Effects of Maternal Diet and Exercise during Pregnancy on Glucose Metabolism in Skeletal Muscle and Fat of Weanling Rats

Obesity during pregnancy contributes to the development of metabolic disorders in offspring. Maternal exercise may limit gestational weight gain and ameliorate these programming effects. We previously showed benefits of post-weaning voluntary exercise in offspring from obese dams. Here we examined whether voluntary exercise during pregnancy influences lipid and glucose homeostasis in muscle and fat in offspring of both lean and obese dams. Female Sprague-Dawley rats were fed chow (C) or high fat (F) diet for 6 weeks before mating. Half underwent voluntary exercise (CE/FE) with a running wheel introduced 10 days prior to mating and available until the dams delivered; others remained sedentary (CS/FS). Male and female pups were killed at postnatal day (PND)19 and retroperitoneal fat and gastrocnemius muscle were collected for gene expression. Lean and obese dams achieved similar modest levels of exercise. At PND1, both male and female pups from exercised lean dams were significantly lighter (CE versus CS), with no effect in those from obese dams. At PND19, maternal obesity significantly increased offspring body weight and adiposity, with no effect of maternal exercise. Exercise significantly reduced insulin concentrations in males (CE/FE versus CS/FS), with reduced glucose in male FE pups. In males, maternal obesity significantly decreased muscle myogenic differentiation 1 (MYOD1) and glucose transporter type 4 (GLUT4) mRNA expressions (FS vs CS); these were normalized by exercise. Maternal exercise upregulated adipose GLUT4, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC1α) mRNA expression in offspring of dams consuming chow. Modest voluntary exercise during pregnancy was associated with lower birth weight in pups from lean dams. Maternal exercise appeared to decrease the metabolic risk induced by maternal obesity, improving insulin/glucose metabolism, with greater effects in male than female offspring.     

Chronic maternal stress affects growth, behaviour and hypothalamo-pituitary-adrenal function in juvenile offspring

Maternal stress during pregnancy, particularly that combined with low socioeconomic status (SES), has been linked to an increased risk for impaired behavioural and emotional development and affective disorders in children. In animal models, acute periods of prenatal stress have profound effects on hypothalamo-pituitary-adrenal (HPA) function and behaviour. However, few studies have determined the impact of chronic exposure to stress in animal models. The objective of this study was to determine the effects of chronic maternal stress (CMS) during the 2nd half of pregnancy and nursing on growth, locomotor behaviour and HPA axis function in juvenile guinea pig offspring. Pregnant guinea pigs were exposed to a random combination of variable stressors every other day over the 2nd half of gestation and from postnatal day (pnd) 1 until weaning (pnd25). CMS mothers displayed increased basal salivary cortisol levels in the later stages of pregnancy compared to control mothers (p < 0.05). The male offspring of CMS mothers had a lower bodyweight, which was maintained to weaning (p < 0.01). In open-field testing, CMS male offspring showed a decrease in activity compared to controls (p < 0.05). There was no effect of CMS on bodyweight or activity in female offspring. In contrast, both male and female offspring born to CMS mothers displayed increased (p < 0.05) basal salivary cortisol at pnd25, but a blunted adrenocortical response to exposure to the novel open-field enclosure. In conclusion, CMS leads to modification of growth trajectory, locomotor activity and adrenocortical responses to stress in juvenile offspring. Further, males appear considerably more vulnerable to these effects than females.     

Maternal LPS Exposure during Pregnancy Impairs Testicular Development,Steroidogenesis and Spermatogenesis in Male Offspring

Lipopolysaccharide (LPS) is associated with adverse developmental outcomes including embryonic resorption, fetal death, congenital teratogenesis and fetal growth retardation. Here, we explored the effects of maternal LPS exposure during pregnancy on testicular development, steroidogenesis and spermatogenesis in male offspring. The pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD) 13 to GD 17. At fetal period, a significant decrease in body weight and abnormal Leydig cell aggregations were observed in males whose mothers were exposed to LPS during pregnancy. At postnatal day (PND) 26, anogenital distance (AGD), a sensitive index of altered androgen action, was markedly reduced in male pups whose mothers were exposed to LPS daily from GD13 to GD 17. At PND35, the weight of testes, prostates and seminal vesicles, and serum testosterone (T) level were significantly decreased in LPS-treated male pups. At adulthood, the number of sperm was significantly decreased in male offspring whose mothers were exposed to LPS on GD 13–17. Maternal LPS exposure during gestation obviously diminished the percent of seminiferous tubules in stages I–VI, increased the percent of seminiferous tubules in stages IX–XII, and caused massive sloughing of germ cells in seminiferous tubules in mouse testes. Moreover, maternal LPS exposure significantly reduced serum T level in male mice whose mothers were exposed to LPS challenge during pregnancy. Taken together, these results suggest that maternal LPS exposure during pregnancy disrupts T production. The decreased T synthesis might be associated with LPS-induced impairments for spermatogenesis in male offspring.     

