Department of Animal Sciences, College of Agriculture, Isfahan University of Technology, 84156-83111, Isfahan, Iran.
Global Agromedicine Research Center (GAMRC), Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, 080-8555, Japan.
Sci Rep. 2020 Sep 30;10(1):16082. doi: 10.1038/s41598-020-73225-7.
High-protein diets contribute to an increase in urea follicular concentrations associated with decreased fertility. Urea has been shown to interfere with the epidermal growth factor (EGF)/EGFR system, which has been shown to have a beneficial effect during in vitro maturation (IVM) of oocytes. Of note, the number of cumulus-oocyte complexes (COCs) in the maturation medium can change the maturation and the developmental competence of COCs. Therefore, it was hypothesized that, the presence of urea and EGF may have a differential effect on the depletion/appearance of AAs and competence of COCs matured individually (I-IVM system) or in groups (G-IVM system). In the G-IVM system, COCs increased consumption (depletion) of AAs compared with other groups in the presence of high-level urea (40 mg/dl) + EGF (10 ng/ml). In the I-IVM system, the non-cleaved COCs depleted more AAs than the cleaved COCs, in particular in the presence of urea. The combination of urea and EGF increased the depletion of AAs in the G-IVM system. However, the EGF abrogated the urea-induced depletion of AAs by the I-IVM COCs. The use of N-acetyl-L-cysteine as an EGFR inhibitor canceled urea-induced depletion of AAs. This shows the inhibiting effect of urea over the EGF/EGFR system. In the presence of urea + EGF, COCs had a lower degree of developmental competence than control in both I- and G-IVM systems. Arginine had the best predictive power to identify highly competent COCs in the G-IVM system, while glutamine was the best predictor of the cleavage in the I-IVM system. In conclusion, this multi-level study shows that COCs matured individually or in groups may have different association with AAs metabolism. These findings provide new insights into the relationships between AA metabolism and the subsequent developmental competence of COCs.
高蛋白饮食会导致卵泡中尿素浓度升高，从而降低生育能力。研究表明，尿素会干扰表皮生长因子（EGF）/表皮生长因子受体（EGFR）系统，该系统在卵母细胞体外成熟（IVM）过程中具有有益作用。值得注意的是，成熟培养基中卵丘-卵母细胞复合物（COCs）的数量可以改变 COCs 的成熟和发育能力。因此，研究假设尿素和 EGF 的存在可能对 AA 的消耗/出现以及单独成熟（I-IVM 系统）或分组成熟（G-IVM 系统）的 COCs 的发育能力产生不同的影响。在 G-IVM 系统中，与其他组相比，高浓度尿素（40mg/dl）+EGF（10ng/ml）存在时，COCs 增加了 AA 的消耗（耗尽）。在 I-IVM 系统中，与分裂 COCs 相比，未分裂 COCs 消耗了更多的 AA，特别是在存在尿素的情况下。尿素和 EGF 的组合增加了 G-IVM 系统中 AA 的消耗。然而，EGF 消除了尿素对 I-IVM COCs 中 AA 的消耗。使用 N-乙酰-L-半胱氨酸作为 EGFR 抑制剂可消除尿素诱导的 AA 消耗。这表明尿素对 EGF/EGFR 系统具有抑制作用。在存在尿素+EGF 的情况下，与对照相比，I-IVM 和 G-IVM 系统中的 COCs 的发育能力都较低。在 G-IVM 系统中，精氨酸对识别高发育能力的 COCs 具有最佳的预测能力，而在 I-IVM 系统中，谷氨酰胺是卵裂的最佳预测因子。总之，这项多层次研究表明，单独或分组成熟的 COCs 可能与 AA 代谢有不同的关联。这些发现为 AA 代谢与 COCs 随后的发育能力之间的关系提供了新的见解。
