Impact of Endometrial Lipids on Uterine Histotroph Composition and Preimplantation Conceptus Development in Dairy Cattle

繁殖是乳品可持续发展的关键组成部分，因为它影响畜群的整体产奶量及其生产效率。然而，哺乳期奶牛的妊娠损失是巨大的，并损害了奶牛场的繁殖效率和盈利能力。着床前胚胎（胚胎和相关的胚胎外膜）的伸长是牛成功怀孕的先决条件，并取决于子宫内膜的组织细胞分泌。然而，大约三分之一的囊胚在发育的第四周结束时不能伸长并存活。提高奶牛的繁殖效率需要制定策略，以尽量减少早期胚胎死亡率，这反过来又需要更好地阐明早期发育生物学中的关键事件。******课程组近期研究了子宫组织细胞的代谢组和受孕细胞在伸长过程中的转录组。我们的研究结果表明，组织细胞中富含脂质，并提示脂质可能通过激活转录因子和细胞信号传导来协调细胞基因表达的显著变化。牛子宫内膜从卵母细胞受精到14天后的受孕延伸开始积累脂质，可能为发育中的受孕提供主要的脂质来源。然而，关于子宫内膜脂质组成及其对组织细胞组成和受孕发育的重要性的详细信息尚不清楚。******该研究计划的长期目标是了解子宫内膜脂质对泌乳奶牛着床前胚胎发育和存活的重要性，并制定营养保健策略，以减少妊娠损失，提高奶牛群的繁殖效率。本研究计划的具体目标是：1)研究在受孕延长开始时，牛子宫内膜中脂质是如何以及哪些脂质积累的；2)研究在延长期，脂质是如何从子宫内膜转移到发育中的母体的；3)评价特定脂类对受孕细胞生物学的影响；4)开发一种能够丰富泌乳奶牛子宫内膜的营养补充品，使其富含有利于妊娠发育和生存的目标脂质。

Reproduction is a critical component of dairy sustainability because it impacts the overall milk yield in a herd and its' production efficiency. Pregnancy loss in lactating cows, however, is substantial and impairs reproductive efficiency and profitability of dairy farms. Elongation of the preimplantation conceptus (embryo and associated extra-embryonic membranes) is a prerequisite for successful pregnancy in cattle and depends on histotroph secretion by the endometrium. Nonetheless, approximately one third of viable blastocysts fail to elongate and survive by the end of the fourth week of development. Improvements in reproductive efficiency of dairy cows will require the development of strategies to minimize early embryonic mortality, which in turn will require a better elucidation of critical events in early developmental biology. ****** Recently, our research group investigated the metabolome of uterine histotroph and the transcriptome of conceptus cells during the process of elongation. Our results demonstrated that the histotroph is rich in lipids, and suggest that significant changes in gene expression of conceptus cells are likely coordinated by lipids through activation of transcription factors and cell signaling. The bovine endometrium accumulates lipids from the time of fertilization of the oocyte to the onset of conceptus elongation 14 days later, and likely provides the main source of lipids for the developing conceptus. However, detailed information on lipid composition in the endometrium and its importance for histotroph composition and conceptus development are unavailable.****** The long-term goals of the proposed research program are to understand the importance of endometrial lipids for preimplantation conceptus development and survival in lactating dairy cows, and to develop nutraceutical strategies to reduce pregnancy losses and improve reproductive efficiency of dairy herds. The specific objectives of this research program are 1) to investigate how and what lipids are accumulated in the bovine endometrium by the time of initiation of conceptus elongation; 2) to investigate how and what lipids are transferred from the endometrium to the developing conceptus during the elongation phase; 3) to evaluate the impact of specific lipids on the biology of conceptus cells; and 4) to develop a nutraceutical supplement capable of enriching the endometrium of lactating cows with target lipids that would favor conceptus development and survival.