Dietary Selenium Across Species.

This review traces the discoveries that led to the recognition of selenium (Se) as an essential nutrient and discusses Se-responsive diseases in animals and humans in the context of current understanding of the molecular mechanisms of their pathogeneses. The article includes a comprehensive analysis of dietary sources, nutritional utilization, metabolic functions, and dietary requirements of Se across various species. We also compare the function and regulation of selenogenomes and selenoproteomes among rodents, food animals, and humans. The review addresses the metabolic impacts of high dietary Se intakes in different species and recent revelations of Se metabolites, means of increasing Se status, and the recycling of Se in food systems and ecosystems. Finally, research needs are identified for supporting basic science and practical applications of dietary Se in food, nutrition, and health across species.

Untangling the placentome gene network of beef heifers in early gestation.

The cotyledon and caruncle tissues provide a functional bridge between the fetus and the dam. However, the relationship between these tissues and the transcriptomic profile that underlies the tissue functions remains elusive. Herein we investigate the expression profile of cotyledon and caruncle from nulliparous beef heifers carrying female fetuses at day 83 of pregnancy to identify changes occurring across tissues that contribute to placental function and their tissue-specific roles. We identified 2654 differentially expressed genes [padj ≤ 0.05, abs(log2FC) ≥ 1], including nutrient transporters and paternally imprinted genes. We found key regulators of tissue function and differentiation, including FOXO4, GATA2, GATA3, and HAND1, rewired between the tissues. Finally, we shed light on the over-represented pathways related to immune tolerance, tissue differentiation and remodeling. Our findings highlighted the intricate and coordinated cross-talk between fetal-maternal tissues. They provided evidence of a fine-tuned gene regulatory network underlying pregnancy and tissue-specific function in the bovine placenta.

Maternal nutrition and developmental programming of offspring.

Developmental programming is the concept that 'stressors' during development (i.e. pregnancy, the perinatal period and infancy) can cause long-term changes in gene expression, leading to altered organ structure and function. Such long-term changes are associated with an increased risk of a host of chronic pathologies, or non-communicable diseases including abnormal growth and body composition, behavioural or cognitive dysfunction, metabolic abnormalities, and cardiovascular, gastro-intestinal, immune, musculoskeletal and reproductive dysfunction. Maternal nutrition during the periconceptual period, pregnancy and postnatally can have profound influences on the developmental program. Animal models, including domestic livestock species, have been important for defining the mechanisms and consequences of developmental programming. One of the important observations is that maternal nutritional status and other maternal stressors (e.g. environmental temperature, high altitude, maternal age and breed, multiple fetuses, etc.) early in pregnancy and even periconceptually can affect not only embryonic/fetal development but also placental development. Indeed, altered placental function may underlie the effects of many maternal stressors on fetal growth and development. We suggest that future directions should focus on the consequences of developmental programming during the offspring's life course and for subsequent generations. Other important future directions include evaluating interventions, such as strategic dietary supplementation, and also determining how we can take advantage of the positive, adaptive aspects of developmental programming.

Nutritional Regulation of Embryonic Survival, Growth, and Development.

Maternal nutritional status affects conceptus development and, therefore, embryonic survival, growth, and development. These effects are apparent very early in pregnancy, which is when most embryonic losses occur. Maternal nutritional status has been shown to affect conceptus growth and gene expression throughout the periconceptual period of pregnancy (the period immediately before and after conception). Thus, the periconceptual period may be an important "window" during which the structure and function of the fetus and the placenta are "programmed" by stressors such as maternal malnutrition, which can have long-term consequences for the health and well-being of the offspring, a concept often referred to as Developmental Origins of Health and Disease (DOHaD) or simply developmental programming. In this review, we focus on recent studies, using primarily animal models, to examine the effects of various maternal "stressors," but especially maternal malnutrition and Assisted Reproductive Techniques (ART, including in vitro fertilization, cloning, and embryo transfer), during the periconceptual period of pregnancy on conceptus survival, growth, and development. We also examine the underlying mechanisms that have been uncovered in these recent studies, such as effects on the development of both the placenta and fetal organs. We conclude with our view of future research directions in this critical area of investigation.

Programming of Embryonic Development.

