Vitamin and mineral supplementation to beef heifers during gestation: impacts on morphometric measurements of the neonatal calf, vitamin and trace mineral status, blood metabolite and endocrine profiles, and calf organ characteristics at 30 h after birth.

To examine the effects of feeding a vitamin and mineral supplement to beef heifers throughout gestation on mineral status and hormone/endocrine profiles in the dam and calf, and morphometric characteristics and organ mass of the calf at 30 h after birth, Angus-based heifers (n = 72, 14 to 15 mo of age, initial body weight [BW] = 380.4 ±â€…50.56 kg) were estrus synchronized and artificially inseminated (AI) with female-sexed semen. Heifers were blocked by BW and randomly assigned to receive either a basal diet (CON; n = 36) or a basal diet plus a vitamin and mineral supplement (VTM; n = 36) via an individual feeding system beginning at breeding, with both diets targeting BW gains of 0.45 kg heifer-1·d-1. Heifers not pregnant after the first AI (CON, n = 19; VTM, n = 18) were rebred via AI 60 d after treatment initiation, and heifers gestating female fetuses (CON, n = 7; VTM, n = 7) received treatments throughout gestation and were experimental units for this study. Calves were separated from their dams and fed colostrum replacer within 2 h of birth and euthanized 30 h after the first feeding. Calf morphometrics were recorded, and tissues were weighed and sampled. Serum from the dam at calving and serum, liver, and muscle from the calf at 30 h were analyzed for concentrations of minerals. Serum from the dam and calf were analyzed for concentrations of leptin, vitamins A, D, and E, cortisol, growth hormone, and insulin-like growth factor 1. All response variables were analyzed using the MIXED procedure of SAS. Calf body morphometrics and BW of the dam at calving (P ≥ 0.32), calf organ weights (P ≥ 0.21), and calf ovarian follicle counts (P ≥ 0.13) were not affected by maternal treatment. Concentrations of Se and Co in calf serum and Se in calf liver were increased (P ≤ 0.02) in VTM. Serum concentrations of Co and vitamin A in the dam were greater (P ≤ 0.01) in supplemented compared with nonsupplemented dams, and serum concentrations of vitamin D were greater (P ≤ 0.0003) in supplemented dams and calves compared with the nonsupplemented cohort. Maternal supplementation supported vitamin and mineral status in the neonate, yet had no discernable impact on BW, organ mass, or circulating hormones/metabolites in the calf. Evaluating offspring at later postnatal time points is warranted to determine if prenatal vitamin and mineral supplementation affects performance, health, metabolism, and efficiency of energy utilization in key metabolic tissues in the calf.

Vitamins and minerals are essential for the reproduction, performance, skeletal support, and overall health of beef cattle. During pregnancy, vitamins and minerals are critical for proper fetal growth, development, and establishment of postnatal micronutrient reserves. The study objectives were to evaluate the impacts of vitamin and mineral supplementation to beef heifers throughout gestation on female offspring morphometric characteristics at birth, mineral status and blood metabolite/endocrine profiles of the dam and calf, histological evaluation of calf ovaries, and organ weights of the neonate at 30 h of age. We hypothesized that vitamin and mineral supplementation to the dam during pregnancy would increase calf size and organ masses, mineral status, and blood metabolite and hormone profiles. We observed no differences in calf body measurements, organ masses, and offspring ovarian reserve between calves from supplemented and nonsupplemented dams. However, Co, Se, and vitamin D status was increased in the supplemented dam and calf, and we propose that enhanced vitamin and mineral status at birth may support the underdeveloped immune system, growth performance, and overall health of the neonate in the postnatal period. Further research is warranted to investigate postnatal offspring health, performance, and efficiency of energy utilization in key metabolic tissues in the calf.

Maternal protein supplementation during mid-gestation improves offspring performance and metabolism in beef cows.

This study examined the impact of maternal protein supplementation during mid-gestation on offspring, considering potential sex-related effects. Forty-three pregnant purebred Tabapuã beef cows (20 female and 23 male fetuses) were collectively managed in a pasture until 100 d of gestation. From 100 to 200 d of gestation, they were randomly assigned to the restricted group [(RES) - basal diet (75% corn silage + 25% sugar cane bagasse + mineral mixture); n = 24] or control group [(CON) - same basal diet + based-plant supplement [40% of crude protein, 3.5 g/kg of body weight (BW); n = 19]. From 200 d of gestation until parturition, all cows were equally fed corn silage and mineral mixture. During the cow-calf phase, cows and their calves were maintained in a pasture area. After weaning, calves were individually housed and evaluated during the backgrounding (255 to 320 d), growing 1 (321 to 381 d), and growing 2 (382 to 445 d) phases. Offspring's blood samples were collected at 210 and 445 d of age. Samples of skeletal muscle tissue were collected through biopsies at 7, 30, and 445 d of age. Muscle tissue samples were subjected to reverse-transcription quantitative polymerase chain reaction analysis. Prenatal treatment and offspring's sex (when pertinent) were considered fixed effects. The significance level was set at 5%. At mid-gestation, cows supplemented with protein reached 98% and 92% of their protein and energy requirements, while nonsupplemented cows attained only 30% and 50% of these requirements, respectively. The RES offspring were lighter at birth (27 vs. 31 kg), weaning (197 vs. 214 kg), and 445 d of age (398 vs. 429 kg) (P ≤ 0.05). The CON calves had greater (P < 0.05) morphometric measurements overall. The CON offspring had ~26% greater muscle fiber area (P ≤ 0.01). There was a trend (P = 0.06) for a greater Mechanistic target of rapamycin kinase mRNA expression in the Longissimus thoracis in the CON group at 7 d of age. The Myogenic differentiation 1 expression was greater (P = 0.02) in RES-females. Upregulation of Carnitine palmitoyltransferase 2 was observed in RES offspring at 445 d (P = 0.04). Expression of Fatty acid binding protein 4 (P < 0.001), Peroxisome proliferator-activated receptor gamma (P < 0.001), and Stearoyl-Coenzyme A desaturase (P < 0.001) was upregulated in CON-females. Therefore, protein supplementation during gestation enhances offspring growth and promotes favorable responses to lipogenesis, particularly in females.

