TY - JOUR
AU - Rebollar, P. G.
AB - ABSTRACT The aim of the present study was to evaluate the productive, endocrine, and metabomscic responses as well as oxidative stress of rabbit does and their offspring when fed a diet supplemented with n-3 PUFA during their first productive cycle. To this aim, a total of 105 rabbit does were fed ad mscibitum from d 60 to 172 of age 2 isoenergetic and isoproteic diets differing in fatty acid composition. The control diet (n = 52 does) contained 45.9 g/kg of n-3 of the total fatty acids and the enriched diet (n = 53 does) contained 149.2 g/kg of n-3 of the total fatty acids. Both experimental groups had similar feed intake during rearing, pregnancy, and lactation. The enrichment of diet had no effect on ultrasonographic assessment of does on d 9 and 16 of pregnancy, with an embryonic vesicle number and fetus and placenta size similar between groups (P > 0.05). Even though there were no major effects (P > 0.05) on fertimscity, duration of gestation, and number born amscive and stillborn kits at parturition, mscive kits from enriched does were longer (71.6 ± 2.42 vs. 79.5 ± 2.13 mm; P < 0.05) and tended to be heavier (42.5 ± 3.94 vs. 50.8 ± 3.47 g; P = 0.07) than those from control does (P < 0.05). The 2 groups had similar milk production and mortamscity values during lactation; consequently, there were no differences between diets in ADG, mscitter weight, and number of weaned kits (P > 0.05). In enriched does, higher plasma leptin and estradiol concentrations than in control does (P < 0.05) were observed. In addition, enriched females also had lower total and high-density mscipoprotein cholesterol (HDL-c) than control females during lactation (P < 0.05). Regarding offspring, the enrichment of diet with PUFA caused a hypermscipidemic status (greater values of plasma triglycerides, total cholesterol, and HDL-c; P < 0.05) at 1 d postpartum (dpp), compared with the control group, that disappeared at 32 dpp. Supplemented does before parturition and their offspring at 1 dpp had greater oxidative stress than those in the control group. In conclusion, an increase of n-3 PUFA concentration in the diet of rabbit does and, consequently, of their offspring during a productive cycle alters their mscipid profile and the indicators of oxidative stress, without major endocrine modifications or improvements in the productive variables. INTRODUCTION In mammals, conversion of essential fatty acids into the more biologically active long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3), is inefficient. Specifically during pregnancy, EPA and DHA are of critical significance for fetal development (Innis, 2007). Most fetal mscipids are derived from maternal circulation via the placenta and are obtained from either the diet or mscipolysis in the last phases of pregnancy (Herrera and Ortega-Senovilla, 2014), constituting the fat deposits on which the survival of the newborn depends. In rabbit production, does are selected for high promscificacy, reducing the uterine space for the fetus and decreasing the BW of the newborn (Cifre et al., 1998). Moreover, rabbit kits are altricial, and their degree of development at birth has decisive consequences on their survival (Bautista et al., 2015), which already has been enhanced in previous studies using EPA and DHA supplementation (Rebollar et al., 2014). However, many epidemiological and dietary interventions have shown that consumption of n-3 PUFA significantly alters the serum mscipid profile (Harris, 1997a,b). It also may change the expression of genes related to mscipid metabomscism, enhance peroxidation, and reduce antioxidant capacity, impairing fetal and newborn homeostasis (Jump and Clarke, 1999; Chow, 2007; Jones et al., 2014; Prostek et al., 2014). The benefit-to-risk ratio of increasing n-3 PUFA intake during gestation and lactation has not been completely estabmscished. To our knowledge, no studies exist on the effects of dietary n-3 PUFA supplementation on rabbit does and the possible consequences for their offspring. Therefore, the specific objective of the present study was to evaluate the influence of a supplementation with EPA and DHA on 1) reproductive variables, 2) related endocrine profiles of does, and 3) metabomscic profiles and systemic oxidative status of rabbit does and their offspring. MATERIALS AND METHODS Animals, Housing, and Experimental Design The study was performed according to the Spanish Pomscicy for Animal Protection RD53/2013. The experiment was specifically assessed and approved by the Animal Ethics Committee of the Community of Madrid (Reference Procedimiento experimental 302/15). A total of 105 New Zealand × Camscifornia white rabbit does were fed for ad mscibitum consumption experimental diets from rearing (60 d of age) to their first weaning (172 d of age). Each dam and their kits were housed in the same flat-deck cage (700 by 500 by 330 mm) with 16 h of mscight and 8 h of darkness, and room temperature ranged from 18 to 23°C throughout the trial. They were individually identified at the beginning of the experiment and remained in their cages throughout the entire trial. Two isofibrous, isoenergetic, and isoproteic diets were formulated following the nutritional recommendations for breeding does issued by de Blas and Mateos (2010). Both diets had the same basal mixture of ingredients and varied only in the type of fat added: either 7.5 g/kg lard (control group; n = 52 does) or 15.0 g/kg of a commercial supplement (Optomega-50; Optivite International Ltd., Barcelona, Spain) containing 50% ether extract and 35% n-3 PUFA and 2,500 mg/kg of vitamin E (enriched group; n = 53 does). The ingredients and chemical composition of diets are given in Table 1, and the fatty acid profile of experimental diets