabolic targets. Stool was collected twice from 30 full-term infants, at 1 month and again between 6 and 12 months. Stool RNA were measured with high-throughput sequencing and aligned to human and microbial databases. Infant growth was measured by weight-for-length z-score at birth and 12 months. Increased RNA transcriptional activity of Clostridia (R = 0.55; Adj p = 3.7E-2) and Burkholderia (R = −0.820, Adj p = 2.62E-3) were associated with infant growth. Of the 25 human RNAs associated with growth, 16 were miRNAs. The miRNAs demonstrated significant target enrichment (Adj p < 0.05) for four metabolic pathways. There were four associations between growth-related miRNAs and growth-related phyla. We have shown that longitudinal trends in gut microbiota activity and human miRNA levels are associated with infant growth and the metabolic targets of miRNAs suggest these molecules may regulate the biosynthetic landscape of the gut and influence microbial activity.

Disturbances affecting early development have broad repercussions on the individual’s health during infancy and adulthood. Multiple observational studies throughout the years have shown that alterations of fetal growth are associated with increased cardiometabolic disease risks. However, the genetic component of this association only started to be investigated in the last 40 years, when single genes with distinct effects were investigated. Birth weight (BW), commonly reported as the outcome of developmental growth, has been estimated to be 20% to 60% heritable. Through Genome-Wide Association (GWA) meta-analyses, 190 different loci have been identified being associated with BW, and while many of these loci designate genes involved in glucose and lipid metabolism, with clear ties to fetal development, the role of others is not yet understood. In addition, due to its influence over the intrauterine environment, the maternal genotype also plays an important part in the determination of offspring BW, with the same loci having independent effects of different magnitude or even direction. There is still much to uncover regarding the genetic determinants of BW and the interactions between maternal, offspring, and even paternal genotype. To fully understand these, diverse and novel cohorts from multiple ancestries collecting extensive neonatal phenotype will be needed. This review compiles, chronologically, the main findings in the investigation of the genetics of BW.

Gut bacteria from the genus Prevotella are found in high abundance in faeces of non-industrialised communities but low abundance in industrialised, Westernised communities. Prevotella copri is one of the principal Prevotella species within the human gut. As it has been associated with developmental health and disease states, we sought to (i) develop a real-time polymerase chain reaction (PCR) to rapidly determine P. copri abundance and (ii) investigate its abundance in a large group of Australian pregnant mothers.

The Barwon Infant Study is a pre-birth cohort study (n = 1074). Faecal samples were collected from mothers at 36 weeks gestation. Primers with a probe specific to the V3 region of P. copri 16S rRNA gene were designed and optimised for real-time PCR. Universal 16S rRNA gene primers amplified pan-bacterial DNA in parallel. Relative abundance of P. copri was calculated using a 2-ΔCt method.

Relative abundance of P. copri by PCR was observed in 165/605 (27.3%) women. The distribution was distinctly bimodal, defining women with substantial (n = 115/165, 69.7%) versus very low P. copri expression (n = 50/165, 30.3%). In addition, abundance of P. copri by PCR correlated with 16S rRNA gene MiSeq sequencing data (r2 = 0.67, P < 0.0001, n = 61).

We have developed a rapid and cost-effective technique for identifying the relative abundance of P. copri using real-time PCR. The expression of P. copri was evident in only a quarter of the mothers, and either at substantial or very low levels. PCR detection of P. copri may facilitate assessment of this species in large, longitudinal studies across multiple populations and in various clinical settings.

Optimal placental function is critical for fetal development, and therefore a crucial consideration for understanding the developmental origins of health and disease (DOHaD). The structure of the fetal side of the placental vasculature is an important determinant of fetal growth and cardiovascular development. There are several imaging modalities for assessing feto-placental structure including stereology, electron microscopy, confocal microscopy, micro-computed tomography, light-sheet microscopy, ultrasonography and magnetic resonance imaging. In this review, we present current methodologies for imaging feto-placental vasculature morphology ex vivo and in vivo in human and experimental models, their advantages and limitations and how these provide insight into placental function and fetal outcomes. These imaging approaches add important perspective to our understanding of placental biology and have potential to be new tools to elucidate a deeper understanding of DOHaD.

