Stearoyl-CoA desaturase activity in bovine cumulus cells protects the oocyte against saturated fatty acid stress.

Stearoyl-CoA desaturase activity in bovine cumulus cells protects the oocyte against saturated fatty acid stress.
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DOI:
10.1095/biolreprod.116.146159
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发表时间:
2017-05-01
影响因子:
3.6
通讯作者:
Roelen BAJ
Roelen BAJ
中科院分区:
生物学2区
文献类型:
--
作者:
Aardema H;van Tol HTA;Wubbolts RW;Brouwers JFHM;Gadella BM;Roelen BAJ

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新陈代谢的富足和贫乏都以游离脂肪酸水平升高为特征,并与女性生育能力受损有关。特别是,饱和游离脂肪酸对卵母细胞的发育能力有剂量依赖性的负面影响,而单不饱和脂肪酸似乎危害较小。卵丘细胞似乎保护卵母细胞免受游离脂肪酸的伤害,本研究的目的是确定这种保护的机制,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,而在卵母细胞中表达较低。COCs成熟过程中暴露于饱和硬脂酸后,卵丘细胞SCD蛋白表达水平无明显变化。在硬脂酸存在的情况下抑制SCD显著降低卵母细胞的发育能力,并增加卵丘细胞的凋亡率。当COCs在成熟过程中暴露于饱和游离脂肪酸时,在SCD抑制剂的存在下,卵丘细胞中性脂肪部分的油酸/硬脂酸的酯化比率降低,这表明在非抑制条件下饱和脂肪酸的SCD专一性转化。卵丘细胞可以通过SCD活性将潜在有毒的硬脂酸脱饱和为油酸,这一观察结果为卵丘细胞如何保护卵母细胞免受饱和脂肪酸的毒性提供了机制上的见解。牛卵丘细胞中的硬脂酰辅酶A去饱和酶将饱和脂肪酸转化为单不饱和脂肪酸,并保护卵母细胞免受脂肪酸诱导的脂肪毒性。
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. Stearoyl-CoA desaturase in bovine cumulus cells converts saturated into monounsaturated fatty acid and protects the oocyte against fatty acid-induced lipotoxicity.
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