Van Hoeck V, Rizos D, Gutierrez-Adan A, Pintelon I, Jorssen E, Dufort I, Sirard M A, Verlaet A, Hermans N, Bols P E J, Leroy J L M R
Department of Veterinary Sciences, Faculty of Biomedical, Pharmaceutical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Departamento de Reproducción Animal y Conservación de Recursos Zoogenéticos, INIA, Ctra. de la Coruna Km 5.9, 28040 Madrid, Spain.
Reprod Fertil Dev. 2015 Jan;27(2):372-84. doi: 10.1071/RD13263.
Maternal metabolic disorders linked to lipolysis are major risk factors for reproductive failure. A notable feature of such disorders is increased non-esterified fatty acid (NEFA) concentrations in the blood, which are reflected in the ovarian follicular fluid. Elevated NEFA concentrations impact on the maturing oocyte and even alter subsequent embryo physiology. The aetiological mechanisms have not been fully elucidated. Therefore, in the present study, bovine in vitro maturing cumulus-oocyte complexes were exposed (24 h) to three different maturation treatments containing: (1) physiological (72 µM) NEFA concentrations (=control); (2) elevated (75 µM) stearic acid (SA) concentrations (=HIGH SA); and (3) elevated (425 µM) NEFA concentrations (=HIGH COMBI). Zygotes were fertilised and cultured following standard procedures. Transcriptomic analyses in resulting Day 7.5 blastocysts revealed that the major pathways affected are related to lipid and carbohydrate metabolism in HIGH COMBI embryos and to lipid metabolism and cell death in HIGH SA embryos. Furthermore, lower glutathione content and a reduced number of lipid droplets per cell were observed in HIGH SA-exposed oocytes and resulting morulae, respectively, compared with their HIGH COMBI-exposed counterparts. Vitrified embryos originating from HIGH SA-exposed oocytes tended to exhibit lower survival rates compared with controls. These data suggest possible mechanisms explaining why females across species suffering lipolytic disorders experience difficulties in conceiving.
与脂肪分解相关的母体代谢紊乱是生殖失败的主要危险因素。此类紊乱的一个显著特征是血液中非酯化脂肪酸(NEFA)浓度升高,这在卵巢卵泡液中也有体现。升高的NEFA浓度会影响成熟卵母细胞,甚至改变后续胚胎的生理状态。其病因机制尚未完全阐明。因此,在本研究中,将牛体外成熟的卵丘-卵母细胞复合体暴露(24小时)于三种不同的成熟处理中,分别含有:(1)生理浓度(72µM)的NEFA(=对照);(2)升高浓度(75µM)的硬脂酸(SA)(=高SA);以及(3)升高浓度(425µM)的NEFA(=高组合)。受精卵按照标准程序进行受精和培养。对所得第7.5天囊胚的转录组分析表明,受影响的主要途径在高组合胚胎中与脂质和碳水化合物代谢有关,在高SA胚胎中与脂质代谢和细胞死亡有关。此外,与暴露于高组合的对应物相比,在暴露于高SA的卵母细胞及其所得桑椹胚中,分别观察到较低的谷胱甘肽含量和每个细胞中脂滴数量减少。与对照相比,源自暴露于高SA卵母细胞的玻璃化胚胎往往表现出较低的存活率。这些数据提示了可能的机制,解释了为什么患有脂肪分解紊乱的跨物种雌性在受孕方面会遇到困难。