Effects Of Maternal Exercise Research Articles

Maternal physical activity in healthy pregnancy: Effect on fetal oxygen supply.

We review evidence for effects of physical activity before and during gestation on the course of pregnancy and ask if there are circumstances where physical activity can stress the fetus due to competition for oxygen and energy substrates. We first summarize physiological responses to exercise in nonpregnant people and known physiological adaptations to pregnancy. Comparing the two, we conclude that physical activity prior to and continuing during gestation is beneficial to pregnancy outcome. The effect of starting an exercise regimen during pregnancy is less easy to assess as few studies have been undertaken. Results from animal models suggest that the effects of maternal exercise on the fetus are transient; the fetus can readily compensate for a short-term reduction in oxygen supply. In general, we conclude that physical activity before and during pregnancy is beneficial, and exercise started during pregnancy is unlikely to affect fetal development. We caution, however, that there are circumstances where this may not apply. They include the intensive exercise regimens of elite athletes and pregnancies at high altitudes where hypoxia occurs even in the resting state.

Effects of maternal exercise on infant mesenchymal stem cell mitochondrial function, insulin action, and body composition in infancy.

Maternal exercise (ME) has been established as a useful non-pharmacological intervention to improve infant metabolic health; however, mechanistic insight behind these adaptations remains mostly confined to animal models. Infant mesenchymal stem cells (MSCs) give rise to infant tissues (e.g., skeletal muscle), and remain involved in mature tissue maintenance. Importantly, these cells maintain metabolic characteristics of an offspring donor and provide a model for the investigation of mechanisms behind infant metabolic health improvements. We used undifferentiated MSC to investigate if ME affects infant MSC mitochondrial function and insulin action, and if these adaptations are associated with lower infant adiposity. We found that infants from exercising mothers have improvements in MSC insulin signaling related to higher MSC respiration and fat oxidation, and expression and activation of energy-sensing and redox-sensitive proteins. Further, we found that infants exposed to exercise in utero were leaner at 1 month of age, with a significant inverse correlation between infant MSC respiration and infant adiposity at 6 months of age. These data suggest that infants from exercising mothers are relatively leaner, and this is associated with higher infant MSC mitochondrial respiration, fat use, and insulin action.

Single cell transcriptomic representation of social dominance in prefrontal cortex and the influence of preweaning maternal and postweaning social environment

Social dominance encompasses winning dyadic contests and gaining priority access to resources and reproduction. Dominance is influenced by environmental factors, particularly during early postnatal life and adolescence. A disinhibitory medial prefrontal cortex (mPFC) microcircuit has been implicated in the expression of dominance in the “tube test” social competition paradigm in mice, but the neuroplasticity underlying dominance is not known. We previously reported that male pups raised by physically active (wheel-running, as opposed to sedentary) dams exhibit tube test dominance and increased reproductive fitness, and here we show that social isolation from weaning also increases dominance. By using single cell transcriptomics, we tested if increased dominance in these models is associated with a specific transcriptional profile in one or more cell-types in the mPFC. The preweaning maternal effect, but not postweaning social isolation, caused gene expression changes in pyramidal neurons. However, both the effect of maternal exercise and social isolation induced the coordinated downregulation of synaptic channel, receptor, and adhesion genes in parvalbumin positive (PV) interneurons, suggesting that development of dominance is accompanied by impaired PV interneuron-mediated inhibition of pyramidal cells. This study may help understand environmentally induced transcriptional plasticity in the PFC and its relationship to tube test dominance.

Maternal Exercise Prior to and during Gestation Induces Sex-Specific Alterations in the Mouse Placenta.