The effects of early rearing environment on the hormonal induction of maternal behavior in virgin rats

The present study investigated the effects of isolation rearing, through the artificial rearing paradigm (AR), on the hormonal induction of maternal behavior (MB) in female Sprague–Dawley rats. Between postnatal days (PND) 4 and 18, rat pups were raised either with their mothers (MR) or artificially, without their mothers (AR). As well, some of the AR pups were provided with additional maternal-like licking stimulation (AR-MAX) while the others were not given any additional stimulation (AR-MIN). At PND 60–100, AR (n = 28) and MR (n = 25) animals were ovariectomized (OVX). One week after the surgery, rats were either treated with a 2-week estrogen (E2) and progesterone (P) hormonal regimen (Bridges, R.S., 1984. A quantitative analysis of the roles of dosage, sequence, and duration of estradiol and progesterone exposure in the regulation of maternal behavior in the rat. Endocrinology 114, 930–940) or not treated with the hormone replacement. Maternal behavior testing with foster pups commenced 24 h following the removal of P treatment. Results demonstrated that MR animals showed increased pup licking and hover-crouching in comparison to AR animals and that hormonally primed groups became maternal more quickly than non-primed groups, regardless of the rearing history. There was also a significant interaction between the rearing condition (MR vs. AR) and hormonal treatment on the quality of maternal behavior exhibited. The highest level of licking and crouching was shown by the hormone-treated MR group. Mechanisms for these effects are discussed.     

Body size-specific maternal effects on the offspring environment shape juvenile phenotypes in Atlantic salmon

Positive associations between maternal investment per offspring and maternal body size have been explained as adaptive responses by females to predictable, body size-specific maternal influences on the offspring’s environment. As a larger per-offspring investment increases maternal fitness when the quality of the offspring environment is low, optimal egg size may increase with maternal body size if larger mothers create relatively poor environments for their eggs or offspring. Here, we manipulate egg size and rearing environments (gravel size, nest depth) of Atlantic salmon (Salmo salar) in a 2 × 2 × 2 factorial experiment. We find that the incubation environment typical of large and small mothers can exert predictable effects on offspring phenotypes, but the nature of these effects provides little support to the prediction that smaller eggs are better suited to nest environments created by smaller females (and vice versa). Our data indicate that the magnitude and direction of phenotypic differences between small and large offspring vary among maternal nest environments, underscoring the point that removal of offspring from the environmental context in which they are provisioned in the wild can bias experimentally derived associations between offspring size and metrics of offspring fitness. The present study also contributes to a growing literature which suggests that the fitness consequences of egg size variation are often more pronounced during the early juvenile stage, as opposed to the egg or larval stage.     

Maternal Separation in Guinea-Pigs: A Study in Behavioural Endocrinology

The aim of this study was to elucidate the modulation of behaviour and endocrine stress responses of guinea‐pig pups by social and spatial factors in a maternal separation paradigm. The animals were kept in two colonies (each colony: nine males, 13 females and their offspring; enclosure size: 6 m²). Blood samples were taken from the ear vessels of eight male and eight female pups (aged 13–14 d) immediately before and 2 h after they were removed from their colony and were placed singly into a novel environment. Furthermore, eight male and eight female pups were tested in their home colony before and after 2 h of sepration from their mothers. Blood samples were taken from control animals (eight male and eight female pups) which remained in the home colonies together with their mothers. Additionally, the behaviour of 16 male and 16 female pups was recorded in their home colonies when their mothers were either present or absent. Male and female pups separated from their mothers showed a significantly higher locomotor activity, with females showing higher frequencies of distress calls, than pups whose mothers were present. The mother's absence did not cause a significant increase in serum cortisol concentrations in the male or the female offspring. This result is entirely different from the endocrine stress response of pups that were placed singly in an unknown environment. These animals showed a significant increase in their serum cortisol concentrations after 2 h of separation from their mothers. The absence of the mother led to distinct changes in the behaviour of the guinea‐pig pups. However, staying in the familiar social and spatial environment buffered the endocrine stress response that normally occurs because of maternal separation.     

