Fetal Programming Effects Research Articles

Metabolomic Profile of Young Adults Born Preterm.

Prematurity is a risk factor for the development of chronic adult diseases. Metabolomics can correlate the biochemical changes to a determined phenotype, obtaining real information about the state of health of a subject at that precise moment. Significative differences in the metabolomic profile of preterm newborns compared to those born at term have been already identified at birth. An observational case–control study was performed at the University Hospital of Siena. The aim was to evaluate and compare the metabolomic profiles of young adults born preterm to those born at term. Urinary samples were collected from 67 young adults (18–23 years old) born preterm (mean gestational age of 30 weeks, n = 49), and at term of pregnancy (mean gestational age of 38 weeks, n = 18). The urinary spectra of young adults born preterm was different from those born at term and resembled what was previously described at birth. The Random Forest algorithm gave the best classification (accuracy 82%) and indicated the following metabolites as responsible for the classification: citrate, CH2 creatinine, fumarate and hippurate. Urine spectra are promising tools for the early identification of neonates at risk of disease in adulthood and may provide insight into the pathogenesis and effects of fetal programming and infants’ outcomes.

106 The Effects of Fetal Programming on Offspring Pancreas DNA Methylation

Abstract It has been well documented that fetal programming, caused by changes to the maternal environment during pregnancy, can impact the overall health and growth of the offspring in livestock and non-livestock species alike. These effects are observed in the F1 offspring as well as across subsequent generations; however, the mechanisms by which this occurs are still poorly understood. Epigenetics is one of the many mechanisms that is hypothesized to have a role in fetal programming and may be mediating the observed effects across multiple generations. It has been demonstrated by others that DNA methylation patterns can be altered by an individuals’ diet and that the pancreas is vulnerable to the effects of fetal programming. Therefore, we evaluated the effects of poor maternal nutrition during gestation on the pancreas tissue of lambs. We have demonstrated that maternal under- or overnutrition during gestation alters the DNA methylation patterns of the offspring pancreas tissue with these effects being diet dependent and sex specific. We have also begun evaluating the effects of maternal diet in murine models using whole-genome bisulfite sequencing to compare species differences and determine if there are any changes conserved across species. This will allow us to focus on a smaller number of critical factors in individuals as they age and across multiple generations in livestock species such as sheep and cattle. From these data we will be able to elucidate the role DNA methylation has in mediating the effects of maternal programming in the pancreas tissue.

Fetal programming by androgen excess impairs liver lipid content and PPARg expression in adult rats.

It is known that prenatal hyperandrogenization induces alterations since early stages of life, contributing to the development of polycystic ovary syndrome affecting the reproductive axis and the metabolic status, thus promoting others associated disorders, such as dyslipidemia, insulin resistance, liver dysfunction, and even steatosis. In this study, we aimed to evaluate the effect of fetal programming by androgen excess on the hepatic lipid content and metabolic mediators at adult life. Pregnant rats were hyperandrogenized with daily subcutaneous injections of 1mg of free testosterone from days 16 to 19 of pregnancy. The prenatally hyperandrogenized (PH) female offspring displayed two phenotypes: irregular ovulatory phenotype (PHiov) and anovulatory phenotype (PHanov), with different metabolic and endocrine features. We evaluated the liver lipid content and the main aspect of the balance between fatty acid (FA) synthesis and oxidation. We investigated the status of the peroxisomal proliferator-activated receptors (PPARs) alpha and gamma, which act as lipid mediators, and the adipokine chemerin, one marker of liver alterations. We found that prenatal hyperandrogenization altered the liver lipid profile with increased FAs levels in the PHanov phenotype and decreased cholesterol content in the PHiov phenotype. FA metabolism was also disturbed, including decreased mRNA and protein PPARgamma levels and impaired gene expression of the main enzymes involved in lipid metabolism. Moreover, we found low chemerin protein levels in both PH phenotypes. In conclusion, these data suggest that prenatal hyperandrogenization exerts a negative effect on the liver and alters lipid content and metabolic mediators' expression at adult age.

Fetal programming effects of early weaning on subsequent parity calf performance.