Maternal treatment with dexamethasone (Dex) in threatening preterm delivery alters activities at the hypothalamic–pituitary–adrenal axis in the offspring. This alteration may interfere with reproductive function. The impact of gestational Dex exposure on male reproductive function of the offspring was investigated. A total of 25 pregnant rats randomly assigned to five groups (n=5) were treated with normal saline (control), Dex (100 μg/kg/day sc) during gestation days (GD) 1–7, 8–14, 15–21 and 1–21, respectively. Birth weight, anogenital distance (AGD), pubertal age, sperm parameters, hormonal profile and histopathology of testis and epididymis were determined in the F1 and F2 offspring. Results showed a significant increase (P<0.05) in pubertal age, serum corticosterone and gonadotropin-releasing hormone (GnRH) levels in the male offspring of DexGD 15–21 and 1–21 groups and a significant decrease (P<0.05) in serum testosterone, luteinizing hormone, birth weight and AGD at birth in the male F1 offspring. In the F2 offspring, there was a significant reduction (P<0.05) in serum corticosterone, testosterone, follicle-stimulating hormone and GnRH when compared with the control. Dex treatment at GD 15–21 and 1–21 significantly reduced (P<0.05) sperm motility and normal morphology in the F1 and F2 offspring. Maternal Dex treatment in rats during late gestation may disrupt sexual development markers in the F1 and F2 male offspring.

In utero diet may be directly related to the risk of fetal hyperinsulinaemia and offspring metabolic health. This review examines the relationship between maternal dietary exposures and sub-clinical fetal hyperinsulinaemia and neonatal adiposity. Articles were identified in MEDLINE, Web of Science, Cochrane Controlled Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, SCOPUS, and SPORTDiscus (September 2019–March 2021) using the preferred reporting items for systematic reviews and meta-analyses guidelines. PROSPERO registration ID CRD42020146453. Studies were selected by two independent reviewers. Randomised controlled trials (RCT) involving a dietary intervention with pregnant women (healthy pregnancy, gestational diabetes mellitus and obesity) and reporting fetal cord-blood insulin, c-peptide, glucose or adiposity estimates were included. One author extracted all information on main study characteristics and outcomes. Risk of bias was assessed using the Cochrane Collaboration’s bias risk assessment tool. A total of 733 articles were identified. Fourteen articles from 11 RCTs (3614 participants) were included. Studies reviewed showed no specific effect of maternal diet on neonatal cord blood insulin, c-peptide or glucose levels. Infants born to mothers who followed a low glycaemic load (GL) had lower skin fold thickness compared to controls. Interventions that provided individualised nutrition counselling to women with obesity or previous infant born > 4 kg were also associated with lower adiposity. The studies reviewed suggest that lifestyle-based dietary interventions to improve glycaemia (low GL) have a protective effect against excess adiposity. Future studies should incorporate multi-modal interventions with dietary counselling to support lifestyle changes throughout gestation and include assessments of maternal insulin resistance at recruitment.

Placental transport of vitamin D and other nutrients (e.g. amino acids, fats and glucose) to the fetus is sensitive to maternal and fetal nutritional cues. We studied the effect of maternal calorific restriction on fetal vitamin D status and the placental expression of genes for nutrient transport [aromatic T-type amino acid transporter-1 (TAT-1); triglyceride hydrolase/lipoprotein uptake facilitator lipoprotein lipase (LPL)] and vitamin D homeostasis [CYP27B1; vitamin D receptor (VDR)], and their association with markers of fetal cardiovascular function and skeletal muscle growth. Pregnant sheep received 100% total metabolizable energy (ME) requirements (control), 40% total ME requirements peri-implantation [PI40, 1–31 days of gestation (dGA)] or 50% total ME requirements in late gestation (L, 104–127 dGA). Fetal, but not maternal, plasma 25-hydroxy-vitamin D (25OHD) concentration was lower in PI40 and L maternal undernutrition groups (P<0.01) compared with the control group at 0.86 gestation. PI40 group placental CYP27B1 messenger RNA (mRNA) levels were increased (P<0.05) compared with the control group. Across all groups, higher fetal plasma 25OHD concentration was associated with higher skeletal muscle myofibre and capillary density (P<0.05). In the placenta, higher VDR mRNA levels were associated with higher TAT-1 (P<0.05) and LPL (P<0.01) mRNA levels. In the PI40 maternal undernutrition group only, reduced fetal plasma 25OHD concentration may be mediated in part by altered placental CYP27B1. The association between placental mRNA levels of VDR and nutrient transport genes suggests a way in which the placenta may integrate nutritional cues in the face of maternal dietary challenges and alter fetal physiology.

Epidemiological studies have demonstrated an increased risk of developing non-transmittable diseases in adults subjected to adverse early developmental conditions. Metabolic and cardiovascular diseases have been the focus of most studies. Nevertheless, data from animal models also suggest early programming of fertility. In humans, it is difficult to assess the impact of the in utero environment retrospectively. Birthweight is commonly used as an indirect indicator of intrauterine development. This research is part of the ALIFERT study. We investigated a potential link between ponderal index at birth and female fertility in adulthood. Data from 51 infertile and 74 fertile women were analysed. BW was on average higher in infertile women, whereas birth length did not differ between the two groups; thus, resulting in a significantly higher ponderal index at birth in infertile women. Ponderal index at birth has been identified as a risk factor for infertility. These results suggest the importance of the intra-uterine environment, not only for long-term metabolic health but also for fertility.