Factors affecting weaning weight in Antarctic fur seals Arctocephalus gazella at South Georgia

Summary Relationships between size, body condition, age and feeding-attendance patterns during pup rearing of female Antacrtic fur seals Arctocephalus gazella and their effects on the timing of birth and weaning, pup weight, growth and condition were studied at South Georgia in 1981–1982. Twenty-seven (6 male, 21 female) mother-pup pairs were followed from birth to weaning. The analysis of maternal effects was limited to female pups because of the small sample size of male weaners. High weaning weight was associated with those female pups whose mothers spent more time ashore attending their offspring. Weaning weight showed no relationship with perinatal duration, number of feeding trips to sea, days at sea or date of weaning. A further 63 mother-pup pairs were analysed for the effects of maternal body condition (weight/length), age and timing of birth on offspring body weight and condition. Pup weight and condition were weakly correlated with maternal age in female pups. Male pups born earlier in the season were heavier and in better condition. Maternal and offspring body weight and condition were unrelated. For the Antarctic fur seal population at South Georgia where the food supply was apparently not limiting in summer, maternal condition and foraging time were subordinate to maternal care on land (as expressed by attendance duration) in determining offspring weight at weaning.     

Effects of quinestrol and levonorgestrel on prolactin serum concentration in lactating Mongolian gerbils (Meriones unguiculatus) and reproductive parameters of their offspring

The effects of the two sterilants, quinestrol (QE) and levonorgestrel (LNG) on serum prolactin (PRL) level in lactating Mongolian gerbils and reproductive parameters of their offspring were examined in the study. Both sterilants increased the serum PRL level in lactating gerbils. The body weight as well as weights of the ovary, testis, epididymides, and seminal vesicles were lower, whereas that of the uterus was higher in the pups originating from QE-treated mothers in comparison to controls. Histological ovarian sections of the offspring from QE-treated mothers contained only growing follicles, whereas their uterine sections showed a thinner endometrium, thicker myometrium, and greater epithelial-cell height than in controls. The histometrical testis characteristics as well as sperm concentration and motility of male pups from QE-treated mothers were lower compared to those of the control group. The serum gonadotropin levels of female pups from mothers treated with QE were lower, whereas the serum estradiol (E₂) and progesterone (P₄) levels were higher than in control gerbils. In contrast, serum gonadotropin and testosterone (T) levels of male pups from QE-treated mothers were lower compared to controls. LNG did not affect the examined parameters of the offspring. The offspring from QE-treated mothers was infertile, whereas the offspring from LNG-treated mothers was fertile. In summary, QE and LNG have a stimulatory effect on PRL level in lactating gerbils. It also appears that QE administered via milk to mothers affects reproductive processes of their offspring.     

Lactating Females Do Not Discriminate Between Their Own Young and Unrelated Pups in the Communally Breeding Rodent, Octodon degus

Females in numerous rodent species engage in communal nesting and breeding, in which they share one or more nests to rear their young. A potential cost of communal nesting and breeding is that mothers divert resources to unrelated offspring. One way mothers could avoid this cost is to recognize and favour their own young over unrelated offspring when allocating maternal effort. We assessed whether female degus (Octodon degus), a communally nesting and breeding caviomorph rodent, discriminate between their own and unrelated offspring during lactation. Female degus previously have been shown to distinguish between their own and unrelated pups when exposed to odours from both. We measured pup discrimination based on differences in the retrieval behaviour of females that were in early or intermediate lactation directed towards their own and unrelated offspring; offspring presented were of similar or different age. Before any event of pup retrieval, lactating females spent similar amounts of time and interacted to a similar extent with their own and unrelated pups. During pup retrieval, all lactating females transported both pups to the nest. Neither relatedness to pups, nor pup‐age differences, influenced the order in which pups were retrieved to the nest. Dams waited similar amounts of time before retrieving the first pup when the first transported young was their own or unrelated. Likewise, females waited similar amounts of time before retrieving the second pup when the pup transported first was their own or unrelated. The time between first and second pup transport events was longer when dams were in early when compared with intermediate lactation, but only when pups were of similar age. All experimental subjects nursed unrelated pups after they were retrieved. Collectively, our results do not support the hypothesis that communally breeding female degus use their recognition ability to discriminate against unrelated offspring in favour of their own young.     