While exercise (EX) during pregnancy is beneficial for both mother and child, little is known about the mechanisms by which maternal exercise mediates changes in utero. Six-week-old female C57BL/6 mice were divided into two groups: with (exercise, EX; N = 7) or without (sedentary, SED; N = 8) access to voluntary running wheels. EX was provided via 24 h access to wheels for 10 weeks prior to conception until late pregnancy (18.5 days post coitum). Sex-stratified placentas and fetal livers were collected. Microarray analysis of SED and EX placentas revealed that EX affected gene transcript expression of 283 and 661 transcripts in male and female placentas, respectively (±1.4-fold, p < 0.05). Gene Set Enrichment and Ingenuity Pathway Analyses of male placentas showed that EX led to inhibition of signaling pathways, biological functions, and down-regulation of transcripts related to lipid and steroid metabolism, while EX in female placentas led to activation of pathways, biological functions, and gene expression related to muscle growth, brain, vascular development, and growth factors. Overall, our results suggest that the effects of maternal EX on the placenta and presumably on the offspring are sexually dimorphic.

Maternal Exercise Protects Male Offspring from Maternal Diet Programmed Non-Alcoholic Fatty Liver Disease Progression.

Maternal obesity programs risk for development of non-alcoholic fatty liver disease (NAFLD) in offspring. Maternal exercise is a potential intervention to prevent developmentally programmed phenotypes. We hypothesized that maternal exercise would protect from progression of NAFLD in offspring previously exposed to maternal obesogenic diet. Female mice were fed chow (CON) or HFFC and bred with lean males. A subset had an exercise wheel introduced 4 weeks after starting diet to allow for voluntary exercise. The offspring were weaned to HFFC diet for 7 weeks to induce NAFLD. Serum, adipose, and liver tissue were collected for metabolic, histologic, and gene expression analyses. Cecal contents were collected for 16S sequencing. Global metabolomics was performed on liver. Female mice fed HFFC diet had increased body weight prior to adding an exercise wheel. Female mice fed HFFC diet had an increase in exercise distance relative to CON during the pre-conception period. Exercise distance was similar between groups during pregnancy and lactation. CON-Active and HFFC-Active offspring exhibited decreased inflammation compared to offspring from sedentary dams. Fibrosis increased in offspring from HFFC-sedentary dams compared to CON-sedentary. Offspring from exercised HFFC dams exhibited less fibrosis than offspring from sedentary HFFC dams. While maternal diet significantly affected the microbiome of offspring, the effect of maternal exercise was minimal. Metabolomics analysis revealed shifts in multiple metabolites including several involved in bile acid, one-carbon, histidine, and acylcarnitine metabolism. This study provides pre-clinical evidence that maternal exercise is a potential approach to prevent developmentally programmed liver disease progression in offspring.

Maternal exercise improves epithelial development of fetal intestine by enhancing apelin signaling and oxidative metabolism.

Obesity in pregnancy is currently the leading cause of gestational complications for the mother and fetus worldwide. Maternal obesity (MO), common in western societies, impedes development of intestinal epithelium in the fetuses, which causes disorders in the nutrient absorption and intestine-related immune responses in offspring. Here, using a mouse model of maternal exercise (ME), we found that exercise during pregnancy protects the impairment of fetal intestinal morphometrical formation and epithelial development due to MO. MO decreased villus length and epithelial proliferation markers in E18.5 fetal small intestine, which was increased due to ME. The expression of the epithelial differentiation markers, Lyz1, Muc2, and Tff3, in fetal small intestine was decreased due to MO, but protected by ME. Consistently, the biomarkers related to mitochondrial biogenesis and oxidative metabolism were downregulated in MO fetal small intestine but recovered by ME. Apelin injection to dams partially mirrored the beneficial effects of ME. ME and apelin injection activated AMPK, the downstream target of apelin receptor signaling, which might mediate the improvement of fetal epithelial development and oxidative metabolism. These findings suggest that ME, a highly accessible intervention, is effective in improving fetal intestinal epithelium of obese dams. Apelin-AMPK-mitochondrial biogenesis axis provides amenable therapeutic targets to facilitate fetal intestinal development of obese mothers.