In tropical conditions, beef cows on pasture often experience protein restriction during mid-to-late gestation, potentially impacting offspring development negatively. To address this, we investigated the effects of strategic protein supplementation for pregnant beef cows fed low-quality forage during mid-gestation on the postnatal growth trajectory of their offspring. The supplementation program, implemented during mid-gestation, increased dry matter intake by addressing nitrogen deficiency in the rumen, resulting in meeting 98% and 92% of protein and energy requirements in supplemented cows. In contrast, nonsupplemented cows met only 30% and 50% of these requirements, respectively. Consequently, protein supplementation positively influenced the postnatal growth trajectory of the offspring, attributed to beneficial changes in secondary myogenesis and hypertrophy processes. Supplementing cows with crude protein also stimulated lipogenesis, potentially contributing to intramuscular fat deposition, particularly in females. Therefore, this study emphasizes the importance of nutritional interventions for pregnant beef cows fed low-quality forage.

Melatonin supplementation in obese mothers reduces hypothalamic inflammation and enhances thermogenesis in mice progeny.

Maternal obesity might induce obesity and metabolic alterations in the progeny. The study aimed to determine the effect of supplementing obese mothers with Mel (Mel) on thermogenesis and inflammation. C57BL/6 female mice (mothers) were fed from weaning to 12 weeks control diet (C, 17% kJ as fat) or a high-fat diet (HF, 49% kJ as fat) and then matted with male mice fed the control diet. Melatonin (10 mg/kg daily) was supplemented to mothers during gestation and lactation, forming the groups C, CMel, HF, and HFMel (n = 10/group). Twelve-week male offspring were studied (plasma biochemistry, immunohistochemistry, protein, and gene expressions at the hypothalamus - Hyp, subcutaneous white adipose tissue - sWAT, and interscapular brown adipose tissue - iBAT). Comparing HFMel vs. HF offspring, fat deposits and plasmatic proinflammatory markers decreased. Also, HFMel showed decreased Hyp proinflammatory markers and neuropeptide Y (anabolic) expression but improved proopiomelanocortin (catabolic) expression. Besides, HFMel sWAT adipocytes changed to a beige phenotype with-beta-3 adrenergic receptor and uncoupling protein-1 activation, concomitant with browning genes activation, triggering the iBAT thermogenic activity. In conclusion, compelling evidence indicated the beneficial effects of supplementing obese mothers with Mel on the health of their mature male offspring. Mel led to sWAT browning-related gene enhancement, increased iBAT thermogenis, and mitigated hypothalamic inflammation. Also, principal component analysis of the data significantly separated the untreated obese mother progeny from the progeny of treated obese mothers. If confirmed in humans, the findings encourage a future guideline recommending Mel supplementation during pregnancy and breastfeeding.

Fetal programming effect of rumen-protected methionine on primiparous Angus × Simmental offspring's performance and skeletal muscle gene expression.

Primiparous Angus × Simmental dams (n = 22) with an average body weight (BW) of 449 ±â€…32 kg of BW were divided based on two nutritional treatments: control (CTRL) and rumen-protected methionine (RPM). The control group received bermudagrass hay, corn gluten, and soybean hulls pellets supplementation (base diet); whereas the RPM group received the base diet in addition to 0.07% of DM of RPM at a fixed rate during the last trimester of gestation and the first ~80 d of lactation, in which calves (n = 17) were early weaned. Only male calves were included in this study. After weaning, calves born to RPM dams also received RPM from weaning (day 1) to day 100. Blood sampling and skeletal muscle biopsies for subsequent quantitative polymerase chain reaction (PCR) analysis were conducted on days 1, 25, 50, and 100 on calves. Quantitative PCR data were analyzed using GLIMMIX, and blood metabolites concentrations, BW, and body condition score (BCS) were analyzed using the MIXED procedure of SAS. There was no difference in maternal BW and BCS between treatments. Glucose and blood metabolites that served as biomarkers for liver health (e.g., aspartate transaminase, albumin, alkaline phosphatase, and alanine transaminase) were in the normal levels for all calves (P > 0.40). Calves in the RPM group had a greater expression of adipogenic genes (e.g., PPARG, LPL, and CEBPD) at day 100 compared with CTRL (P < 0.01). In addition, DNA methylation (DNMT1) and oxidative stress-related genes (SOD2 and NOS3) in the RPM group were upregulated at day 100 compared with CTRL (P < 0.01). These results may suggest that calves born to primiparous dams exposed to RPM supplementation are more prone to develop greater adipose tissue than CTRL calves. Furthermore, RPM supplementation may improve methylation processes, as shown by the upregulation of DNMT1. The results shown in our study aim at expanding the knowledge on fetal programming and early-life growth and development of beef cattle under supplementation with RPM.