Maternal effects are long‐lasting and influence female offspring's reproductive strategy in the swordtail fish Xiphophorus multilineatus

The adaptive benefits of maternal investment into individual offspring (inherited environmental effects) will be shaped by selection on mothers as well as their offspring, often across variable environments. We examined how a mother's nutritional environment interacted with her offspring's nutritional and social environment in Xiphophorus multilineatus, a live‐bearing fish. Fry from mothers reared on two different nutritional diets (HQ = high quality and LQ = low quality) were all reared on a LQ diet in addition to being split between two social treatments: exposed to a large adult male during development and not exposed. Mothers raised on a HQ diet produce offspring that were not only initially larger (at 14 days of age), but grew faster, and were larger at sexual maturity. Male offspring from mothers raised on both diets responded to the exposure to courter males by growing faster; however, the response of their sisters varied with mother's diet; females from HQ diet mothers reduced growth if exposed to a courter male, whereas females from LQ diet mothers increased growth. Therefore, we detected variation in maternal investment depending on female size and diet, and the effects of this variation on offspring were long‐lasting and sex specific. Our results support the maternal stress hypothesis, with selection on mothers to reduce investment in low‐quality environments. In addition, the interaction we detected between the mother's nutritional environment and the female offspring's social environment suggests that female offspring adopted different reproductive strategies depending on maternal investment.     

Maternal care interacts with prenatal stress in altering sexual dimorphism in male rats

The present study analyzes the interaction between prenatal stress and mother's behavior on brain, hormonal, and behavioral development of male offspring in rats. It extends to males our previous findings, in females, that maternal care can alter behavioral dimorphism that becomes evident in the neonates when they mature. Experiment 1 compares the maternal behavior of foster mothers toward cross-fostered pups versus mothers rearing their own litters. Experiment 2 ascertains the induced “maternal” behavior of the male pups, derived from Experiment 1 when they reached maturity. The most striking effect was that the males non-exposed to the stress as fetuses and raised by stressed foster mothers showed the highest levels of “maternal” behavior of all the groups (i.e., induction of maternal behavior and retrieving behavior), not differing from the control, unstressed, female groups. Furthermore, those males showed significantly fewer olfactory bulb mitral cells than the control males that were non-stressed as fetuses and raised by their own non-stressed mothers. They also presented the lowest levels of plasma testosterone of all the male groups.     

Prolactin administration during early postnatal life decreases hippocampal and olfactory bulb neurogenesis and results in depressive-like behavior in adulthood

Tight regulation of hormone and neurochemical milieu during developmental periods is critical for adequate physiological functions. For instance, activation of peptide systems during early life stress induces morphological changes in the brain resulting in depression and anxiety disorders. Prolactin (PRL) exerts different actions within the brain; it regulates neurogenesis and modulates neuroendocrine functions in the adult. However, PRL effects during early postnatal life are hardly known. Therefore, we examined whether neonatal administration of PRL influences cell survival in the hippocampal dentate gyrus (DG) and in the olfactory bulb (OB) and whether such influence results in behavioral consequences in adulthood. PRL-treated rat pups (13 mg/kg; PND1 to PND14), injected with BrdU at postnatal day 5 (PND5), showed a decrease in the density of DG BrdU/DCX and BrdU/NeuN-positive cells that survive at PND15. Similarly, PRL treatment decreased the density of BrdU + cells in the OB compared with VEH. Fluorojade B analysis showed no significant changes in the amount of cell death in the DG between the groups. Postnatal PRL administration induced a passive coping strategy in the forced swimming test in male and female adult rats when compared with control and vehicle groups. Corticosterone endogenous levels at PND12 were not affected by PRL or VEH treatment. Altogether, these results suggest that opposed to its effects in the adult, postnatal PRL treatment affects neurogenesis and results in psychopathology later in life. High PRL levels, as observed in neonates under several pathological states, might contribute to detrimental effects on the developing brain.     

Older mothers follow conservative strategies under predator pressure: the adaptive role of maternal glucocorticoids in yellow-bellied marmots

When the maternal environment is a good predictor of the offspring environment, maternal glucocorticoid (GC) levels might serve to pre-program offspring to express certain phenotypes or life-history characteristics that will increase their fitness. We conducted a field study to assess the effects of naturally occurring maternal GC levels on their offspring in yellow-bellied marmots (Marmota flaviventris) subjected to different predator pressures. Maternal fecal corticosteroid metabolites (FCM) were positively correlated with predator pressure. Predators had both direct and indirect effects on pups. We found that older mothers with higher FCM levels had smaller and female-biased litters. Moreover, sons from older mothers with high FCM levels dispersed significantly more than those from older mothers with low FCM levels, whereas the opposite pattern was found in pups from younger mothers. These age-related effects may permit females to make adaptive decisions that increase their pups' fitness according to their current situation.     

