Effects Of Maternal Dietary Restriction Research Articles

Multi-Omics Analysis Reveals the Potential Effects of Maternal Dietary Restriction on Fetal Muscle Growth and Development.

In terms of fetal muscle growth, development, and health, maternal nutrition is a crucial influence, although the exact biochemical mechanism by which this occurs is still not fully understood. To examine the potential impacts of maternal dietary restriction on fetal muscle development, the sheep maternal dietary restriction model was developed for this study. In our study, 12 pregnant ewes were evenly split into two experimental groups and fed either 75% or 100% of a maternal nutrient. In addition, a multi-omics analysis was used to study the embryonic longissimus dorsis on gestational days (GD) 85 and 135. The fetal weight at GD 135 was significantly below normal due to the maternal restricted diet (p < 0.01). When fetuses were exposed to the dietary deficit, 416 mRNAs and 40 proteins were significantly changed. At GD 85, the multi-omics analysis revealed that maternal dietary restriction led to a significant up-regulation of the cell cycle regulator CDK2 gene in the cellular senescence signaling pathway, and the results of the qRT-PCR were similar to the multi-omics analysis, which showed that SIX1, PAX7, the cell cycle factors CDK4 and CDK6, and the BCL-2 apoptosis factor were up-regulated and several skeletal muscle marker genes, such as MYF5 and MyoD were down-regulated. At GD 135, maternal dietary restriction blocks the muscle fiber differentiation and maturation. The multi-omics analysis revealed that the TEAD1 gene was in the Hippo signaling pathway, the muscle marker genes MYF5 and MyoG were significantly down-regulated, and the TEAD1 binding of the down-regulated VGLL3 gene might be potential mechanisms affecting myofiber differentiation and maturation. Knocking down the CDK2 gene could inhibit the proliferation of primary embryonic myoblasts, and the expression levels of cell cycle regulatory factors CDK4 and CDK6 were significantly changed. Under low nutrient culture conditions, the number of myoblasts decreased and the expression of CDK2, CDK6, MYF5, PAX7 and BCL-2 changed, which was in perfect agreement with the multi-omics analysis. All of the findings from our study helped to clarify the potential effects of maternal dietary restriction on fetal muscle growth and development. They also provided a molecular foundation for understanding the molecular regulatory mechanisms of maternal nutrition on fetal muscle growth and development, as well as for the development of new medications and the management of related metabolic diseases.

0775 Effects of maternal dietary restriction during the second trimester on offspring growth and feedlot performance

0775 Effects of maternal dietary restriction during the second trimester on offspring growth and feedlot performance

Regulation of ribosomal RNA expression across the lifespan is fine-tuned by maternal diet before implantation

Cells and organisms respond to nutrient deprivation by decreasing global rates of transcription, translation and DNA replication. To what extent such changes can be reversed is largely unknown. We examined the effect of maternal dietary restriction on RNA synthesis in the offspring. Low protein diet fed either throughout gestation or for the preimplantation period alone reduced cellular RNA content across fetal somatic tissues during challenge and increased it beyond controls in fetal and adult tissues after challenge release. Changes in transcription of ribosomal RNA, the major component of cellular RNA, were responsible for this phenotype as evidenced by matching alterations in RNA polymerase I density and DNA methylation at ribosomal DNA loci. Cellular levels of the ribosomal transcription factor Rrn3 mirrored the rRNA expression pattern. In cell culture experiments, Rrn3 overexpression reduced rDNA methylation and increased rRNA expression; the converse occurred after inhibition of Rrn3 activity. These observations define novel mechanism where poor nutrition before implantation irreversibly alters basal rates of rRNA transcription thereafter in a process mediated by rDNA methylation and Rrn3 factor.