Mature Simmental × Angus cows [n = 147; body weight (BW) = 590 ± 72 kg] were used to evaluate the effects of early weaning on subsequent parity calf growth performance and carcass characteristics. Cows were assigned to one of two treatments based on their previous calf’s weaning age: early wean (EW) or conventional wean (CW). Dams assigned to the EW treatment had calves previously weaned at 88 ± 6 d of age, whereas dams assigned to the CW treatment had calves previously weaned at 185 ± 6 d of age. Cow BW and body condition scores (BCS) were monitored during the experiment. All cows were managed as a common group from the onset of the experiment at breeding until final pregnancy check of their next production cycle 462 d later. All calves in the experiment were managed as one group and weaned at a single time point, then feedlot performance and carcass characteristics were evaluated. Initial cow BW was different (P < 0.05), so it was included as a covariate for cow BW analysis. There was a treatment × date interaction (P < 0.01) for cow BW and cow BCS. Cow BW was consistently greater for the EW treatment from day 39 to the end of the experiment (P < 0.01). Cow BCS were not different at the onset of the experiment (P = 0.20), although after breeding and throughout lactation, BCS diverged between treatments and the EW treatment consistently had greater (P < 0.01) BCS than the CW treatment throughout the entire subsequent lactation. Gestation length was not different (P = 0.21) between treatments, yet calf birth BW was greater (P = 0.05) for the EW treatment. Neither artificially inseminated pregnancy percentage nor overall pregnancy percentage was different between treatments (P ≥ 0.61). Despite the greater birth BW for the EW treatment and no difference (P = 0.25) in milk production, weaning BW was not different (P = 0.50) between treatments. Feedlot performance measures were not different (P ≥ 0.13) between treatments, including feedlot arrival weight, final BW, average daily gain, dry matter intake, and gain to feed. Final carcass characteristics were not different (P ≥ 0.33) between treatments, including dressing percentage, hot carcass weight, LM area, 12th rib fat thickness, kidney, pelvic, heart fat percentage, USDA yield grade, and marbling score. Thus, early weaning resulted in improved BW and BCS of cows as well as increased birth BW of subsequent calf, although that did not transpire into differences in postnatal growth performance or carcass traits.

Singleton or twin male lambs: Effects on their reproductive development

Because intrauterine environment differs between twins and singletons, twin-born lambs are often studied when effects of fetal programming are evaluated. In sheep, fetal programming might have effects on reproductive physiology and behavior after sexual maturation. The aim of this study was to compare sperm output and sexual behavior in developing singleton- or twin-born lambs of similar body weight. Singleton lambs (n = 12) and twin (n = 9) male-male lambs were used. From 5.4 until 9.1 months of age, body weight, scrotal circumference (every 3–4 weeks), sexual behavior (every 14 days) and semen characteristics (every 28 days) were evaluated. In the third ejaculate, singleton lambs ejaculated a larger volume of semen than twins (P = 0.03). Considering a pool of the three ejaculates, twin lambs ejaculated semen with a greater sperm concentration than singleton lambs (P = 0.015). There was an interaction between group and time to the onset of courtship behavior (P = 0.02) and a tendency for an interaction in the number of mount attempts (P = 0.052). Singleton-born lambs, during the first evaluation period began courtship behavior earlier than twin-born lambs (P < 0.0001). In conclusion, there were only slight differences in semen and sexual behavior between male ram lambs born as singletons or twins with similar weight. Male ram lambs born as singletons initiated the courtship behavior earlier than twins during the first sexual behavioral evaluation period, ejaculated a larger volume of semen in the third consecutive ejaculate, and there was a lesser sperm concentration in the three ejaculates.