Plane of nutrition plays a critical role in fetal and postnatal growth in beef cattle offspring. Methionine, a limiting amino acid in ruminants, is also involved in DNA methylation due to its role as S-adenosyl methionine precursor. A complete randomized design experiment was conducted to assess the fetal programming effect of rumen-protected methionine (RPM) supplementation on beef cattle. Calves born to primiparous beef heifers, that individually received RPM during the last trimester of gestation and lactation, had a greater expression of genes related to adipose tissue development, oxidative stress, and DNA methylation compared with those born to dams that did not receive rumen-protected supplementation. No difference in animal performance or blood parameters that serve as biomarkers for liver health status was detected. Our results suggest that maternal supplementation with RPM during the last trimester of gestation and lactation, and supplementation to the offspring after early weaning, could potentially increase adipose tissue development on male calves.

Supplementing vitamins and minerals to beef heifers during gestation: impacts on mineral status in the dam and offspring, and growth and physiological responses of female offspring from birth to puberty.

We evaluated the effects of feeding a vitamin and mineral supplement to nulliparous beef heifers throughout gestation on the mineral status of the dam, calf, placenta, and colostrum; offspring growth performance; and physiological responses of offspring raised as replacement heifers. Angus-based heifers (n = 31, initial body weight [BW] = 412.5 ±â€…53.68 kg) were adapted to an individual feeding system for 14 d, estrus synchronized and bred with female-sexed semen. Heifers were ranked by BW and randomly assigned to receive either a basal diet (CON; n = 14) or the basal diet plus 113 g heifer-1 d-1 of the vitamin and mineral supplement (VTM; n = 17). Targeted BW gains for both treatments was 0.45 kg heifer-1 d-1. Liver biopsies were obtained from dams at breeding, days 84 and 180 of gestation. At calving, liver biopsies were taken from dams and calves; colostrum, placenta, and blood samples were collected; and calf body measurements were recorded. After calving, all cow-calf pairs received a common diet through weaning, and F1 heifer calves were managed similarly after weaning. Offspring growth performance, feeding behavior, blood metabolites, and hormones were evaluated from birth through 15 mo of age. Data were analyzed using the MIXED procedure in SAS with repeated measures where appropriate. Hepatic concentrations of Se decreased in VTM dams (P ≤ 0.05) from day 84 to calving, while concentrations of Cu decreased in VTM and CON (P ≤ 0.05) from day 84 to calving. Calf liver concentrations of Se, Cu, Zn, and Co at birth were greater for VTM than CON (P ≤ 0.05), but calf birth BW and body measurements were not different (P = 0.45). Placental Se, colostrum quantity, total Se, Cu, Zn, and Mn in colostrum were greater (P ≤ 0.04) in VTM dams than CON. Finally, offspring from VTM dams were heavier than CON (P < 0.0001) from weaning through 15 mo of age. These results were coupled with greater (P ≤ 0.04) blood glucose at birth, decreased (P ≤ 0.05) blood urea nitrogen at pasture turn out and weaning, and altered feeding behaviors in VTM offspring compared with CON. Maternal gestational vitamin and mineral supplementation enhanced mineral status in dams and F1 progeny, augmented postnatal offspring growth and blood metabolites. Consequently, in utero vitamin and mineral supplementation may exert programming outcomes on the performance and productivity of females raised as herd replacements and should be considered when developing diets for gestating cows and heifers.

Great variation exists in management decisions to offer a vitamin and mineral supplement to cow­calf herds in the Northern Great Plains. Decisions to supplement (or not) vitamins/minerals during critical periods of fetal development may have lasting postnatal impacts on the offspring; however, there is a lack of reports focusing on the long-term offspring outcomes. Our objectives were to determine the impacts of supplementing vitamins/minerals during gestation in beef heifers on mineral status in the dam, calf, placenta, and colostrum; offspring postnatal performance and feeding behavior; blood metabolite and endocrine profiles; and puberty attainment in heifer calves. We observed enhanced hepatic mineral status in heifers receiving supplemental vitamins/minerals during pregnancy, at calving, and in their neonatal calves compared with non-supplemented cohorts. Calves born to supplemented dams had improved measures of growth during postnatal development, increased concentrations of key blood metabolites, and differences in body measurements and carcass ultrasound traits at post-weaning evaluation. These results suggest that fetal nutritional environment is pivotal for the long-term growth and success of the offspring. We hypothesize that fetal programming outcomes on the offspring in this experiment may have the potential to affect the subsequent generation of beef calves.

