Maternal Exercise Research Articles

Maternal exercise improves markers of metabolic signaling and reduces inflammation in brown adipose tissue of offspring

Maternal obesity impacts approximately one-third of pregnant people and impacts offspring through the transmission of obesogenic and diabetic traits. Pregnant patients often spend considerable time sedentary, which has been associated with harmful cardiometabolic changes. Our recent data show that compared with sedentary conditions, voluntary exercise during pregnancy in mice shifts adipose distribution of offspring away from energy storing white adipose tissue towards energy burning brown adipose tissue (BAT), which could improve energy metabolism over the lifespan. The objective of this study was to test the hypothesis that voluntary exercise in pregnant mice improves metabolic signaling pathways and reduces markers of inflammation in BAT from offspring. To test this, female C57BL/6J mice were placed on control diet and allocated to sedentary versus voluntary running wheel exercise cages. Voluntary wheel running was allowed for two weeks prior to breeding and throughout weaning. When offspring were 16 weeks of age, they were euthanized for collection of BAT. The study groups were male sedentary (n=9), female sedentary (n=11), male exercise (n=12), female exercise (n=8). Quantitative real-time polymerase chain reaction was used to measure mRNA of fibroblast-growth factor receptors (β-klotho, Fgfr1, Fgfr2) and inflammation markers (IL10, IL1β, TNFα) in BAT. Outcomes were analyzed by two-way ANOVA to assess effects of exercise, sex, and their interaction. Offspring from exercised mothers had a significant decrease in mRNA of IL1β (1.4±0.4 male sedentary vs. 0.4±0.1 male exercise vs. 1.1±0.2 female sedentary vs. 0.8 ±0.2 female exercise; PSex=0.668, PEX=0.006, PInt=0.098) and TNFα (0.9±0.1 male sedentary vs. 0.5±0.1 male exercise vs. 1.3±0.3 female sedentary vs. 0.6 ±0.1 female exercise; PSex=0.126, PEX=0.007, PInt=0.562) and an increase in Fgfr2 (1.1±0.2 male sedentary vs. 1.7±0.3 male exercise vs. 1.3±0.3 female sedentary vs. 3.8 ±1.2 female exercise; PSex=0.063, PEX=0.011, PInt=0.096) in BAT, which was largely independent of sex. There was no significant main effect of either sex or exercise on IL10, Fgfr1, or β-klotho mRNA in BAT. These data suggest that maternal exercise is associated with decreased inflammation and increased protective metabolic signaling in BAT. This could impact energy metabolism given increasing evidence for advantageous metabolic adaptations with increased BAT health and signaling. Additional studies are needed to further understand the impact of maternal exercise on adipose health, energy metabolism, and cardiovascular outcomes in offspring over the lifespan. American Heart Association Undergraduate Summer Fellowship, Department of Obstetrics and Gynecology at Penn State Milton S Hershey Medical Center, and Dani Peress MD Memorial Fund from the Society of Maternal Fetal Medicine This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Maternal polychlorinated biphenyl 126 (PCB 126) exposure modulates offspring gut microbiota irrespective of diet and exercise

The gut microbiota plays an important role throughout the lifespan in maintaining host health, and several factors can modulate microbiota composition including diet, exercise, and environmental exposures. Maternal microbiota is transferred to offspring during early life; thus, environmental exposures before gestation may also modulate offspring microbiota. Here we aimed to investigate the effects of maternal exposure to dioxin-like polychlorinated biphenyls (PCBs) on the microbiota of aged offspring and to determine if lifestyle factors, including maternal exercise or offspring high-fat feeding alter these associations. To test this, dams were exposed to PCB 126 (0.5 μmole/kg body weight) or vehicle oil by oral gavage during preconception, gestation, and during lactation. Half of each group was allowed access to running wheels for ≥ 7 days before and during pregnancy and up through day 14 of lactation. Female offspring born from the 4 maternal groups (PCB exposure or not, with/without exercise) were subsequently placed either on regular diet or switched to a high-fat diet during adulthood. Microbiota composition was quantified in female offspring at 49 weeks of age by 16 S rRNA sequencing. Maternal exposure to PCB 126 resulted in significantly reduced richness and diversity in offspring microbiota regardless of diet or exercise. Overall compositional differences were largely driven by offspring diet, but alterations in specific taxa due to maternal PCB 126 exposure, included the depletion of Verrucomicrobiaceae and Akkermansia muciniphila, and an increase in Anaeroplasma. Perturbation of microbiota due to PCB 126 may predispose offspring to a variety of chronic diseases later in adulthood.

