2. 中国农业大学动物科学技术学院, 北京 100193;
3. 中国农业科学院北京畜牧兽医研究所, 北京 100193;
4. 甘肃农业大学动物科学技术学院, 兰州 730070;
5. 宁波三生生物科技有限公司, 宁波 315100
2. College of Animal Science and Technology, China Agricultural University, Beijing 100193, China;
3. Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China;
4. College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China;
5. Ningbo Sansheng Biotechnology Co., Ltd., Ningbo 315100, China
绵羊(Ovis aries)产羔数是影响养羊业发展的关键因素,产羔数的增加对于养羊经济效益的提高具有重要意义。胚胎产前损失是哺乳动物繁殖过程中的一个主要问题,绵羊和大多数哺乳动物胚胎死亡率约20%~40%,其中三分之二发生在附植期[1]。目前,尚无有效方法减少早期妊娠胚胎损失,严重制约了家畜繁殖性能的发挥。母体营养是影响子宫内环境的主要因素,在调节胎儿存活、生长和发育中起重要作用。其中,营养的均衡性和质量都可能影响到胚胎发育。研究表明,精氨酸是体内合成一氧化氮(nitric oxide,NO)、蛋白质等物质的前体,能够调控胎盘的营养运输,促进胎盘和胎儿发育[2],精氨酸通过内皮型一氧化氮合酶(endothelial nitric oxide synthase, eNOS)和诱导型一氧化氮合酶(inducible nitric oxide synthase, iNOS)合成的NO对胚胎发育、着床和滋养层侵入、胎盘血管生成具有积极的调控作用[3-7]。鉴于精氨酸对胚胎发育的重要促进机制,很多研究在饲料中添加N-乙酰谷氨酸(N-acetylglutamate,NAG)的类似物[8]N-氨甲酰谷氨酸(N-carbamylglutamate,NCG),以激活精氨酸内源合成的必需辅助因子氨甲酰磷酸合成酶-Ⅰ(Carbamyl phosphate synthetase Ⅰ, CPS-Ⅰ),促进精氨酸内源合成[9]。通过妊娠饲粮中添加NCG提高了胚胎存活率,显著改善了母猪繁殖性能[10-11],NCG还能降低过高血浆氨导致的胚胎和胎儿死亡风险[12]。有研究曾对限饲母羊补饲NCG,使胎盘肉阜和子叶组织中Tie-2 mRNA表达量、p-p70S6K蛋白表达量和脐静脉血中的NO浓度显著升高,进而促进了胎盘生长发育[13],NCG添加还促进了营养不良母羊的胎儿生长[14-15],但目前还未见母羊妊娠早期饲喂NCG效果的相关报道。为此,本研究拟在经产母羊妊娠早期饲粮中添加不同水平NCG,探索其对产羔性能的影响,以期为提高养羊业经济效益提供技术支持。
1 材料与方法 1.1 试验材料NCG的有效含量为97%,由国家饲料工程技术研究中心生产。
1.2 试验动物与试验设计选择160只2~3岁、胎次(2~3胎)和体重相近(约60 kg)、繁殖机能正常的湖羊母羊,随机分为4组,每组40只,每只母羊为1个重复。参照NRC(2004)标准,根据相应体重母绵羊妊娠前期营养需要量配制基础饲粮(表 1)。精料和粗饲料混合饲喂,对照组每只羊每天饲喂2.7 kg,其中精料0.162 kg、大麦草0.621 kg、苜蓿草0.135 kg、玉米青贮1.782 kg。以饲喂基础饲粮的为对照组,饲喂在基础饲粮中分别添加0.05%、0.08%和0.11%NCG的为试验组。配种公羊为澳洲白,母羊采用同期排卵-子宫角定时输精方式配种,腹腔镜子宫角输精1次,自配种当天(计为妊娠第0天)开始进行饲喂试验,饲喂40 d后,各组均饲喂基础饲粮,直到分娩。