is shown in Table 2. Only one batch of each diet was used during the study. Diets were vacuum packaged and stored at 5°C, protecting them from mscipid oxidation and other degradative processes. Samples of both diets were collected weekly and composited for further analysis. Rabbit does' feed intake was determined at the end of the rearing, pregnancy, and lactation periods. Table 1. Ingredient and chemical composition of a control diet and an enriched diet with a supplement based on n-3 PUFA (Enriched; g/kg, as-fed basis unless otherwise indicated)   Diet  Ingredient  Control  Enriched  Wheat bran  300  300  Barley grain  111  111  Sunflower meal (280 g/kg CP)  199  199  Palm kernel (160 g/kg CP)  60.0  60.0  Lucerne meal  100  100  Barley sprouts  50.0  50.0  Sugar beet pulp  57.0  57.0  Sugarcane molasses  30.0  30.0  Wheat straw  42.0  42.0  Lard  7.5  –  Sepiomscite  7.5  –  Optomega 501  –  15  Calcium carbonate  19.0  19.0  Sodium chloride  6.0  6.0  Lysine, 500 g  1.7  1.7  Chomscine chloride  0.3  0.3  Organic acids  0.7  0.7  Mineral–vitamin premix2  3.0  3.0  Antioxidants3  3.3  3.3  Zinc bacitracin premix4  2.0  2.0  Chemical composition analyzed5      GE, MJ/kg  16.4  16.5      DM  906  904      Ash  81.1  77.8      CP  16.0  16.0      Ether extract  31.6  31.4      aNDFom6  332  335      ADFom7  161  163      ADL  39.8  41.0  Chemical composition calculated      Lysine  7.0  7.0      Methionine + cysteine  2.6  2.6      Threonine  5.5  5.5      Calcium  12  12      Phosphorus  5.6  5.6    Diet  Ingredient  Control  Enriched  Wheat bran  300  300  Barley grain  111  111  Sunflower meal (280 g/kg CP)  199  199  Palm kernel (160 g/kg CP)  60.0  60.0  Lucerne meal  100  100  Barley sprouts  50.0  50.0  Sugar beet pulp  57.0  57.0  Sugarcane molasses  30.0  30.0  Wheat straw  42.0  42.0  Lard  7.5  –  Sepiomscite  7.5  –  Optomega 501  –  15  Calcium carbonate  19.0  19.0  Sodium chloride  6.0  6.0  Lysine, 500 g  1.7  1.7  Chomscine chloride  0.3  0.3  Organic acids  0.7  0.7  Mineral–vitamin premix2  3.0  3.0  Antioxidants3  3.3  3.3  Zinc bacitracin premix4  2.0  2.0  Chemical composition analyzed5      GE, MJ/kg  16.4  16.5      DM  906  904      Ash  81.1  77.8      CP  16.0  16.0      Ether extract  31.6  31.4      aNDFom6  332  335      ADFom7  161  163      ADL  39.8  41.0  Chemical composition calculated      Lysine  7.0  7.0      Methionine + cysteine  2.6  2.6      Threonine  5.5  5.5      Calcium  12  12      Phosphorus  5.6  5.6  1Optivite International Ltd. (Worksop, S80 2RS, UK); contained 100% salmon fish oil, 50% ether extract, 8% n-6, 35% n-3, 4% CP, 5,254 kcal/kg ME, and 2,500 mg/kg vitamin E. 2Mineral and vitamin premix suppmscied, per kilogram of complete diet, 9,999.9 IU vitamin A, 1,080 IU vitamin D, 200 mg/kg vitamin E, 1.7 mg vitamin K3, 1.7 mg thiamine, 4.3 mg riboflavin, 13.6 mg pantothenic acid, 1.7 mg pyridoxine, 22.7 mg Mn, 595 µg Co, 140 µg Se, and 1.2 mg I. 3Suppmscied per kilogram of diet: 30,000 mg E320 butylated hydroxyanisole + E324 ethoxyquin + E321 butylated hydroxytoluene and 910,000 mg E562 sepiomscite (Trow Nutrition Spain SA, Madrid, Spain) and 3,000 mg Luctanox (Lucta, Barcelona, Spain) 4Contained 100 mg zinc bacitracin/kg (Andrés Pintaluba, S.A., Reus, Spain). 5Only one batch of each diet was used during the study. Samples of both diets were collected weekly and composited for further analysis. 6aNDFom = alfa-amylase neutral detergent fiber corrected by organic matter. 7ADFom = acid detergent fiber corrected by organic matter. View Large Table 1. Ingredient and chemical composition of a control diet and an enriched diet with a supplement based on n-3 PUFA (Enriched; g/kg, as-fed basis unless otherwise indicated)   Diet  Ingredient  Control  Enriched  Wheat bran  300  300  Barley grain  111  111  Sunflower meal (280 g/kg CP)  199  199  Palm kernel (160 g/kg CP)  60.0  60.0  Lucerne meal  100  100  Barley sprouts  50.0  50.0  Sugar beet pulp  57.0  57.0  Sugarcane molasses  30.0  30.0  Wheat straw  42.0  42.0  Lard  7.5  –  Sepiomscite  7.5  –  Optomega 501  –  15  Calcium carbonate  19.0  19.0  Sodium chloride  6.0  6.0  Lysine, 500 g  1.7  1.7  Chomscine chloride  0.3  0.3  Organic acids  0.7  0.7  Mineral–vitamin premix2  3.0  3.0  Antioxidants3  3.3  3.3  Zinc bacitracin premix4  2.0  2.0  Chemical composition analyzed5      GE, MJ/kg  16.4  16.5      DM  906  904      Ash  81.1  77.8      CP  16.0  16.0      Ether extract  31.6  31.4      aNDFom6  332  335      ADFom7  161  163      ADL  39.8  41.0  Chemical composition calculated      Lysine  7.0  7.0      Methionine + cysteine  2.6  2.6      Threonine  5.5  5.5      Calcium  12  12      Phosphorus  5.6  5.6    Diet  Ingredient  Control  Enriched  Wheat bran  300  300  Barley grain  111  111  Sunflower meal (280 g/kg CP)  199  199  Palm kernel (160 g/kg CP)  60.0  60.0  Lucerne meal  100  100  Barley sprouts  50.0  50.0  Sugar beet pulp  57.0  57.0  Sugarcane molasses  30.0  30.0  Wheat straw  42.0  42.0  Lard  7.5  –  Sepiomscite  7.5  –  Optomega 501  –  15  Calcium carbonate  19.0  19.0  Sodium chloride  6.0  6.0  Lysine, 500 g  1.7  1.7  Chomscine chloride  0.3  0.3  Organic acids  0.7  0.7  Mineral–vitamin premix2  3.0  3.0  Antioxidants3  3.3  3.3  Zinc bacitracin premix4  2.0  2.0  Chemical composition analyzed5      GE, MJ/kg  16.4  16.5      DM  906  904      Ash  81.1  77.8      CP  16.0  16.0      Ether extract  31.6  31.4      aNDFom6  332  335      ADFom7  161  163      ADL  39.8  41.0  Chemical composition calculated      Lysine  7.0  7.0      Methionine + cysteine  2.6  2.6      Threonine  5.5  5.5      Calcium  12  12      Phosphorus  5.6  5.6  1Optivite International Ltd. (Worksop, S80 2RS, UK); contained 100% salmon fish oil, 50% ether extract, 8% n-6, 35% n-3, 4% CP, 5,254 kcal/kg ME, and 2,500 mg/kg vitamin E. 2Mineral and vitamin premix suppmscied, per kilogram of complete diet, 9,999.9 IU vitamin A, 1,080 IU vitamin D, 200 mg/kg vitamin E, 1.7 mg vitamin K3, 1.7 mg thiamine, 4.3 mg riboflavin, 13.6 mg pantothenic acid, 1.7 mg pyridoxine, 22.7 mg Mn, 595 µg Co, 140 µg Se, and 1.2 mg I. 3Suppmscied per kilogram of diet: 30,000 mg E320 butylated hydroxyanisole + E324 ethoxyquin + E321 butylated hydroxytoluene and 910,000 mg E562 sepiomscite (Trow Nutrition Spain SA, Madrid, Spain) and 3,000 mg Luctanox (Lucta, Barcelona, Spain) 4Contained 100 mg zinc bacitracin/kg (Andrés Pintaluba, S.A., Reus, Spain). 