Risk factors for dystocia in primiparous and pluriparous beef cows at the Besuki Animal Health Center, Situbondo Regency, East Java, Indonesia

This study aims to determine the risk factors for dystocia in primiparous and pluriparous dams at the study site. Cases of dystocia, both maternal and fetal, were obtained as secondary data from records at the Situbondo Regency Animal Husbandry Service for year 2020 and 2021. Tracking on these secondary data was carried out to look for cows experienced dystocia and the owners’ names and addresses for interviews using a questionnaire worksheet. Interviews were conducted in February - May 2022 to obtain data on the maternal breed, age, feeding, fetal sex, and exercise frequency during pregnancy of the cows. Dystocia in the working area of the Besuki Animal Health Center in Sitobondo Regency in 2020 and 2021 occured in 50 cows which included primiparous (26%) and pluriparous (74%) cows. Breed, age, feed, and sex of the calves were not significantly different (p >0.05) between primiparous and pluriparous dams. However, the frequency of the exercises differed significantly (p <0.05) between primiparous and pluriparous dams. It could be concluded that the dystocia of cows in the study area was dominated by pluriparous parturition with exercises factor as the main cause.

Risk factors for dystocia in primiparous and pluriparous beef cows at the Besuki Animal Health Center, Situbondo Regency, East Java, Indonesia

This study aims to determine the risk factors for dystocia in primiparous and pluriparous dams at the study site. Cases of dystocia, both maternal and fetal, were obtained as secondary data from records at the Situbondo Regency Animal Husbandry Service for year 2020 and 2021. Tracking on these secondary data was carried out to look for cows experienced dystocia and the owners’ names and addresses for interviews using a questionnaire worksheet. Interviews were conducted in February - May 2022 to obtain data on the maternal breed, age, feeding, fetal sex, and exercise frequency during pregnancy of the cows. Dystocia in the working area of the Besuki Animal Health Center in Sitobondo Regency in 2020 and 2021 occured in 50 cows which included primiparous (26%) and pluriparous (74%) cows. Breed, age, feed, and sex of the calves were not significantly different (p >0.05) between primiparous and pluriparous dams. However, the frequency of the exercises differed significantly (p <0.05) between primiparous and pluriparous dams. It could be concluded that the dystocia of cows in the study area was dominated by pluriparous parturition with exercises factor as the main cause.

Starting maternal exercise, unlike reducing the intensity of exercise during pregnancy, prevents memory deficits in female offspring subject to maternal deprivation

Maternal deprivation (MD) leads to long-lasting memory deficits. Conversely, maternal exercise could potently modify the offspring's cellular machinery. Here, we tested whether starting to run or reducing the intensity of running during pregnancy can protect prepubertal female offspring against MD-induced memory deficits. Female rats were divided into different groups submitted or not to MD: one started to run before pregnancy and reduced the intensity during the pregnancy (PGE); another started to run at the beginning of pregnancy (GE); and, finally, a control group (CT) was not submitted to exercise. All the rats but those of the CT ran on a treadmill until the delivery day (PND 0). Subsequently, MD was performed from PND 1 to 10. We assessed object recognition (OR) and spatial memory (SM) of female offspring after weaning (PND22, pre-pubertal stage). MD caused OR memory deficit; GE female offspring did not present this deficit, but PGE did. Both PGE and GE alone enhanced offspring spatial learning, but their combination with MD impaired it. MD promoted hippocampal lipid peroxidation increase, which both PGE and GE prevented. Total antioxidant capacity in the hippocampus was higher in both MD-exercised groups compared to all others. Although the antioxidant effects of exercise were similar in both MD exercise groups, we observed better results in the memory tests in the GE group than in the PGE group. These results suggest that starting to exercise during pregnancy is better than reducing the exercise intensity during pregnancy to prevent MD-induced memory deficits in female offspring.