Long-Term Effects of Maternal Nutrition and Childhood Growth on Later Health

Objectives: This paper reviews the importance of maternal nutrition and weight gain with birthweigh and neonatal/childhood growth, and highlights the r isk of chronic diseases in later life. Methods: The data was sourced based on the result of original and review articles relating to the life exposures, pregnancy weight gain, birth weight, childhood growth and the risk of chronic diseases in adult life. Findings: Experimental studies have suggested that both maternal undernutrition and overnutrition are involved in later disease risk. Maternal macronutrient deficiency leads to LBW and subsequently insulin resistance and adiposity in later life. It seems that micronutrient deficiencies contribute to long-term negative effects such as metabolic syndrome and related disorders. As well as fetal life, early infancy, the adiposity rebound period and puberty also account as critical periods for the development of obesity in adulthood. Conclusion: It is now widely accepted that the risks of adult chronic diseases may have their developmental origins in fetal life. Maternal under-nutrition or over-nutrition affect the infant’s health . Both macro- and micro-nutrients are critical for appropriate pregnancy outcomes. Understanding their precise patho-physiological mechanism are critical to apply new strategies to prevent the adverse effects of maternal dietary restriction and environmental factors in early stages of life.

Effects of Female Dietary Restriction in a Rabbit Growth Line During Rearing onReproductive Performance and Embryo Quality.

Maternal diet prior to mating has an effect on reproductive performance. We analysed the effect of maternal dietary restriction during rearing on reproductive performance, the embryo development and foetal growth. Females were categorized in two groups: (i) does with ad libitum access to feed or (ii) restricted. Two experiments were performed: (i) after 1 month, receptive females from both experimental groups were artificially inseminated and the reproductive performance was recorded during three reproductive cycles; at the first insemination, the body weight and perirenal fat thickness were recorded, and (ii) females from both experimental groups were inseminated, and 24 h later, embryos were recovered and transferred to recipient females from a maternal line. Later, embryonic implantation was assessed at day 14 by laparoscopy and foetal growth was monitored by ultrasound examination. In experiment 1, no differences in kindling rate was found, but prolificacy was showed to be higher in ad libitum does, which also were heavier than restricted ones. In experiment 2, no differences among does either in body weight, in perirenal fat thickness or in reproductive performance (ovulation rate and embryo recovery rate) were related to differences in feed intake. However, despite similar embryonic implantation losses, embryos from restricted females demonstrated higher foetal and gestational losses. Embryos from restricted does presented lower foetal growth than embryos from ad libitum does. Therefore, our results demonstrated that nutrition before first conception in a rabbit line selected for growth rate may impact on the embryo and results in a disturbance in gestational losses and foetal growth over all reproductive life.

Long Term Effects of Maternal Nutrition and Childhood Growth on Later Health

Objectives: This paper reviews the importance of maternal nutrition and weight gain with birthweigh and neonatal/childhood growth, and highlights the r isk of chronic diseases in later life. Methods: The data was sourced based on the result of original and review articles relating to the life exposures, pregnancy weight gain, birth weight, childhood growth and the risk of chronic diseases in adult life. Findings: Experimental studies have suggested that both maternal undernutrition and overnutrition are involved in later disease risk. Maternal macronutrient deficiency leads to LBW and subsequently insulin resistance and adiposity in later life. It seems that micronutrient deficiencies contribute to long-term negative effects such as metabolic syndrome and related disorders. As well as fetal life, early infancy, the adiposity rebound period and puberty also account as critical periods for the development of obesity in adulthood. Conclusion: It is now widely accepted that the risks of adult chronic diseases may have their developmental origins in fetal life. Maternal under-nutrition or over-nutrition affect the infant’s health . Both macro- and micro-nutrients are critical for appropriate pregnancy outcomes. Understanding their precise patho-physiological mechanism are critical to apply new strategies to prevent the adverse effects of maternal dietary restriction and environmental factors in early stages of life.