Gestational nutrient restriction under extensive grazing conditions: Effects on muscle characteristics and meat quality in heavy lambs

We evaluated maternal undernutrition effects induced by a lower natural pasture allowance (gestation days 30–143) on histological-biochemical and meat traits in muscles Semitendinosus, cranial Gluteobiceps and Supraspinatus from 200-day old male and female lambs. Maternal undernutrition increased oxidative and reduced glycolytic fibers in all muscles (P ≤ 0.01). Maternal undernutrition reduced the diameter of glycolytic fibers in the cranial Gluteobiceps of exclusively female lambs (P = 0.05) and reduced the diameter of oxidative fibers in the Supraspinatus of exclusively male lambs (P = 0.02). Maternal undernutrition increased lipid content in the Supraspinatus of females (P = 0.001), reduced lactate content (P = 0.03) and WB shear force (P = 0.02) in the Semitendinosus of females, and increased cooking losses in the Semitendinosus of males (P = 0.0069). In conclusion, gestational nutrient restriction induced fetal programming effects on muscle characteristics of lambs. Moreover, our study demonstrates that maternal undernutrition influences muscle and meat characteristics in a sex and muscle-dependent way.

Fetal Programming Effects of a Mild Food Restriction During Pregnancy in Mice: How Does It Compare to Intragestational Ghrelin Administration?

To explore in mice if a 15% food restriction protocol during pregnancy programs the offspring postnatal development, with emphasis on reproductive function, and to assess if ghrelin (Ghrl) administration to mouse dams exerts effects that mimic those obtained under mild caloric restriction. Mice were 15% food-restricted, injected with 4 nmol/animal/day of Ghrl, or injected with the vehicle (control) thorough pregnancy. After birth, the pups did not receive further treatment. Pups born from food-restricted dams (FR pups) were lighter than Ghrl pups at birth, but reached normal weight at adulthood. Ghrl pups were heavier at birth and gained more weight than control pups (C pups). This effect was not associated with plasma IGF-1. FR pups showed a delay in pinna detachment and eye opening, while an advance was observed in Ghrl pups. FR pups showed also impairment in the surface-righting reflex. In both female FR and Ghrl pups, there was an advance in vaginal opening and, in adulthood, FR pups showed a significant decrease in their own litter size and plasma progesterone, and an increase in embryo loss. A delay in testicular descent was evident in male Ghrl pups. Changes in puberty onset were not associated with differences in the expression of Kiss1 in hypothalamic nuclei. Finally, in adulthood, FR pups showed a significant decrease in sperm quality. In conclusion, a mild food restriction thorough gestation exerted programming effects on the offspring, affecting also their reproductive function in adulthood. These effects were not similar to those of intragestational Ghrl administration.

Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta.

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Evaluation of reproductive traits and the effect of nutrigenetics on bulls submitted to fetal programming

Nutritional stimuli during the gestational period in dams have long-term effects on the offspring in terms of health and production rates. This study assessed the effect of fetal programming in 126 pregnant Nellore cows on reproductive and nutrigenetic traits of the progeny during the rearing phase. For that purpose, three nutritional treatments were used in these cows during pregnancy: PP – protein-energy supplementation in the final third, FP – protein-energy supplementation during the entire pregnancy, and NP – (control) only mineral supplementation. The male progeny (64 bulls) was evaluated for scrotal circumference and seminal traits at 12, 15, and 18 months of age. In addition, we performed a genomic association (35 K SNPs) for scrotal circumference at 12 and 18 months of age. Only the total sperm defects showed significant difference between groups (P < 0.05), regardless of age, while major and minor sperm defects and vigor showed tendencies (P < 0.10). In the time analysis, only the minor sperm defects did not differ between ages, regardless of treatment (P = 0.92). We found genes that are associated with genetic variance at different ages and treatments (BTBD9, WNT2, ASZ1, WWOX and SLC26A8). Thus, prenatal protein-energy supplementation showed effects on the total of abnormal sperm cells between treatments, genotype-environment interaction, and some SNPs that explain more than 1% of the genetic variance on bulls during the rearing phase. These are evidences that different strategies of prenatal supplementation may have acted on epigenetic factors and may have caused changes in gene expression of animals. This contributes to the knowledge about mechanisms that involve fetal programming in beef cattle.