Fetal and maternal Doppler adaptation to maternal exercise during pregnancy: a randomized controlled trial

Background Regular and supervised exercise during pregnancy is worldwide recommended due to its proven benefits, but, during exercise, maternal blood flow is redirected from the viscera to the muscles and how fetal wellbeing may be affected by this redistribution is still not well known. Objective To analyze the longitudinal effect of a supervised moderate physical exercise program during pregnancy on uteroplacental and fetal Doppler parameters. Methods This is a planned secondary analysis of an randomized controlled trial (RCT), performed at Hospital Universitario de Torrejón, Madrid, Spain, including 124 women randomized from 12+0 to 15+6 weeks of gestation to exercise vs. control group. Fetal umbilical artery (UA), middle cerebral artery, and uterine artery pulsatility index (PI), were longitudinally collected by Doppler ultrasound assessment throughout gestation, and derived cerebroplacental ratio (normalized by z-score), and maternal mean PI in the uterine arteries (normalized by multiplies of the median). Obstetric appointments were scheduled at 12 (baseline, 12+0 to 13+5), 20 (19+0 to 24+2), 28 (26+3 to 31+3) and 35 weeks (32+6 to 38+6) of gestation. Generalized estimating equations were adjusted to assess longitudinal changes in the Doppler measurements according to the randomization group. Results No significant differences in the fetal or maternal Doppler measurements were found at any of the different checkup time points studied. The only variable that consistently affected the Doppler standardized values was gestational age at the time of assessment. The evolution of the UA PI z-score during the pregnancy was different in the two study groups, with a higher z-score in the exercise group at 20 weeks and a subsequent decrease until delivery while in the control group it remained stable at around zero. Conclusions A regular supervised moderate exercise program during pregnancy does not deteriorate fetal or maternal ultrasound Doppler parameters along the pregnancy, suggesting that the fetal well-being is not compromised by the exercise intervention. Fetal UA PI z-score decreases during pregnancy to lower levels in the exercise group compared with the control group.

Maternal Dietary Carbohydrate Restriction and Mild-to-Moderate Exercise during Pregnancy Modify Aspects of Fetal Development in Rats

To determine whether acute bouts of exercise during pregnancy would predispose the fetus to increased risk if maternal dietary carbohydrate were restricted, untrained pregnant rats were randomly assigned to a 0% (low), 12% (moderate) or 60% (high) glucose diet, and either rested or exercised daily for 20 min from d 16 to term on a rodent treadmill at a mild (15.5 m/min) or moderate (24.3 m/min) intensity. A 3 ՠ3 nested factorial model with and without food intake as a covariate was employed. Both greater exercise intensity and the lower levels of dietary carbohydrate independently decreased term maternal liver and plantaris glycogen concentrations and increased plasma lactate concentrations. However, significant differences due to exercise disappeared (except for plasma lactate) with food intake controlled for in the model, indicating that energy deficits modulated these exercise effects. In contrast, for the offspring, when food intake was controlled for, a restricted level of maternal dietary carbohydrate significantly lowered fetal weight, plasma glucose and insulin concentrations and liver glycogen concentrations measured at term. Exercise alone did not reduce mean fetal weight if nested weights within a litter were used in the statistical analysis. Mild to moderate maternal exercise lowered only fetal plasma glucose concentrations and only if maternal food intake was not controlled for. These results indicate that acute exercise during pregnancy can have detrimental effects on fetal development only if dietary glucose is severely restricted. Otherwise, adequate glucose and energy in the maternal diet in untrained pregnant rats during repeated bouts of acute exercise seem to protect the fetus.

Maternal treadmill exercise ameliorates impairment of neurological outcome, caspase-1 and NLRP3 gene expression alteration in neonatal hypoxia-ischemia rats.

