脯氨酸促进胎猪生长发育的分子机制研究

The pig has no brown adipose tissue to oxidize long-chain fatty acids or glucose to water and CO2 and, consequently, naturally gains excessive amounts of subcutaneous white adipose tissue during pregnancy. While this metabolic feature may be beneficial for conserving maternal nutrient reserves in the face of limited food intake, adverse impacts of such a maternal adaptation mechanism during species evolution include impairments of both embryonic/fetal survival and sow’s lactation performance post partum. Therefore, in the current production practice, gestating gilts are fed 2 to 2.2 kg diet daily (approximately 50% of their ad libitum feed intake) to minimize white fat accretion. However, because of inadequate provision of amino acids in diets, the pig continues to exhibit the highest rate of embryonic mortality and the highest rate of fetal growth restriction among livestock species worldwide. One of such nutritionally important amino acids may be L-proline (Pro), which had been considered a “nutritionally nonessential amino acid”. In our recent studies, we discovered that Pro is a major precursor for the synthesis of polyamines and pyrroline-5-carboxylate (P5C) in the porcine placenta. Polyamines (particularly putrescine) and P5C are crucial for DNA and protein synthesis as well as placental redox signaling, and therefore, embryonic/fetal growth, development and survival. Such a novel metabolic pathway is likely significant both nutritionally and physiologically, because arginine is not utilized by the porcine placenta for synthesis of polyamines (including putrescine) or P5C. We hypothesizes that: (1) Pro plays an important role in activating the mTOR signaling pathway in the placenta and embryos, thereby enhancing protein synthesis and inhibiting proteolysis as well as the growth and survival of the conceptus; (2) Pro regulates epigenetic expression of genes in the porcine fetus that may influence postnatal metabolism, growth of offspring, and the efficiency of their nutrient utilization. Findings from the present research will enhance our understanding of amino acid biochemistry and nutrition in gestating swine thus have broad impacts on improving reproductive efficiency in mammalian livestock species.

猪体内无褐色脂肪组织，因此不能氧化分解长链脂肪酸。这就导致母猪在孕期积蓄额外的皮下白色脂肪。这一代谢特性对胚胎／胎猪的存活产生巨大负面影响。因此，需对妊娠母猪进行限饲以减少脂肪沉积。然而，由于日粮中氨基酸的补充不足，导致猪生产中极高的胚胎死亡率及胎猪生长受限率。脯氨酸（L-proline, Pro）一直被视为非必需氨基酸。然而我们最近发现，Pro是猪胎盘中合成多胺及二氢吡咯-5-羧酸的主要前体。多胺及二氢吡咯-5-羧酸对DNA与蛋白质的合成及胎盘的氧化还原信号至关重要，直接影响胚胎／胎猪的生长、发育及存活。本研究的假设为：1）Pro可激活胎盘及胚胎中的mTOR信号通路，促进蛋白质合成和抑制蛋白降解，从而促进孕体的生长与存活；2）Pro可通过调节猪胚胎基因的表观遗传表达，影响出生后猪的代谢、生长及养分利用率。本研究的发现不仅能深化对妊娠母猪氨基酸营养生化的理解，并为提高家畜繁殖效率提供参考。

妊娠期母体组织的营养直接影响胚胎发育和繁殖性能。在实践生产中，常通过限饲来减少妊娠母猪的体脂的过度蓄积，这可能在一程度上影响胚胎的营养供给和存活，影响母猪繁殖性能的发挥。脯氨酸（L-proline, Pro）一直被视为非必需氨基酸，然而我们最近发现，Pro是胎盘中合成多胺及二氢吡咯-5-羧酸的主要前体。多胺及二氢吡咯-5-羧酸对DNA与蛋白质的合成及胎盘的氧化还原信号至关重要，直接或间接影响胚胎的生长、发育及存活。本项目研究发现，脯氨酸添加明显提高胎盘中营养物质转运载体的表达，促进了血管生成因子表达和蛋白质的合成，提高了窝产仔数和胚胎的存活率，但对雌性子代的胚胎存活和繁殖性能无影响。脯氨酸显著提高外周血中B淋巴细胞（CD3、CD19+），NK细胞（CD3+ NK1.1）和树突状细胞（CD11c+MHCII+）中的含量。降低了外周血中中性粒细胞（CD11b+F4/80-）比例，显著增加血浆中免疫球蛋白Ig G2b和Ig M的含量。体外研究发现，脯氨酸明显提高了胚胎滋养层细胞的屏障功能和蛋白质周转，增强了细胞抗氧化能力。这些发现拓展了脯氨酸生营养和生理功能，并为通过脯氨酸提高家畜繁殖效率提供了数据参考。