Effects Of Maternal Food Restriction Research Articles

Maternal food restriction during pregnancy affects offspring development and swimming performance in a placental live-bearing fish.

ABSTRACTHow pregnant mothers allocate limited resources to different biological functions such as maintenance, somatic growth, and reproduction can have profound implications for early life development and survival of offspring. Here, we examined the effects of maternal food restriction during pregnancy on offspring in the matrotrophic (i.e. mother-nourishment throughout gestation) live-bearing fish species Phalloptychus januarius (Poeciliidae). We fed pregnant females with either low or high food levels for 6 weeks and quantified the consequences for offspring size and body fat at birth and 1 week after birth. We further measured fast-start escape performance of offspring at birth, as well as swimming kinematics during prey capture at 0, 2 and 7 days after birth. We found that the length of maternal food restriction during pregnancy negatively affected offspring dry mass and lean dry mass at birth, as well as body fat gain during the first week after birth. Moreover, it impacted the locomotor performance of offspring during prey capture at birth and during the first week after birth. We did not observe an effect of food restriction on fast-start escape performance of offspring. Our study suggests that matrotrophic poeciliid fish are maladapted to unpredictably fluctuating resource environments, because sudden reductions in maternal food availability during pregnancy result in smaller offspring with slower postnatal body fat gain and an inhibition of postnatal improving swimming skills during feeding, potentially leading to lower competitive abilities after birth.

Breastfeeding undernutrition changes iBAT-involved thermogenesis protein expression and leads to a lean phenotype in adult rat offspring

Nutritional insults early in life have been associated with metabolic diseases in adulthood. We aimed to evaluate the effects of maternal food restriction during the suckling period on metabolism and interscapular brown adipose tissue (iBAT) thermogenically involved proteins in adult rat offspring. Wistar rats underwent food restriction by 50% during the first two-thirds of lactation (FR50 group). Control rats were fed ad libitum throughout lactation (CONT group). At birth, the litter size was adjusted to eight pups, and weaning was performed at 22 days old. Body weight and food and water intake were assessed every two days. High- (HCD, 4,589 cal) and normal-caloric diet (NCD, 3,860 cal) preferences, as well as food intake during the dark part of the cycle, were assessed. At 100 days old, the rats were euthanized, and blood and tissues were removed for further analyses. Adult FR50 rats, although hyperphagic and preferring to eat HCD (P<.001), were leaner (P<.001) than the CONT group. The FR50 rats, were normoglycemic (P=.962) and had hypertriglyceridemia (P<.01). In addition, the FR50 rats were dyslipidemic (P<.01), presenting with a high atherogenic risk by the Castelli indexes (P<.01), had a higher iBAT mass (P<.01), fewer β3 adrenergic receptors (β3-AR, P<.05) and higher iBAT expression of uncoupled protein 1 (UCP1, P<.05) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, P<.001) than the CONT rats. In conclusion, maternal food restriction during early breastfeeding programs rat offspring to have a lean phenotype, despite hyperphagia, and increased iBAT UCP1 and PGC-1α protein expression.

Long-term effects of pro-opiomelanocortin methylation induced in food-restricted dams on metabolic phenotypes in male rat offspring.

ObjectiveMaternal malnutrition affects the growth and metabolic health of the offspring. Little is known about the long-term effect on metabolic indices of epigenetic changes in the brain caused by maternal diet. Thus, we explored the effect of maternal food restriction during pregnancy on metabolic profiles of the offspring, by evaluating the DNA methylation of hypothalamic appetite regulators at 3 weeks of age.MethodsSprague-Dawley rats were divided into 2 groups: a control group and a group with a 50% food-restricted (FR) diet during pregnancy. Methylation and expression of appetite regulator genes were measured in 3-week-old offspring using pyrosequencing, real-time polymerase chain reaction, and western blotting analyses. We analyzed the relationship between DNA methylation and metabolic profiles by Pearson's correlation analysis.ResultsThe expression of pro-opiomelanocortin (POMC) decreased, whereas DNA methylation significantly increased in male offspring of the FR dams, compared to the male offspring of control dams. Hypermethylation of POMC was positively correlated with the levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol in 3-week-old male offspring. In addition, there were significant positive correlations between hypermethylation of POMC and the levels of triglycerides, HDL-C, and leptin in 6-month-old male offspring.ConclusionOur findings suggest that maternal food restriction during pregnancy influences the expression of hypothalamic appetite regulators via epigenetic changes, leading to the development of metabolic disorders in the offspring.