Dietary restriction in the periconceptional period in normal-weight or obese ewes results in increased abundance of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1R) in the absence of changes in ACE or AT1R methylation in the adrenal of the offspring

Exposure to dietary restriction during the periconceptional period in either normal or obese ewes results in increased adrenal growth and a greater cortisol response to stress in the offspring, but the mechanisms that programme these changes are not fully understood. Activation of the angiotensin type 1 receptor (AT1R) has been demonstrated to stimulate adrenal growth and steroidogenesis. We have used an embryo transfer model in the sheep to investigate the effects of exposure to dietary restriction in normal or obese mothers from before and 1 week after conception on the methylation status, expression, abundance and localisation of key components of the renin-angiotensin system (RAS) in the adrenal of post-natal lambs. Maternal dietary restriction in normal or obese ewes during the periconceptional period resulted in an increase in angiotensin-converting enzyme (ACE) and AT1R abundance in the absence of changes in the methylation status or mRNA expression of ACE and AT1R in the adrenal of the offspring. Exposure to maternal obesity alone also resulted in an increase in adrenal AT1R abundance. There was no effect of maternal dietary restriction or obesity on ACE2 and AT2R or on ERK, calcium/calmodulin-dependent kinase II abundance, and their phosphorylated forms in the lamb adrenal. Thus, weight loss around the time of conception, in both normal-weight and obese ewes, results in changes within the intra-adrenal RAS consistent with increased AT1R activation. These changes within the intra-adrenal RAS system may contribute to the greater adrenal stress response following exposure to signals of adversity in the periconceptional period.

Maternal Undernutrition in Cows Impairs Ovarian and Cardiovascular Systems in Their Offspring1

Severe prenatal undernutrition is usually associated with low birth weights in offspring and disorders including hypertension, obesity, and diabetes. Whether alterations in maternal nutrition insufficient to impair birth weight or prenatal growth impact the cardiovascular, stress, or metabolic systems is unknown. In addition, little is known about the effects of maternal dietary restriction on development of the reproductive system in mammals. Here, we use the bovine model, which has a gestational length and birth rate similar to humans, to show that offspring from nutritionally restricted dams (during the first trimester) were born with identical birth weights and had similar postnatal growth rates (to 95 wk of age), puberty, glucose metabolism, and responses to stress compared to offspring from control mothers. However, an increase in maternal testosterone concentrations was detected during dietary restriction, and these dams had offspring with a diminished ovarian reserve (as assessed by a reduction in antral follicle count, reduced concentrations of anti-Müllerian hormone, and increased follicle-stimulating hormone concentrations), enlarged aorta, and increased arterial blood pressure compared with controls. Our study links transient maternal undernutrition and enhanced maternal androgen production with a diminished ovarian reserve as well as potential suboptimal fertility, enlarged aortic trunk size, and enhanced blood pressure independent of alterations in birth weight, postnatal growth, or stress response and glucose tolerance. The implications are that relatively mild transient reductions in maternal nutrition during the first trimester of pregnancy (even those that do not affect gross development) should be avoided to ensure healthy development of reproductive and cardiovascular systems in offspring.

Maternal dietary restriction and selenium supply alters messenger ribonucleic acid expression of angiogenic factors in maternal intestine, mammary gland, and fetal jejunal tissues during late gestation in pregnant ewe lambs1