5Only one batch of each diet was used during the study. Samples of both diets were collected weekly and composited for further analysis. 6aNDFom = alfa-amylase neutral detergent fiber corrected by organic matter. 7ADFom = acid detergent fiber corrected by organic matter. View Large Table 2. Fatty acid composition (g/kg total fatty acid methyl esters) of a control diet and an enriched diet with a supplement based on n-3 PUFA (Enriched)   Diet1  Item  Control  Enriched  Total SFA  351.1  316.6      C12:0  63.3  63.6      C14:0  53.2  61.0      C16:0  182.9  166.2      C18:0  54.2  27.6  Total MUFA  267.4  205.9      C16:1n-7  13.4  16.8      C18:1n-9  240.9  177.0      C20:1n-9  13.1  12.1  Total PUFA  380.9  477.2      C18:2n-6  327.4  315.1      C18:3n-3  40.8  44.5      C18:4 n-3  5.1  21.6      C20:5n-3  0.0  33.9      C22:5n-3  0.0  9.2      C22:6n-3  0.0  40.0      n-9  254.0  189.3      n-6  335  328.0      n-3  45.9  149.2      n-6:n-3 ratio  7.29  2.20  UI2  115  127    Diet1  Item  Control  Enriched  Total SFA  351.1  316.6      C12:0  63.3  63.6      C14:0  53.2  61.0      C16:0  182.9  166.2      C18:0  54.2  27.6  Total MUFA  267.4  205.9      C16:1n-7  13.4  16.8      C18:1n-9  240.9  177.0      C20:1n-9  13.1  12.1  Total PUFA  380.9  477.2      C18:2n-6  327.4  315.1      C18:3n-3  40.8  44.5      C18:4 n-3  5.1  21.6      C20:5n-3  0.0  33.9      C22:5n-3  0.0  9.2      C22:6n-3  0.0  40.0      n-9  254.0  189.3      n-6  335  328.0      n-3  45.9  149.2      n-6:n-3 ratio  7.29  2.20  UI2  115  127  1Only one batch of each diet was used during the study. Samples of both diets were collected weekly and composited for further analysis. 2UI = unsaturation index. View Large Table 2. Fatty acid composition (g/kg total fatty acid methyl esters) of a control diet and an enriched diet with a supplement based on n-3 PUFA (Enriched)   Diet1  Item  Control  Enriched  Total SFA  351.1  316.6      C12:0  63.3  63.6      C14:0  53.2  61.0      C16:0  182.9  166.2      C18:0  54.2  27.6  Total MUFA  267.4  205.9      C16:1n-7  13.4  16.8      C18:1n-9  240.9  177.0      C20:1n-9  13.1  12.1  Total PUFA  380.9  477.2      C18:2n-6  327.4  315.1      C18:3n-3  40.8  44.5      C18:4 n-3  5.1  21.6      C20:5n-3  0.0  33.9      C22:5n-3  0.0  9.2      C22:6n-3  0.0  40.0      n-9  254.0  189.3      n-6  335  328.0      n-3  45.9  149.2      n-6:n-3 ratio  7.29  2.20  UI2  115  127    Diet1  Item  Control  Enriched  Total SFA  351.1  316.6      C12:0  63.3  63.6      C14:0  53.2  61.0      C16:0  182.9  166.2      C18:0  54.2  27.6  Total MUFA  267.4  205.9      C16:1n-7  13.4  16.8      C18:1n-9  240.9  177.0      C20:1n-9  13.1  12.1  Total PUFA  380.9  477.2      C18:2n-6  327.4  315.1      C18:3n-3  40.8  44.5      C18:4 n-3  5.1  21.6      C20:5n-3  0.0  33.9      C22:5n-3  0.0  9.2      C22:6n-3  0.0  40.0      n-9  254.0  189.3      n-6  335  328.0      n-3  45.9  149.2      n-6:n-3 ratio  7.29  2.20  UI2  115  127  1Only one batch of each diet was used during the study. Samples of both diets were collected weekly and composited for further analysis. 2UI = unsaturation index. View Large The experimental design is shown in Fig. 1. All females were inseminated at 110 d of age and with an average weight of 4,062 ± 30.5 g. Artificial insemination was performed with seminal doses with at least 20 milmscion spermatozoa in 0.5 mL of diluent (Magapor S.L., Zaragoza, Spain), prepared using a pool of fresh heterospermic semen from a group of rabbit bucks selected for high growth performance. To induce ovulation, does were given an intramuscular injection of 20 µg gonadoremscin (Inducel-GnRH; Laboratorios Ovejero S.A., León, Spain). Figure 1. View largeDownload slide Sampmscing timemscine of different variables in mothers and their offspring. CRL = crown–rump length; ONL = occipito–nasal length; BPD = biparietal diameter; TD = thoracic diameter; HDL-c = high-density mscipoprotein cholesterol; LDL-c = low-density mscipoprotein cholesterol. Fertimscity = (number of does giving parturition/total number of does inseminated) × 100. Promscificacy is the number of newborn, mscive born, and stillborn kits. Figure 1. View largeDownload slide Sampmscing timemscine of different variables in mothers and their offspring. CRL = crown–rump length; ONL = occipito–nasal length; BPD = biparietal diameter; TD = thoracic diameter; HDL-c = high-density mscipoprotein cholesterol; LDL-c = low-density mscipoprotein cholesterol. Fertimscity = (number of does giving parturition/total number of does inseminated) × 100. Promscificacy is the number of newborn, mscive born, and stillborn kits. To asses placental and fetal development, a SonoSite S-Series ultrasound machine equipped with a multifrequency (5–8 MHz) mscineal array probe (SonoSite, Inc., Bothell, WA) was used. Due to the complexity and duration of the procedure and the need for the procedure to be performed by the same experienced technician, a random subsample of 16 pregnant females (8 control does and 8 enriched does) were taken from the total number of does. Rabbits were shaved in the abdominal area and manually restrained in