Cis-9, trans-11 and trans-10, cis-12 conjugated linoleic acid gastric administration during the pregestational and gestational periods does not influence the follicular endowment of the progeny.

Fetal programming suggests that maternal stimulation and nutrition during the period of fetal development can program the progeny. Conjugated linoleic acid (CLA), an isomer of linoleic acid, has been characterized in several aspects, but few studies have been performed on its involvement in reproduction and fetal programming. The aim of this study was to evaluate the F1, F2 and F3 progeny of female mice supplemented with CLA during the pregestational and gestational periods with respect to biometric and reproductive parameters, as well as ovarian morphophysiology. The F1 progeny of mothers supplemented with CLA exhibited stable weight gain, while the F2 progeny showed no effects (P=0.0187 and P=0.0245, respectively). A reduction in Lee's Index was observed in both generations at the second post-weaning evaluation week in the animals treated with CLA (P=0.0100 and P=0.0078, respectively). The F2 generation showed an increase in the anogenital index in both sexes of the animals treated with CLA (P= 0.0114 and P<0.0001, female and male respectively). CLA administration to mothers did not affect any of the following in their progeny: ovarian follicle mobilization (P>0.05), follicle number (P>0.05) and the integrated density of the lipid content of oocytes included in antral follicles (P>0.05). This study evaluated the use of CLA in mothers and found that it did not affect the progeny regarding murine reproductive performance, suggesting that this supplement can be used safely.

High-fat diet during pregnancy promotes fetal skeletal muscle fatty acid oxidation and insulin resistance in an ovine model.

Maternal diet during pregnancy is associated with offspring metabolic risk trajectory in humans and animal models, but the prenatal origins of these effects are less clear. We examined the effects of a high-fat diet (HFD) during pregnancy on fetal skeletal muscle metabolism and metabolic risk parameters using an ovine model. White-faced ewes were fed a standardized diet containing 5% fat wt/wt (CON), or the same diet supplemented with 6% rumen-protected fats (11% total fat wt/wt; HFD) beginning 2 wk before mating until midgestation (GD75). Maternal HFD increased maternal weight gain, fetal body weight, and low-density lipoprotein levels in the uterine and umbilical circulation but had no significant effects on circulating glucose, triglycerides, or placental fatty acid transporters. Fatty acid (palmitoylcarnitine) oxidation capacity of permeabilized hindlimb muscle fibers was >50% higher in fetuses from HFD pregnancies, whereas pyruvate and maximal (mixed substrate) oxidation capacities were similar to CON. This corresponded to greater triacylglycerol content and protein expression of fatty acid transport and oxidation enzymes in fetal muscle but no significant effect on respiratory chain complexes or pyruvate dehydrogenase expression. However, serine-308 phosphorylation of insulin receptor substrate-1 was greater in fetal muscle from HFD pregnancies along with c-jun-NH2 terminal kinase activation, consistent with prenatal inhibition of skeletal muscle insulin signaling. These results indicate that maternal high-fat feeding shifts fetal skeletal muscle metabolism toward a greater capacity for fatty acid over glucose utilization and favors prenatal development of insulin resistance, which may predispose offspring to metabolic syndrome later in life.NEW & NOTEWORTHY Maternal diet during pregnancy is associated with offspring metabolic risk trajectory in humans and animal models, but the prenatal origins of these effects are less clear. This study examined the effects of a high-fat diet during pregnancy on metabolic risk parameters using a new sheep model. Results align with findings previously reported in nonhuman primates, demonstrating changes in fetal skeletal muscle metabolism that may predispose offspring to metabolic syndrome later in life.

Folate and Cobalamin Deficiencies during Pregnancy Disrupt the Glucocorticoid Response in Hypothalamus through N-Homocysteinilation of the Glucocorticoid Receptor.

Vitamin B9 (folate)/B12 (cobalamin) deficiency is known to induce brain structural and/or functional retardations. In many countries, folate supplementation, targeting the most severe outcomes such as neural tube defects, is discontinued after the first trimester. However, adverse effects may occur after birth because of some mild misregulations. Various hormonal receptors were shown to be deregulated in brain tissue under these conditions. The glucocorticoid receptor (GR) is particularly sensitive to epigenetic regulation and post-translational modifications. In a mother-offspring rat model of vitamin B9/B12 deficiency, we investigated whether a prolonged folate supplementation could restore the GR signaling in the hypothalamus. Our data showed that a deficiency of folate and vitamin B12 during the in-utero and early postnatal periods was associated with reduced GR expression in the hypothalamus. We also described for the first time a novel post-translational modification of GR that impaired ligand binding and GR activation, leading to decrease expression of one of the GR targets in the hypothalamus, AgRP. Moreover, this brain-impaired GR signaling pathway was associated with behavioral perturbations during offspring growth. Importantly, perinatal and postnatal supplementation with folic acid helped restore GR mRNA levels and activity in hypothalamus cells and improved behavioral deficits.

