环江香猪妊娠早期孕体多胺代谢与胎盘发育调控

This research discovered that the growth and metabolism of placenta belonging to fetus with different birth weight differed significantly during the early trimester of pregnancy in Huanjiang mini-pigs; dietary supplementing 0.83% arginine promoted placental production of nitric oxide, which resulted in the increase of growth and development of the fetus during the early trimester of pregnancy. Researches with pig embryonic trophectoderm cells (pTr2) in vitro showed that the arginine via NO production regulated the mTOR signaling pathway, increased protein synthesis and decreased its degradation, thereby promoted the growth of pTr2; putrescine also increased protein synthesis via regulating mTOR signaling pathway, and promoted the growth of pTr2. The research team already published 11 papers until now, 4 of which included by SCI Journal, trained two postgraduates, and obtained one of National Science and Technology Progress Award (Second). Polyamines are very importance to the placental development. In the pig placenta, not arginine, but mainly proline is the precursors of polyamines. The project plans to further study the metabolic regulation of polyamines in conceptus during the early trimester of pregnancy in sows and its regulating role to placental development by supplementing proline or inhibiting polyamine synthesis, in order to clarify the physio-biochemical differences of polyamine metabolism in fetus with different body weight. Furthermore, the pTr2 cell model will be used to reveal these mechanisms, which maybe include the transport of amino acids, regulation of related metabolic enzymes, protein turnover and cell apoptosis of the conceptus. The project will supply some theoretical information for promoting the placenta development and fetus survival in sows.

本项目研究发现，妊早期环江香猪不同体重胎猪对应胎盘的生长与代谢显著不同；日粮添加0.83％精氨酸可促进妊早期胎盘NO生成和胎猪生长发育；体外处理猪胚胎滋养外胚层细胞(pTr2)，发现精氨酸可通过生成NO调节mTOR信号通路，增加蛋白质合成并降低其降解，从而促进pTr2生长；腐胺也可通过调节mTOR信号通路增加蛋白质合成、促进pTr2生长。本项目已发表论文11篇，其中SCI收录4篇；培养硕士生2名，获国家科技进步二等奖1项。鉴于多胺对胎盘发育的重要性，而猪胎盘中的多胺不能由精氨酸生成、主要由脯氨酸生成，故本项目拟进一步通过补充脯氨酸或抑制多胺合成，研究妊早期母猪孕体多胺代谢规律及其对胎盘发育的调控，阐明不同体重胎猪对应的胎盘中多胺代谢的生理生化差异，并结合pTr2模型研究，从孕体氨基酸转运、相关代谢酶调节、蛋白质周转和细胞凋亡等方面揭示其机制，为促进猪的胎盘发育、提高胎猪成活提供理论依据。

多胺是胚胎形成、血管生成、胎盘和胎儿生长发育的关键调控物质，而猪胎盘中的多胺主要由脯氨酸生成。本项目研究了妊娠早期环江香猪孕体多胺代谢规律及其对胎盘发育的调控，阐明不同体重胎猪对应胎盘中多胺代谢的生理生化差异，并揭示其机制，为促进猪的胎盘发育、提高胎猪成活提供依据。研究发现：① 妊娠环江香猪胎盘中存在脯氨酸-鸟氨酸-多胺代谢通路，不同胎龄、不同体重胎儿对应胎盘中上述代谢通路的发育规律存在显著差异，并明确了氨基酸营养调控胎盘发育的关键期和作用靶点。② 胎猪体重与胎盘发育以及羊水和尿囊液中部分营养素及其代谢产物的含量均呈显著正相关；70日龄不同体重胎猪胎盘滋养层细胞蛋白组特性方面，与小体重胎猪相比，大体重胎猪显著上调蛋白有76种、显著下调蛋白有72种，差异表达蛋白在细胞组分方面细胞器所占比例最大、在分子功能方面结合蛋白所占比例最大、在生物过程方面细胞内氨基酸代谢蛋白和细胞粘附蛋白所占比例最大，主要作用蛋白包括天冬氨酸转氨酶、细胞质、D-3-磷酸甘油酸脱氢酶、钙网蛋白、线粒体、细胞分裂控制蛋白42同源物等，差异蛋白主要集中于碳代谢通路。③ 饲粮添加脯氨酸可改变妊娠环江香猪及其子代的营养代谢和生长发育，通过多胺途径激活胚胎滋养层细胞mTOR信号通路、调节氨基酸转运和关键代谢酶表达等途径正向调控胎盘细胞增殖和蛋白质周转，从而促进胎盘发育。④ 饲粮添加脯氨酸可提高70日龄胎猪体重，显著上调70日龄胎猪胎盘滋养层细胞中57个蛋白、显著下调28个蛋白。在受调控蛋白中，细胞组成方面细胞器蛋白所占比例最大为56%、分子功能方面结合蛋白所占比例最大为72%、生物过程方面生物调控蛋白所占比列最大为29%，最大差异蛋白归属于半乳糖代谢通路。上述研究结果为猪的胎儿生长发育和繁殖性能调控提供了新的靶点。项目执行期间，发表论文17篇，其中SCI收录6篇；获省自然科学一等奖、中华农业科技一等奖和国家自然科学二等奖各1项，申请发明专利1项。