Pregestasyonel Diyabet ve Fetal Programlama

Pregestasyonel diyabetli gebelerde maternal, fetal ve neonatal komplikasyonların ortaya çıkma riski artmaktadır. İntrauterin çevre; gen ekspresyonundaki değişiklikler, oksidatif stres ve epigenetik modifikasyon gibi yolaklar üzerinden fetal programlanmaya katkıda bulunur. Özellikle fetüsün maternal dönemde hiperglisemi ile karşılaşmış olması intrauterin çevresi için endişe verici bir konudur. Bu nedenle hiperglisemi riski olan bireylerde, gebelik öncesi dönemde glisemik kontrol sağlanana kadar aile planlaması yapılmalıdır. Gestasyonel dönemde ise fetal riskleri ve gebelik komplikasyonlarını en aza indirgeyebilmek için ortalama kan glukoz düzeyi 100 mg/dL (5.6 mmol/L) ve HbA1c değeri &lt;%6 seviyelerinde tutulmalıdır. Fetal programlamanın etkisi anne karnındaki olumsuz çevresel koşullara maruziyet süresi ile yakından ilişkilidir. Diyabetik ortam, anne ve fetüs arasında kanal görevi gören plasentada değişikliklere neden olarak erken dönemde gebelik kaybı, büyümenin kısıtlanması, preeklampsi riskinin artışı ve plasentomegaliye yol açabilir. Bu derlemenin amacı, pregestasyonel diyabetli gebelerde fetal programlamanın sonuçları hakkında genel bir bakış açısı sağlamaktır.

The Role of Early Programming and Early Nutrition on the Development and Progression of Celiac Disease: A Review.

Experimental and epidemiological evidence has shown that modifications of the intrauterine environment can have deleterious consequences for individuals, expressed as an increased risk of suffering non-communicable pathologies in adult life, which is known as the hypothesis of the early origin of diseases or fetal programming. On the other hand, changes in gene expression patterns through epigenetic modifications can be the basis for long-term maintenance of the effects of fetal programming. In this sense, epigenetics comprises the study of intrauterine disturbances, which develop diseases in the adult, including celiac disease (CD). In addition, early feeding practices could influence the risk of CD development, such as breastfeeding timing and duration and age of gluten introduction in the diet. Gluten acts as a trigger for CD in genetically predisposed subjects, although approximately 30% of the world population has HLA DQ2 or DQ8, the prevalence of the disease is only 1–3%. It is not known what factors act to modify the risk of disease in genetically at-risk subjects. Taking into account all these considerations, the aim of the current review is to elucidate the role of early programming and the effect of early nutrition on the development and progression of CD. It is logical that attention has been paid to gluten as a key element in preventing the disease. However, there is no strong evidence in favor of the protective factor of breastfeeding, timing of introduction of gluten during lactation, and the development of CD. Diet, genetic risk, microbiota, and environmental interaction are possible triggers of the change in tolerance to an immune response to gluten, but large-scale cohort studies are needed. Emerging scientific concepts, such as epigenetics, may help us establish the role of these factors.

Maternal Brown Fat Thermogenesis Programs Glucose Tolerance in the Male Offspring

Environmental temperature is a driving factor in evolution, and it is commonly assumed that metabolic adaptations to cold climates are the result of transgenerational selection. Here, we show in mice that even minor changes in maternal thermogenesis alter the metabolic phenotype already in the next generation. Male offspring of mothers genetically lacking brown adipose tissue (BAT) thermogenesis display increased lean mass and improved glucose tolerance as adults, while females are unaffected. The phenotype is replicated in offspring of mothers kept at thermoneutrality; conversely, mothers with higher gestational BAT thermogenesis produce male offspring with reduced lean mass and impaired glucose tolerance. Running-wheel exercise reverses the offspring's metabolic impairments, pointing to the muscle as target of these fetal programming effects. Our data demonstrate that gestational BAT activation negatively affects metabolic health of the male offspring; however, these unfavorable fetal programming effects may be negated by active lifestyle.

Programmed Adult Kidney Disease: Importance of Fetal Environment.

The Barker hypothesis strongly supported the influence of fetal environment on the development of chronic diseases in later life. Multiple experimental and human studies have identified that the deleterious effect of fetal programming commonly leads to alterations in renal development. The interplay between environmental insults and fetal genome can induce epigenetic changes and lead to alterations in the expression of renal phenotype. In this review, we have explored the renal development and its functions, while focusing on the epigenetic findings and functional aspects of the renin-angiotensin system and its components.