The objectives of this study were to evaluate effects of maternal dietary restriction and Se supply on angiogenic factor mRNA expression in intestinal and mammary tissues, and jejunal crypt cell proliferation and vascularity in late-term fetal intestines. In Exp. 1, pregnant ewe lambs (n = 32; initial BW = 45.6 +/- 2.3 kg) were allotted randomly to 1 of 4 treatments. Treatments (initiated d 50 +/- 5 of gestation) were control (3.5 microg of Se.kg of BW(-1).d(-1)), Se-wheat (75 microg of Se.kg of BW(-1).d(-1)), selenate (Se3; providing 75 microg of Se.kg of BW(-1).d(-1)), selenate (Se15; providing 375 microg of Se.kg of BW(-1).d(-1)). Diets (DM basis) were similar in CP (15.5%) and ME (2.68 Mcal/kg). In Exp. 2, pregnant ewe lambs (n = 36; initial BW 53.8 +/- 1.3 kg) were allotted randomly to treatments in a 2 x 2 factorial arrangement. Factors were nutrition (control, 100% of requirements vs. restricted nutrition, 60% of controls) and dietary Se (adequate Se; 6 microg of Se.kg of BW(-1).d(-1) vs. high Se; 80 microg of Se.kg of BW(-1).d(-1)). Selenium treatments were initiated 21 d before breeding, and nutritional treatments were initiated on d 64 of gestation. Diets (DM basis) were 16% CP and 2.12 Mcal/kg of ME. In Exp. 1, Se15 increased (P = 0.07) vascular endothelial growth factor (VEGF) mRNA expression, whereas Se supplementation decreased (P = 0.06) kinase insert domain receptor (KDR) mRNA in maternal mucosal scrape on d 134 of gestation. Expression of VEGF mRNA was decreased by Se (P = 0.10) in fetal jejunum. In mammary tissue, fms-related tyrosine kinase 1 and KDR mRNA were greater in Se-wheat compared with Se3, and KDR expression was increased (P = 0.10) in Se15 compared with Se3. In Exp. 2, dietary restriction increased (P < or = 0.07) expression of mRNA for VEGF, fms-related tyrosine kinase 1, KDR, neuropilin 1, neuropilin 2, and hypoxia-inducible factor 1, alpha subunit in mucosal scrapes from maternal jejunum. In fetal jejunum, soluble guanylate cyclase, was decreased (P = 0.01) by maternal dietary restriction from d 64 to 135 of gestation. Total microvascularity in fetal jejunum was reduced (P = 0.002) by maternal dietary restriction. Mammary gland expression of VEGF, neuropilin 1, angiopoietin receptor (endothelial tyrosine kinase), and endothelial nitric oxide synthase 3 increased (P < or = 0.09), whereas angiopoietin 1 decreased (P = 0.05) due to nutrient restriction. Data indicate that expression of angiogenic factors and receptors in maternal intestine, mammary gland, and fetal jejunum are responsive to maternal nutrition and likely explain observed changes in tissue vascularity.

Effect of maternal dietary restriction during pregnancy in rats on PPARα-regulated genes in the heart of the male offspring

Effect of maternal dietary restriction during pregnancy in rats on PPARα-regulated genes in the heart of the male offspring

Effect of maternal dietary restriction during pregnancy on lamb carcass characteristics and muscle fiber composition1

Two experiments were conducted to determine whether the decreased proportion of fast muscle fibers seen previously in 2-wk-old lambs from ewes that were dietary restricted from d 30 to 70 of gestation are still evident in older lambs and what the consequences may be in terms of growth rates and carcass composition. Throughout both experiments, ewes were fed on an individual basis according to the recommended dietary allowance throughout pregnancy relative to metabolic BW (BW(0.73)). Control groups were fed as above, and the treatment groups had their nutrient supply reduced to 50% of this recommended allowance from d 30 to 70 (Exp. 1) or d 30 to 85 (Exp. 2) of gestation, after which they were returned to the same level of nutrition as the control group. All twin lambs were kept with their dams, and at 2 wk were given access to creep. After weaning, lambs were individually housed and fed ad libitum to 24 or 17 wk of age for Exp. 1 and 2, respectively. Although not significant (P = 0.18), growth to 24 wk (Exp. 1) resulted in a small decrease in the protein content and therefore an increase in the fat:lean ratio in the carcass of lambs subjected to maternal dietary restriction. This was not apparent when animals were slaughtered at 17 wk (Exp. 2; P > 0.68). Few significant effects of maternal dietary restriction on the fiber type composition of muscles were observed. In Exp. 1 the number of fast fibers increased (P < 0.008) with no effect on slow fiber number in LM. In Exp. 2 an increase in the total number of fibers in male lambs and an increase in type II (A and B) fibers in female lambs were observed in the LM, and an increase in IIB fiber number was observed in semitendinosus (ST) muscle from male lambs. Prenatal maternal dietary restriction during the time of muscle differentiation demonstrated an increase in type IIB muscle fibers and increase in intramuscular fat; although significant, effects on subsequent carcass quality of lambs were relatively small. These data suggest that the lambs adapted to changes in muscle fiber composition previously observed at 2 wk. However, lambs in this study were well fed during postnatal growth. Whether offspring would still have been able to compensate if they had received poor nutrition postnatally and whether that failure to compensate would have influenced carcass composition remain to be determined.