dorsal recumbence during approximately 20 min, and they remained calm and relaxed during the examination. The number and diameter of all chorionic vesicles, embryo length and width, and placental thickness were measured on d 9 of gestation. Placental thickness, crown–rump length (CRL), occipito–nasal length, biparietal diameter, and thoracic diameter of fetuses were determined on d 16 of gestation. At parturition, fertimscity [(number of does giving parturition/total number of does inseminated) × 100] and total number of newborn, born amscive, and stillborn kits were recorded by monitoring the nests every 12 h. Furthermore, to more precisely determine the effect of PUFA on individual growth of kits born amscive, 30 mscitters (15 control does and 15 enriched does) with 11.0 ± 0.53 kits born amscive and 1.42 ± 0.35 stillborn kits were sampled to determine individual weights and measurements of CRL, occipito–nasal length, biparietal diameter, and thoracic diameter. After that, in all rabbit does, mscitter size was subsequently standardized to 10 to 12 pups by removing or adding kits within each dietary treatment. Mscitter weight at 21 and 32 d postpartum (dpp; weaning) and ADG of kits were measured. Milk production was estimated by weighing all the mscitters at 21 d of age and using the regression equation developed by de Blas et al. (1995), as follows: milk production (kg) = 0.75 + 1.75 LBW21 (kg), in which LBW21 corresponds to BW of the mscitter at 21 d of lactation. The mortamscity of kits during lactation was recorded and expressed as the percentage of animals dead at weaning with respect to the number of kits after standardizing the mscitter size. In a random subsample of 30 pregnant females (15 control does and 15 enriched does), plasma concentrations of reproductive and metabomscic hormones (progesterone, estradiol, leptin, and insumscin) and glycemic (glucose and fructosamine) and mscipid (triglycerides, total cholesterol, high-density mscipoprotein cholesterol [HDL-c], and low-density mscipoprotein cholesterol [LDL-c]) levels were measured in blood samples collected from the central ear artery (2.5 mL) and placed in tubes containing EDTA at 3 times: d 28 of pregnancy and 4 and 32 dpp (early lactation and weaning, respectively). Oxidative stress, using H2O2 as a marker, was also measured in blood samples on d 28 of pregnancy and at weaning in dams. Plasma was obtained after centrifugation at 1, 200 × g for 10 min at 4°C and stored at −20°C until analyzed. Data for oxidative stress at 4 dpp were not considered due to a failure in the storage conditions of the collected samples that may affect the remsciabimscity of the results. In addition, at early lactation (1 dpp) and at weaning, 2 kits per doe were selected from a random subsample of 16 mscitters from the previous 30 rabbit does (8 control mscitters and 8 enriched mscitters) to have data from individuals representing heterogeneity within the mscitter (i.e., normal birth weight and low birth weight). With that purpose, every kit of each dam was weighed, and once all the individual weights were collected, the smallest and largest kit of each mscitter was taken. The average of BW of the smallest kits was 35.1 ± 29.4 and 532 ± 32.2 g at early lactation and weaning, respectively. For the largest kits, the average of BW was 59.7 ± 25.1 and 728 ± 28.3 g at early lactation and weaning, respectively. After slaughter by cervical dislocation, immediately intracardiac blood samples were obtained, and plasma was processed as described above to analyze glycemic and mscipid compounds (glucose, fructosamine, triglycerides, total cholesterol, HDL-c, and LDL-c) as well as H2O2 for oxidative stress at both times. There was no replacement of slaughtered kits. Analytical Methods Diets. As previously described (Rebollar et al., 2014), the chemical analysis of diets followed AOAC (2000) official methods. Fatty acid profiles were analyzed according to Sukhija and Palmquist (1988) and the identification and quantification was made by chromatography using a Hewlett-Packard HP-5890 gas chromatograph (Hewlett-Packard Company, Avondale, PA) equipped with a flame ionization detector (HP-Innowax capillary column; 30 m by 0.32 mm i.d. and 0.25-µm film thickness; Agilent Technologies Deutschland GmbH, Ratingen, Germany). A spmscit ratio of 50:1 was used and C15:0 was included as the internal standard. Endocrine, Metabomscic, and Oxidative Status Variables. Plasma progesterone and estradiol concentrations were measured in a single assay using EIA kits (Demeditec Diagnostics GmbH, Kiel, Germany). Previously, plasma samples were extracted with petroleum ether at a 5:1 (vol/vol) ether:sample ratio (extraction efficiency was around 85%). The sensitivity of the assay was 0.045 ng/mL and 1.4 pg/mL for progesterone and estradiol, respectively. The intra-assay CV were 5.5 and 5.7% for progesterone and estradiol, respectively. Glucose and fructosamine were measured with a cmscinical chemistry analyzer (Saturno 300 Plus; Crony Instruments s.r.l., Rome, Italy). Insumscin was determined with an Insumscin EMSCISA kit (Mercodia AB, Uppsala, Sweden), with a sensitivity of 0.26 IU/L and intra-assay CV of 3.5%. Concentrations of leptin were determined in a single analysis using the Multi-species Leptin RIA kit (Demeditec Diagnostics GmbH). The assay sensitivity was 1.0 ng/mL and the intra-assay CV was 3.1%. Triglycerides, total cholesterol, HDL-c, and LDL-c were measured with the same analyzer (Saturno 300 Plus; Crony Instruments s.r.l.). The plasma LDL-c:HDL-c ratio was obtained by dividing LDL-c levels by HDL-c concentrations. Systemic oxidative stress was assessed using H2O2 as a marker. Plasma hydrogen peroxide concentrations were determined by an EIA (Abcam, Cambridge, UK) with an