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表 1 饲粮组成和营养水平(干物质基础) Table 1 Composition and nutrient levels of diets (dry matter basis) |
试验在甘肃武威普康集团进行。各组根据试验设计饲喂日粮,每天分08:30和16:00两次饲喂。保证舍内清洁干燥、通风良好、温度适宜,并进行常规清洁和定时消毒。在妊娠第0、20、40天上午8:00,每组选择10只母羊空腹颈静脉采血10 mL,置于有肝素钠的离心管内,混匀,静置20 min,4 ℃ 3 000×g离心10 min分离血浆样品,将血浆分装于1 mL的离心管,-20 ℃冻存,用于测定血浆中氨基酸、尿素、TNOS、iNOS、NO、生长激素、雌二醇、孕酮和氨的浓度。
1.4 测定指标及方法1.4.1 母羊产羔性能 记录窝产羔羊数、窝产活羔数、死羔数、羔羊初生重等指标。
1.4.2 血浆氨基酸浓度的测定 采用德国赛卡姆Sykam(S-433D)(德国赛卡姆公司)氨基酸自动分析仪,测定血浆氨基酸浓度。取0.5 mL血浆样品与10%磺基水杨酸按1:3比例稀释,高速振荡1 min,冰上静置15 min,4 ℃ 10 000×g离心15 min,取上清液过滤装瓶, 上机测定氨基酸浓度。
1.4.3 血浆TNOS、iNOS、NO、氨、尿素、生长激素、雌二醇和孕酮浓度的测定 用比色法测定TNOS、iNOS、NO、尿素和氨的浓度,用酶联免疫吸附法(ELISA)测定生长激素、雌二醇和孕酮浓度,均按试剂盒操作说明进行各指标测定。TNOS、iNOS、NO和氨试剂盒均购自南京建成生物工程研究所;尿素、生长激素、雌二醇和孕酮检测试剂盒均购自江苏宝莱生物科技有限公司。
1.5 数据处理剔除试验期间掉栓、返情、空怀的试验羊,4个处理组实际分娩母羊的数量分别为22、21、22和22只。用SPSS 23.0统计软件对试验数据进行单因素方差分析(one-way ANOVA),以P < 0.05作为显著性判断标准,所有数据均以“平均值±标准误”表示。
2 结果 2.1 妊娠早期饲粮中添加NCG对母羊产羔性能的影响如表 2所示,与对照组相比,添加0.08%和0.11%NCG组,母羊窝产羔分别提高0.64(P < 0.05)和0.59只(P < 0.05);窝产活羔数分别提高0.59(P < 0.05)和0.68只(P < 0.05);活羔初生个体重分别减少0.73(P < 0.05)和0.78 kg(P < 0.05),但活羔初生窝重提高不显著(P>0.05)。对照组2只母羊各产1只死胎,0.08%NCG组1只母羊产3只死胎。说明妊娠早期添加0.08%和0.11%NCG,能显著增加湖羊窝产羔数,改善湖羊产羔性能。
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表 2 妊娠早期饲粮中添加NCG对母羊产羔性能的影响 Table 2 Effects of different dietary NCG supplementation on the lambing performance of ewes during early pregnancy |
如表 3所示,添加NCG对妊娠20和40 d母羊血浆游离氨基酸浓度影响不显著(P>0.05),但血浆精氨酸浓度随NCG增加呈逐渐升高趋势; 妊娠40 d时,血浆脯氨酸浓度随NCG添加量增加呈升高趋势。说明绵羊妊娠早期饲粮中添加NCG后血浆精氨酸和脯氨酸浓度有逐渐升高趋势。
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表 3 妊娠早期饲粮中添加NCG对母羊血浆游离氨基酸浓度的影响 Table 3 Effects of different dietary NCG supplementation on the concentration of free amino acids in plasma of ewes during early pregnancy |