Assisted reproductive techniques (ART) and parental nutritional status have profound effects on embryonic/fetal and placental development, which are probably mediated via "programming" of gene expression, as reflected by changes in their epigenetic landscape. Such epigenetic changes may underlie programming of growth, development, and function of fetal organs later in pregnancy and the offspring postnatally, and potentially lead to long-term changes in organ structure and function in the offspring as adults. This latter concept has been termed developmental origins of health and disease (DOHaD), or simply developmental programming, which has emerged as a major health issue in animals and humans because it is associated with an increased risk of non-communicable diseases in the offspring, including metabolic, behavioral, and reproductive dysfunction. In this review, we will briefly introduce the concept of developmental programming and its relationship to epigenetics. We will then discuss evidence that ART and periconceptual maternal and paternal nutrition may lead to epigenetic alterations very early in pregnancy, and how each pregnancy experiences developmental programming based on signals received by and from the dam. Lastly, we will discuss current research on strategies designed to overcome or minimize the negative consequences or, conversely, to maximize the positive aspects of developmental programming.

Body composition changes of crossbred Holstein × Gyr cows and conceptus during pregnancy.

This study aimed to evaluate the effects of plane of nutrition and advancing days of pregnancy (DP) on maternal body composition and fetal development. Differing planes of nutrition were established by 2 feeding regimens (FR): ad libitum (AL) or maintenance (MA). Sixty-two nonlactating multiparous Holstein × Gyr cows with average body weight of 480 ± 10.1 kg and an age of 5 ± 0.5 yr were used. Cows were divided into 3 groups: pregnant (n = 44), nonpregnant (n = 12), and baseline reference cows (n = 6). The 56 pregnant and nonpregnant cows were randomly allocated into 2 different FR: AL or MA. Cows fed at MA received 1.15% of their body weight on a dry matter (DM) basis, receiving corn silage and a concentrate-based diet at a ratio of 93:7 on a DM basis. Reference group cows were slaughtered at the beginning of the experimental period to estimate body composition and empty body weight. To evaluate the effects of DP, pregnant and nonpregnant animals were slaughtered at d 140, 200, 240, and 270 of gestation. Feeding regimen affected maternal tissue composition. Days of pregnancy affected fresh weight (FW), DM, and energy content, but no differences were observed for crude protein (CP) and ether extract (EE) because of DP. Feeding regimen affected mammary gland components (CP, EE, and energy content), but not fresh or dry weights. Days of pregnancy influenced almost all mammary gland components except energy content. Regarding the uterus, FR affected only fresh and dry weights; however, DP affected every uterus component measured. The only interaction between FR and DP in this study was observed for placental FW. Cows fed AL on d 270 presented the same placental FW as cows at MA and AL on d 200 and 240. Further, pregnant cows fed at MA on d 270 had greater placental FW than cows fed AL at this day. Days of pregnancy, but not FR, influenced the composition of fetal fluids in pregnant cows. Finally, cows fed at MA had greater FW for the fetus than cows fed AL; however, fetus composition changed over DP. The FW, DM, EE, and energy content increased until d 270, but CP decreased. In conclusion, the novelty of our data presents how changes due to FR and DP occur in maternal tissues and the conceptus.

Ovine placental steroid synthesis and metabolism in late gestation.

Steroid synthesis is required for pregnancy maintenance and for parturition, but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to (1) determine placental enzyme activity, progesterone, and estradiol measured by immunoassay in late gestation ewes on low-, moderate-, and high-nutritional planes, (2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism. In the second experiment, steroid profiles were examined comprehensively in blood and tissues by liquid chromatography tandem mass spectrometry for the first time in this species. Dietary intake altered progesterone and estradiol serum concentrations but without correlated changes in placental 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase/17,20-lyase cytochrome P450 or aromatase activity. 5alpha-reduced pregnane metabolites were identified in ewes at 145 days of gestation, but concentrations were lower than those of progesterone. Finasteride inhibited 5alpha-reduced progesterone metabolism but did not impact serum progesterone concentrations in these ewes. We conclude that (1) diet-induced changes in serum progesterone and estradiol concentrations are not likely a result of altered placental synthesis of sex steroid but most likely by their metabolism, and (2) metabolism by 5α-reduction is not a major determinant of systemic progesterone concentrations in late gestation ewes.

Mustard and cumin seeds improve feed utilisation, milk production and milk fatty acids of Damascus goats.