Effects of maternal exercise during pregnancy on neonatal weight and subcutaneous fat thickness

Effects of maternal exercise during pregnancy on neonatal weight and subcutaneous fat thickness

Maternal exercise intergenerationally drives muscle-based thermogenesis via activation of apelin-AMPK signaling.

SummaryBackgroundSarcolipin and uncoupling protein 3 (UCP3) mediate muscle-based non-shivering thermogenesis (NST) to improve metabolic homeostasis. The impacts of maternal obesity (MO) and maternal exercise (ME) on NST in offspring muscle remain unexamined.MethodsFemale mice were fed with a control diet or high fat diet to induce obesity. Then, obese mice were further separated into two groups: obesity only (OB) and OB plus daily exercise (OB/Ex). Fetal muscle was collected at embryonic day 18.5 and offspring mice at 3-month-old. Apelin administration during pregnancy and apelin receptor (APJ) knockout mouse were further used for investigating the mediatory role of APJ on muscle-based thermogenesis. To explore the direct effects of exercise on AMP-activated protein kinase (AMPK) downstream targets, AMPK knockout mouse was used.FindingsMO inhibited while ME activated AMPK and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in fetal muscle. AMPK activation increased sarcolipin expression, which inhibited the uptake of calcium ions into sarcoplasmic reticulum, thereby activating CaMKK2. Consistently, the expression of UCP3 and sarcolipin was suppressed due to MO but activated in ME fetal muscle. Importantly, changes of UCP3 and sarcolipin maintained in offspring muscle, showing the transgenerational effects. Furthermore, apelin administration during pregnancy mimicked the effects of ME on AMPK and CaMKK2 activation, and UCP3 and sarcolipin expression, underscoring the mediatory roles of apelin-AMPK signaling in improving fetal muscle development.InterpretationME, via activation of apelin signaling-AMPK axis, enhances NST gene expression in fetal and offspring muscle impaired due to MO, which intergenerationally protects offspring from diet-induced obesity and metabolic disorders.FundingThis work was supported by National Institutes of Health Grant R01-HD067449.

Effects of Maternal Exercise During Pregnancy on Perinatal Growth and Childhood Obesity Outcomes: A Meta-analysis and Meta-regression.

Perinatal growth abnormalities program susceptibility to childhood obesity, which is further exaggerated by maternal overweight and obesity (MO) during pregnancy. Exercise is highly accessible, but reports about the benefits of maternal exercise on fetal growth and childhood obesity outcomes are inconsistent, reducing the incentives for pregnant women to participate in exercise to improve children's perinatal growth. This systematic review and meta-analysis aims to establish evidence-based efficacy of exercise in mothers with normal weight (MNW) and MO during pregnancy in reducing the risks of perinatal growth abnormalities and childhood obesity. In addition, the impacts of exercise volume are also assessed. The PubMed, ScienceDirect, Web of Science, and Cochrane Library databases were searched from inception to February 15, 2020. We included randomized controlled trials with exercise-only intervention or exercise with other confounders in pregnant MNW (body mass index, BMI 18.5-24.9kg/m2) and MO (BMI ≥ 25kg/m2), which were further subgrouped in the meta-analysis. Primary outcomes included birth weight, preterm birth, small for gestational age (SGA), large for gestational age (LGA), infant and childhood weight, and childhood obesity. A linear meta-regression analysis was also used to explore the effects of exercise volume on outcomes. 99 studies were included in the meta-analysis (n = 596,876), and individual study quality ranged from fair to good according to the Newcastle-Ottawa scale assessment. Exercise only interventions in MNW reduced preterm birth by 15% (26 studies, n = 76,132; odds ratio [OR] 0.85; 95% CI 0.72, 1.01; I2 = 83.3%), SGA by 17% (33 studies, n = 92,351; OR 0.83; 95% CI 0.71, 0.98; I2 = 74.5%) and LGA by 17% (29 studies, n = 84,310; OR 0.83; 95% CI 0.74, 0.95; I2 = 60.4%). Exercise only interventions in MO reduced preterm birth by 33% (2 studies, n = 3,050; OR 0.67; 95% CI 0.70, 0.96; I2 = 0%), SGA by 27% (8 studies, n = 3,909; OR 0.73; 95% CI 0.50, 1.05; I2 = 40.4%) and LGA by 55% (9 studies, n = 81,581; OR 0.45; 95% CI 0.18, 1.11; I2 = 98.3%). Exercise only interventions in MNW reduced childhood obesity by 53% (3 studies, n = 6,920; OR 0.47; 95% CI 0.36, 0.63; I2 = 77.0%). However, no significant effect was observed in outcomes from exercise confounders in either MNW or MO. In the meta-regression, the volume of exercise-only intervention in MNW was negatively associated with birth weight, greatly driven by volumes more than 810 metabolic equivalents (MET)-min per week. Other outcomes were not associated with exercise volume. This systematic review and meta-analysis suggests that exercise during pregnancy in both MNW and MO safely and effectively reduce the risks of preterm birth, SGA, and LGA. Furthermore, MNW exercise also reduces the risk of childhood obesity. Overall, regardless of prepregnancy BMI, maternal exercise during pregnancy provides an excellent opportunity to mitigate the high prevalence of adverse birth outcomes and childhood obesity.

