Lu Xingrong, Song Jingyuan, Liang Gan, Zhong Huapei, Xu Yuanyuan, Xie Yingxue, Shi Deshun, Luo Chan
Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, 75 Xiuling Road, Nanning 530005, China.
Guangxi Key Laboratory of Buffalo Genetics, Reproduction and Breeding, Guangxi Buffalo Research Institute, Chinese Academy of Agricultural Science, Nanning 530001, China.
Metabolites. 2025 Sep 17;15(9):615. doi: 10.3390/metabo15090615.
While economically vital, buffalo exhibits low reproductive efficiency largely due to embryonic losses during implantation. Successful implantation requires precise embryo-maternal communication and metabolic/immune adaptations in the endometrium. We aimed to identify key serum metabolic signatures and associated peripheral immune responses that characterize the endometrial receptivity window during early pregnancy in water buffalo. Blood samples from pregnant (Preg, = 12) and non-pregnant (Non-P, = 10) buffaloes were collected on days 15, 18, and 21 post-artificial insemination (AI). We measured leukocyte counts and hormone levels and performed untargeted serum metabolomic profiling using LC-MS. Pregnant buffaloes showed significantly reduced total white blood cell count, lymphocyte (LYM%), and neutrophil (NEU%) percentages, indicating immune remodeling at the beginning of pregnancy establishment. Metabolomic analysis identified 131 differentially expressed metabolites (DEMs) associated with pregnancy status at different stages. Enriched pathways included steroid hormone synthesis, retinol metabolism, starch/sucrose metabolism, and phenylalanine biosynthesis. Crucially, alterations in unsaturated fatty acids, retinol, and phenylalanine metabolism, along with monocyte (MON%)/LYM% ratios, were strongly linked to receptivity changes and successful implantation. Endometrial receptivity in buffalo during the embryonic implantation window was associated with changes in immune cells and metabolism in the blood, suggesting that immunometabolism may play an essential role in modulating endometrial receptivity during the implantation window. This study provides potential clues and a metabolic framework for understanding the underlying mechanisms of buffalo embryonic implantation.
水牛虽然在经济上至关重要，但其繁殖效率较低，这主要是由于植入过程中的胚胎损失。成功植入需要精确的胚胎与母体之间的沟通以及子宫内膜的代谢/免疫适应。我们旨在确定关键的血清代谢特征以及相关的外周免疫反应，这些特征可表征水牛早期妊娠期间子宫内膜的接受窗。在人工授精（AI）后的第15、18和21天，收集了怀孕（Preg，n = 12）和未怀孕（Non-P，n = 10）水牛的血样。我们测量了白细胞计数和激素水平，并使用液相色谱-质谱联用技术进行了非靶向血清代谢组学分析。怀孕的水牛显示总白细胞计数、淋巴细胞（LYM%）和中性粒细胞（NEU%）百分比显著降低，表明在妊娠建立初期存在免疫重塑。代谢组学分析确定了131种与不同阶段妊娠状态相关的差异表达代谢物（DEM）。富集的途径包括类固醇激素合成、视黄醇代谢、淀粉/蔗糖代谢和苯丙氨酸生物合成。至关重要的是，不饱和脂肪酸、视黄醇和苯丙氨酸代谢的改变，以及单核细胞（MON%）/淋巴细胞（LYM%）比率，与接受性变化和成功植入密切相关。水牛胚胎植入窗期间的子宫内膜接受性与血液中免疫细胞和代谢的变化有关，这表明免疫代谢可能在调节植入窗期间的子宫内膜接受性中起重要作用。本研究为理解水牛胚胎植入的潜在机制提供了潜在线索和代谢框架。