The experiments reported in this Research Paper aimed to study the effects of mustard and cumin seeds inclusion on feed utilisation, milk production, composition, and profile of milk fatty acids in lactating Damascus goats. The study was a completely randomised design with repeated measurements in time using fifteen goats (6 ± 2 d of lactation) divided into 3 treatments (5 goats per treatment). Goats were offered a control diet of berseem clover and concentrates (1 : 1 dry matter (DM) basis) or the control diet supplemented with either 10 g/d of dried mustard seeds (mustard treatment) or 10 g/d of cumin seeds (cumin treatment) for 12 weeks. Treatments had no effect (P > 0·05) on feed intake, but enhanced (P < 0·05) digestibility of DM, organic matter, non-structural carbohydrates, and fibre fractions. Digestibility was greater (P < 0·001) with cumin treatment compared with mustard treatment. Mustard and cumin seeds had greater (P < 0·05) ruminal total short chain fatty acids (SCFA) production, and molar proportion of propionate, with greater (P < 0·001) SCFA production for cumin vs. mustard treatment. Mustard and cumin seeds increased (P < 0·05) concentrations of serum total proteins, globulin, and glucose and lowered (P < 0·05) serum cholesterol concentration. Mustard and cumin seeds inclusion elevated milk production (P = 0·007), while cumin increased milk contents (P < 0·05) of fat and lactose. Cumin treatment lowered (P < 0·05) milk saturated fatty acids (SFA) and had greater total unsaturated fatty acids (UFA) and total conjugated linoleic acid (CLA) contents. Overall, supplementing diets of Damascus goats with mustard or cumin seeds at 10 g/daily enhanced feed digestion, ruminal fermentation, milk yield (actual production by 6·8 and 11·1%, and energy corrected milk yield by 10·1 and 15·4%, respectively) and positively modified milk fatty acid profile with a 3·9% decrease in milk individual and total SFA, and an increase in individual and total UFA by about 9·7%, and total CLA by about 23·1%.

Maternal nutrient restriction during pregnancy impairs an endothelium-derived hyperpolarizing factor-like pathway in sheep fetal coronary arteries.

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway.

lncRNA-gene network analysis reveals the effects of early maternal nutrition on mineral homeostasis and energy metabolism in the fetal liver transcriptome of beef heifers.

Maternal nutrition during pregnancy influences fetal development; however, the regulatory markers of fetal programming across different gestational phases remain underexplored in livestock models. Herein, we investigated the regulatory role of long non-coding RNAs (lncRNAs) on fetal liver gene expression, the impacts of maternal vitamin and mineral supplementation, and the rate of maternal body weight gain during the periconceptual period. To this end, crossbred Angus heifers (n=31) were randomly assigned to a 2×2 factorial design to evaluate the main effects of the rate of weight gain (low gain [LG, avg. daily gain of 0.28 kg/day] vs. moderate gain [MG, avg. daily gain of 0.79 kg/day]) and vitamins and minerals supplementation (VTM vs. NoVTM). On day 83±0.27 of gestation, fetuses were collected for morphometric measurements, and fetal liver was collected for transcriptomic and mineral analyses. The maternal diet significantly affected fetal liver development and mineral reserves. Using an RNA-Seq approach, we identified 320 unique differentially expressed genes (DEGs) across all six comparisons (FDR <0.05). Furthermore, lncRNAs were predicted through the FEELnc pipeline, revealing 99 unique differentially expressed lncRNAs (DELs). The over-represented pathways and biological processes (BPs) were associated with energy metabolism, Wnt signaling, CoA carboxylase activity, and fatty acid metabolism. The DEL-regulated BPs were associated with metal ion transport, pyrimidine metabolism, and classical energy metabolism-related glycolytic, gluconeogenic, and TCA cycle pathways. Our findings suggest that lncRNAs regulate mineral homeostasis- and energy metabolism-related gene networks in the fetal liver in response to early maternal nutrition.

Differing planes of nutrition alter serum and histotroph amino acid composition in nonpregnant, multiparous beef cows on day three of the estrous cycle.