The GLP-1 analog, liraglutide prevents the increase of proinflammatory mediators in the hippocampus of male rat pups submitted to maternal perinatal food restriction

BackgroundPerinatal maternal malnutrition is related to altered growth of tissues and organs. The nervous system development is very sensitive to environmental insults, being the hippocampus a vulnerable structure, in which altered number of neurons and granular cells has been observed. Moreover, glial cells are also affected, and increased expression of proinflammatory mediators has been observed. We studied the effect of Glucagon-like peptide-1 receptor (GLP-1R) agonists, liraglutide, which have very potent metabolic and neuroprotective effects, in order to ameliorate/prevent the glial alterations present in the hippocampus of the pups from mothers with food restriction during pregnancy and lactation (maternal perinatal food restriction—MPFR).MethodsPregnant Sprague-Dawley rats were randomly assigned to 50% food restriction (FR; n = 12) or ad libitum controls (CT, n = 12) groups at day of pregnancy 12 (GD12). From GD14 to parturition, pregnant FR and CT rats were treated with liraglutide (100 μg/kg) or vehicle. At postnatal day 21 and before weaning, 48 males and 45 females (CT and MPFR) were sacrificed. mRNA expression levels of interleukin-1β (IL1β), interleukin-6 (IL-6), nuclear factor-κβ, major histocompatibility complex-II (MHCII), interleukin 10 (IL10), arginase 1 (Arg1), and transforming growth factor (TGFβ) were assessed in the hippocampus by quantitative real-time polymerase chain reaction. Iba1 and GFAP-immunoreactivity were assessed by immunocytochemistry.ResultsThe mRNA expression IL1β, IL6, NF-κB, and MHCII increased in the hippocampus of male but not in female pups from MPFR. In addition, there was an increase in the percentage of GFAP and Iba1-immupositive cells in the dentate gyrus compared to controls, indicating an inflammatory response in the brain. On the other hand, liraglutide treatment prevented the neuroinflammatory process, promoting the production of anti-inflammatory molecules such as IL10, TGFβ, and arginase 1, and decreasing the number and reactivity of microglial cells and astrocytes in the hippocampus of male pups.ConclusionTherefore, the GLP-1 analog, liraglutide, emerges as neuroprotective drug that minimizes the harmful effects of maternal food restriction, decreasing neuroinflammation in the hippocampus in a very early stage.

Unitary Physiology.

The common relationships among a great variety of biological phenomena seem enigmatic when considered solely at the level of the phenotype. The deep connections in physiology, for example, between the effects of maternal food restriction in utero and the subsequent incidence of metabolic syndrome in offspring, the effects of microgravity on cell polarity and reproduction in yeast, stress effects on jellyfish, and their endless longevity, or the relationship between nutrient abundance and the colonial form in slime molds, are not apparent by phenotypic observation. Yet all of these phenomena are ultimately determined by the Target of Rapamycin (TOR) gene and its associated signaling complexes. In the same manner, the unfolding of evolutionary physiology can be explained by a comparable application of the common principle of cell-cell signaling extending across complex developmental and phylogenetic traits. It is asserted that a critical set of physiologic and phenotypic adaptations emanated from a few crucial, ancestral receptor gene duplications that enabled the successful terrestrial transition of vertebrates from water to land. In combination, mTor and its cognate receptors and a few crucial genetic duplications provide a mechanistic common denominator across a diverse spectrum of biological responses. The proper understanding of their purpose yields a unified concept of physiology and its evolutionary development. © 2018 American Physiological Society. Compr Physiol 8:761-771, 2018.