The effect of maternal exercise and altitude training on performance in hypoxic environment: a brief review

Environmental and maternal exercise experienced even during the very earliest stages of life has the potential to cause developmental changes. The growing evidence demonstrated that diverse environmental stressors affect offspring in various aspects in early stage of life and can be transmitted directly or indirectly by both parental lines. The development of normobaric hypoxic environment facilities began in recent years after athletes born and trained at high altitude continued to update their records in sports competition, especially marathons and other endurance sports. Although a large number of studies have proved the effect of hypoxic training in the field of sports science and competition, the effectiveness of this training model on exercise performance/capacity and physiological variables is still controversial. Therefore, this study makes a brief review of the papers related to this scope and attempted to understand the potential mechanism of maternal exercise in hypoxic environment on exercise performance and reduction of metabolic risk factors.

Maternal Inactivity Programs Skeletal Muscle Dysfunction in Offspring Mice by Attenuating Apelin Signaling and Mitochondrial Biogenesis

SUMMARYAlthough maternal exercise (ME) becomes increasingly uncommon, the effects of ME on offspring muscle metabolic health remain largely undefined. Maternal mice are subject to daily exercise during pregnancy, which enhances mitochondrial biogenesis during fetal muscle development; this is correlated with higher mitochondrial content and oxidative muscle fibers in offspring muscle and improved endurance capacity. Apelin, an exerkine, is elevated due to ME, and maternal apelin administration mirrors the effect of ME on mitochondrial biogenesis in fetal muscle. Importantly, both ME and apelin induce DNA demethylation of the peroxisome proliferator-activated receptor γ coactivator-1α (Ppargc1a) promoter and enhance its expression and mitochondrial biogenesis in fetal muscle. Such changes in DNA methylation were maintained in offspring, with ME offspring muscle expressing higher levels of PGC-1α1/4 isoforms, explaining improved muscle function. In summary, ME enhances DNA demethylation of the Ppargc1a promoter in fetal muscle, which has positive programming effects on the exercise endurance capacity and protects offspring muscle against metabolic dysfunction.