Endometrial-derived uterine histotroph is a critical component of nutrient supply to a growing conceptus throughout gestation; however, the effect of nutritional plane on histotroph nutrient composition remains unknown in multiparous cows. We hypothesized that differing planes of nutrition would alter histotroph and serum nutrient composition in beef cattle. Thus, we evaluated serum and histotroph amino acid and glucose composition, and serum non-esterified fatty acids (NEFA) and blood urea nitrogen (BUN) in cows individually fed to maintain body weight (0 kd/d, n = 9; CON) compared with those losing moderate body weight (-0.7 kg/d, n = 9; NEG). After 49 d of differing nutritional planes, cows were subjected to the 7-d CoSynch + CIDR estrus synchronization protocol and then slaughtered on d 62. Blood serum (d 0 and 62) and uterine histotroph [d 62; from uterine horns ipsilateral and contralateral to the corpus luteum (CL)] were collected and analyzed for concentrations of amino acids, glucose, and NEFA. Performance characteristics, body composition via ultrasound (d 0 and 62), and carcass characteristics were collected. Body condition score, change in body weight, average daily gain (ADG), dry matter intake (DMI), and gain:feed (G:F) were decreased (P ≤ 0.05) in NEG vs. CON cows. There were no differences in body composition or carcass characteristics, except an increase (P ≤ 0.05) in dressing percentage in NEG cows due to differences in gut fill, consistent with study design. Serum NEFA increased (P ≤ 0.05) in the NEG group, but there were no differences between NEG vs. CON in glucose or BUN. Serum histidine increased (P ≤ 0.05) and alanine, isoleucine and tryptophan decreased (P ≤ 0.05) in NEG vs. CON cows. Compared with that of the uterine horn ipsilateral to the CL, histotroph from the uterine horn contralateral to the CL had increased (P ≤ 0.05) isoleucine, asparagine, and proline concentrations in NEG cows, and decreased (P ≤ 0.05) tryptophan as a proportion of essential and total amino acids. There were no differences in glucose concentrations of histotroph contralateral or ipsilateral to the CL. Cow nutritional plane does alter serum and histotroph amino acid composition, although the presence of an embryo may be necessary to fully elucidate these changes. Differences in serum and histotroph tryptophan should be given consideration in future studies due to its importance as an essential amino acid in protein synthesis and bioactive affects.

One-carbon metabolite supplementation increases vitamin B12, folate, and methionine cycle metabolites in beef heifers and fetuses in an energy dependent manner at day 63 of gestation.

One-carbon metabolites (OCM) are metabolites and cofactors which include folate, vitamin B12, methionine, and choline that support methylation reactions. The objectives of this study were to investigate the effects of moderate changes in maternal body weight gain in combination with OCM supplementation during the first 63 days of gestation in beef cattle on (1) B12 and folate concentrations in maternal serum (2) folate cycle intermediates in maternal and fetal liver, allantoic fluid (ALF), and amniotic fluid (AMF) and (3) metabolites involved in one-carbon metabolism and related metabolic pathways in maternal and fetal liver. Heifers were either intake restricted (RES) and fed to lose 0.23 kg/d, or fed to gain 0.60 kg/d (CON). Supplemented (+OCM) heifers were given B12 and folate injections weekly and fed rumen protected methionine and choline daily, while non-supplemented (-OCM) heifers were given weekly saline injections. These two treatments were combined in a 2 × 2 factorial arrangement resulting in four treatments: CON-OCM, CON+OCM, RES-OCM, and RES+OCM. Samples of maternal serum, maternal and fetal liver, ALF, and AMF were collected at slaughter on day 63 of gestation. Restricted maternal nutrition most notably increased (P ≤ 0.05) the concentration of: vitamin B12 in maternal serum, 5,10-methylenetetrahydrofolate and 5,10-methenyltetrahydrofolate in maternal liver, and of cystathionine in fetal liver; conversely, maternal restriction decreased (P = 0.05) 5,10-methylenetetrahydrofolate concentration in fetal liver. Supplementing OCM increased (P ≤ 0.05) the concentrations of: maternal serum B12, folate and folate intermediates, ALF and AMF 5-methyltetrahydrofolate concentration, and altered (P ≤ 0.02) other maternal liver intermediates including S-adenosylmethionine, dimethylglycine, cystathionine Glutathione reduced, glutathione oxidized, taurine, serine, sarcosine, and pyridoxine. These data demonstrate that OCM supplementation was effective at increasing maternal OCM status. Furthermore, these data are similar to previously published literature where restricted maternal nutrition also affected maternal OCM status. Altering OCM status in both the dam and fetus could impact fetal developmental outcomes and production efficiencies. Lastly, these data demonstrate that fetal metabolite abundance is highly regulated, although the changes required to maintain homeostasis may program altered metabolism postnatally.