Maternal food restriction, brain polysomes and poly-U stimulated protein synthesis in the newborn and 21-day-old rat progeny

Effect of maternal dietary restriction during the period of gestation (EI) and during the period of growth, gestation and lactation (EII) on (i) the polysomal profiles (ii) distribution of 14C-phenylalanine and 3H-orotate into membrane bound and free polysomes and ribosomes and (iii) ribosomal response to the addition of poly-U in the incorporation of 14C-phenylalanine was investigated in the brain of the neonatal (N) and 21-day-old (T) progeny. Polysomal profile showed variable degrees of reductions in the membrane bound ribosomes, free polysomes and monoribosomes in the brain of N and T progeny of EI and EII groups compared with WF group. Distribution of radioactive phenylalanine and orotate also showed variable responses in the membrane bound ribosomes free polysomes and the monoribosomes of the brain of N and T progeny of EI and EII groups. EII N progeny generally had a lower distribution and EII group T progeny had a higher distribution than EI group in each component of the polysomal profile. Ribosomes from the brain of N and T progeny of EI and EII groups responded less actively to the addition of poly-U than WF group. Synthesis of protein/synthesis of polyphenylalanine ratio (which roughly represents polysomes/monosomes ratio) demonstrated variable responses in the brain of N and T progeny of EI and EII groups compared with WF group. In T progeny when WF polysomes were incubated with EI or EII group pH-5 enzymes, the incorporation increased significantly and was higher in EII group than EI group. Incubation of EI polysomes with EII pH-5 enzyme demonstrated a significant increase in the incorporation. These results clearly demonstrate that maternal food restriction during various physiological periods had a profound effect on brain polysomes and consequently the protein synthesizing machinery in the N and T progeny.

Effects of Maternal Dietary Restriction in Vitamin B-6 on Neocortex Development in Rats: B-6 Vitamer Concentrations, Volume and Cell Estimates

Influence of the time of maternal restriction in dietary vitamin B-6 on vitamer concentrations and morphological development of neocortex was examined. Rats were fed ad libitum a vitamin B-6—free diet supplemented with 0.0 or 0.6 mg pyridoxine hydrochloride (PN·HCl)/kg diet during gestation followed by a control diet (7.0 mg PN·HCl/kg) during lactation or were supplemented with 0.6 or 7.0 mg PN·HCl/kg diet throughout gestation and lactation. During postweaning offspring received the maternal diets fed during lactation. Neocortices of offspring were examined at 30 d of age by liquid chromatography and light microscopy. Vitamin restriction during gestation and 30 d postnatal was the only vitamin B-6—restricted treatment of the three administered that altered B-6 vitamer levels in neocortex; all vitamers were depressed equally. Brain weight and volume of neocortex were not changed significantly by the maternal restrictions imposed. However, each restriction adversely affected neurogenesis and neuron longevity of the neocortex and when expressed as percent reduction from control, neuron longevity was affected more severely than neurogenesis.

Effects of maternal dietary restriction during gestation and lactation, muscle, sex and age on various indices of skeletal muscle growth in the rat.

Induced impairment of growth rate and mature size in the rat was used to characterize and compare histological and biochemical indices of skeletal muscle hyperplastic and hypertrophic growth. Maternal nutritional restriction during gestation and lactation caused a 54% reduction in progeny body weight before realimentation was begun at weaning. A compensatory growth response was observed in restricted male progeny. Muscle fiber number in soleus and extensor digitorum longus (EDL) were not different between treatments, sexes or muscles after 12 wk of realimentation. Muscle nuclei per fiber transverse section was greater in soleus than EDL, but was unaffected by early nutritional restriction or sex. Capacity for protein synthesis (RNA:DNA ratio) and translational activity per ribosome (RNA:protein ratio) were not less in restricted progeny after realimentation. Therefore, it was concluded that phenotypic expression of genetic potential for cell size, but not cell number, is affected by prenatal and early postnatal nutritional restriction that causes permanent growth impairment in the rat. The significantly greater DNA concentration in the soleus, which is also reflected in nuclear counts, and markedly different pattern of growth exhibited by it, suggest that the soleus may be atypical compared with most hind limb muscles of the rat and may not be the best model for further study of the regulation of skeletal muscle growth.