Food restriction during pregnancy and female offspring fertility: adverse effects of reprogrammed reproductive lifespan

BackgroundFood restriction during pregnancy can influence the health of the offspring during the adulthood. The aim of the present study was to examine the effect of maternal food restriction (MFR) on the reproductive performance in female rat offspring from the first (FR1) and second (FR2) generations.MethodsAdult virgin Wistar female rats were given free access to tap water and were fed ad libitum on standard rodent chow, were mated with virgin adult males, and then were randomly divided into two groups: controls (that was fed ad libitum) and food-restricted group (FR, that was given only 50% of ad libitum food throughout gestation). Their first (FR1) and the second (FR2) generation of offspring were fed ad libitum and sacrificed before puberty and at adulthood. Their ovaries were removed and their histology evaluated by estimating the number of follicles (total and at various stages of folliculogenesis), and the presence of multi-nuclei oocytes and multi-oocyte follicles.ResultsTotal number of ovarian follicles was lower in FR1 females at week 4 in comparison with controls, while it was not different in FR2 females vs. controls. The number of the primordial follicle was lower in FR1 and FR2 females vs. controls at both week 4 and at week 8. When compared to the controls, the follicles containing multi-nuclei oocytes were more frequent in ovaries from FR1 and FR2 females at week 4, and higher and lower respectively in ovaries form FR1 and FR2 females at week 8.ConclusionMFR affects ovarian histology by inducing the development of abnormal follicles in the ovaries in first and second generation offspring. This finding could influence the ovarian function resulting in an early pubertal onset and an early decline in reproductive lifespan.

Enhanced thymocyte apoptosis induced by maternal undernutrition in late gestation results in declined mature T cells in rat fetal thymus

This study was designed to observe the effects of maternal food restriction (MFR) on the development of fetal thymus in different gestation periods. Timed pregnant rats were randomized into 3 groups: CN (free access to standard chow throughout gestation), MFR0-21 (50% MFR throughout gestation), MFR0-14 (50% MFR from gestational day (GD) 0 to GD14, early-mid gestation). Results showed that MFR during early-mid period had few impact on the fetal thymus and T cell subpopulations. However, MFR throughout gestation resulted in thymic atrophy, deceased frequency of both CD4+ and CD8+ single positive (SP) T cells and enhanced thymocyte apoptosis in fetus. Our results suggest the fetal thymus is more vulnerable to the adverse intrauterine environments in the late gestation period, and the decreased number of SP T cells could result from the enhanced thymocyte apoptosis.

Food deprivation in F0 generation and hypercaloric diet in F1 generation reduce F2 generation astrogliosis in several brain areas after immune challenge

AimsThe effects of maternal food restriction during gestation in F0 generation followed by hypercaloric diet (HD) during puberty in F1 generation (F1HD) were investigated on astrocyte behavior of F2 generation. Also, the astrocyte behavior, after an immune challenge, was examined by the immunohistochemical expression of glial fibrillary acidic protein (GFAP) in several brain areas. MethodsThe body weight gain (BW) during development and in postnatal day (PND) 90–95, the retroperitoneal fat weight (RPF), and the size of larger and smaller adipocytes in the F1 generation were assessed to observe the effects of HD in female rats. The BW, RPF weight and size of smaller and larger adipocytes was also measured to evaluate the transgenerational effects of F0 and F1 diets on F2 generation, treated or not with lipopolysaccharide (LPS). Key findingsThe F1HD group exhibited a higher BW gain than the F1 treated with normocaloric diet (ND, group F1ND), from weaning to PND65. In the frontal/parietal cortex, nucleus accumbens, hypothalamic arcuate/periventricular nuclei, molecular/granular layers of the cerebellum areas, excepting the pons, GFAP expression was greater in F1HD group relative to F1ND group. A reduced GFAP expression was observed in both groups born from F1 generation fed with HD (groups F2HDS and F2HDLPS) in relation to F2 generation born from dams fed with ND (groups F2NDS and F2NDLPS), independently of LPS challenge. SignificanceThese data show an attenuation of LPS effect on GFAP expression, probably by a transgenerational effect of both maternal food deprivation in F0 generation and HD in F1 generation.

Effect of Maternal Food Restriction on the Uterus of Female Rats from the First and Second Generation