Effects of early life social stress on endocrinology,maternal behavior,and lactation in rats

Exposure to early life stress is a predictor of mental health disorders, and two common forms of early life stress are social conflict and impaired maternal care, which are predominant features of postpartum mood disorders. Exposure of lactating female rats to a novel male intruder involves robust social conflict and induces deficits in maternal care towards the F1 offspring. This exposure is an early life social stressor for female F1 pups that induces inefficient lactation associated with central changes in oxytocin (OXT), prolactin (PRL), and arginine vasopressin (AVP) gene expression in adult F1 females.     

Effects of dietary omega-3 PUFAs on growth and development: Somatic,neurobiological and reproductive functions in a murine model

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are relevant to fetal and infant growth and development. Objective: to assess whether long-term exposure to dietary ω-3 PUFA imbalance alters pre- and/or postnatal pups' development and reproductive function later in life. Mice dams were fed with ω-3 PUFA Control (soybean oil, 7%), Deficient (sunflower oil, 7%) or Excess (blend oil; 4.2% cod-liver+2.8% soybean) diet before conception and throughout gestation-lactation and later on, their pups received the same diet from weaning to adulthood. Offspring somatic, neurobiological and reproductive parameters were evaluated. Excess pups were lighter during the preweaning period and shorter in length from postnatal day (PND) 7 to 49, compared to Control pups (P<.05). On PND14, the percentage of pups with eye opening in Excess group was lower than those from Control and Deficient groups (P<.05). In Excess female offspring, puberty onset (vaginal opening and first estrus) occurred significantly later and the percentage of parthenogenetic oocytes on PND63 was higher than Control and Deficient ones (P<.05). Deficient pups were shorter in length (males: on PND14, 21, 35 and 49; females: on PND14, 21 and 42) compared with Control pups (P<.05). Deficient offspring exhibited higher percentage of bending spermatozoa compared to Control and Excess offspring (P<.05). These results show that either an excessively high or insufficient ω-3 PUFA consumption prior to conception until adulthood seems inadvisable because of the potential risks of short-term adverse effects on growth and development of the progeny or long-lasting effects on their reproductive maturation and function.     

The Effect of Locomotion on the Mobilization of Minerals from the Maternal Skeleton

Bone is a dynamic tissue from which minerals are deposited or withdrawn according to the body’s demand. During late pregnancy and lactation, female mammals mobilize mineral from bone to support the ossification of offspring skeleton(s). Conversely, in response to mechanical loading, minerals are deposited in bone enabling it to develop a stronger architecture. Despite their central importance to reproductive performance and skeletal integrity, the interactions between these potentially opposing forces remains poorly understood. It is possible that inter-individual differences in the loading imposed by different forms of locomotion may alter the amount of mineral mobilized during reproduction. Here, the impact of vertical versus horizontal locomotion on bone mobilization was examined during reproduction in the laboratory mouse. The vertical, or climbing, group had access to a 60-cm tower, increasing strain on their appendicular skeleton. The horizontal, or tunnel, group had access to a 100-cm tunnel, which encouraged movements within the horizontal plane. Form of locomotion did not impact the amount of bone females mobilized during reproduction or the amount of mineral females deposited in the litter, but maternal bone architecture differed between groups. The climbing group displayed more trabeculae than the tunnel group, whereas the tunnel group displayed greater cortical bone mineral density mid-shaft. Interestingly, pups born to mothers in the climbing group had a higher concentration of total body calcium at 16 days than pups of mothers in the tunnel group. As maternal total body calcium composition and the amount of calcium invested in the full litter were not different between groups, the difference in the relative calcium content of pups between groups is not suspected to reflect difference in mineral allocation. Future research should consider the impact of maternal activity on the efficiency of offspring skeletal ossification via hormones and other bioactive factors transferred in utero and in milk.     