Adipocytokines, which are secreted during fetal development by both mothers and fetuses, may influence fetal lung development, but little human data are available. We used data from the HOME Study to investigate the associations of cord blood adipocytokine concentrations with children’s lung forced expiratory volume (FEV1; N = 160) and their risk of wheeze (N = 281). We measured umbilical cord serum adipocytokine concentrations using enzyme-linked immunosorbent assays and FEV1 using a portable spirometer at ages 4 and 5 to calculate the percent predicted FEV1 (%FEV1). Parents completed standardized questionnaires of their child’s wheeze symptoms every 6 months from birth to age 5, then again at ages 6 and 8. We used multivariable linear mixed models and modified Poisson regression with generalized estimating equations to estimate associations of adipocytokine concentrations (log2-transformed) with children’s %FEV1 and the risk of wheeze, respectively, adjusting for sociodemographic, perinatal, and child factors. Cord serum leptin was not associated with children’s %FEV1. Higher cord serum adiponectin concentrations were associated with higher %FEV1 in girls (β = 3.1, 95% confidence interval [CI]: 0.6, 5.6), but not in boys (β = −1.3, 95% CI: −5.9, 3.3) (sex × adiponectin p-value = 0.05). Higher leptin was associated with lower risk of wheeze in girls (RR = 0.74, 95% CI: 0.66, 0.84), but not boys (RR = 0.87, 95% CI: 0.69, 1.11) (sex × leptin p-value = 0.01). In contrast, higher adiponectin concentrations were associated with lower risk of wheeze (RR = 0.84, 95% CI: 0.73, 0.96) in both boys and girls. These data suggest that fetal adipocytokines may impact lung development and function in early childhood. Future studies are needed to confirm these findings and explore the mechanisms underlying these associations.

The hypothesis that vitamin content of the diet during gestation alters macronutrient choice, food intake and the expression of serotonin receptors and proopiomelanocortin (POMC) in the hypothalamus of the offspring was investigated. Pregnant Wistar rats (n = 10/group) were fed the AIN-93G diet containing a multivitamin mix at the recommended (RV) content or10-fold higher (high vitamin, HV) content. Male offspring were weaned to a choice of 10% and 60% casein diets. Intake regulation by the serotonergic system was determined by measuring food choice daily for 7 weeks, and following tryptophan (TRP) or mCPP (a serotonin receptor agonist) injections at 4 and 6 weeks post-weaning. mRNA expressions of hypothalamic serotonin receptor and POMC were measured at birth, weaning and sacrifice (7 weeks post-weaning). No differences were found in body weight at birth or weaning. HV offspring had lower food intake for the duration of the study (P < 0.001), and 11% lower body weight (P < 0.05) and 23% lower fat pad mass (P < 0.05) at 7 weeks post-weaning. They selected less protein following 12 h of food deprivation (P < 0.05) and were less responsive to TRP (P = 0.05) and mCPP (P < 0.05) injections at 6 weeks post-weaning. Expressions of mRNA for serotonin receptors 5-HT1A/2A/2C at weaning (P < 0.01) and of POMC at weaning and 7 weeks post-weaning (P < 0.05) were lower. In conclusion, intake of multivitamins above the requirements during pregnancy affected macronutrient choice, food intake and the expression of serotonin receptors and POMC in the hypothalamus.

Although bariatric surgery is approved for a woman of child-bearing age with an interest in subsequent pregnancy, reports of in utero growth issues during pregnancy have garnered a closer look at the impact of maternal surgical weight loss on the pre- and postpartum periods. Offspring of dams having received vertical sleeve gastrectomy (VSG) are born small-for-gestational age and have increased risk for metabolic syndrome later in life. Here, we aimed to determine whether the postnatal catch-up growth trajectory of bariatric offspring may be affected by milk composition. Milk samples were collected at postnatal day 15/16 from dams having received VSG surgery and fed a high-fat diet (HFD) (H-VSG), Sham surgery and fed chow (C-Sham), or Sham surgery and fed HFD (H-Sham). Milk obtained from H-VSG dams had elevated glucose (P < 0.05) and significantly reduced triglyceride content (P < 0.01). Milk from H-Sham dams had the lowest amount of milk protein (P < 0.05). Fatty acid composition measured by fractionation was largely not affected by surgery but rather maternal diet. No difference was observed in milk leptin levels; however, insulin, adiponectin, and growth hormone levels were significantly increased in milk from H-VSG animals. H-Sham had the lowest level of immunoglobulin (Ig)A, whereas IgG was significantly reduced in H-VSG. Taken together, the quality of milk from H-VSG dams suggests that milk composition could be a factor in reducing the rate of growth during the lactation period.