Neonatal hypoxia-ischemia (HI) is one of the most important causes of neurological disorders in children. Various studies suggest that maternal exercise during pregnancy has a beneficial impact on the health status of offspring infants. In this study, the effect of maternal treadmill exercise during pregnancy on neurological and molecular changes induced by HI in newborn rats was investigated. In this experiment, 24 pregnant female rats were divided into two groups; the first group was subjected to treadmill exercise for six weeks. The treadmill exercise program was initiated by running for 17 min at 5-10 m/min at 0 inclination in the first week, followed by running for 21 min at 5-25 m/min at 5° inclination in the second week, running for 25 min at 5-30 m/min at 10° inclination in the third and fourth weeks, running for 25 min at 5-15 m/min at 10° inclination in the fifth and sixth weeks. The second group was left untreated and did not perform the exercise. Newborn rats were assigned to four groups; (1) control, (2) control+exercise, (3) HI, and (4) HI+exercise. HI was developed in the offspring on the 8th postnatal day. One week following the induction of HI, the Garcia test was carried out. The histological morphology of neonates was assessed, and the expression levels of caspase-1 and NLRP3 were evaluated. The data showed that maternal exercise during pregnancy significantly improved neural cell death (P<0.001) and the Garcia score (P<0.05), while it attenuated the expression levels of caspase-1 (P<0.001) and NLRP3 (P<0.05) genes in newborn rats induced by HI. These results demonstrated that maternal treadmill exercise during pregnancy could reverse the neurological deficits, as well as the expression levels of caspase-1 and NLRP3 genes, which occur in neonatal hypoxia-ischemia.

Can Maternal Exercise Prevent High-Altitude Pulmonary Hypertension in Children?

Leslie, Eric, Ann L. Gibson, Laura V. Gonzalez Bosc, Christine Mermier, Sean M. Wilson, and Michael R. Deyhle. Review: can maternal exercise prevent high-altitude pulmonary hypertension in children? High Alt Med Biol. 24:1-6, 2023.-Chronic high-altitude exposure reduces oxygen delivery to the fetus during pregnancy and causes pathologic pulmonary artery remodeling, This increases the risk of high-altitude pulmonary hypertension (PH), which is a particularly fatal disease that is difficult to treat. Therefore, finding ways to prevent high-altitude PH, including during the neonatal period, is preferable. Cardiorespiratory exercise can improve functional capacity and quality of life in patients with high-altitude PH. However, similar to other treatments and surgical procedures, the benefits are not enough to cure the disease after a diagnosis. Cardiorespiratory exercise by mothers during pregnancy (i.e., maternal exercise) has not been previously evaluated to prevent the development of high-altitude PH in children born and living at high altitude. This focused review describes the pathophysiology of high-altitude PH and the potential benefit of maternal exercise for preventing the disease caused by high-altitude pregnancies.

Maternal voluntary physical exercise in the adult rat: evidence of exercise-associated differences in maternal food intake, and in brain effects on the progeny

ABSTRACT Objectives: Maternal physical activity may impact behavioral and electrophysiological aspects of brain function, with short- and long-term effects on pre- and postnatal neurodevelopment of the offspring. This study evaluated in the rat the effects of maternal voluntary physical activity (MVPA) on food intake and weight gain in the dams, as well as anxiety-like behavior, short-term memory and the brain excitability-related phenomenon known as cortical spreading depression (CSD) on the mother-pup dyad. Methods: Female Wistar rats (n=33) were individually housed in cages containing a running wheel for a 30-days adaptation period before mating. Rats were classified as inactive (I); active (A) or very active (VA) according to the distance spontaneously travelled daily. During gestation, the dams continued to have access to the running wheel. Mothers and their respective pups (1 pup per mother) were evaluated in the open field test (OFT), object recognition test (ORT), elevated plus maze test (EPMT) and the CSD propagation features. Results: MVPA was directly associated with increased food intake and weight gain during gestation, and maternal anxiolytic-like behavioral responses in the OFT. Pups from VA mothers showed a high discrimination index for shape recognition memory (ORT) and decreased propagation velocities of CSD, when compared with the inactive group. Discussion: The data suggest that MVPA during the gestational period induces neuroplasticity and may modulate the brain functions in the mother-infant dyad in the rat.

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.