Postnatal life is affected by changes in fetal development due to adverse events. The present study examined the effect of maternal food restriction on uterine structure and capacity in female rats from the first and second generations (FR1 and FR2) before and after puberty. Pregnant rats were fed ad libitum (Control, C) or maintained under food-restriction conditions (50%FR) during pregnancy. After delivery, all groups were given free access to food. Females from the first generation (FR1) were divided into two subgroups for either uterine dissection or to produce the next generation (FR2). Similar to FR1, FR2 females were exposed to maternal food restriction following the same procedure. FR2 females were also assigned into two subgroups for either uterine dissection or for mating to examine pregnancy outcomes. Uteri from the C, FR1 and FR2 groups were dissected at 4 weeks of age (before puberty) or at 8 weeks of age (after puberty) to evaluate uterine weight and uterine horn length. Tissues were stained with eosin and haematoxylin for examination vialight microscopy. The results showed that food restriction did not affect uterine weight or uterine horn length in FR1 and FR2 females before puberty. However, there were effects of maternal food restriction on uterine weight and length at 8 weeks of age. Uterine weight and uterine horn length were significantly reduced in the FR1 and FR2 groups compared with the values of the controls. This was associated with changes in pregnancy outcomes. Litter size was not affected in the FR1 group; however, litter weight was significantly reduced, leading to an 18% reduction in pup weight at birth. Unlike with FR1 litters, the size of FR2 litters was significantly reduced, leading to a lower degree of pup body weight reduction at birth (only 7%). The gestational length was normal in FR1 females but was significantly decreased in FR2 females. No histopathological changes were observed. These results showed that the uterus was affected by maternal food restriction. It seemed that FR2 females had a different reproductive strategy: they tended to reduce litter size to maintain pup weight at birth. In conclusion, maternal food restriction affects the uteri of the first and second generation. Females from the FR1 and FR2 groups followed different reproductive strategies according to their previous experience with exposure to intrauterine food restriction.

Proteomic Analysis of One-carbon Metabolism-related Marker in Liver of Rat Offspring

Maternal food intake has a significant effect on the fetal environment, and an inadequate maternal diet may result in intrauterine growth restriction. Intrauterine growth restriction newborn rat pups nursed by normal diet-fed dams exhibited rapid catch-up growth, which plays a critical role in the risk for metabolic and cardiovascular disease in later life. Specifically, one-carbon metabolism in the liver plays a critical role in placental and fetal growth. Impaired functioning of one-carbon metabolism is associated with increased homocysteine levels. In this study, we applied a comprehensive proteomic approach to identify differential expression of proteins related to one-carbon metabolism in the livers of rat offspring as an effect of maternal food restriction during gestation. Data are available via ProteomeXchange with identifier PXD002578. We determined that betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial (ATP5B) expression levels were significantly reduced in the livers of rat offspring exposed to maternal food restriction during gestation compared with in the offspring of rats fed a normal diet (p < 0.05). Moreover, the expression levels of betaine-homocysteine S-methyltransferase 1, methylenetetrahydrofolate dehydrogenase 1, and ATP synthase subunit beta mitochondrial were negatively correlated with serum homocysteine concentration in male offspring exposed to maternal food restriction during gestation and normal diet during lactation. However, in female offspring only expression levels of methylenetetrahydrofolate dehydrogenase 1 were negatively correlated with homocysteine concentration. This study shows that maternal food restriction during late gestation and normal diet during lactation lead to increased homocysteine concentration through disturbance of one-carbon metabolism in the livers of male offspring. This suggests that male offspring have an increased gender-specific susceptibility to disease in later life through fetal programming.

Metyrapone alleviates deleterious effects of maternal food restriction on lung development and growth of rat offspring.

Maternal food restriction (MFR) causes intrauterine growth restriction, a known risk factor for developing chronic lung disease. However, it is unknown whether this negative outcome is gender specific or preventable by blocking the MFR-induced hyperglucocorticoidism. Using a well-established rat model, we used metyrapone (MTP), an inhibitor of glucocorticoid synthesis, to study the MFR-induced lung changes on postnatal day (p) 21 in a gender-specific manner. From embryonic day 10 until delivery, pregnant dams were fed either an ad libitum diet or a 50% caloric restricted diet with or without MTP supplementation. Postnatally, the offspring were fed ad libitum from healthy dams until p21. Morphometric, Western blot, and immunohistochemical analysis of the lungs demonstrated that MTP mitigated the MFR-mediated decrease in alveolar count, decrease in adipogenic protein peroxisome proliferator-activated receptor γ, increase in myogenic proteins (fibronectin, α-smooth muscle actin, and calponin), increase in Wnt signaling intermediates (lymphoid enhancer-binding factor 1 and β-catenin), and increase in glucocorticoid receptor (GR) levels. The MFR-induced lung phenotype and the effects of MTP were similar in both genders. To elucidate the mechanism of MFR-induced shift of the adipogenic-to-myogenic phenotype, lung fibroblasts were used to independently study the effects of (1) nutrient restriction and (2) excess steroid exposure. Nutrient deprivation increased myogenic proteins, Wnt signaling intermediates, and GR, all changes blocked by protein supplementation. MTP also blocked, likely by normalizing nicotinamide adenine dinucleotide phosphate levels, the corticosterone-induced increase in myogenic proteins, but had no effect on GR levels. In summary, protein restriction and increased glucocorticoid levels appear to be the key players in MFR-induced lung disease, affecting both genders.