Influence of Maternal Nutrition and One-Carbon Metabolites Supplementation during Early Pregnancy on Bovine Fetal Small Intestine Vascularity and Cell Proliferation.

To investigate the effects of nutrient restriction and one-carbon metabolite (OCM) supplementation (folate, vitamin B12, methionine, and choline) on fetal small intestine weight, vascularity, and cell proliferation, 29 (n = 7 ± 1 per treatment) crossbred Angus beef heifers (436 ± 42 kg) were estrous synchronized and conceived by artificial insemination with female sexed semen from a single sire. Then, they were allotted randomly to one of four treatments in a 2 × 2 factorial arrangement with the main factors of nutritional plane [control (CON) vs. restricted feed intake (RES)] and OCM supplementation [without OCM (-OCM) or with OCM (+OCM)]. Heifers receiving the CON level of intake were fed to target an average daily gain of 0.45 kg/day, which would allow them to reach 80% of mature BW by calving. Heifers receiving the RES level of intake were fed to lose 0.23 kg/heifer daily, which mimics observed production responses in heifers that experience a diet and environment change during early gestation. Targeted heifer gain and OCM treatments were administered from d 0 to 63 of gestation, and then all heifers were fed a common diet targeting 0.45 kg/d gain until d 161 of gestation, when heifers were slaughtered, and fetal jejunum was collected. Gain had no effect (p = 0.17) on the fetal small intestinal weight. However, OCM treatments (p = 0.02) displayed less weight compared to the -OCM groups. Capillary area density was increased in fetal jejunal villi of RES - OCM (p = 0.02). Vascular endothelial growth factor receptor 2 (VEGFR2) positivity ratio tended to be greater (p = 0.08) in villi and was less in the crypts (p = 0.02) of the RES + OCM group. Cell proliferation decreased (p = 0.02) in villi and crypts of fetal jejunal tissue from heifers fed the RES + OCM treatment compared with all groups and CON - OCM, respectively. Spatial cell density increased in RES - OCM compared with CON + OCM (p = 0.05). Combined, these data show OCM supplementation can increase expression of VEGFR2 in jejunal villi, which will promote maintenance of the microvascular beds, while at the same time decreasing small intestine weight and crypt cell proliferation.

One-carbon metabolite supplementation to nutrient-restricted beef heifers affects placental vascularity during early pregnancy.

We hypothesized that restricted maternal nutrition and supplementation of one-carbon metabolites (OCM; methionine, folate, choline, and vitamin B12) would affect placental vascular development during early pregnancy. A total of 43 cows were bred, and 32 heifers successfully became pregnant with female calves, leading to the formation of four treatment groups: CON - OCM (n = 8), CON + OCM (n = 7), RES - OCM (n = 9), and RES + OCM (n = 8). The experimental design was a 2 × 2 factorial, with main factors of dietary intake affecting average daily gain: control (CON; 0.6 kg/d ADG) and restricted (RES; -0.23 kg/d ADG); and OCM supplementation (+OCM) in which the heifers were supplemented with rumen-protected methionine (7.4 g/d) and choline (44.4 g/d) and received weekly injections of 320 mg of folate and 20 mg of vitamin B12, or received no supplementation (-OCM; corn carrier and saline injections). Heifers were individually fed and randomly assigned to treatment at breeding (day 0). Placentomes were collected on day 63 of gestation (0.225 of gestation). Fluorescent staining with CD31 and CD34 combined with image analysis was used to determine the vascularity of the placenta. Images were analyzed for capillary area density (CAD) and capillary number density (CND). Areas evaluated included fetal placental cotyledon (COT), maternal placental caruncle (CAR), whole placentome (CAR + COT), intercotyledonary fetal membranes (ICOT, or chorioallantois), intercaruncular endometrium (ICAR), and endometrial glands (EG). Data were analyzed with the GLM procedure of SAS, with heifer as the experimental unit and significance at P ≤ 0.05 and a tendency at P > 0.05 and P < 0.10. Though no gain × OCM interactions existed (P ≥ 0.10), OCM supplementation increased (P = 0.01) CAD of EG, whereas nutrient restriction tended (P < 0.10) to increase CAD of ICOT and CND of COT. Additionally, there was a gain × OCM interaction (P < 0.05) for CAD within the placentome and ICAR, such that RES reduced and supplementation of RES with OCM restored CAD. These results indicate that maternal rate of gain and OCM supplementation affected placental vascularization (capillary area and number density), which could affect placental function and thus the efficiency of nutrient transfer to the fetus during early gestation.