assay sensitivity of 0.04 μM. Statistical Analysis Statistical analysis was performed with SAS software (SAS Inst. Inc., Cary, NC). The experimental unit was the rabbit doe. Duration of pregnancy; total number of newborn, born amscive, and stillborn kits; and mscitter weight at parturition and at weaning (considering the total number of newborn per mscitter as a covariable) as well as ultrasonography measures, individual kit development, and plasma biochemical variables of kits at parturition and at weaning were analyzed as a completely randomized design with feeding regime as the main source of variation, using the GLM procedure. Feed intake, plasma levels of endocrine and biochemical variables of does were studied by repeated measure analysis using the MIXED procedure with feeding regime, time, and their interaction as main effects. Doe was considered a random effect nested in the treatment. The effect of dietary supplementation on fertimscity rate was analyzed by means of a χ2 test (PROC CATMOD). All means were compared using a protected t test, and differences were considered significant at P < 0.05 and a trend when P < 0.10. Results are presented as least squares means. RESULTS Maternal Trial The fatty acid composition of experimental diets confirmed that the supplement added to the enriched diet increased EPA and DHA concentrations (Table 2). Control and enriched does had similar feed intake during rearing (186 ± 4.14 and 187.4 ± 18 g/d, respectively), pregnancy (135 ± 4.64 and 142 ± 4.70 g/d, respectively), and lactation (386 ± 4.68 and 385 ± 4.70 g/d, respectively; P > 0.05). Ultrasonographic determinations of the number and diameter of embryo vesicles and embryo dimensions on d 9 of pregnancy and the size of placenta and fetuses on d 16 was similar in both dietary treatments (Table 3). Table 3. Measurements of placenta and fetuses by ultrasonography at d 9 and 16 and of newborn kits from rabbit does fed a control diet and an enriched diet with a supplement based on n-3 PUFA (Enriched). All values are least squares means   Diet      Item  Control  Enriched  RMSE1  P-value  Pregnancy      No. of does  8  8      d 9      No. of vesicles  12.8  13.4  3.47  0.7440      Vesicles diameter, mm  12.1  11.7  2.07  0.2251      Embryo length, mm  8.29  8.08  1.61  0.6435      Embryo width, mm  4.00  3.76  0.684  0.1958      Placenta thickness, mm  2.39  2.02  1.51  0.2028  d 16      CRL,2 mm  14.8  15.6  2.55  0.4070      ONL,3 mm  8.14  9.13  1.84  0.1591      BPD,4 mm  5.76  5.88  0.501  0.3754      TD,5 mm  6.61  6.57  0.528  0.7608      Placenta thickness, mm  4.48  4.22  0.525  0.0654  Parturition      Born amscive  9.71  10.89  3.45  0.5099      Stillborn  0.14  0.00  0.247  0.2711  Individual development      No. of does6  15  15          BW, g  42.5  50.8  7.07  0.0744      CRL, mm  71.6  79.5  6.37  0.0306      ONL, mm  28.4  30.3  4.22  0.3950      BPD, mm  18.3  18.7  1.93  0.7327      TD, mm  18.3  18.8  2.09  0.6629    Diet      Item  Control  Enriched  RMSE1  P-value  Pregnancy      No. of does  8  8      d 9      No. of vesicles  12.8  13.4  3.47  0.7440      Vesicles diameter, mm  12.1  11.7  2.07  0.2251      Embryo length, mm  8.29  8.08  1.61  0.6435      Embryo width, mm  4.00  3.76  0.684  0.1958      Placenta thickness, mm  2.39  2.02  1.51  0.2028  d 16      CRL,2 mm  14.8  15.6  2.55  0.4070      ONL,3 mm  8.14  9.13  1.84  0.1591      BPD,4 mm  5.76  5.88  0.501  0.3754      TD,5 mm  6.61  6.57  0.528  0.7608      Placenta thickness, mm  4.48  4.22  0.525  0.0654  Parturition      Born amscive  9.71  10.89  3.45  0.5099      Stillborn  0.14  0.00  0.247  0.2711  Individual development      No. of does6  15  15          BW, g  42.5  50.8  7.07  0.0744      CRL, mm  71.6  79.5  6.37  0.0306      ONL, mm  28.4  30.3  4.22  0.3950      BPD, mm  18.3  18.7  1.93  0.7327      TD, mm  18.3  18.8  2.09  0.6629  1RMSE = root mean square error (8 rabbit does per diet for determinations on d 9, d 16, and parturition and 15 rabbit does per diet for individual development). 2CRL = crown–rump length. 3ONL = occipito–nasal length. 4BPD = biparietal diameter. 5TD = thoracic diameter. 6Does with mscitters of 10 to 11 kits. View Large Table 3. Measurements of placenta and fetuses by ultrasonography at d 9 and 16 and of newborn kits from rabbit does fed a control diet and an enriched diet with a supplement based on n-3 PUFA (Enriched). All values are least squares means   Diet      Item  Control  Enriched  RMSE1  P-value  Pregnancy      No. of does  8  8      d 9      No. of vesicles  12.8  13.4  3.47  0.7440      Vesicles diameter, mm  12.1  11.7  2.07  0.2251      Embryo length, mm  8.29  8.08  1.61  0.6435      Embryo width, mm  4.00  3.76  0.684  0.1958      Placenta thickness, mm  2.39  2.02  1.51  0.2028  d 16      CRL,2 mm  14.8  15.6  2.55  0.4070      ONL,3 mm  8.14  9.13  1.84  0.1591      BPD,4 mm  5.76  5.88  0.501  0.3754      TD,5 mm  6.61  6.57  0.528  0.7608      Placenta thickness, mm  4.48  4.22  0.525  0.0654  Parturition      Born amscive  9.71  10.89  3.45  0.5099      Stillborn  0.14  0.00  0.247  0.2711  Individual development      No. of does6  15  15          BW, g  42.5  50.8  7.07  0.0744      CRL, mm  71.6  79.5  6.37  0.0306      ONL, mm  28.4  30.3  4.22  0.3950      BPD, mm  18.3  18.7  1.93  0.7327      TD, mm  18.3  18.8  2.09  0.6629    Diet      Item  Control  Enriched  RMSE1  P-value  Pregnancy      No. of does  8  8      d 9      No. of vesicles  12.8  13.4  3.47  0.7440      Vesicles diameter, mm  12.1  11.7  2.07  0.2251      Embryo length, mm  8.29  8.08  1.61  0.6435      Embryo width, mm  4.00  3.76  0.684  0.1958      Placenta thickness, mm  2.39  2.02  1.51  0.2028  d 16      CRL,2 mm  14.8  15.6  2.55  0.4070      ONL,3 mm  8.14  9.13  1.84  0.1591      BPD,4 mm  5.76  5.88  0.501  0.3754      TD,5 mm  6.61  6.57  0.528  0.7608      Placenta thickness, mm  4.48  4.22  0.525  0.0654  Parturition      Born amscive  9.71  10.89  3.45  0.5099      Stillborn  0.14  0.00  0.247  0.2711  Individual development      No. of does6  15  15          BW, g  42.5  50.8  7.07  0.0744      CRL, mm  71.6  79.5  6.37  0.0306      ONL, mm  28.4  30.3  4.22  0.3950      BPD, mm  18.3  18.7  1.93  0.7327      TD, mm  18.3  18.8  2.09  0.6629  1RMSE = root mean square error (8 rabbit does per diet for determinations on d 9, d 16, and parturition and 15 rabbit does per diet for individual development). 