Effects of maternal food restriction on offspring lung extracellular matrix deposition and long term pulmonary function in an experimental rat model

Intrauterine growth restriction (IUGR) increases the risk of respiratory compromise throughout postnatal life. However, the molecular mechanism(s) underlying the respiratory compromise in offspring following IUGR is not known. We hypothesized that IUGR following maternal food restriction (MFR) would affect extracellular matrix deposition in the lung, explaining the long-term impairment in pulmonary function in the IUGR offspring. Using a well-established rat model of MFR during gestation to produce IUGR pups, we found that at postnatal day 21, and at 9 months (9M) of age the expression and abundance of elastin and alpha smooth muscle actin (αSMA), two key extracellular matrix proteins, were increased in IUGR lungs when compared to controls (P < 0.05, n = 6), as determined by both Western and immunohistochemistry analyses. Compared to controls, the MFR group showed no significant change in pulmonary resistance at baseline, but did have significantly decreased pulmonary compliance at 9M (P < 0.05 vs. control, n = 5). In addition, MFR lungs exhibited increased responsiveness to methacholine challenge. Furthermore, exposing cultured fetal rat lung fibroblasts to serum deprivation increased the expression of elastin and elastin-related genes, which was blocked by serum albumin supplementation, suggesting protein deficiency as the predominant mechanism for increased pulmonary elastin deposition in IUGR lungs. We conclude that accompanying the changes in lung function, consistent with bronchial hyperresponsiveness, expression of the key alveolar extracellular matrix proteins elastin and αSMA increased in the IUGR lung, thus providing a potential explanation for the compromised lung function in IUGR offspring.

Transgenerational programming of hypertension by maternal food restriction during pregnancy

As human food poverty often spans generations, the aim was to determine whether the hypertensive influence of maternal food restriction during pregnancy is amplified across generations. Control Wistar rat mothers were exposed to ad libitum food intake in utero and then had free access to food while pregnant (CM); food restricted mothers were exposed to food restriction (50% of the pregnant control rat ad libitum intake from day 1 of pregnancy until birth) in utero and then had free access to food while pregnant (FRM); double food restricted mothers were exposed to 50% food restriction in utero and then were fed 50% of ad libitum while pregnant (DFRM). Systolic blood pressures (BP) did not differ between FRM (120.4 ± 1.7, n = 8) and DFRM (118.9 ± 1.0, n = 6) but were significantly higher than CM prior to mating (113.5 ± 1.0 mmHg, n = 6, P < 0.05). At 9 weeks, the BP of male offspring from FRM (120.1 ± 1.9, n = 15) was significantly higher than that of CM (109.3 ± 1.7, n = 11, P < 0.001); the BP of DRFM offspring was higher still (135.7 ± 1.5 mmHg, n = 12, P < 0.01 vs FRM). There was no correlation between maternal and offspring BP (r = 0.26, P = 0.12), implying that the higher BP of the DFRM offspring was not due to higher maternal BP. These data show that the programming effects of maternal food restriction are amplified across generations. Funded by the Fetal Programming of Diseases Research Chair, King Saud University.

Effects of maternal food restriction on physical growth and neurobehavior in newborn Wistar rats

Maternal nutrition plays a critical role in physical growth and neurobehavior of offspring. The aim of this study was to assess the nature of maternal undernutrition on the physical growth and neurobehavior of newborn male and female rat pups. To attain this aim, a model of maternal 50% food restriction (FR50) was induced in Wistar rats. After parturition, the physical growth and neurobehavior were tested in male and female pups. Compared with gender-matched controls, both male and female FR50 pups showed delayed physical growth, such as pinna detachment, hair growth, eruption of incisor teeth and eye opening. Also, they showed a delay of neurobehavior in surface righting reflex and cliff avoidance reflex. In addition, FR50 male pups exhibited a delay in achieving negative geotaxis response compared to normal male pups. These data obtained are useful to provide baseline information about the neurodevelopmental delay of maternal undernutrition of both sexes in rat pups and help to gain a better understanding of undernutrition during human fetal and neonatal periods.