Fetal programming effects of pentaerythritol tetranitrate in a rat model of superimposed preeclampsia

Preeclampsia is a common medical condition during pregnancy and a major cause of maternal and prenatal mortality. The present study was conducted to investigate the effects of maternal treatment with pentaerythritol tetranitrate (PETN) in Dahl salt-sensitive rats (DSSR), a model of superimposed preeclampsia. F0 parental DSSR were treated with PETN (50 mg/kg) from the time point of mating to the end of lactation. Maternal PETN treatment improved fetal growth and had no effect on blood pressure in DSSR offspring fed with normal chow or high-salt diet. Upon high-fat diet (HFD) feeding, offspring from PETN-treated mother showed improved glucose tolerance despite similar weight gain. Unexpectedly, maternal PETN treatment significantly potentiated the HFD-induced blood pressure elevation in male DSSR offspring. Endothelium-derived hyperpolarization factor (EDHF)-mediated vasodilation was similar between NCD-fed and HFD-fed control offspring but was markedly reduced in HFD-fed PETN offspring. EDHF genes were downregulated in the vasculature of HFD-fed PETN offspring, which was associated with epigenetic changes in histone modifications. In conclusion, maternal PETN treatment in DSSR shows both beneficial and unfavorable effects. It improves fetal growth and ameliorates glucose tolerance in the offspring. Although maternal PETN treatment has no effect on blood pressure in offspring fed with normal chow or high-salt diet, the offspring is at higher risk to develop HFD-induced hypertension. PETN may potentiate the blood pressure response to HFD by epigenetic modifications of EDHF genes.Key messagesThe core findings of this article suggest that maternal PETN treatment of DSSR, a rat model of a spontaneous superimposed preeclampsia, leads to• Improvement of fetal growth;• No changes of maternal blood pressure or markers of preeclampsia;• Amelioration of HFD-induced glucose intolerance in adult offspring;• No changes in blood pressure development of the offspring on normal chow or high salt-diet;• Potentiation of blood pressure elevation of the offspring on HFD.

Effects of frequency of supplementation of low-quality gestation diets on beef cow performance from mid-gestation through lactation and preweaning calf performance

ABSTRACT Objective This study’s objective was to determine whether supplementation and frequency of supplementation for low-quality roughage diets were sufficient for cows to maintain condition during gestation, wean a healthy calf, and become pregnant for bearing a calf on a yearly basis. Materials and Methods Pregnant crossbred beef cows (2016; n = 102, BW = 661 ± 89; 2017, n = 76, BW = 727 ± 100 kg) were allocated in mid-gestation to 1 of 5 nutritional regimens in a completely randomized design. Nutritional regimens (DM basis) included (1) 70% haylage, 30% millet straw fed ad libitum (HAYL); (2) haylage fed at 1.0% DM basis of cow BW with ad libitum millet straw (MSHAYL); and (3) MSHAYL fed an energy-protein supplement (0.22% of BW) at 1 d/wk, (4) 2 d/wk, or (5) 3 d/wk. Growth performance and body condition were evaluated from the second trimester until weaning. Results and Discussion The HAYL cows had greater (P 0.05). Most cow growth performance traits were not affected (P > 0.05) by supplementation or supplementation frequency. Implications and Applications Supplement use at this rate cannot be recommended because there were no improvements in cow performance that would justify its purchase. Although feeding the MSHAYL ration alone could be viable, there are concerns for fetal programming effects that would affect progeny performance.

Why and How Imprinted Genes Drive Fetal Programming.

Imprinted genes mediate fetal and childhood growth and development, and early growth patterns drive fetal programming effects. However, predictions and evidence from the kinship theory of imprinting have yet to be directly integrated with data on fetal programming and risks of metabolic disease. I first define paternal-gene and maternal-gene optima with regard to early human growth and development. Next, I review salient evidence with regard to imprinted gene effects on birth weight, body composition, trajectories of feeding and growth, and timing of developmental stages, to evaluate why and how imprinted gene expression influences risks of metabolic disease in later life. I find that metabolic disease risks derive primarily from maternal gene biases that lead to reduced placental efficacy, low birth weight, low relative muscle mass, high relative white fat, increased abdominal adiposity, reduced pancreatic β-cell mass that promotes insulin resistance, reduced appetite and infant sucking efficacy, catch-up fat deposition from family foods after weaning, and early puberty. Paternal gene biases, by contrast, may contribute to metabolic disease via lower rates of brown fat thermiogenesis, and through favoring more rapid postnatal catch-up growth after intrauterine growth restriction from environmental causes. These disease risks can be alleviated through dietary and pharmacological alterations that selectively target imprinted gene expression and relevant metabolic pathways. The kinship theory of imprinting, and mother-offspring conflict more generally, provide a clear predictive framework for guiding future research on fetal programming and metabolic disease.