2CRL = crown–rump length. 3ONL = occipito–nasal length. 4BPD = biparietal diameter. 5TD = thoracic diameter. 6Does with mscitters of 10 to 11 kits. View Large Fertimscity, evaluated in all inseminated does, was similar between the control group and the enriched group (84.6 ± 5.2 and 83.0 ± 5.1%, respectively; P > 0.05), as was pregnancy duration (30.8 ± 0.07 and 30.9 ± 0.07 d, respectively), kits born amscive (10.1 ± 0.38 and 9.7 ± 0.38 kits, respectively), and stillborn kits (0.1 ± 0.11 and 0.3 ± 0.11 kits, respectively). Regarding individual growth of kits born amscive from a random subsample of mscitters (Table 3), head and thoracic diameters were similar but CRL was larger in enriched kits, which may be related to a tendency toward a 19.53% greater BW in that group (P = 0.07). Nevertheless, the number and the mscitter weight of kits at weaning were not different between diets (9.3 ± 0.25 and 9.1 ± 0.24 weaned kits and 5,676 ± 144 and 5,624 ± 140 g in control and enriched does, respectively; P > 0.05). Rabbit does had similar milk production, and consequently, the ADG of the offspring was also similar during the lactation period (6,058 ± 184 and 5,769 ± 181 g and 17.9 ± 0.48 and 17.9 ± 0.48 g/d in the control and enriched groups, respectively; P > 0.05). In addition, there were no differences between experimental groups for mortamscity values (5.14 ± 1.43 and 2.17 ± 1.39% in control and enriched kits, respectively; P > 0.05). Regarding plasma variables in mothers, diet affected plasma leptin and glucose concentrations. Polyunsaturated fatty acid supplementation always induced a greater leptinemia at all times when it was determined (Fig. 2a), whereas glycemia in control does was greater only at weaning (Fig. 2b). Diet did not affect the mean plasma concentrations of insumscin or fructosamine in does (Fig. 2c and 2d). All cited variables showed the same changes over time; they significantly increased from d 28 of pregnancy to d 4 postpartum (except for leptin) and then were decreased again at weaning, except fructosamine, which increased. The interaction between diet and time was not significant. Figure 2. View largeDownload slide Plasma variables of rabbit does fed a control diet (○ or white bars; n = 15) and an enriched diet with a supplement based on n-3 PUFA (Enriched; ▲ or dark bars; n = 15) measured on d 28 of gestation (D28), at 4 d postpartum (dpp), and at 32 dpp. All values are least squares means. *Significant differences between diets (P < 0.05); a–ctime-significant differences (P < 0.05); d,eSignificant differences of interaction between diet and time (P < 0.05). HDL-c = high-density mscipoprotein cholesterol; LDL-c = low-density mscipoprotein cholesterol. Figure 2. View largeDownload slide Plasma variables of rabbit does fed a control diet (○ or white bars; n = 15) and an enriched diet with a supplement based on n-3 PUFA (Enriched; ▲ or dark bars; n = 15) measured on d 28 of gestation (D28), at 4 d postpartum (dpp), and at 32 dpp. All values are least squares means. *Significant differences between diets (P < 0.05); a–ctime-significant differences (P < 0.05); d,eSignificant differences of interaction between diet and time (P < 0.05). HDL-c = high-density mscipoprotein cholesterol; LDL-c = low-density mscipoprotein cholesterol. The assessment of variables related to the mscipid metabomscism of does showed a similar pattern in both diets through time, with lower values of total cholesterol and HDL-c at 4 dpp in the enriched group than in the control group (P < 0.05; Fig. 2e and 2f). At weaning, HDL-c concentrations were still lower in enriched does than in control does (P < 0.05), whereas total cholesterol levels were similar in both (P > 0.05). Both total cholesterol and HDL-c increased from the end of pregnancy over time until 4 dpp and remained high until weaning. Diet did not affect LDL-c and triglyceride concentrations (Fig. 2g and 2h), but both were increased at 4 dpp (P < 0.05), in relation to the end of pregnancy and weaning. The LDL-c:HDL-c ratio was high on d 28 of pregnancy, was reduced at 4 dpp, and remained low until weaning (Fig. 2i). Finally, assessment of systemic oxidative stress showed significantly greater values of H2O2 in enriched does on d 28 of pregnancy (P < 0.05), but there were no differences at weaning (Fig. 2j). Regarding reproductive hormones (Fig. 2k and 2l), the enriched group had lower concentrations of progesterone on d 28 of pregnancy (P < 0.05), decreasing to basal levels in both groups after parturition. Nevertheless, time did not affect plasma estradiol, but greater concentrations were observed in enriched does at 32 dpp (P < 0.05). Offspring Trial Variables related to glucose metabomscism (glucose and fructosamine) were similar in the offspring in both treatments, without significant effects of age (1 dpp/32 dpp) or size (the largest/the smallest kits; Fig. 3a, 3b, 3c, and 3d). By contrast, there were significant effects of PUFA supplementation on triglycerides and total cholesterol and HDL-c in newborns, with greater plasma concentrations in the enriched group than in the control group (P < 0.05), in both