In cow­calf production, periods of poor forage availability or quality can result in nutrient restriction during pregnancy. Previous studies have shown that even moderate maternal feed restriction during pregnancy, including very early in pregnancy, has profound effects on fetal and placental development, potentially having lasting impacts on calf growth and body composition later in life. One-carbon metabolites (OCM) in the diet are biomolecules required for methylation reactions and participate in the regulation of gene expression. Our objective was to evaluate the effects of nutrient restriction and OCM supplementation (specifically methionine, choline, folate, and vitamin B12) on placental vascular development during early pregnancy. Proper placental vascular development is necessary for healthy pregnancy outcomes, reflected by normal birth weight and healthy offspring. Our results indicated that maternal rate of gain and OCM supplementation affect placental vascularization, which could affect placental function and thereby fetal development throughout gestation. In the context of beef cattle production, our study sheds light on strategies that could enhance placental vascular development during early pregnancy. However, it is essential to recognize the nuances in our data, highlighting the need for further research to fully comprehend these intricate processes.

Disrupted one-carbon metabolism in heifers negatively affects their health and physiology.

The objective of this study was to determine the dose-dependent response of one-carbon metabolite (OCM: methionine, choline, folate, and vitamin B12) supplementation on heifer dry matter intake on fixed gain, organ mass, hematology, cytokine concentration, pancreatic and jejunal enzyme activity, and muscle hydrogen peroxide production. Angus heifers (n = 30; body weight [BW] = 392.6 ±â€…12.6 kg) were individually fed and assigned to one of five treatments: 0XNEG: total mixed ration (TMR) and saline injections at days 0 and 7 of the estrous cycle, 0XPOS: TMR, rumen-protected methionine (MET) fed at 0.08% of the diet dry matter, rumen-protected choline (CHOL) fed at 60 g/d, and saline injections at days 0 and 7, 0.5X: TMR, MET, CHOL, 5-mg B12, and 80-mg folate injections at days 0 and 7, 1X: TMR, MET CHOL, 10-mg vitamin B12, and 160-mg folate at days 0 and 7, and 2X: TMR, MET, CHOL, 20-mg vitamin B12, and 320-mg folate at days 0 and 7. All heifers were estrus synchronized but not bred, and blood samples were collected on days 0, 7, and at slaughter (day 14) during which tissues were collected. By design, heifer ADG did not differ (P = 0.96). Spleen weight and uterine weight were affected cubically (P = 0.03) decreasing from 0XPOS to 0.5X. Ovarian weight decreased linearly (P < 0.01) with increasing folate and B12 injection. Hemoglobin and hematocrit percentage were decreased (P < 0.01) in the 0.5X treatment compared with all other treatments. Plasma glucose, histotroph protein, and pancreatic α-amylase were decreased (P ≤ 0.04) in the 0.5X treatment. Heifers on the 2X treatment had greater pancreatic α-amylase compared with 0XNEG and 0.5X treatment. Interleukin-6 in plasma tended (P = 0.08) to be greater in the 0XPOS heifers compared with all other treatments. Lastly, 0XPOS-treated heifers had reduced (P ≤ 0.07) hydrogen peroxide production in muscle compared with 0XNEG heifers. These data imply that while certain doses of OCM do not improve whole animal physiology, OCM supplementation doses that disrupt one-carbon metabolism, such as that of the 0.5X treatment, can induce a negative systemic response that results in negative effects in both the dam and the conceptus during early gestation. Therefore, it is necessary to simultaneously establish an optimal OCM dose that increases circulating concentrations for use by the dam and the conceptus, while avoiding potential negative side effects of a disruptive OCM, to evaluate the long-term impacts of OCM supplementation of offspring programming.

The feeding of one-carbon metabolites (including methionine and B vitamins) has been shown to improve fetal growth and milk production in species such as mice, sheep, and dairy cattle. Extending this to beef cattle around the time of breeding is a growing area of research. Our group previously determined that one-carbon metabolite supplementation to beef heifers altered the abundance of circulating methionine-folate cycle intermediates in a dose-dependent manner. Therefore, we aimed to determine a whole-body response to one-carbon metabolite supplementation in heifers by measuring the effects on specific physiological systems as well as a total systemic response. We determined that treatments that negatively altered the methionine-folate cycle yielded a fundamental negative whole-body response to supplementation.