Effect of Maternal Dietary Restriction on Fetal Growth and Placental Transfer of α-Amino Isobutyric Acid in Rats

Maternal net weight gain, plasma clearance, and placental and fetal accumulation of I.V. administered 14C-α amino isobutyric acid (AIB) on day 20 of gestation were measured in pregnant rats: 1) fed ad libitum throughout gestation (Control), 2) fed 50% of the normal daily food intake during the last week of gestation (catabolic phase), and 3) fed 50% of the normal daily food intake throughout gestation. Dietary restriction during the catabolic phase only resulted in a loss of 54% of the net maternal weight gained during the first two weeks of gestation, while dietary restriction throughout gestation resulted in a net loss of 5.4% of the dams prepregnant weight. Both dietary regimens caused significant growth retardation of the fetus. Maternal plasma clearance of AIB was rapid and occurred at the same rate in all three groups. Placental accumulation and transfer of AIB to the fetus was reduced relative to the controls only in dams fed the restricted diet throughout gestation. Fetal to placental AIB concentration ratios were similar for each group indicating no difference in ability of placentas to release amino acid into the fetal circulation. The results indicate that mechanisms other than reduced nutrient transfer may be responsible for fetal growth retardation induced by maternal malnutrition during the catabolic phase of pregnancy only.dietary restriction pregnancy fetal growth placental transfer

Effect of Maternal Dietary Restriction during Pregnancy on Maternal Weight Gain and Fetal Birth Weight in the Rat

The effects of the following dietary regimes on maternal body weight and weights of the products of conception were investigated in the laboratory rat: 50% dietary restriction during the catabolic phase (days 15--21) of gestation; 50% dietary restriction during the anabolic phase (days 1--14) but adequate nutrition during the catabolic phase, and 50% dietary restriction throughout gestation. Total body weight and net maternal weight at term were significantly reduced in all three test groups. Restricting dietary intake during the anabolic phase resulted in decreased maternal weight gain. Feeding an adequate diet during the catabolic phase, following restriction during the anabolic phase, caused only a slight decrease in net maternal weight, while term fetal weight approximated that of controls. Dietary restriction during the catabolic phase, or throughout gestation, caused increased net maternal weight loss. Term fetal weight in both groups was significantly lower than that of the controls, but not different from each other. The results indicate that the dam is able to mobilize nutrients stored during the anabolic phase of pregnancy. Mobilization of these nutrients did not significantly increase fetal growth, however, supporting the hypothesis that the dam is able to compartmentalize available nutrients during malnutrition and prevent serious depletion of these stores by the fetus.

Effects of maternal dietary restriction on hydroxyproline levels in urine and tissues of the young.

SummaryStudies to determine the effect of maternal dietary restriction during gestation and lactation on hydroxyproline excretion of the progeny were undertaken. Results indicate that urinary hydroxyproline excretion was consistently and significantly increased in the male and female progeny of dietary restricted mothers than those of ad libitum fed ones. Similar findings were obtained when the results were expressed either as amounts of hydroxyproline per unit of body weight or the ratio of hydroxyproline per milligram of creatinine. Whether this enhancement is due to changes in the pool size of any of the forms of collagen or changes in the rate of conversion of one form of collagen to another is not clear. Additional experiments revealed that a significant increase in 14CO2 production was noted in the offspring from dietary restricted mothers after intramuscular injection of protein-U-14C. However, the in vivo incorporation of proline-14C into tissue proteins appeared to be unaffected by maternal dieta...

Further Studies on Growth and Feed Utilization in Progeny of Underfed Mother Rats

Previous studies have demonstrated growth-stunting and metabolic derangements, including reduced feed efficiency, in progeny of McCollum strain rat dams restricted to 50% dietary intake during gestation and lactation. These effects now have been duplicated in rats of the Sprague-Dawley strain. In addition, fostering techniques have allowed separate evaluation of the effects of maternal dietary restriction during gestation alone, and their comparison with the effect produced during the combined periods of gestation and lactation. Our results show, as suggested in earlier works, that restriction during gestation alone has a similar though perhaps lesser effect than restriction during gestation and lactation.