Maternal dietary restriction during lactation influences postnatal growth and behavior in the offspring of mice

It is well known that maternal nutritional status is important to the development of mammalian offspring. We examined the effect of maternal food restriction during lactation on offspring in mice. From 1 to 21 days after parturition, control dams (CDs) were fed with the standard amounts of daily food consumption, whereas dietary restricted dams (RDs) received 70% of daily food consumption. Although the mean body weight of RDs was not significantly different from that of the CDs, body weight of the offspring from RD (RD offspring) was significantly lower than that of the offspring from CD (CD offspring). The difference was detectable until 10 weeks of age. Body lengths and brain weights of RD offspring at postnatal day 22 were lower than those of the CD offspring. Plasma concentrations of leptin in RD offspring decreased significantly. But plasma concentrations of growth hormone and thyroxin were not different between the two groups. In the open field tests, total distance was significantly decreased in RD offspring compared with CD offspring. In the hole-board test, head dip latency was increased and the number of dips was decreased significantly in RD offspring. In the elevated plus maze test, total distance and risk assessment were significantly decreased in the RD offspring. There was no difference between the two groups in the rota-rod and wire-hang tests. These results suggest that maternal dietary restriction during lactation can affect the growth, locomotor activity and anxiety behavior of offspring, but not motor or neuromuscular function.

Undernutrition of the GK rat during gestation improves pancreatic IGF-2 and beta-cell mass in the fetuses

The Goto–Kakizaki (GK) rat is a type 2 diabetes model with a defective beta-cell mass detectable in late fetal development. Diminished IGF-2 production seems to be involved in this effect. Herein, we analyzed the effect of maternal food-restriction on the beta-cell mass of GK fetuses and the involvement of the IGF system, highly responsive to nutritional status in this process. To this end, in undernourished GK fetuses (U-GK), we measured serum GH/IGF levels, beta-cell mass, replication and differentiation, and IGF-1/-2 protein content in liver and pancreas tissue. Pregnant GK females were food restricted (65% restriction) during the last week of gestation. Our results show that maternal malnutrition ameliorates beta-cell mass in U-GK fetuses and a specific pancreatic IGF-2 increase may be instrumental in this effect. Further studies are needed to determine whether maternal undernutrition is sufficient to delay or decrease the risk of the GK rat for developing diabetes.

Effect of maternal food restriction on fetal rat lung lipid differentiation program

Although "fetal programming" has been extensively studied in many organs, there is only limited information on pulmonary effects in the offspring following intrauterine growth restriction (IUGR). We aimed to determine the effects of nutrient restriction on the lung structure and lung lipid differentiation programs in offspring using an animal mode of maternal food restriction (MFR). We utilized a rodent model of 50% MFR from day 10 of gestation to term and then using lung morphology, Western blotting, Real Time RT-PCR and Oil Red O staining, lung structure and development of the offspring were examined at postnatal days (p) 1, p21, and 9 months (9M). At postnatal day 1, MFR pups weighed significantly less compared to control pups, but at p21 and 9M, they weighed significantly more. However, lung weight, expressed as a percentage of body weight between the two groups was not different at all time-points examined. The MFR group had significantly decreased alveolar number and significantly increased septal thickness at p1 and 9M, indicating significantly altered lung structure in the MFR offspring. Furthermore, although at p1, compared to the control group, lung lipid accumulation was significantly decreased in the MFR group, at 9M, it was significantly increased. There were significant temporal changes in the parathyroid hormone-related protein/peroxisome proliferator-activated receptor gamma signaling pathway and surfactant synthesis. We conclude that MFR alters fetal lung lipid differentiation programming and lung morphometry by affecting specific epithelial-mesenchymal signaling pathways, offering the possibility for specific interventions to overcome these effects.