The crosstalk between maternal stress exposure and fetal development may be mediated by epigenetic mechanisms, including DNA methylation (DNAm). To address this matter, we collect 32 cord blood samples from low-income Brazilian pregnant adolescents participants of a pilot randomized clinical intervention study (ClinicalTrials.gov, Identifier: NCT02807818). We hypothesized that the association between the intervention and infant neurodevelopmental outcomes at 12 months of age would be mediated by DNAm. First, we searched genome methylation differences between cases and controls using different approaches, as well as differences in age acceleration (AA), represented by the difference of methylation age and birth age. According to an adjusted p-value ≤ 0.05 we identified 3090 differentially methylated positions- CpG sites (DMPs), 21 differentially methylated regions (DMRs) and one comethylated module weakly preserved between groups. The intervention group presented a smaller AA compared to the control group (p = 0.025). A logistic regression controlled by sex and with gestational age indicated a coefficient of −0.35 towards intervention group (p = 0.016) considering AA. A higher cognitive domain score from Bayley III scale was observed in the intervention group at 12 months of age. Then, we performed a potential causal mediation analysis selecting only DMPs highly associated with the cognitive domain (adj. R2 > 0.4), DMRs and CpGs of hub genes from the weakly preserved comethylated module and epigenetic clock as raw values. DMPs in STXBP6, and PF4 DMR, mediated the association between the maternal intervention and the cognitive domain at 12 months of age. In conclusion, DNAm in different sites and regions mediated the association between intervention and cognitive outcome.

Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.

Poor fetal growth and associated prepubertal growth acceleration are linked to increased risk of cardiometabolic dysfunction in later life, but whether obesity is integral to ‘catch-up’ growth and its ensuing risks are unknown. In microswine offspring exposed to perinatal maternal protein restriction (MPR), we measured body and organ sizes (during MPR); linear growth and weight gain (birth to 5 months of age); feed intake and utilization efficiency (5–14 weeks); and body composition at 6 and 11 weeks of age (by dual-energy X-ray absorptiometry, DEXA). During MPR, low protein offspring (LPO) showed asymmetric growth restriction with reduced body weight (Wt):length (Lth) at birth and elevated heart Wt:liver Wt ratio by 2 weeks of age. In LPO, after slow early postnatal growth (0–5 weeks), subsequent linear growth on ad libitum normal feed was absolutely accelerated (cm/week; P < 0.001) over 6–11 weeks but normal thereafter, whereas absolute weight gain (kg/week) was similar to controls but accelerated relative to lower LPO nadir weights. Concurrently, rates of fat and lean tissue accrual in LPO over 6–11 weeks were similar to normal protein offspring in absolute terms (g/5 weeks) but increased relative to lower mass at 6 weeks, yielding normal lean:Lth but reduced fat:Lth ratios at 11 weeks. LPO had higher relative feed intake (g/kg/meal) in both sexes and higher feed efficiency in females over 5–11 weeks of age. Findings suggest that postnatal linear growth acceleration preserved thinness in juvenile LPO. Given separately reported abnormalities of vascular (Bagby et al., 2011) and adipocyte function in juvenile LPO, (DuPriest et al., 2011) findings demonstrate that perinatal MPR programs catch-up growth and cardiovascular abnormalities independently of obesity.

In animal models, exposure to excess testosterone during gestation induces polycystic ovary syndrome (PCOS)-like reproductive and metabolic traits in female offspring, suggesting that the hyperandrogenemic intrauterine environment may have a role in the etiology of PCOS. Additionally, few studies have also addressed metabolic and reproductive outcomes in male offspring. In the present study, the intravenous glucose tolerance test (IGTT) was used to assess the insulin–glucose homeostasis at various ages during sexual development in male sheep born to testosterone-treated ewes. To further analyze the programming effect of testosterone on insulin–glucose homeostasis, indexes of insulin sensitivity were assessed in orchidectomized post-pubertal males born to testosterone-treated ewes (Torq-males) and orchidectomized post-puberal controls (Corq-males) before and 48 h after a testosterone injection. There was no difference in insulin sensitivity indexes between males born to testosterone-treated ewes (T-males) and control males born to control ewes (C-males) at 5, 10, 20 and 30 weeks of age, representing the infantile, early and late pre-pubertal, and early post-pubertal stage of sexual development, respectively. In orchidectomized males, basal levels of insulin and glucose were not different between both groups before and after the testosterone injection; however, Torq-males released more insulin before and after T challenge during the first 20 min of the test. Despite this, plasma glucose concentrations were not different in both groups during IVGTT, resulting in an insulin sensitivity index composite similar between groups. We concluded that the effect of prenatal exposure to excess testosterone may reprogram the pancreatic β-cells insulin release in ovine males, with effects more evident in castrated males versus intact males.