Placental AA/EPA Ratio Is Associated with Obesity Risk Parameters in the Offspring at 6 Years of Age.

During pregnancy, maternal polyunsaturated fatty acids (PUFA) are transferred to the fetus through the placenta by specific FA transporters (FATP). A higher perinatal exposure to n-6 over n-3 PUFA could be linked to excess fat mass and obesity development later in life. In this context, we aimed to assess the associations between long chain PUFAs (LC-PUFAs) (n-6, n-3, and n-6/n-3 ratios) measured in the placenta at term birth with obesity-related parameters in the offspring at 6 years of age and assess whether these associations are dependent on the placental relative expression of fatty acid transporters. As results, the PUFAn-6/PUFAn-3 ratio was 4/1, which scaled up to 15/1 when considering only the arachidonic acid/eicosapentaenoic acid ratio (AA/EPA ratio). Positive associations between the AA/EPA ratio and offspring's obesity risk parameters were found with weight-SDS, BMI-SDS, percent fat mass-SDS, visceral fat, and HOMA-IR (r from 0.204 to 0.375; all p < 0.05). These associations were more noticeable in those subjects with higher expression of fatty acid transporters. Therefore, in conclusion, a higher placental AA/EPA ratio is positively associated with offspring's visceral adiposity and obesity risk parameters, which become more apparent in subjects with higher expressions of placental FATPs. Our results support the potential role of n-6 and n-3 LC-PUFA in the fetal programming of obesity risk in childhood. For the present study, 113 healthy pregnant women were recruited during the first trimester of pregnancy and their offspring were followed up at 6 years of age. The fatty acid profiles and the expression of fatty acid transporters (FATP1 and FATP4) were analyzed from placental samples at birth. Associations between LC-PUFA (n-6, n-3, and n-6/n-3 ratios) and obesity risk parameters (weight, body mass index (BMI), percent fat mass, visceral fat, and homeostatic model assessment of insulin resistance (HOMA-IR)) in the offspring at 6 years of age were examined.

Effects of Late Gestation Supplements Differing in Fatty Acid Amount and Profile to Beef Cows on Cow Performance, Steer Progeny Growth Performance through Weaning, and Relative mRNA Expression of Genes Associated with Muscle and Adipose Tissue Development.

Strategic supplementation during late gestation has the potential to alter progeny performance. Mature fall-calving Simmental × Angus cows were used to evaluate the effects of late gestation supplementation of fatty acids to beef cows on cow performance, steer progeny growth performance during pre-weaning and backgrounding periods, and relative mRNA expression of genes associated with myogenesis and adipogenesis. Cows (n = 190; 4 pasture groups of cows/treatment) grazed endophyte-infected tall fescue and were supplemented during late gestation with calcium salts of either saturated fatty acid/monounsaturated fatty acid (SFA/MUFA), polyunsaturated fatty acid (PUFA), or an isocaloric and isonitrogenous control (CON). There were no differences (p ≥ 0.11) in cow body weight (BW) or body condition scores from pre-supplementation to weaning or steer BW at birth, weaning, or at the end of the backgrounding period. Concentrations of C18:2n-6 in plasma were greater (p = 0.01) in SFA/MUFA and PUFA cows compared to CON cows during supplementation. For mRNA expression in the longissimus muscle of steer progeny from birth to weaning: PAX7 decreased to a greater (p < 0.01) extent for SFA/MUFA and PUFA steers; AGPAT1 and CPT1 increased to a greater (p ≤ 0.02) extent for CON steers. The expression of MYH7 mRNA during the pre-weaning period was greater (p = 0.01) in PUFA. In conclusion, late gestation fatty acid supplementation modified plasma relative concentrations of fatty acids for dams and progeny and modified mRNA expression of genes related to myogenesis and adipogenesis but had limited effects on progeny growth performance during pre-weaning and backgrounding periods.

Prenatal Choline Supplement in a Maternal Obesity Model Modulates Offspring Hepatic Lipidomes.

Maternal obesity during pregnancy adversely impacts offspring health, predisposing them to chronic metabolic diseases characterized by insulin resistance, dysregulated macronutrient metabolism, and lipid overload, such as metabolic-associated fatty liver disease (MAFLD). Choline is a semi-essential nutrient involved in lipid and one-carbon metabolism that is compromised during MAFLD progression. Here, we investigated under high-fat (HF) obesogenic feeding how maternal choline supplementation (CS) influenced the hepatic lipidome of mouse offspring. Our results demonstrate that maternal HF+CS increased relative abundance of a subclass of phospholipids called plasmalogens in the offspring liver at both embryonic day 17.5 and after 6 weeks of postnatal HF feeding. Consistent with the role of plasmalogens as sacrificial antioxidants, HF+CS embryos were presumably protected with lower oxidative stress. After postnatal HF feeding, the maternal HF+CS male offspring also had higher relative abundance of both sphingomyelin d42:2 and its side chain, nervonic acid (FA 24:1). Nervonic acid is exclusively metabolized in the peroxisome and is tied to plasmalogen synthesis. Altogether, this study demonstrates that under the influence of obesogenic diet, maternal CS modulates the fetal and postnatal hepatic lipidome of male offspring, favoring plasmalogen synthesis, an antioxidative response that may protect the mouse liver from damages due to HF feeding.

