RESUMO
Obese women are subfertile and have reduced assisted reproduction success, which may be due to reduced oocyte competence. We hypothesize that consumption of a high-fat/high-sugar diet induces ovarian inflammation, which is a primary contributor to decreased oocyte quality and pre-implantation embryo development. To test this hypothesis, C57BL/6 (B6) mice with a normal inflammatory response and C3H/HeJ (C3H) mice with a dampened inflammatory response due to dysfunctional Toll-like receptor 4 were fed either normal chow or high-fat/high-sugar diet. In both B6 and C3H females, high-fat/high-sugar diet induced excessive adiposity and hyperglycemia compared to normal chow-fed counterparts. Conversely, ovarian CD68 levels and oocyte expression of oxidative stress markers were increased when collected from B6 high-fat/high-sugar but not C3H high-fat/high-sugar mice. Following in vitro fertilization of in vivo matured oocytes, blastocyst development was decreased in B6-high-fat/high-sugar but not C3H high-fat/high-sugar mice. Expression of cumulus cell markers of oocyte quality were altered in both B6 high-fat/high-sugar and C3H high-fat/high-sugar. However, there were no diet-dependent differences in spindle abnormalities in either B6 or C3H mice, suggesting potential defects in cytoplasmic maturation. Indeed, there were significant increases in the abundance of maternal effect gene mRNAs in oocytes from only B6 high-fat/high-sugar mice. These differentially expressed genes encode proteins of the subcortical maternal complex and associated with mRNA metabolism and epigenetic modifications. These genes regulate maternal mRNA degradation at oocyte maturation, mRNA clearance at the zygotic genome activation, and methylation of imprinted genes suggesting a mechanism by which inflammation induced oxidative stress impairs embryo development.
Assuntos
Técnicas de Maturação in Vitro de Oócitos , Receptor 4 Toll-Like , Animais , Feminino , Camundongos , Desenvolvimento Embrionário/fisiologia , Inflamação/metabolismo , Herança Materna , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/complicações , Oócitos/metabolismo , RNA Mensageiro/metabolismo , Açúcares/metabolismo , Açúcares/farmacologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , GravidezRESUMO
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 (nâ =â 8), CONâ +â OCM (nâ =â 7), RES - OCM (nâ =â 9), and RESâ +â OCM (nâ =â 8). The experimental design was a 2â ×â 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 (CARâ +â 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 Pâ ≤â 0.05 and a tendency at Pâ >â 0.05 and Pâ <â 0.10. Though no gainâ ×â OCM interactions existed (Pâ ≥â 0.10), OCM supplementation increased (Pâ =â 0.01) CAD of EG, whereas nutrient restriction tended (Pâ <â 0.10) to increase CAD of ICOT and CND of COT. Additionally, there was a gainâ ×â OCM interaction (Pâ <â 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.
Assuntos
Complexo Ferro-Dextran , Placenta , Feminino , Gravidez , Animais , Bovinos , Melhoramento Vegetal , Metionina/farmacologia , Racemetionina , Carbono , Colina/farmacologia , Suplementos Nutricionais , Ácido Fólico/farmacologia , Vitamina B 12/farmacologia , Dieta/veterináriaRESUMO
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 (nâ =â 31, initial body weight [BW]â =â 412.5â ±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; nâ =â 14) or the basal diet plus 113 g heifer-1 d-1 of the vitamin and mineral supplement (VTM; nâ =â 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 (Pâ ≤â 0.05) from day 84 to calving, while concentrations of Cu decreased in VTM and CON (Pâ ≤â 0.05) from day 84 to calving. Calf liver concentrations of Se, Cu, Zn, and Co at birth were greater for VTM than CON (Pâ ≤â 0.05), but calf birth BW and body measurements were not different (Pâ =â 0.45). Placental Se, colostrum quantity, total Se, Cu, Zn, and Mn in colostrum were greater (Pâ ≤â 0.04) in VTM dams than CON. Finally, offspring from VTM dams were heavier than CON (Pâ <â 0.0001) from weaning through 15 mo of age. These results were coupled with greater (Pâ ≤â 0.04) blood glucose at birth, decreased (Pâ ≤â 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.
Assuntos
Suplementos Nutricionais , Vitaminas , Bovinos , Animais , Gravidez , Feminino , Vitaminas/farmacologia , Ração Animal/análise , Placenta , Dieta/veterinária , Minerais , Vitamina A , Vitamina KRESUMO
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.
RESUMO
IMPORTANCE: Emerging evidence suggests that microbiome-targeted approaches may provide a novel opportunity to reduce the incidence of reproductive failures in cattle. To develop such microbiome-based strategies, one of the first logical steps is to identify reproductive microbiome features related to fertility and to isolate the fertility-associated microbial species for developing a future bacterial consortium that could be administered before breeding to enhance pregnancy outcomes. Here, we characterized the vaginal and uterine microbiota in beef cattle that became pregnant or remained open via artificial insemination and identified microbiota features associated with fertility. We compared similarities between vaginal and uterine microbiota and between heifers and cows. Using culturing, we provided new insights into the culturable fraction of the vaginal and uterine microbiota and their antimicrobial resistance. Overall, our findings will serve as an important basis for future research aimed at harnessing the vaginal and uterine microbiome for improved cattle fertility.
Assuntos
Microbiota , Reprodução , Gravidez , Bovinos , Animais , Feminino , Vagina/microbiologia , Inseminação Artificial/veterinária , FertilidadeRESUMO
Early life microbial colonization and factors affecting colonization patterns are gaining interest due to recent developments suggesting that early life microbiome may play a role in Developmental Origins of Health and Disease. In cattle, limited information exists on the early microbial colonization of anatomical sites involved in bovine health beyond the gastrointestinal tract. Here, we investigated 1) the initial microbial colonization of seven different anatomical locations in newborn calves and 2) whether these early life microbial communities and 3) serum cytokine profiles are influenced by prenatal vitamin and mineral (VTM) supplementation. Samples were collected from the hoof, liver, lung, nasal cavity, eye, rumen (tissue and fluid), and vagina of beef calves that were born from dams that either received or did not receive VTM supplementation throughout gestation (n = 7/group). Calves were separated from dams immediately after birth and fed commercial colostrum and milk replacer until euthanasia at 30 h post-initial colostrum feeding. The microbiota of all samples was assessed using 16S rRNA gene sequencing and qPCR. Calf serum was subjected to multiplex quantification of 15 bovine cytokines and chemokines. Our results indicated that the hoof, eye, liver, lung, nasal cavity, and vagina of newborn calves were colonized by site-specific microbiota, whose community structure differed from the ruminal-associated communities (0.64 ≥ R2 ≥ 0.12, p ≤ 0.003). The ruminal fluid microbial community was the only one that differed by treatment (p < 0.01). However, differences (p < 0.05) by treatment were detected in microbial richness (vagina); diversity (ruminal tissue, fluid, and eye); composition at the phylum and genus level (ruminal tissue, fluid, and vagina); and in total bacterial abundance (eye and vagina). From serum cytokines evaluated, concentration of chemokine IP-10 was greater (p = 0.02) in VTM calves compared to control calves. Overall, our results suggest that upon birth, the whole-body of newborn calves are colonized by relatively rich, diverse, and site-specific bacterial communities. Noticeable differences were observed in ruminal, vaginal, and ocular microbiota of newborn calves in response to prenatal VTM supplementation. These findings can derive future hypotheses regarding the initial microbial colonization of different body sites, and on maternal micronutrient consumption as a factor that may influence early life microbial colonization.