背景:输卵管(OF)和子宫液(UF)中存在的胞外囊泡(EV)已被证明可以通过降低脂质含量和调节脂质代谢相关基因(LMGs)来提高体外培养过程中的牛胚胎质量。同时也影响细胞增殖,表明它们参与了不同生物学途径的调节。与细胞分化相关的信号通路的调节,扩散,代谢对早期胚胎发育至关重要,可以决定妊娠的成败。母体生殖液中EV内的生物活性分子,如microRNAs(miRNAs),可能有助于这种调节过程,因为它们通过转录后机制调节基因表达。
结果:从20个差异表达的miRNAs中,19在UF-EV中上调(bta-miR-134,bta-miR-151-3p,bta-miR-155,bta-miR-188,bta-miR-181b,bta-miR-181d,bta-miR-224,bta-miR-23b-3p,bta-miR-24-3p,bta-miR-27a-3p,bta-miR-29a,bta-miR-324,bta-miR-326,bta-miR-345-3p,OF-EV中的bta-miR-410,bta-miR-652,bta-miR-677,bta-miR-873和bta-miR-708)和一个(bta-miR-148b)。这些miRNA被预测为调节几种途径,如Wnt,河马,MAPK,和脂质代谢和降解。在黄体早期的OF-EV和黄体中期的UF-EV中发现的miRNA差异可能反映了不同的环境以满足胚胎不断变化的需求。此外,miRNA可能参与,特别是在子宫里,在调节胚胎脂质代谢,免疫系统,和植入。这项研究评估了黄体早期OF-EV和黄体中期UF-EV中的miRNA货物,与胚胎在体内输卵管和子宫内的运输相吻合,及其对早期胚胎发育至关重要的LMGs和信号通路的可能影响。共检测到333个miRNAs,有11只属于OF,59到UF,和263在两组之间是常见的。
结论:我们的研究表明OF-和UF-EV中的miRNA可以调节牛胚胎发育和质量,提供对可能参与调节脂质代谢的复杂母体-胚胎通讯的见解,免疫反应,和早期妊娠期间的植入。
BACKGROUND: Extracellular vesicles (EVs) present in oviductal (OF) and uterine fluid (UF) have been shown to enhance bovine embryo quality during in vitro culture by reducing lipid contents and modulating lipid metabolism-related genes (LMGs), while also influencing cell proliferation, suggesting their involvement on the regulation of different biological pathways. The regulation of signaling pathways related to cell differentiation, proliferation, and metabolism is crucial for early embryo development and can determine the success or failure of the pregnancy. Bioactive molecules within EVs in maternal reproductive fluids, such as microRNAs (miRNAs), may contribute to this regulatory process as they modulate gene expression through post-transcriptional mechanisms.
RESULTS: From the 20 differentially expressed miRNAs, 19 up-regulated in UF-EVs (bta-miR-134, bta-miR-151-3p, bta-miR-155, bta-miR-188, bta-miR-181b, bta-miR-181d, bta-miR-224, bta-miR-23b-3p, bta-miR-24-3p, bta-miR-27a-3p, bta-miR-29a, bta-miR-324, bta-miR-326, bta-miR-345-3p, bta-miR-410, bta-miR-652, bta-miR-677, bta-miR-873 and bta-miR-708) and one (bta-miR-148b) in OF-EVs. These miRNAs were predicted to modulate several pathways such as Wnt, Hippo, MAPK, and lipid metabolism and degradation. Differences in miRNAs found in OF-EVs from the early luteal phase and UF-EVs from mid-luteal phase may reflect different environments to meet the changing needs of the embryo. Additionally, miRNAs may be involved, particularly in the uterus, in the regulation of embryo lipid metabolism, immune system, and implantation. This study evaluated miRNA cargo in OF-EVs from the early luteal phase and UF-EVs from the mid-luteal phase, coinciding with embryo transit within oviduct and uterus in vivo, and its possible influence on LMGs and signaling pathways crucial for early embryo development. A total of 333 miRNAs were detected, with 11 exclusive to OF, 59 to UF, and 263 were common between both groups.
CONCLUSIONS: Our study suggests that miRNAs within OF- and UF-EVs could modulate bovine embryo development and quality, providing insights into the intricate maternal-embryonic communication that might be involved in modulating lipid metabolism, immune response, and implantation during early pregnancy.