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

繁殖是奶牛可持续发展的关键组成部分，因为它影响牛群的总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，并损害了奶牛养殖场的繁殖效率和盈利能力。植入前胚胎(胚胎和相关的胚外膜)的延长是牛成功怀孕的先决条件，并依赖于子宫内膜的组织滋养细胞分泌。尽管如此，大约三分之一的可存活的囊胚在发育的第四周结束时未能延长并存活下来。奶牛繁殖效率的提高将需要制定将早期胚胎死亡率降至最低的战略，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。*最近，我们课题组研究了子宫组织细胞的代谢组和胚胎细胞在伸长过程中的转录组。我们的结果表明，胎盘细胞含有丰富的脂类，提示胎盘细胞基因表达的显著变化可能是通过激活转录因子和细胞信号的脂类来协调的。牛子宫内膜从卵母细胞受精到14天后胚胎伸长开始积累脂质，很可能为发育中的胚胎提供了主要的脂质来源。然而，关于子宫内膜脂质成分及其对组织细胞组成和胚胎发育的重要性的详细信息尚不清楚。*拟议研究计划的长期目标是了解子宫内膜脂质对奶牛着床前胚胎发育和存活的重要性，并开发营养策略来减少怀孕损失和提高奶牛群的繁殖效率。该研究计划的具体目标是：1)研究牛在胚胎伸长开始时，子宫内膜如何以及积累了哪些脂质；2)研究在胚胎伸长阶段，子宫内膜如何以及哪些脂质被转移到发育中的胚胎；3)评估特定脂类对胚胎细胞生物学的影响；4)开发一种营养补充剂，能够用有利于胚胎发育和存活的靶向脂类来丰富哺乳期奶牛的子宫内膜。

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.