Fetal Hepatic Lipidome Is More Greatly Affected by Maternal Rate of Gain Compared with Vitamin and Mineral Supplementation at day 83 of Gestation.

Herein, we evaluated the hepatic lipid metabolic profiles of bovine fetuses in response to maternal vitamin and mineral supplementation (VMSUP; supplemented (VTM) or not (NoVTM)) and two different rates of gain (GAIN; low gain (LG), 0.28 kg/d, or moderate gain (MG), 0.79 kg/d). Crossbred Angus heifers (n = 35; initial BW = 359.5 ± 7.1 kg) were randomly assigned to a 2 × 2 factorial arrangement, resulting in the following treatment combinations: NoVTM-LG (n = 9), NoVTM-MG (n = 9), VTM-LG (n = 9), and VTM-MG (n = 8). Heifers received their treatments until d 83 of gestation, when they were ovariohysterectomized. Fetuses were harvested and liver samples were analyzed via ultrahigh-performance liquid chromatography-tandem mass spectroscopy to characterize lipid profiles and abundances. We identified 374 biochemicals/metabolites belonging to 57 sub-pathways of the lipid metabolism super-pathway. The majority of the biochemicals/metabolites (n = 152) were significantly affected by the main effect of GAIN. Maternal moderate rates of gain resulted in greater abundances (p ≤ 0.0001) of ω-3 fatty acids (eicosapentaenoate, docosapentaenoate, and docosahexaenoate) and lower abundances (p ≤ 0.0001) of ω-6 fatty acids. Further, MG resulted in the accumulation of several diacylglycerols and depletion of the majority of the monoacylglycerols. Concentrations of nearly all acylcarnitines (p ≤ 0.03) were decreased in VTM-LG fetal livers compared to all other treatment combinations, indicating a greater rate of complete oxidation of fatty acids. Levels of secondary bile acids were impacted by VMSUP, being greater (p ≤ 0.0048) in NoVTM than in VTM fetal livers. Moreover, NoVTM combined with lower rate of gain resulted in greater concentrations of most secondary bile acid biochemicals/metabolites. These data indicate that maternal diet influenced and altered fetal hepatic lipid composition in the first trimester of gestation. Maternal body weight gain exerted a greater influence on fetal lipid profiles than vitamin and mineral supplementation. Specifically, lower rate of gain (0.28 kg/d) resulted in an increased abundance of the majority of the biochemicals/metabolites identified in this study.

Impacts of Different Prenatal Supplementation Strategies on the Plasma Metabolome of Bulls in the Rearing and Finishing Phase.

This study investigated the effects of maternal nutrition on the plasma metabolome of Nellore bulls in the rearing and finishing phases, and metabolic differences between these phases. For this study, three nutritional approaches were used in 126 cows during pregnancy: NP-(control) mineral supplementation; PP-protein-energy supplementation in the final third; and FP-protein-energy supplementation during the entire pregnancy. We collected blood samples from male offspring in the rearing (450 ± 28 days old) and finishing phases (660 ± 28 days old). The blood was processed, and from plasma samples, we performed the targeted metabolome analysis (AbsoluteIDQ® p180 Kit). Multiple linear regression, principal component analysis (PCA), repeated measures analysis over time, and an enrichment analysis were performed. PCA showed an overlap of treatments and time clusters in the analyses. We identified significant metabolites among the treatments (rearing phase = six metabolites; finishing phase = three metabolites) and over time (21 metabolites). No significant metabolic pathways were found in the finishing phase, however, we found significant pathways in the rearing phase (Arginine biosynthesis and Histidine metabolism). Thus, prenatal nutrition impacted on plasma metabolome of bulls during the rearing and finishing phase and the different production stages showed an effect on the metabolic levels of bulls.

Effect of the Supplementation Using an Herbal Mixture as a Choline Source during Early Gestation in Rambouillet Ewes.

Previous research indicates that adequate choline nutrition during late gestation improves fetal development. However, there is a lack of studies describing choline's role during early gestation. Thus, the current study hypothesizes that an herbal mixture as a source of choline (Biocholine) positively affects offspring development from ewes supplemented during early gestation. Therefore, the objectives were to evaluate the impact of biocholine on the programming of the offspring early in life through the evaluation of dams and newborn performance. Twenty-eight four-year-old Rambouillet ewes were assigned randomly to two treatments: non-supplementation and 4 gd-1 of biocholine during the early gestation. Compared with the dams without supplementation, the ewes supplemented using biocholine showed no increase in parameters such as birth and weaning weight (p > 0.05). Additionally, the milk yield and quality of colostrum and milk did not present statistical differences (p > 0.05). However, the placental membrane development was reduced in the ewes that received supplementation with biocholine; interestingly, those dams increased the weight of the newborns during the lambing period (p < 0.05). Finally, the current study proposes necessary elucidation of how placental size is programmed and if less placental development has potential benefits in the fetus's development.