159. MATERNAL NUTRITION AND GESTATIONAL AGE AFFECT PLACENTAL microRNA EXPRESSION IN THE GUINEA PIG

Maternal undernutrition restricts placental growth and nutrient supply to the fetus, but induces compensatory alterations in structure and function of the placenta. Maternal undernutrition in guinea pigs also restricts placental growth and alters structure, and changes expression of Igf1, Igf2, Slc2a1, Slc38a2 mRNA in mid and late gestation, consistent with nutritionally induced changes in nutrient transport across the placenta. MicroRNAs are non-coding RNAs that regulate expression of target genes by translational inhibition and mRNA degradation and are present in the mammalian placenta. Effects of maternal undernutrition on their expression are unknown. We hypothesised that altered expression of key functional genes in the placenta in maternal undernutrition are in part due to altered expression of regulatory microRNAs. The effect of maternal food restriction on the expression of microRNAs in the guinea pig placenta was examined at D30 and D60 of gestation (term = D70). Guinea pigs were fed either ad libitum (AL) or restricted (R). MicroRNA expression was determined by Exiqon microarray v.8.1. In AL placentas, 119 microRNAs were upregulated (p&lt;0.05), whilst 40 were down-regulated (p&lt;0.05) at late compared to early gestation. In R placentas, 163 microRNAs were upregulated (p&lt;0.05), whilst 123 were down-regulated (p&lt;0.05) at late compared to early gestation. Of the 20 most abundant up-regulated microRNAs miR-Plus (ID 17871) and hsa-miR-411 were altered only in AL and hsa-miR-376a and -376b were altered only in R placenta. Of the 20 most abundant down-regulated microRNAs, 13 were altered only in AL and 14 only in R placentas. Placental expression of microRNAs changed with gestation, and maternal undernutrition modified this pattern and altered expression of many additional microRNAs in the guinea pig placenta. This suggests that miRNAs and factors that influence their expression may play a role in the structural and/or functional development of the placenta and hence fetal growth.

Effect of maternal food restriction during gestation on early development of F1 and F2 offspring in the rat-like hamster ( Cricetulus triton)

Maternal food restriction (FR) may have strong and long-term effects on body weight, brain and behavior development of offspring. However, it is still not well understood whether such an effect is carried over to the next generation. Our objective was to examine the differences of maternal behavior, body growth, cranial growth and early development of F1 and F2 offspring of rat-like hamsters between a FR group and a control group. Results show that FR has a significant influence on maternal gathering behavior. The body weight of F1 offspring was significantly lower in the food-restricted group compared with that of the control animals, while the body weight of food-restricted F2 offspring was not significantly different from that of the control group. The physical development and neurodevelopment of food-restricted F1 and F2 offspring were significantly delayed compared to the controls. These results suggest that FR in female rat-like hamsters affected negatively the body growth of F1 offspring, and the physical and neurodevelopment of both F1 and F2 offspring. The effect of maternal FR on F2 offspring was smaller than that on F1 offspring. These factors may, in turn, play an important role in the population regulation of this species.

Food restriction affects reproduction and survival of F1 and F2 offspring of Rat-like hamster ( Cricetulus triton)

Food restriction in parent may have long-term consequence on the reproductive capabilities of the offspring, and these consequences may, in turn, play an important role in population regulation. In this paper, we systematically examined the effect of maternal food restriction on reproduction and survival of maternal individuals, and F1 and F2 offspring of Rat-like hamsters ( Cricetulus triton). Food restriction to 75% of that eaten by ad libitum-fed hamsters (75% FR) did not affect the reproductive organs and hormone concentration of maternal females, but 50% FR significantly reduced the size of ovarian organ and estradiol concentration of maternal females. 75% FR significantly reduced the testosterone concentration of maternal males; 50% FR significantly reduced both the size of epididymides and concentration of testosterone of maternal males. 70% FR in maternal females significantly reduced the sizes of reproductive organs and hormone concentrations of both their male and female F1 offspring. FR maternal females also produced significantly more male than female F1 offspring. The sizes of reproductive organs or hormone concentration of F2 males of maternal FR continued to significantly decline, but no such effect was observed in F2 females. However, the number of F2 offspring per F1 female of FR maternal females at birth became significantly smaller and with significantly more males than females. Survival to weaning of F1 and F2 offspring of FR maternal females became significantly smaller during the period from birth to weaning. Thus, the effects of maternal food restriction could be an important mechanism to explain the prolonged low population density that is commonly observed after the population crash of this species.