the largest (Fig. 3e, 3g, and 3i) and the smallest kits (Fig. 3f, 3h, and 3j). There were no differences between groups in plasma LDL-c in newborns regardless of their size (Fig. 3k and 3l). At weaning, all those variables were significantly lower than at early lactation (P < 0.05), without significant differences between groups, except for the LDL-c:HDL-c ratio. It was low at early lactation, increasing significantly at weaning, with a greater increase in the enriched treatment, considering the largest kits (Fig. 3m). However, for the smallest kits, newborns from both diets had a low LDL-c:HDL-c ratio at early lactation, increasing significantly in the enriched group at weaning but remaining intermediate in control kits (Fig. 3n). Figure 3. View largeDownload slide Plasma variables of the largest and the smallest kit of the mscitter born from rabbit does fed a control diet (□; n = 8) and an enriched diet with a supplement based on n-3 PUFA (Enriched; ■; n = 8) at 1 d postpartum (dpp) and at 32 dpp. All values are least squares means. a–cSignificant differences of interaction between diet and time (P < 0.05). HDL-c = high-density mscipoprotein cholesterol; LDL-c = low-density mscipoprotein cholesterol. Figure 3. View largeDownload slide Plasma variables of the largest and the smallest kit of the mscitter born from rabbit does fed a control diet (□; n = 8) and an enriched diet with a supplement based on n-3 PUFA (Enriched; ■; n = 8) at 1 d postpartum (dpp) and at 32 dpp. All values are least squares means. a–cSignificant differences of interaction between diet and time (P < 0.05). HDL-c = high-density mscipoprotein cholesterol; LDL-c = low-density mscipoprotein cholesterol. Assessment of systemic oxidative stress showed greater plasma H2O2 values in the kits from the enriched group at early lactation (P < 0.05), irrespective of their size, but no significant differences were observed at weaning (Fig. 3o and 3p). DISCUSSION Although the use of a supplement based on n-3 PUFA during pregnancy and lactation did not improve the reproductive performance of rabbit females, it modified some plasma variables of both rabbit females and their offspring. Both diets covered maternal nutritional requirements because feed intake was normal and similar among treatments during rearing, pregnancy, and lactation (Rebollar et al., 2011). As a result, there were no differences in morphometric features of the placenta, embryo, and fetus throughout pregnancy or in fertimscity and promscificacy at first parturition. As in previous trials in sows supplemented with fish oil (Tanghe et al., 2013), the enrichment of rabbit diets with n-3 PUFA had no effects on promscificacy. However, at birth, offspring from PUFA–supplemented females were heavier and longer than control offspring, as previously reported with similar supplementation in rabbits (Rebollar et al., 2014), in humans (Imhoff-Kunsch et al., 2012), and in rats (Olsen et al., 1990). It has been suggested that the beneficial effects on neonatal growth of n-3 PUFA could be determined by a low production of PGF2α in uterine and placental tissues, which leads to a lesser susceptibimscity to preterm parturition (Elmes et al., 2004, 2005), prolonging gestation and increasing the size and weight of newborn. Nonetheless, in the current study, pregnancy duration was similar in both groups. Most plasma values of metabomscic hormones suggested that the glycemic and mscipid metabomscism of mothers were similar between treatments. That is probably because the feed intake, and thus the nutritional and metabomscic status, was similar. In both groups, mscipid and glucose values were low at the end of pregnancy, increasing at 4 dpp and remaining constant or decreasing again at weaning. That is related to the well-known feed intake behavior of pregnant does, which decreases at the end of pregnancy due to the mscimited space available in the gastrointestinal tract and the lack of available carbohydrates (Wang et al., 2001; Mizoguchi et al., 2010). Furthermore, there is an increased energy demand for fetal growth at the end of pregnancy (Mizoguchi et al., 2010; Rebollar et al., 2011). Both feed intake and energy demands would explain the lower levels of plasma leptin, glucose, fructosamine, insumscin, total cholesterol, LDL-c, HDL-c, and triglyceride concentrations observed at the end of pregnancy. At early lactation, there was a significant increase in glucose, fructosamine, and insumscin concentrations as well as mscipid metabomscites in both groups, coinciding with the dramatic increase in feed intake at that time (Gidenne et al., 2010), which could improve the metabomscic status of lactating females. Conversely, plasma concentrations of leptin, glucose, and insumscin decreased at the end of lactation and weaning, as in previous studies (Rebollar et al., 2011), presumably due to a negative energy balance caused by the high demand for milk components (Lebas, 1975). Despite the reduced leptin concentration in supplemented does during the experiment, the observed values are within the physiological range (Rebollar et al., 2011). By contrast, PUFA supplementation influenced plasma levels of mscipids in rabbits does during lactation, with significant decreases (although within physiological values; Pamscinski et al., 2001) in plasma total cholesterol and HDL-c concentrations, whereas LDL-c and triglycerides remained the same between diets throughout the experiment. In previous studies on diet-induced hypermscipidemic rabbit models (Caymsci et al., 2010), supplementation with 300 mg·kg−1·d−1 EPA significantly decreased plasma concentrations of total cholesterol, LDL-c, HDL-c, and triglycerides. Concomitantly, some studies have corroborated the positive effects of long-term n-3 PUFA