Long-chain n-3 PUFA given before and throughout gestation and lactation in rats prevent high-fat diet-induced insulin resistance in male offspring in a tissue-specific manner.

This study investigated whether long-chain n-3 PUFA (LC n-3 PUFA) given to pregnant rats fed a high-fat (HF) diet may prevent fetal programming in male offspring at adulthood. Six weeks before mating, and throughout gestation and lactation, female nulliparous Sprague-Dawley rats were given a chow (C) diet, HF (60·6 % fat from maize, rapeseed oils and lard) or HF in which one-third of fat was replaced by fish oil (HF n-3). At weaning, the three offspring groups were randomly separated in two groups fed C diet, or HF without LC n-3 PUFA, for 7 weeks until adulthood. Glucose tolerance and insulin sensitivity were assessed by an oral glucose tolerance test both at weaning and at adulthood. Insulin signalling was determined in liver, muscle and adipose tissue by quantification of the phosphorylation of Akt on Ser 473 at adulthood. At weaning, as at adulthood, offspring from HF-fed dams were obese and displayed glucose intolerance (GI) and insulin resistance (IR), but not those from HFn-3 fed dams. Following the post-weaning C diet, phosphorylation of Akt was strongly reduced in all tissues of offspring from HF dams, but to a lesser extent in liver and muscle of offspring from HFn-3 dams. However, it was abolished in all tissues of all offspring groups fed the HF post-weaning diet. Thus, LC n-3 PUFA introduced in a HF in dams partially prevented the transmission of GI and IR in adult offspring even though they were fed without LC n-3 PUFA from weaning.

Adult mice offspring of obese mothers supplemented with melatonin show lessened liver steatosis, inflammation, oxidative stress, and endoplasmic reticulum stress.

AIMS: To investigate, in the liver of adult offspring, the possible effects of melatonin supplementation in the obese mother during pregnancy and lactation. MAIN METHODS: C57BL/6 females were fed with a control (C) or a high-fat (HF) diet and supplemented with melatonin (Mel) during the pregnancy and lactation, forming the groups: C, CMel, HF, and HFMel. After weaning until three months old, the offspring only received the C diet. KEY FINDINGS: The HF mothers and their offspring showed higher body weight (BW) than the C mothers and offspring. However, at 3-mo-old, BW was reduced in HFMel vs. HF offspring. Also, plasmatic and liver lipid markers increased in HF vs. C offspring but were reduced in HFMel vs. HF offspring. Liver lipid content was lessened in HFMel vs. HF offspring by 50 %. Also, lipid metabolism, pro-inflammatory and endoplasmic reticulum (ER) stress genes were higher expressed in HF vs. C offspring but reduced in HFMel vs. HF offspring. Contrarily, beta-oxidation and antioxidant enzyme genes were less expressed in HF vs. C offspring but improved in HFMel vs. HF offspring. Finally, AMPK/mTOR pathway genes, initially dysregulated in the HF, were restored in the HFMel offspring. SIGNIFICANCE: The obese mother leads to liver alterations in the offspring. Current findings demonstrated the maternal melatonin supplementation during pregnancy and lactation in adult offspring's liver. Consequently, the effects were seen in mitigating the liver's AMPK/mTOR pathway genes, lipogenesis, beta-oxidation, inflammation, oxidative stress, and ER stress, preventing liver disease progression in the offspring.

Nutritional, pharmacological, and environmental programming of NAFLD in early life.

Nonalcoholic fatty liver disease (NAFLD) is the main liver disease worldwide, and its prevalence in children and adolescents has been increasing in the past years. It has been demonstrated that parental exposure to different conditions, both preconceptionally and during pregnancy, can lead to fetal programming of several metabolic diseases, including NAFLD. In this article, we review some of the maternal and paternal conditions that may be involved in early-life programing of adult NAFLD. First, we describe the maternal nutritional factors that have been suggested to increase the risk of NAFLD in the offspring, such as an obesogenic diet, overweight/obesity, and altered lipogenesis. Second, we review the association of certain vitamin supplementation and the use of some drugs during pregnancy, for instance, glucocorticoids, with a higher risk of NAFLD. Furthermore, we discuss the evidence showing that maternal-fetal pathologies, including gestational diabetes mellitus (GDM), insulin resistance (IR), and intrauterine growth restriction (IUGR), as well as the exposure to environmental contaminants, and the impact of microbiome changes, are important factors in early-life programming of NAFLD. Finally, we review how paternal preconceptional conditions, such as exercise and diet (particularly obesogenic diets), may impact fetal growth and liver function. Altogether, the presented evidence supports the hypothesis that both in utero exposure and parental conditions may influence fetal outcomes, including the development of NAFLD in early life and adulthood. The study of these conditions is crucial to better understand the diverse mechanisms involved in NAFLD, as well as for defining new preventive strategies for this disease.