The Effects of Different Exercise Programs on the Prevention of Perinatal Depression: A Systematic Review and Meta-Analysis

Background: To evaluate the preventive effect of different exercise programs on perinatal depression and to provide practical suggestions to guide the maternal daily exercise plan. Methods: Nine electronic bibliographic databases were searched from inception until 18 January 2022. Meta-analysis of all data was performed using RevMan 5.4. Results: Sixteen RCTs consisting of 2233 maternal cases were included. Compared to women in the control group, women who received exercise effectively prevented maternal perinatal depression (Std. mean difference [SMD] = –1.31, 95% confidence interval [CI] –1.40 to –1.21). Prenatal exercise (SMD = –1.45), aerobic exercise (SMD = –1.78), personal exercise (SMD = –2.03), &lt;30 minutes per single duration (SMD = –1.84), &gt;3 times a week (SMD = –1.91) was the best preventive measure of maternal depression. Conclusions: Exercise can effectively improve the mental health status of perinatal pregnant women, and different exercise start time, exercise content, exercise frequency, exercise form, and single duration of exercise can improve depressive symptoms differently. It is recommended that pregnant women begin from the prenatal period of personal aerobic exercise 3 times a week, each exercise lasting less than 30 minutes, and adjust appropriately according to their own physical conditions.

Lumbopelvic pain and sick leave during pregnancy: A comparison of Italy and Norway.

Pregnancy-related lumbopelvic pain is a frequently reported musculoskeletal disorder, but few studies have compared data between countries. Examine prevalence, severity, and sick leave and explore potential risk factors associated with pregnancy-related lumbopelvic pain in Italian women and compare the results to a similar study in Norway, utilizing the same questionnaire. Cross-sectional. Italian (n = 481) and Norwegian women (n = 435) were allocated from two public hospitals in Rome (Fatebenefratelli San Giovanni Calibita-Isola Tiberina) and Oslo (Oslo University Hospital), as well as four antenatal clinics in Modena (Italy). The questionnaire was completed between gestation weeks 32 and 36, addressing women's experiences of pregnancy-related lumbopelvic pain and sick leave in current week, and retrospectively for prepregnancy, first and second trimesters. In Italy and Norway, 39% and 57% of pregnant women reported pregnancy-related lumbopelvic pain, respectively, with 11% and 25% experiencing severe pregnancy-related lumbopelvic pain. Pregnancy-related lumbopelvic pain was associated with sick leave in Norway (p < 0.01), but not in Italy (p = 0.66) at late gestation. In both countries, women with pregnancy-related lumbopelvic pain versus those with no pregnancy-related lumbopelvic pain were more likely to be multiparous (Italy: 40% versus 31%, p = 0.06 and Norway: 53% versus 38%, p < 0.01), and have gestational weight gain above guidelines (Italy: 21% versus 13%, p = 0.02% and Norway: 27% versus 14%, p < 0.01) and previous experience of pregnancy-related lumbopelvic pain (Italy: 15% versus 2%, p < 0.01 and Norway: 31% versus 4%, p < 0.01). Maternal exercise (⩾2 times weekly) was associated with less pregnancy-related lumbopelvic pain (Italy: odds ratio = 0.33, 95% confidence interval = 0.11-1.0, p = 0.05 and Norway: odds ratio = 0.55, 95% confidence interval = 0.29-1.0, p = 0.06). We observed high rates of pregnancy-related lumbopelvic pain in Italy and Norway, with Norwegian women reporting the highest prevalence and severity level. While both countries had similar rates of sick leave in late gestation, an association between pregnancy-related lumbopelvic pain and sick leave was observed among Norwegian women only. Health care providers should be proactive in addressing pregnancy-related lumbopelvic pain through open communication and seeking input from pregnant individuals. However, it is essential to acknowledge that the current evidence on effective treatments remains limited and inconclusive, highlighting the need for further research in this field.