Redox Mechanism for the Beneficial Effect of Maternal Exercise to Improve OffSpring Metabolic Health

Redox Mechanism for the Beneficial Effect of Maternal Exercise to Improve OffSpring Metabolic Health

Maternal exercise conveys protection against NAFLD in the offspring via hepatic metabolic programming

Maternal exercise (ME) during pregnancy has been shown to improve metabolic health in offspring and confers protection against the development of non-alcoholic fatty liver disease (NAFLD). However, its underlying mechanism are still poorly understood, and it remains unclear whether protective effects on hepatic metabolism are already seen in the offspring early life. This study aimed at determining the effects of ME during pregnancy on offspring body composition and development of NAFLD while focusing on proteomic-based analysis of the hepatic energy metabolism during developmental organ programming in early life. Under an obesogenic high-fat diet (HFD), male offspring of exercised C57BL/6J-mouse dams were protected from body weight gain and NAFLD in adulthood (postnatal day (P) 112). This was associated with a significant activation of hepatic AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPARα) and PPAR coactivator-1 alpha (PGC1α) signaling with reduced hepatic lipogenesis and increased hepatic β-oxidation at organ programming peak in early life (P21). Concomitant proteomic analysis revealed a characteristic hepatic expression pattern in offspring as a result of ME with the most prominent impact on Cholesterol 7 alpha-hydroxylase (CYP7A1). Thus, ME may offer protection against offspring HFD-induced NAFLD by shaping hepatic proteomics signature and metabolism in early life. The results highlight the potential of exercise during pregnancy for preventing the early origins of NAFLD.

700-P: Mechanism for the Beneficial Effects of Maternal Exercise to Improve Offspring Metabolic Health

Poor maternal diet and obesity increase the risk of obesity and type 2 diabetes in offspring, fueling the worldwide epidemic of these diseases. Recent animal studies have shown that maternal exercise (MatEx) improves the metabolic phenotype of offspring in adulthood, including improved glucose tolerance and liver function. Here, we determined the molecular mechanisms responsible for these critical effects of MatEx. Female mice were fed a chow or high fat diet and housed in cages with (Trained) or without (Sedentary) running wheels for 2 wks prior to breeding and during gestation. Offspring were sedentary and chow-fed. MatEx improved glucose tolerance and liver function in adult offspring. Beginning at embryonic day 13.5, MatEx increased expression of TCA cycle and fatty acid oxidation genes in offspring liver, and increased DNA demethylation at promoters of these hepatic genes. Next, we identified a novel MatEx-induced AMPK/isocitrate dehydrogenase/αketoglutarate/Tet axis in offspring liver controlling DNA demethylation. Primary hepatoblasts treated with serum from trained dams, but not sedentary dams or trained non-pregnant females stimulated this pathway, suggesting the effects of MatEx on offspring stem from a placenta-derived serum factor(s). LC-MS/MS of serum and RNAseq of placenta from trained dams identified this factor as superoxide dismutase 3 (Sod3), and recombinant SOD3 treatment of hepatoblasts increased AMPK-Tet signaling and hepatic gene expression. The effects of MatEx to increase liver AMPK-Tet signal, alter liver DNA methylation and gene expression, and improve offspring glucose tolerance in vivo were ablated in placenta-specific Sod3 KO mice. Finally, SOD3 was increased in serum and placenta from highly physically active pregnant women. Sod3 is an exercise-induced, placenta-derived protein that improves glucose homeostasis via epigenetic changes in offspring liver, defining a novel paradigm for the beneficial effects of exercise on metabolic health. Disclosure J. Kusuyama: None. A.B. Wagner: None. R.H. Conlin: None. N.S. Makarewicz: None. M. Møller: None. E.M. Miele: None. R. Middelbeek: None. N. Jessen: None. P.G. Ovesen: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen, Colgate-Palmolive, Eli Lilly and Company, Medtronic. K.B. Adamo: None. E.N. Grayck: None. L.J. Goodyear: None. Funding National Institutes of Health (DK101043)

695-P: Grand-Maternal Exercise Improves Glucose Tolerance in Second Generation Offspring