Cattle adapted to tropical and subtropical environments: social, nutritional, and carcass quality considerations.

Beef production needs to increase from 60 million to 130 million tons by 2050 to feed a growing world population, and 70% of this production increase is expected from beef industries located in subtropical and tropical regions of the world. Bos indicus-influenced cattle predominate in these regions but are often managed using practices developed for Bos taurus breeds reared in temperate climates. Hence, a fundamental step to meet the increasing global demand for beef is to develop specific management for B. indicus-influenced cattle in tropical or subtropical environments. Bos taurus and B. indicus are different subspecies, and diverge in social and biological functions due to selection pressure caused by complex evolutionary and domestication processes. Bos indicus cattle display different social responses compared with B. taurus counterparts, which must be taken into account by management planning as these traits directly impact cattle performance and welfare. In tropical and subtropical regions, warm-season perennial C4 grasses are the dominant forages, and their availability has a significant influence on the productivity of beef cattle systems. The resilience of C4 grasses under adverse conditions is one of their most important characteristics, even though these forages have reduced nutritive value compared with forages from temperate climates. Accordingly, nutritional planning in tropical and subtropical conditions must include management to optimize the quantity and quality of C4 forages. Nutritional requirements of cattle raised within these conditions also require special attention, including inherent metabolic compromises to cope with environmental constraints and altered energy requirements due to body composition and heat tolerance. Nutritional interventions to enhance beef production need to be specifically tailored and validated in B. indicus-influenced cattle. As an example, supplementation programs during gestation or early life to elicit fetal programming or metabolic imprinting effects, respectively, yield discrepant outcomes between subspecies. Bos indicus-influenced cattle produce carcasses with less marbling than B. taurus cattle, despite recent genetic and management advances. This outcome is mostly related to reduced intramuscular adipocyte volume in B. indicus breeds, suggesting a lesser need for energy stored intramuscularly as a mechanism to improve thermotolerance in tropical and subtropical climates.

PSXIII-33 Polyunsaturated fatty acid and their fetal programming effect on the FFARs from ewe lambs’ ovaries

Abstract Free fatty acids (FA) receptors (FFAR) are critical for metabolic functions and energy homeostasis. The FFAR1 and FFAR4 are activated by long-chain polyunsaturated FA, but FFAR2 and FFAR3 join to short-chain FA. There is no evidence fetal programming on nutritional effects on those receptors, insulin receptor (INS-R) and stereological enzyme in lambs’ ovaries. The objective of this study was to evaluate the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation to ewes during late gestation on finishing lamb ovary gene expression. Lambs born from ewes supplemented with Ca salts of EPA and DHA (PUFA), or palm FA distillate (PFAD) high in palmitic and oleic acid at 0.39% DM during the last 50d of gestation were used. After weaning and high concentrate diet adaptation (45d), 14 Hampshire x Dorset cross females lambs were blocked by initial BW and used in a 2x2 factorial arrangement of treatments using the factors of dam supplementation and lamb diets (PUFA or PFAD at 1.5% DM). At day 42, lambs were euthanized and ovary samples were obtained for FFARs, INS-R and steroid acute regulatory protein (STAR) mRNA concentration analysis. There was a dam diet effect on the abundance of FFAR4 mRNA (P = 0.05); lambs born from PUFA dams showed greater concentration than PFAD. Also, PUFA lambs tend to have greater concentration of FFAR4 (P = 0.07). The abundance of FFAR2, INS-R, and STAR mRNA was not significant for dam or lamb diet effect (P &amp;gt; 0.1). The mRNA of FFAR1 and FFAR3 were no found in the samples. However, mRNA concentration of FFAR2 and STAR were positively associated (r = 0.74 P &amp;lt; 0.05). In conclusion, dam and lamb diets modified FFAR4 mRNA concentration; and there might be a functional association between FFAR2 and STAR.