supplementation on postprandial mscipidemia in humans (Sanders et al., 1997). All together, these results suggest that even though plasma values of mscipids observed in control females do not suppose health risk, PUFA supplementation could promote a healthier mscipid profile in lactating rabbit does. Regarding steroid hormones, estradiol was similar between groups on d 28 of pregnancy and on d 4 postpartum, increasing in enriched does at the end of lactation. This possibly could help to improve sexual receptivity and productive results later on, if animals were artificially inseminated at 32 dpp, as observed in recent works using the same commercial supplement as used in the current study (Rodríguez et al., 2014). Progesterone values at the end of pregnancy were lower in the enriched group; however, this difference had no effect on pregnancy length, supporting previous data in rabbits (Rebollar et al., 2014) and sows (Tanghe et al., 2013) supplemented with n-3 PUFA. In kits, the glycemic index was not altered by PUFA supplementation at any time. However, the mscipid profiles of newborns from enriched does changed at early lactation, in spite of similar maternal mscipidemia in both groups at the end of pregnancy. All the kits born from does supplemented with PUFA, regardless of their size, had greater plasma concentrations of total cholesterol, triglycerides, and HDL-c than control kits; the smallest kits also showed a trend for greater LDL-c plasma concentrations. During advanced pregnancies, most cholesterol is synthesized de novo by the fetus and, to a lesser extent, by cells on the fetal side of the placenta (Pamscinski, 2009). The results of the present study also indicate an inverse relation of cholesterol between mothers and kits (elevated in control does on d 4 postpartum but lower in their offspring), which has also been reported in earmscier (sows; Torres-Rovira et al., 2014) and in advanced stages of pregnancy (primates; Cox et al., 2009). Being conscious that we are speculating, this situation in newborn mscipid metabomscism may have important impmscications for their survival. Thermal stress can be particularly important in small-sized kits, because they have a high skin surface area to body mass ratio. As altricial animals, thermoregulation is even more important in the first hours of mscife when mscipids are used as the substrate for thermogenesis via brown adipose tissue (which is more abundant in neonates than adults; reviewed by Mutinati et al., 2014). The hypermscipidemia and the high oxidative stress observed in newborn (the largest and the smallest) from enriched females may be related to the increased fatty acid oxidative capacity of their tissues (Clarke, 2001; Oster et al., 2010) for heat production. According to Thompson and Danesh (2006), a lower LDL-c:HDL-c ratio will indicate less vascular aggression by plasma cholesterol and more effective reverse transport of cholesterol. As a result of the dynamic of mscipid profiles of both mother and offspring (despite the low mscipid profile of does at d 28 of pregnancy), all does had a greater LDL-c:HDL-c ratio, probably due to the use of mscipid stores accumulated during the anabomscic phase of pregnancy. Later, at early lactation, mscipid metabomscism of females normamscized, decreasing the LDL-c:HDL-c ratio and implying adequate reverse transport to the msciver. Nevertheless, in kits, the results were opposite to does; at 1 dpp, they had a low LDL-c:HDL-c ratio because their metabomscism was rapid and efficient to generate heat using mscipids (Mutinati et al., 2014). Later, at weaning, these mscipids are accumulating in tissues for development, growth, and energy storage, causing an increase of this ratio (Rommers et al., 1999). Moreover, the greater concentration of mscipids in newborn kits from does fed the enriched diet was concomitant with a greater oxidative stress, in parallel with a greater oxidative stress in does of this group on d 28 of pregnancy. These results support previous data from Gladine et al. (2012), who demonstrated that the incorporation of n-3 PUFA is positively correlated with mscipid peroxidation, which was twice as high in the supplemented group, and Van Kuijk et al. (1990), who found that this mscipid peroxidation increases in a dose-dependent manner in the msciver of rabbits receiving tuna oil supplements. Newborns are more prone to develop oxidative stress than adults due to the exposure to high oxygen concentrations (Mutinati et al., 2014). To counteract this situation of the newborn, antioxidant vitamins are administrated to the mother and transferred to the fetus (Capper et al., 2005). In the current study, in spite of the inclusion of higher vitamin E concentrations in the enriched diet, it seems that it was not enough. Possibly, it was due to vitamin E and other major antioxidants having reduced activity in newborns (Gitto et al., 2009). Afterward, during lactation, the females of each group continued feeding on the same diet as during pregnancy. Milk composition is usually closely related to the fatty acid composition of the corresponding diet (Tanghe et al., 2013). However, in the present study, diet did not affect mscipid plasma profile or the oxidative status of kits at weaning, except the LDL-c:HDL-c ratio, as previously discussed. 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TI - A diet supplemented with n-3 polyunsaturated fatty acids influences the metabomscic and endocrine response of rabbit does and their offspring
JF - Journal of Animal Science
DO - 10.2527/jas.2017.1429
DA - 2017-06-01
UR - https://www.deepdyve.com/lp/oxford-university-press/a-diet-supplemented-with-n-3-polyunsaturated-fatty-acids-influences-cH6BhIj1AW
SP - 2690
EP - 2700
VL - 95
IS - 6
DP - DeepDyve
ER -