Maternal obesity and diet are critical risk factors for development of obesity and diabetes in both first (F1) and second (F2) generation offspring. Maternal exercise in mice improves F1 metabolic health and prevents the detrimental effects of maternal high-fat-diet (HFD) on F1 offspring. Whether the beneficial effects of maternal exercise can be transmitted to the F2 generation is unknown. Here, C57BL/6 females were fed a chow or HFD and subdivided into cages with (Exercise) or without (Sedentary) running wheels for 2wks before breeding and during ∼3wks gestation. Male F1 offspring were sedentary and chow-fed, and at 8 wks of age were bred with age-matched females from untreated parents. F2 offspring were studied based on grand-maternal treatment: chow sedentary; chow trained; HFD sedentary; HFD trained (n= ∼10 litters/group; 348 total mice). F2 offspring were sedentary and chow-fed and studied up to 52 wks of age. For F2 males, grand-maternal exercise significantly improved glucose tolerance at 24, 36 and 52 wks and decreased insulin concentrations at 52 wks. Grand-maternal exercise also resulted in F2 males with lower body weights, decreased fat mass and increased lean mass at 52wks. Grand-maternal HFD decreased glucose uptake in skeletal muscles and adipose tissue in F2 males, but there was no effect of grand-maternal exercise, suggesting that the mechanism for improved glucose tolerance in F2 males does not involve glucose uptake in these tissues. For female F2, grand-maternal exercise had no effect on insulin concentrations, body weights or tissue glucose uptake. However, grand-maternal exercise significantly improved glucose tolerance in female F2 at 36 and 52 wks, and decreased fat mass and increased lean mass. Maternal exercise has beneficial effects on the metabolic health of adult F2 male and female offspring. These novel findings suggest that maternal exercise can prevent obesity and diabetes in multiple generations and may help reduce the incidence of these diseases worldwide. Disclosure A.B.A. Wagner: None. J. Kusuyama: None. P. Nigro: None. N.S. Makarewicz: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen, Colgate-Palmolive, Eli Lilly and Company, Medtronic. L.J. Goodyear: None. Funding American Diabetes Association (1-17-PMF-009 to A.B.A.W.); National Institutes of Health (R01DK101043)

Effect of Maternal Exercise on Diet-induced Redox Imbalance in Hippocampus of Adult Offspring

Physical exercise practice has been increasingly recommended in the prevention and treatment of chronic diseases, causing a positive effect from body weight/fat loss to improved cognitive function. Maternal exercise seems to induce the same positive lifelong adaptations to the offspring. We hypothesized that maternal exercise can prevent redox imbalance in adult offspring’s hippocampus exposed to a high-fat diet (HFD). Female Wistar rats were divided into three groups before and during pregnancy: (1) sedentary, (2) swimming exercise, and (3) swimming exercise with overload. On 60 days of age, the male pups were divided into standard diet or HFD for one month, yielding normal and HFD subgroups for each maternal condition. Maternal interventions did not alter gestational parameters, birth outcomes, and offspring weight gain from weaning to 90 days of age. The HFD consumption increased body fat, which was not prevented by maternal exercise. Serum glucose levels were increased by HFD, an effect that was prevented by unload maternal exercise. In the hippocampus, both maternal exercise intensities could increase antioxidant defense. Hippocampal redox homeostasis was impaired by HFD, causing increased superoxide levels, which was prevented by exercise without load, while overload caused only a reduction of the effect. In summary, the practice of swimming exercise without overload during pregnancy seems to be more beneficial when evaluated in animal model, preventing HFD induced redox imbalance and increasing antioxidant defense while overload swimming exercise during pregnancy demonstrated a negative effect on offspring submitted to HFD consumption.