PSIV-B-26 Late-Breaking: Polyunsaturated fatty acids and methionine supplementation during late gestation alters fetal liver development in sheep

Abstract Supplementation with polyunsaturated fatty acids or methionine have a fetal programming effect in mammals. However, the effect of both nutrients on fetal development and DNA methylation have not been explored. The objective of this study was to evaluate the effects of supplementing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), methionine, or both to ewes during late gestation on fetus development and liver global DNA methylation. Twenty ewes (n = 5) were supplemented from day 100 to 145 of gestation. The treatments were: 1) control diet (CONT) without EPA and DHA supplementation (PUFA) or methionine supplementation (MET); 2) control plus PUFA (1 % Ca salts of fatty acids intake, Strata G113®); 3) control plus MET (0.1 % rumen protected methionine intake, Smartamine®); and 4) control plus PUFA and MET (PUFA+MET). On day 145, ewes were euthanized and fetuses were removed. Ewe, fetus, placenta, and fetal liver were weighed. Plasma samples were collected from ewes and fetuses to measure concentration of glucose and NEFA. Liver global DNA methylation was analyzed. Data was analyzed as a complete randomized experiment with a 2x2 factorial arrangement of treatments. Ewe supplementation did not affect (P &amp;gt; 0.1) fetus and placental weight. There was an interaction of treatment effect (P = 0.02) on fetal liver weight and ewe BW; CONT and PUFA+MET were grater that PUFA and MET. There were no differences (P &amp;gt; 0.10) on ewe and fetus NEFA as well as fetus glucose, but MET increased (P = 0.03) ewe plasma glucose concentration. Both treatments affected liver global DNA methylation of fetus (main effects P &amp;lt; 0.01; interaction P = 0.32); all the treatments increased global DNA methylation compared, with CONT, and PUFA+MET has greater than PUFA and MET. In conclusion PUFA and methionine supplementation in late gestation modified fetus liver development and DNA methylation.

PSXIV-4 Fetal programming effect of rumen-protected methionine on Angus-Simental heifer offspring’s performance and adipogenesis, oxidative stress and DNA methylation gene expression regulation

Abstract An extensive body of literature reported positive effects of Rumen-Protected Methionine (RPM) on dairy cattle; however, its effects are unknown on beef cattle. The objective of this study was to assess the effect of RPM supplementation on Angus-Simmental heifer’s offspring during late gestation, lactation, and after weaning (~65d). Ninety days prior to calving, 22 Angus-Simmental heifers were stratified by body weight (454 ± 85 kg; BW) and randomly assigned to dietary treatments: 1) Control diet (CTRL), and 2) Control diet + RPM (RPM). Dams had access to Bermuda hay ad libitum, and a soy hull:corn gluten based supplement. After weaning, calves were allocated by dietary treatments based on their dam’s treatment. Calves received Bermuda hay ad libitum and early-wean feed supplement after weaning. Offspring’s BW and Longissimus dorsi (LM) muscle samples were obtained on days 0, 25, 50, 100 after weaning. Messenger RNA was extracted from LM for RT-qPCR analysis. There was a tendency for RPM calves to be heavier at birth compared to control calves (P = 0.07). Although, no differences in BW were detected at weaning and after weaning (P = 0.20). Calves average daily gain between birth and weaning was greater for RPM calves as compared to CON (P = 0.02) suggesting a greater milk production, with no differences after weaning (P = 0.53). RT-qPCR results showed a treatment × time interaction for PPARG, LPL, CEBPG, DNMT1, SOD2 and NOS3 (P &amp;lt; 0.05). Furthermore, PPARG had a treatment and a time effect, which was upregulated in RPM calves (P &amp;lt; 0.01) from 50 to 100 days after weaning. In conclusion, dam’s RPM supplementation during late gestation increased offspring’s BW when inside the womb and probably their milk production. Offspring’s RPM supplementation after weaning potentially stimulates an early differentiation of adipocytes in LM samples, detected by PPARG upregulation.