Hemodynamic Fetal Response to Maternal Isometric Exercise in Pregnant Patients with Hypertension

Hemodynamic Fetal Response to Maternal Isometric Exercise in Pregnant Patients with Hypertension

Hemodynamic Fetal Response to Maternal Isometric Exercise in Pregnant Patients with Diabetes

Hemodynamic Fetal Response to Maternal Isometric Exercise in Pregnant Patients with Diabetes

Offspring neurobehavioral phenotype following maternal exercise versus sedentary behavior

Offspring neurobehavioral phenotype following maternal exercise versus sedentary behavior

Maternal exercise shifts adiposity distribution in offspring towards energy burning brown fat

Human epidemiological and animal studies show the maternal in utero environment significantly impacts offspring development. This includes sedentary lifestyle, which is linked to developmental programming of metabolic dysfunction. The aim of this study was to investigate metabolic outcomes in offspring of sedentary mice versus mice that exercised in pregnancy. C57BL/6J female mice were placed on control diet and allocated to sedentary (SED) versus voluntary running wheel exercise (EX) cages. Voluntary wheel running was allowed 2 weeks prior to breeding and throughout weaning. Offspring underwent body composition measurement and insulin and glucose tolerance tests at 6 and 12 weeks of age, were placed in an indirect calorimetry system to assess energy balance at 14 weeks, and were euthanized for collection of adipose depots at 16 weeks. Outcomes were analyzed by two-way ANOVA to assess effects of exercise, sex, and their interaction. We studied metabolic function in 11 male SED, 13 female SED, 15 male EX, and 13 female EX offspring. While body mass and adiposity were similar among groups, EX mice had less subcutaneous white adipose (% body mass: 1.26±0.09 male SED vs. 0.87±0.06 male EX vs. 1.15±0.11 female SED vs. 0.95 ±0.04 female EX; PSex=0.871, PEX=0.001, PInt=0.237) and more brown adipose (% body mass: 0.31±0.03 male SED vs. 0.47±0.05 male EX vs. 0.27±0.02 female SED vs. 0.48 ±0.05 female EX; PSex=0.704, PEX=0.001, PInt=0.527). There were no differences in fasting glucose and insulin levels, insulin sensitivity, glucose tolerance, or measures of energy balance (e.g., food intake, energy expenditure) among groups. These data suggest that despite no change in overall body mass or body composition, maternal exercise shifts adiposity distribution of offspring away from energy storing white fat towards energy burning brown fat. This change may impact energy metabolism over the lifespan given increasing evidence for advantageous metabolic adaptations with increased brown fat.

Novel circRNA-miRNA-mRNA networks regulated by maternal exercise in fetal hearts of pregestational diabetes

BackgroundMaternal exercise lowers the incidence of congenital heart defects (CHDs) induced by pregestational diabetes. However, the molecular mechanisms underlying the beneficial effects of maternal exercise remain unclear. The present study aimed to identify circular RNA (circRNA), microRNA (miRNA) and mRNA networks that are regulated by maternal exercise in fetal hearts of pregestational diabetes. MethodsPregestational diabetes was induced in adult C57BL/6 female mice by streptozotocin. The expression profiles of circRNAs, miRNAs and mRNAs in E10.5 fetal hearts of offspring of control and diabetic mothers with or without exercise were analyzed using next generation sequencing. circRNA-miRNA-mRNA networks in fetal hearts were mapped and key candidate transcripts were verified by qPCR analysis. ResultsPregestational diabetes dysregulated the expression of 206 circRNAs, 66 miRNAs and 391 mRNAs in fetal hearts. Maternal exercise differentially regulated 188 circRNAs, 57 miRNAs and 506 mRNAs in fetal hearts of offspring of pregestational diabetes. A total of 5 circRNAs, 12 miRNAs, and 28 mRNAs were incorporated into a final maternal exercise-associated regulatory network in fetal hearts of offspring of maternal diabetes. Notably, maternal exercise normalized the dysregulated circ_0003226/circ_0015638/miR-351-5p and circ_0002768/miR-3102-3p.2-3p pairs in fetal hearts of pregestational diabetes. ConclusionMaternal exercise reverses the dysregulated circ_0003226/circ_0015638/miR-351-5p and circ_0002768/miR-3102-3p.2-3p pairs, and partially normalizes circRNA, miRNA, and mRNA expression profiles in fetal hearts of pregestational diabetes. These findings shed new light on the potential mechanisms of the beneficial effects of maternal exercise on the developing heart in diabetic pregnancies.

Maternal exercise upregulates the DNA methylation of Agtr1a to enhance vascular function in offspring of hypertensive rats.