如表 4所示,妊娠第40天时,0.05%、0.08%和0.11%NCG组NO浓度显著高于对照组(P < 0.05),各添加组间差异不显著(P>0.05);0.05%、0.08%和0.11%NCG组TNOS浓度比对照组高,但差异不显著(P>0.05);0.11%NCG组的iNOS浓度显著高于对照组(P < 0.05),其余各组差异不显著(P>0.05)。说明妊娠早期添加0.11%NCG,能够显著增加妊娠第40天绵羊血浆NO和iNOS的浓度。
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表 4 妊娠早期饲粮中添加NCG对母羊血浆NO、TNOS、iNOS浓度的影响 Table 4 Effects of different dietary NCG supplementation on the concentrations of NO, TNOS and iNOS in plasma of ewes during early pregnancy |
如表 5所示,添加NCG对生长激素和雌二醇影响不显著(P>0.05);0.11%NCG组妊娠第20天孕酮浓度比对照组高223.41 pmol·L-1(P < 0.05),其余各组间孕酮浓度差异不显著(P>0.05)。说明妊娠早期添加0.11%NCG,能够显著增加妊娠第20天绵羊血浆孕酮的浓度。
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表 5 妊娠早期饲粮中添加NCG对母羊血浆激素浓度的影响 Table 5 Effects of different dietary NCG supplementation on the concentrations of hormone in plasma of ewes during early pregnancy |
如表 6所示,添加NCG对血浆尿素浓度影响不显著(P>0.05),0.08%和0.11%NCG组,妊娠第20天氨浓度显著低于对照组和0.05%NCG组(P < 0.05),0.11%NCG组妊娠第40天血氨浓度显著低于对照组(P < 0.05),其余各组间差异不显著(P>0.05)。说明妊娠早期添加NCG,能够显著降低妊娠第20天0.08%和0.11%NCG组及妊娠第40天0.11%NCG组绵羊血浆氨的浓度。
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表 6 妊娠早期饲粮中添加NCG对母羊血浆尿素和氨浓度的影响 Table 6 Effects of different dietary NCG supplementation on the concentrations of urea and ammonia in plasma of ewes during early pregnancy |
本研究表明,妊娠早期添加NCG,能增加母羊窝产羔数、窝产活羔数,改善湖羊产羔性能。母体营养是影响子宫内环境最主要的因素,母体营养不足和营养过剩都会降低胎盘-胎儿血流量,影响胎儿的生长发育和存活[16],尤其在着床期和胎盘发育期,胎儿发育最容易受到蛋白质缺乏的影响,适宜的营养是提高胚胎存活率和促进胎儿生长发育的首要因素[10, 17]。NCG作为精氨酸内源合成关键酶CPS-Ⅰ的激活剂,在体内能促进精氨酸合成,在动物机体中发挥多种有益作用,如促进血管生成、改善氮代谢、促进泌乳和生长、增强动物繁殖和免疫能力[18],尤其是能促进绵羊滋养外胚层细胞系增殖、迁移和蛋白质合成[19-20],减少多胎母羊胚胎损失,增加羔羊出生体重,提高胎羔成活率[21-22]。经产母猪整个妊娠期饲粮添加0.1%NCG,窝产活仔数提高0.55头,仔猪初生窝重提高1.39 kg,初生个体重提高70 g,90 d血浆脯氨酸浓度显著升高[12],妊娠早期母猪饲粮添加NCG,显著增加了窝产活仔数[11]。本试验首次在湖羊妊娠早期添加NCG,也显著改善了母羊产羔性能。