Intergenerational transmission of the behavioral consequences of early experience in prairie voles

We examined intergenerational and epigenetic effects of early handling manipulations on the social behavior of the prairie vole (Microtus ochrogaster), a monogamous rodent. Laboratory-born parents and their newborn pups were assigned to either a MAN0 “zero handling” manipulation (transfer with a cup during weekly cage changes) or a MAN1 “gloved handling” manipulation (transfer with a gloved hand). Previous studies from our laboratory (Bales et al., 2007) showed that MAN0 juvenile males that received this manipulation as pups are less alloparental and that MAN0 adult females that received this manipulation as pups display impaired pair-bonding. In the present study, when MAN0 and MAN1 pups reached adulthood, they were mated in three combinations (MAN1 female × MAN1 male; MAN0 female × MAN1 male; MAN1 female and MAN0 male). Once the pairs produced offspring, we examined their parental behavior towards their own pups. The offspring of these pairings (F2 generation) also were tested as juveniles for alloparental behavior. MAN1 females paired with a MAN0 male displayed higher levels of parenting behaviors. In the F2 generation, juvenile offspring with a MAN0 parent were less alloparental than were offspring from other pairs. These results suggest that early experiences can be transmitted intergenerationally.     

Older mothers follow conservative strategies under predator pressure: The adaptive role of maternal glucocorticoids in yellow-bellied marmots

When the maternal environment is a good predictor of the offspring environment, maternal glucocorticoid (GC) levels might serve to pre-program offspring to express certain phenotypes or life-history characteristics that will increase their fitness. We conducted a field study to assess the effects of naturally occurring maternal GC levels on their offspring in yellow-bellied marmots (Marmota flaviventris) subjected to different predator pressures. Maternal fecal corticosteroid metabolites (FCM) were positively correlated with predator pressure. Predators had both direct and indirect effects on pups. We found that older mothers with higher FCM levels had smaller and female-biased litters. Moreover, sons from older mothers with high FCM levels dispersed significantly more than those from older mothers with low FCM levels, whereas the opposite pattern was found in pups from younger mothers. These age-related effects may permit females to make adaptive decisions that increase their pups' fitness according to their current situation.     

Maternal investment in a bee species with facultative nest guarding and males heavier than females

1. Maternal investment can be influenced by several factors, especially maternal quality and possibilities for future reproduction. Mass provisioning Hymenoptera are an excellent group for measuring maternal investment because mothers distribute food sources to each brood cell for each offspring separately. Generally in aculeate Hymenoptera, larger females produce larger offspring and invest more in female offspring than in male offspring. 2. This study investigated patterns of maternal investment in Ceratina chalcites, which has an uncommon type of sexual size dimorphism in Hymenoptera: on average, males are heavier than females. It was found that larger females produce a significantly higher proportion of male offspring, as males are the costlier sex in this species. 3. Facultative nest guarding by females was observed. Females can guard offspring until adulthood, as is typical for bees of genus Ceratina (34.43% of nests); however, in the majority of cases (65.56% of nests), females plug and abandon the nest. Significant differences were found in the amount of investment between guarded and unguarded nests. Guarded nests had a greater number of provisioned brood cells and a higher proportion of male offspring. It is suggested that mothers have two facultative strategies – either she makes a large investment in the offspring of one nest or she abandons the first nest and carries out a second nesting elsewhere.     

Maternal obesity at conception programs obesity in the offspring

Risk of obesity in adult life is subject to programming during gestation. To examine whether in utero exposure to maternal obesity increases the risk of obesity in offspring, we developed an overfeeding-based model of maternal obesity in rats utilizing intragastric feeding of diets via total enteral nutrition. Feeding liquid diets to adult female rats at 220 kcal/kg(3/4) per day (15% excess calories/day) compared with 187 kcal/kg(3/4) per day for 3 wk caused substantial increase in body weight gain, adiposity, serum insulin, leptin, and insulin resistance. Lean or obese female rats were mated with ad libitum AIN-93G-fed male rats. Exposure to obesity was ensured to be limited only to the maternal in utero environment by cross-fostering pups to lean dams having ad libitum access to AIN-93G diets throughout lactation. Numbers of pups, birth weight, and size were not affected by maternal obesity. Male offspring from each group were weaned at postnatal day (PND)21 to either AIN-93G diets or high-fat diets (45% fat calories). Body weights of offspring from obese dams did not differ from offspring of lean dams when fed AIN-93G diets through PND130. However, offspring from obese dams gained remarkably greater (P < 0.005) body weight and higher % body fat when fed a high-fat diet. Body composition was assessed by NMR, X-ray computerized tomography, and weights of adipose tissues. Adipose histomorphometry, insulin sensitivity, and food intake were also assessed in the offspring. Our data suggest that maternal obesity at conception leads to fetal programming of offspring, which could result in obesity in later life.