The angiotensin II signaling system regulates vascular dysfunction and is involved in the programming of hypertension. Maternal exercise has been linked to both short-term and long-term benefits for the mother and fetus. However, the impacts of maternal exercise on the intravascular renin-angiotensin system (RAS) in hypertensive offspring remain unexamined. This study examined whether maternal exercise has an epigenetic effect in repressing angiotensin II type 1 receptor (AT1R) expression, which leads to favorable alterations in the mesenteric artery (MA) function of spontaneously hypertensive offspring. Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) pregnant rats were randomly divided into an exercise group and a control group. Blood pressure, vascular tone, AT1R protein and mRNA expression, and AT1R gene (Agtr1a) promoter methylation status were examined in the MAs of 3-month-old male offspring. Maternal exercise significantly reduced the resting blood pressure and cardiovascular reactivity of offspring from SHRs. Furthermore, Ang II-AT1R activity in regulating vascular tone and AT1R expression was decreased in the MAs of the SHR offspring from the exercise groups. Importantly, exercise during gestation suppressed AT1R expression via hypermethylation of the Agtr1a promoter region and upregulated DNA methyltransferase (DNMT) expression in MAs of SHR offspring. These results suggest that maternal exercise upregulates DNMT expression, resulting in hypermethylation and repression of the Agtr1a gene, which may prevent MA dysfunction in the offspring of SHRs. A mechanistic model on the epigenetics of exercise during pregnancy. Maternal exercise during pregnancy triggers hypermethylation and transcriptional suppression of the Agtr1a gene via increased DNMT1 and DNMT3B expression in MAs of SHR offspring. Downregulation of AT1R expression reduces the contribution of Ang II to vascular tone, ultimately improving vascular structure and function. VSMC vascular smooth muscle cell; Ang II angiotensin II; AT1aR angiotensin type 1 receptor (AT1R) alpha subtypes; Agtr1a AT1R alpha isoform gene; MAs mesenteric arteries; BP blood pressure.

The effects of a set amount of regular maternal exercise during pregnancy on gut microbiota are diet-dependent in mice and do not cause significant diversity changes.

Diet and exercise can affect the gut microbiota (GM); however, the effects of the same amount of exercise on gut microbiota changes in people on a low-fat diet (LFD) and high-fat diet (HFD) during pregnancy are unknown. Do different nutritional conditions respond equally to exercise intervention? This study aimed to investigate the effects of regular maternal exercise during pregnancy on the GM in mice fed different diets during pregnancy. Six-week-old nulliparous female KunMing mice were fed either a HFD or LFD before and during pregnancy. Each group of mice were then randomly divided into two groups upon confirmation of pregnancy: sedentary (HFD or LFD; n=4 and 5, respectively) and exercised (HFDex or LFDex, n=5 and 6, respectively). Mice were sacrificed on day 19 of gestation and their colon contents were collected. We then performed 16S rDNA gene sequencing of the V3 and V4 regions of the GM. The pregnancy success rate was 60% for LFDex and 100% for HFDex. Both Chao1 and Simpson indices were not significantly different for either LFD vs. LFDex or HFD vs. HFDex. Desulfobacterota, Desulfovibrionia Desulfovibrionales, Desulfovibrionaceae, Desulfovibrio, Coriobacteriia, Coriobacteriales, and Eggerthellaceae were markedly decreased after exercise intervention in LFDex vs. LFD, whereas Actinobacteria, Bifidobacteriales, Bifidobacteriaceae, Bifidobacterium, and Bifidobacterium pseudolongum were significantly increased in LFDex vs. LFD. Furthermore, decreased Peptostreptococcales-Tissierellales and Peptostreptococcaceae and increased Bacteroides dorei were identified in the HFDex vs. HFD group. p_Desulfobacterota, c_Desulfovibrionia, o_Desulfovibrionales, f_Desulfovibrionaceae and g_Desulfovibrio were markedly decreased in the LFDex group vs. HFDex group. Our data suggested that quantitative maternal exercise during pregnancy resulted in alterations in GM composition, but did not significantly change the diversity of the GM. These findings may have important implications when considering an individual's overall diet when recommending exercise during pregnancy.