Effect of maternal exercise on maternal and foetal health in obese pregnant women

Background: Obesity during pregnancy represents a global problem and is a major risk factor for complications during pregnancy and labour. Emerging evidence suggests that physical activity during pregnancy might be beneficial for both maternal and foetal health without side effects. The purpose of this systematic review was to review trials evaluating the effect of physical activity on maternal and foetal health in obese pregnant women. Methods: PRISMA guidelines were followed. We searched for randomized controlled trials published until June 2018 on the PubMed, PEDro and CENTRAL databases. We included articles that had a well described physical activity intervention and studied obese pregnant women with BMI &gt; 30 kg/m2.Results: Ten articles were included in the review. All articles included a physical activity intervention, seven articles included also a dietary intervention. Four articles included a pedometer-based intervention, six articles opted for a supervised physical activity intervention. Physical activity with or without dietary intervention had no effect on lowering the risk for gestational diabetes mellitus or improving neonatal or other maternal outcomes. There were mixed results in gestational weight gain and mode of delivery. Conclusion: We can conclude that physical activity during pregnancy has mixed results on maternal and foetal health in obese pregnant women. There is no evidence from randomized controlled trials that PA during pregnancy in obese women improves maternal or neonatal outcomes, and therefore no clear statements on beneficial effects of PA in this population can currently be made.

Effects of Maternal Exercise During Pregnancy on Offspring Body Composition and Voluntary Exercise

The Developmental Origins of Health and Disease hypothesis posits that various factors experienced early in life can predispose individuals to being healthy or unhealthy as adults. For example, children with high birth weight, either by being born to obese mothers or mothers who experience high gestational weight gain during pregnancy, are more likely to be obese as adults. Although maternal diet has been shown to affect offspring body weight in both humans and rodents, the role of maternal exercise remains unclear.We studied a novel animal model, mice from 4 replicate High Runner (HR) lines selectively bred for ~85 generations for voluntary wheel running and 4 non‐selected Control (C) lines. HR mice run ~3‐fold longer distances than C on a daily basis. In the present study, 80 female mice (prospective dams) were given wheel access starting at 12 weeks of age, paired with males after 2 weeks for a period of 18 days, and allowed continued wheel access until 10 days after giving birth. An additional 80 dams were not given wheels. Offspring body composition was measured at weaning (3 weeks of age), after sexual maturity (7 weeks of age), and after breeding (20 weeks of age for males, 24 weeks of age for females). Offspring wheel running was measured at 7 weeks of age for 6 days, as is used in the selection experiment.During the 14 days prospective dams were housed individually, and consistent with many previous studies, HR dams ran ~3‐fold more than C (HR mean = 16,215 rev/day, range = 10,898 to 21,653 revs/day; C mean = 5,478 rev/day, range = 3,338 to 8,422 revs/day, p &lt; 0.0001). During the first 5 days after giving birth, dams ran very little (HR mean = 1,758 rev/day, range = 145 to 2,816 revs/day; C mean = 1,445 rev/day, range = 707 to 2,574 revs/day; p = 0.1519) and during days 6–10 after birth they ran even less (HR mean = 1,377 rev/day, range = 92 to 3,851 revs/day; C mean = 1,109 rev/day, range = 210 to 2,408 revs/day; p = 0.5229).Maternal wheel access did not significantly affect either time from pairing to giving birth or litter size. Maternal wheel access did not significantly affect offspring wheel‐running distance, but HR offspring ran ~2.75‐fold more than C for males (HR mean = 8,495 rev/day, range = 3,051 to 16,733 revs/day; C mean = 3,080 rev/day, range = 376 to 6,002 revs/day; p = 0.0012) and ~3‐fold more for females (HR mean = 11,448 rev/day, range = 4,316 to 21,128 revs/day; C mean = 3,703 rev/day, range = 448 to 7,894 revs/day; p = 0.0002), as expected. At 7 weeks of age (after sexual maturity), maternal wheel access had an interactive effect on female offspring (p = 0.0117), increasing lean mass for C mice but decreasing it for HR mice.Overall, our results show that although maternal wheel access during pregnancy did not alter litter size or offspring wheel‐running behavior, it did have effects on offspring body composition at sexual maturity, but the effects varied between the sexes and in relation to genetic background (linetype).