Effects of rate of body weight gain during the first trimester of gestation on beef heifer and offspring performance, concentrations of hormones and metabolites, and response to vaccination.

Our study objectives were to evaluate the effects of divergent rates of body weight (BW) gain during early gestation in beef heifers on F0 performance, metabolic and endocrine status, colostrum immunoglobulins, and subsequent F1 calf characteristics, growth performance, concentrations of hormones and metabolites, and response to vaccination. Angus-based heifers (n = 100; BW = 369 ± 2.5 kg) were adapted to individual feeding for 14 d and bred using artificial insemination with female-sexed semen. Heifers were ranked by BW assigned to either a basal diet targeting 0.28 kg/d gain (LG, n = 50) or the basal diet plus an energy/protein supplement targeting 0.79 kg/d gain (MG, n = 50) until d 84 of gestation. Dam BW and blood samples were collected at 6 time points during gestation; body composition was evaluated at d -10 and 84; and fetal measurements were taken on d 42, 63, and 84. At calving (LG, n = 23; MG, n = 23), dam and calf BW were recorded; and colostrum, calf body measurements, and blood samples were collected. Cow-calf pairs were managed on a common diet from calving to weaning, followed by a common postnatal development period for all F1 female offspring. Growth performance, hormone and metabolite profiles, feeding behavior, and reproductive performance were assessed from birth to pre-breeding in F1 heifers. Offspring were vaccinated against respiratory disease and bovine viral diarrhea pathogens on d 62.3 ± 4.13 and 220.3 ± 4.13 post-calving. By design, MG dams were heavier (P < 0.0001) than LG at d 84, and the BW advantage persisted until subsequent weaning of F1 calves. Concentrations of serum IGF-1 and glucose were increased throughout gestation (P < 0.001) for MG dams, whereas concentrations of NEFA were decreased (P < 0.001) in LG dams. Calves from MG dams were 2.14 kg heavier (P = 0.03) and had larger chest circumference (P = 0.04) at birth compared with LG cohorts. Heifers from MG dams continued to have greater (P ≤ 0.03) BW gain and feed efficiency during the development period, but no differences were observed (P ≥ 0.13) in body composition, concentrations of hormones and metabolites, feeding behavior, puberty attainment, and response to vaccination in F1 offspring. Hence, early gestation rate of gain impacted BW and concentrations of glucose and IGF-1 throughout gestation in the F0 dam, resulting in altered F1 calf BW and measurements at birth and increased gain and efficiency during the development period.

Influence of Maternal Supplementation with Vitamins, Minerals, and (or) Protein/Energy on Placental Development and Angiogenic Factors in Beef Heifers during Pregnancy.

The effect of vitamins and minerals supplementation (VTM) and/or two rates of body weight gain (GAIN) on bovine placental vascular development and angiogenic factors gene expression were evaluated in two experiments: In Exp. 1, crossbred Angus heifers (n = 34) were assigned to VTM/NoVTM treatments at least 71 days before breeding to allow changes in the mineral status. At breeding, through artificial insemination (AI), heifers were assigned to low-gain (LG) 0.28 kg/d or moderate-gain (MG) 0.79 kg/d treatments, resulting in NoVTM-LG (Control; n = 8), NoVTM-MG (n = 8), VTM-LG (n = 9), and VTM-MG (n = 9) until day 83 of gestation; In Exp. 2, crossbred angus heifers (n = 28), were assigned to control (CON; n = 12), receiving a basal total mixed ration (TMR) or TMR + VTM (VTM; n = 16) from breeding until parturition. Placentomes from Exp. 1 and cotyledons (COT) from Exp. 2 were evaluated by immunohistochemistry for COT vascular density area. COTs from Exp. 1 were evaluated for angiogenic factor (ANGPT-1, ANGPT-2, eNOS2, eNOS3, FLT1, KDR, TEK, VEGFA) gene expression. In Exp. 1, COT vascularity was not affected by the interaction of VTM and GAIN (p = 0.67) or the main effects of VTM (p = 0.50) and GAIN (p = 0.55). Likewise, angiogenic factors were not differentially expressed between treatments (p < 0.05). In Exp. 2, COT vascularity was greater in VTM vs. CON (p = 0.07). In conclusion, there is a suggested later-stage influence of vitamin and mineral supplementation on placental vascularity, emphasizing the importance of supplementation beyond early pregnancy.