此外,本研究中添加NCG虽然提高了窝重,但0.08%和0.11%NCG组活羔初生个体重显著降低,主要原因是添加NCG使产羔数显著增加, 由于总营养的限制性和个体的营养竞争作用,导致活羔初生个体重显著降低;同时,经产母猪中一般在整个妊娠期[12]或妊娠后期[23]添加NCG,增加了仔猪数量,促进了胎儿的发育,本研究为减少早期妊娠胚胎损失,提高绵羊的产羔性能,在妊娠早期添加NCG,活羔初生个体重在3.6 kg以上,达到了一般羊场羔羊初生重为1.8 kg以上的健康标准。
3.2 添加NCG对母羊血浆NO和iNOS浓度的影响本研究发现,0.05%、0.08%、0.11%NCG组在妊娠第40天时血浆NO显著升高,有研究报道,添加NCG提高了妊娠母猪血浆NO含量[2, 12, 23],限饲母羊补饲0.1%NCG使脐静脉血中的NO浓度显著升高,进而促进了胎盘生长发育[13],和本研究结果一致。动物体内的NO是由精氨酸在NOS参与下合成[3],NO是一种重要的内皮源性舒张因子,通过调控胎盘-胎儿间血流,在母体向胎儿提供养分和氧气的过程中发挥重要的调控作用[24],还通过重构细胞外基质调节胚胎着床[25],为胎儿在子宫中的发育提供大量营养素[26],在胎盘血管发育中起重要作用[4],血管生成的起始需要VEGF的表达[27],其有丝分裂效应由NO介导[28-29],NO可诱导来自不同血管床的胎儿内皮细胞增殖[30-31],并调节中心血管口径[32]。大量的证据表明,NO是胎盘血管生成、胚胎发育以及胎盘和胎儿生长的重要调控因子[27-32]。妊娠早期NO浓度升高促进了胎盘发育,同时也提高了胚胎的存活和着床率,这可能是妊娠早期添加NCG增加绵羊产羔数的作用机理。妊娠0~28 d的母猪饲粮添加NCG,促进了胚胎存活和发育,使妊娠第28天的总胎和活胎数显著增加,死亡率显著降低[10],这一结果支持了本试验对产羔数增加作用机理的推测。此外,Liu等[33]研究表明,NCG可能通过microRNAs调控NOS和血管内皮生长因子等活性,这进一步印证了本试验中添加NCG提高iNOS浓度的结果,也为本研究结果给出了科学合理的解释。
3.3 添加NCG对母羊血浆激素水平的影响雌激素和孕激素是调控妊娠的主要激素,它们在卵细胞的生殖道转运、内皮细胞增殖和分化、子宫内皮细胞蜕膜化以及在胚胎着床过程中,都扮演着重要的调控角色,对哺乳动物妊娠的建立和维持起着至关重要的作用。本试验在妊娠早期饲粮中添加NCG,提高了妊娠第20天的血液孕酮浓度,尤其0.11%NCG组在妊娠第20天的血浆孕酮显著增加,因精氨酸也是一种激素促分泌素,能够促进胰岛素、生长激素等激素的合成与分泌[26, 34]。妊娠初期,孕激素能促进子宫内膜增生,使腺体发育、功能增强,从而有利于胚胎附植[35],此阶段孕酮浓度的升高,可能也是添加NCG增加产羔数的原因之一。
3.4 添加NCG对母羊血浆氨浓度的影响经产母猪整个妊娠期饲粮中添加0.1%NCG后,血浆尿素和氨浓度降低[12],本试验中添加NCG组母羊血浆尿素浓度没有明显变化,其原因可能是物种不同。在饲粮中添加NCG能够提高中国荷斯坦奶牛产奶量、显著增加血浆NO水平、降低血浆氨水平、提高氮的利用率[36]。在人类医学中,NCG已被应用于临床进行代谢疾病的治疗,用NCG处理后,血浆氨和谷氨酰胺水平明显降低[37],血浆氨浓度降低有利于胚胎和胎儿的存活[12]。本试验中添加NCG也降低了母羊血浆氨浓度,说明绵羊饲粮中添加NCG提高了氮的利用率,也为胎儿提供了更安全的发育环境。
4 结论妊娠早期母羊饲粮添加NCG可提高母羊体循环iNOS、NO和孕酮浓度,改善胎盘营养与妊娠维持状态;降低血浆氨浓度,提高胎儿发育环境安全性,改善母羊产羔性能,提高母羊窝产羔数和窝产活羔数。
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