Maternal exercise during pregnancy prevents neurocognitive impairments in the juvenile offspring induced by prenatal stress

PurposeMaternal exercise has shown beneficial effects on maternal/foetal health; however, the effects of maternal exercise on neurocognitive development in prenatally stressed offspring are unknown. The aim of the current study was to determine if maternal exercise during pregnancy prevents the effects of stress on spatial memory and learning as well as on the dendritic outgrowth of hippocampal neurons in prenatally stressed offspring. MethodsTen pregnant mice were divided into three groups: control (C), restraint stress (RS) and restraint stress + voluntary wheel running (RS + VWR). Between gestational day 1 and 14 the dams from the RS + VWR group were subjected to the VWR protocol for 4 h per day. Moreover, from gestational day 14 until delivery the pregnant females from RS and RS + VWR group were subjected to three daily stress sessions. Between postnatal day 52 and 56, the male mice born of the three groups of dams were evaluated in the Morris Water Maze, and then, their neuronal morphology was analysed. ResultsThe stressed mice showed higher escape latencies and a significant reduction in both the number of entries to and in the time spent in the quadrant target of the maze, compared to controls, along with a reduction in the dendritic outgrowth of the hippocampal neurons. Moreover, stressed mice born from exercised mothers showed an improvement in spatial learning and memory, along with an increase in the dendritic length of dentate granule cells. ConclusionsMaternal exercise during pregnancy may be a beneficial factor to prevent the cognitive impairments and to ameliorate partially the impairments in the hippocampal dendritic outgrowth exhibited by prenatally stressed mice.

722-P: Maternal Exercise Improves Metabolic Health of Grand-Offspring

Maternal environments are critical factors in determining risk for obesity and diabetes in both first generation (F1) and second generation (F2) offspring. Maternal exercise in mice has been shown to improve metabolic health in F1, including prevention of the detrimental effects of maternal high-fat feeding on F1 offspring. Whether the beneficial effects of maternal exercise can be transmitted to the F2 generation (grand-offspring) is not known. To test this, C57BL/6 females were fed a chow or high fat diet (60% fat) and grouped by housing in cages with (Exercise Trained) or without (Sedentary) running wheels for 2 weeks before breeding (7.04±0.5 km/day) and during gestation (2.2±0.3 km/day). Females were bred with chow-fed, sedentary males. F1 offspring were sedentary and chow-fed. At 8 weeks of age, two male mice (F1) from each litter (selected based on average body weight of the litter), were bred with age-matched female mice from untreated parents. Thus, four groups of F2 offspring resulted based on grand-maternal treatment: sedentary and chow-fed; sedentary and high fat-fed; trained and chow-fed; trained and high fat-fed (n=5-10 litters/group). F2 offspring were sedentary and chow-fed post-weaning. Unexpectedly, there was no effect of grand-maternal high fat diet on F2 glucose tolerance at any age. There was also no effect of grand-maternal exercise on glucose tolerance in offspring at 16 or 24 weeks of age. However, grand-maternal exercise resulted in a tendency for improvement in glucose tolerance in 36-week-old offspring (P=0.07), and a significant improvement at 52 weeks (males: P=0.03; females: P=0.0001). Male and female body weights were not different among F2 groups. F2 offspring from exercise-trained grand-mothers had decreased % fat mass (males: P=0.04; females: P=0.05) and increased % lean mass in males (P=0.04), with a tendency to increase in females (P=0.06) at 52 weeks of age. In conclusion, grand-maternal exercise training has beneficial effects in the metabolic health of adult male and female F2 offspring. Disclosure A.B.A. Wagner: None. J. Kusuyama: None. P. Nigro: None. M.F. Hirshman: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., Amgen Inc., Colgate-Palmolive Company, Medtronic. L.J. Goodyear: None. Funding American Diabetes Association (1-17-PMF-009 to A.B.A.W.); National Institutes of Health (R01DK101043)