Expression, Regulation, and Function of ß-Defensins in the Bovine Mammary Glands: Current Knowledge and Future Perspectives.

ß-Defensins are cationic antimicrobial peptides (AMPs) that play an important role in the innate immune defense of bovines. They are constitutively expressed in mammary glands and induced differently in response to pathogens. Their expression is influenced by various factors, including hormones, plant-derived compounds, and dietary energy imbalance. The toll-like receptors (TLRs)/nuclear factor-kappa B (NF-κB) pathway plays a crucial role in ß-defensin induction, while alternative pathways such as mitogen-activated protein kinase (MAPK) and epigenetic regulation also make substantial contributions. ß-Defensins exhibit bactericidal activity against a wide range of pathogens, including two major mastitis pathogens, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), primarily through membrane disruption. ß-Defensins have low cytotoxicity to host cells and demonstrate immunomodulatory properties, and pathogens also display minimal resistance to these AMPs. Given the increasing concern in antimicrobial resistance, the potential of ß-defensins as natural antimicrobials has garnered considerable attention. This article provides an overview of the characteristics of bovine ß-defensins, their expression pathways, their mode of action, and factors influencing their expression in the mammary glands of cattle. Additionally, it identifies the current gaps in research within this field and suggests areas that require further investigation. Understanding the regulation and function of ß-defensins offers valuable insights to develop effective strategies for strengthening the immune system of mammary glands, reducing the reliance on synthetic antimicrobials, and explore novel natural antimicrobial alternatives.

Paternal effects on fetal programming.

Paternal programming is the concept that the environmental signals from the sire's experiences leading up to mating can alter semen and ultimately affect the phenotype of resulting offspring. Potential mechanisms carrying the paternal effects to offspring can be associated with epigenetic signatures (DNA methylation, histone modification and non-coding RNAs), oxidative stress, cytokines, and the seminal microbiome. Several opportunities exist for sperm/semen to be influenced during development; these opportunities are within the testicle, the epididymis, or accessory sex glands. Epigenetic signatures of sperm can be impacted during the pre-natal and pre-pubertal periods, during sexual maturity and with advancing sire age. Sperm are susceptible to alterations as dictated by their developmental stage at the time of the perturbation, and sperm and seminal plasma likely have both dependent and independent effects on offspring. Research using rodent models has revealed that many factors including over/under nutrition, dietary fat, protein, and ingredient composition (e.g., macro- or micronutrients), stress, exercise, and exposure to drugs, alcohol, and endocrine disruptors all elicit paternal programming responses that are evident in offspring phenotype. Research using livestock species has also revealed that sire age, fertility level, plane of nutrition, and heat stress can induce alterations in the epigenetic, oxidative stress, cytokine, and microbiome profiles of sperm and/or seminal plasma. In addition, recent findings in pigs, sheep, and cattle have indicated programming effects in blastocysts post-fertilization with some continuing into post-natal life of the offspring. Our research group is focused on understanding the effects of common management scenarios of plane of nutrition and growth rates in bulls and rams on mechanisms resulting in paternal programming and subsequent offspring outcomes. Understanding the implication of paternal programming is imperative as short-term feeding and management decisions have the potential to impact productivity and profitability of our herds for generations to come.

Maternal Mineral Nutrition Regulates Fetal Genomic Programming in Cattle: A Review.

Maternal mineral nutrition during the critical phases of fetal development may leave lifetime impacts on the productivity of an individual. Most research within the developmental origins of the health and disease (DOHaD) field is focused on the role of macronutrients in the genome function and programming of the developing fetus. On the other hand, there is a paucity of knowledge about the role of micronutrients and, specifically, minerals in regulating the epigenome of livestock species, especially cattle. Therefore, this review will address the effects of the maternal dietary mineral supply on the fetal developmental programming from the embryonic to the postnatal phases in cattle. To this end, we will draw a parallel between findings from our cattle model research with data from model animals, cell lines, and other livestock species. The coordinated role and function of different mineral elements in feto-maternal genomic regulation underlies the establishment of pregnancy and organogenesis and, ultimately, affects the development and functioning of metabolically important tissues, such as the fetal liver, skeletal muscle, and, importantly, the placenta. Through this review, we will delineate the key regulatory pathways involved in fetal programming based on the dietary maternal mineral supply and its crosstalk with epigenomic regulation in cattle.