Department of Farm Animal Health, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Biol Reprod. 2017 May 1;96(5):982-992. doi: 10.1095/biolreprod.116.146159.
Metabolic rich and poor conditions are both characterized by elevated free fatty acid levels and have been associated with impaired female fertility. In particular, saturated free fatty acids have a dose-dependent negative impact on oocyte developmental competence, while monounsaturated free fatty acids appear less harmful. Cumulus cells seem to protect the oocyte against free fatty acids, and the aim of this study was to determine the mechanism behind this protection In particular, the role of the enzyme stearoyl-CoA desaturase (SCD) that converts saturated into monounsaturated fatty acids was investigated. SCD gene and protein were abundantly expressed in cumulus cells, but expression was low in oocytes. The level of SCD protein expression in cumulus cells did not change when COCs were exposed to saturated stearic acid during maturation. SCD inhibition in the presence of stearic acid significantly reduced the developmental competence of oocytes and increased the incidence of apoptosis in cumulus cells. The esterified oleic/stearic acid ratio of the neutral lipid fraction in cumulus cells decreased in the presence of SCD inhibitors when COCs were exposed to saturated free fatty acids during maturation, indicating the SCD-specific conversion of saturated fatty acids under noninhibiting conditions. The observation that cumulus cells can desaturate the potentially toxic stearic acid into oleic acid via SCD activity provides a mechanistic insight into how the cumulus cells protect the oocyte against toxicity by saturated fatty acid.
代谢丰富和贫瘠的条件都以升高的游离脂肪酸水平为特征,并与受损的女性生育能力有关。特别是,饱和游离脂肪酸对卵母细胞发育能力有剂量依赖性的负面影响,而单不饱和游离脂肪酸的危害似乎较小。卵丘细胞似乎可以保护卵母细胞免受游离脂肪酸的侵害,本研究旨在确定这种保护背后的机制。特别是,研究了将饱和脂肪酸转化为单不饱和脂肪酸的酶硬脂酰辅酶 A 去饱和酶(SCD)的作用。SCD 基因和蛋白在卵丘细胞中大量表达,但在卵母细胞中表达水平较低。当 COCs 在成熟过程中暴露于饱和硬脂酸时,卵丘细胞中 SCD 蛋白的表达水平没有变化。在存在硬脂酸的情况下抑制 SCD 显著降低了卵母细胞的发育能力,并增加了卵丘细胞的凋亡发生率。当 COCs 在成熟过程中暴露于饱和游离脂肪酸时,卵丘细胞中性脂质部分中酯化的油酸/硬脂酸比在 SCD 抑制剂存在下降低,表明在非抑制条件下 SCD 特异性地将饱和脂肪酸转化。观察到卵丘细胞可以通过 SCD 活性将潜在毒性的硬脂酸转化为油酸,这为卵丘细胞如何通过饱和脂肪酸保护卵母细胞免受毒性提供了一种机制上的见解。