Maternal melatonin treatment rescues endocrine, inflammatory, and transcriptional deregulation in the adult rat female offspring from gestational chronodisruption.

Introduction: Gestational chronodisruption impact maternal circadian rhythms, inhibiting the nocturnal increase of melatonin, a critical hormone that contributes to maternal changes adaptation, entrains circadian rhythms, and prepares the fetus for birth and successful health in adulthood. In rats, we know that gestational chronodisruption by maternal chronic photoperiod shifting (CPS) impaired maternal melatonin levels and resulted in long-term metabolic and cardiovascular effects in adult male offspring. Here, we investigated the consequences of CPS on mother and adult female offspring and explored the effects of melatonin maternal supplementation. Also, we tested whether maternal melatonin administration during gestational chronodisruption rescues maternal circadian rhythms, pregnancy outcomes, and transcriptional functions in adult female offspring. Methods: Female rats raised and maintained in photoperiod 12:12 light: dark were mated and separated into three groups: (a) Control photoperiod 12:12 (LD); (b) CPS photoperiod; and (c) CPS+Mel mothers supplemented with melatonin in the drinking water throughout gestation. In the mother, we evaluated maternal circadian rhythms by telemetry and pregnancy outcomes, in the long-term, we study adult female offspring by evaluating endocrine and inflammatory markers and the mRNA expression of functional genes involved in adrenal, cardiac, and renal function. Results: In the mothers, CPS disrupted circadian rhythms of locomotor activity, body temperature, and heart rate and increased gestational length by almost 12-h and birth weight by 12%, all of which were rescued by maternal melatonin administration. In the female offspring, we found blunted day/night differences in circulating levels of melatonin and corticosterone, abnormal patterns of pro-inflammatory cytokines Interleukin-1a (IL1a), Interleukin-6 (IL6), and Interleukin-10 (IL10); and differential expression in 18 out of 24 adrenal, cardiac, and renal mRNAs evaluated. Conclusion: Maternal melatonin contributed to maintaining the maternal circadian rhythms in mothers exposed to CPS, and the re-establishing the expression of 60% of the altered mRNAs to control levels in the female offspring. Although we did not analyze the effects on kidney, adrenal, and heart physiology, our results reinforce the idea that altered maternal circadian rhythms, resulting from exposure to light at night, should be a mechanism involved in the programming of Non-Communicable Diseases.

Low Nephron Number Induced by Maternal Protein Restriction Is Prevented by Nicotinamide Riboside Supplementation Depending on Sirtuin 3 Activation.

A reduced nephron number at birth, due to critical gestational conditions, including maternal malnutrition, is associated with the risk of developing hypertension and chronic kidney disease in adulthood. No interventions are currently available to augment nephron number. We have recently shown that sirtuin 3 (SIRT3) has an important role in dictating proper nephron endowment. The present study explored whether SIRT3 stimulation, by means of supplementation with nicotinamide riboside (NR), a precursor of the SIRT3 co-substrate nicotinamide adenine dinucleotide (NAD+), was able to improve nephron number in a murine model of a low protein (LP) diet. Our findings show that reduced nephron number in newborn mice (day 1) born to mothers fed a LP diet was associated with impaired renal SIRT3 expression, which was restored through supplementation with NR. Glomerular podocyte density, as well as the rarefaction of renal capillaries, also improved through NR administration. In mechanistic terms, the restoration of SIRT3 expression through NR was mediated by the induction of proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α). Moreover, NR restored SIRT3 activity, as shown by the reduction of the acetylation of optic atrophy 1 (OPA1) and superoxide dismutase 2 (SOD2), which resulted in improved mitochondrial morphology and protection against oxidative damage in mice born to mothers fed the LP diet. Our results provide evidence that it is feasible to prevent nephron mass shortage at birth through SIRT3 boosting during nephrogenesis, thus providing a therapeutic option to possibly limit the long-term sequelae of reduced nephron number in adulthood.

Effects of maternal dietary fatty acids during mid-gestation on growth, glucose metabolism, carcass characteristics, and meat quality of lamb progeny that were fed differing levels of dry matter of intake.

This experiment evaluated growth, glucose metabolism, carcass characteristics, and meat quality of market lambs that were offered ad libitum or restricted (85% of ad libitum) feed intake following two different maternal fatty acid (FA) supplementations while in-utero. Ewes received either a diet supplemented with polyunsaturated FA or saturated/monounsaturated FA during mid- to late-gestation. Following weaning, progeny wethers were fed either ad libitum or a restricted level of feed intake. Ewe FA supplementation did not affect (P ≥ 0.11) growth, meat quality, nor plasma glucose or insulin concentrations of the progeny. Carcass body fat and yield grade of the progeny were affected (P = 0.01) by maternal FA supplementation and restricted feed intake. In summary, maternal FA supplementation did not affect progeny growth, while feed restriction during finishing did not affect meat quality. The interaction between maternal FA supplementation and finishing strategy for body fat accretion indicates that metabolism and the supply of FA during gestation may warrant further investigation.