Fayezi Shabnam, Ghaffari Novin Marefat, Darabi Masoud, Norouzian Mohsen, Nouri Mohammad, Farzadi Laya, Darabi Maryam
1 Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Reprod Sci. 2018 Jun;25(6):844-853. doi: 10.1177/1933719117698578. Epub 2017 Mar 27.
Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in lipid metabolism and is expressed in cumulus cells. The objective of the present study was to evaluate the effect of SCD1 inhibition in human cumulus cells on triglyceride content, steroidogenesis, and oocyte in vitro maturation. Human cumulus cells were exposed to SCD1 inhibitor CAY10566 (SCDinhib) alone or in combination with oleic acid in primary culture. The SCDinhib markedly suppressed triglyceride accumulation (-47%, P = .01), aromatase gene expression (-36%, P = .02), and estradiol production (-49%, P = .01) even at a dose not affecting cell viability and apoptosis. Human immature oocytes at the germinal vesicle (GV) stage were cocultured with pretreated cumulus cells. The rate of oocytes reaching the metaphase II stage was significantly lower in coculture with SCDinhib-treated cumulus cells than with control cumulus cells (-18%, P < .01), which recovered by oleic acid supplementation. This finding on in vitro maturation rate was also reproducible with mouse GV oocytes. The results suggest that SCD1 activity is required for cumulus cell lipid storage and steroidogenesis. In addition, oocyte maturation is negatively affected by SCD1 inhibition in cumulus cells, possibly due to a deficient lipid-mediated paracrine support.
硬脂酰辅酶A去饱和酶1(SCD1)是脂质代谢中的关键酶,在卵丘细胞中表达。本研究的目的是评估抑制人卵丘细胞中的SCD1对甘油三酯含量、类固醇生成及卵母细胞体外成熟的影响。在原代培养中,将人卵丘细胞单独或与油酸联合暴露于SCD1抑制剂CAY10566(SCDinhib)。即使在不影响细胞活力和凋亡的剂量下,SCDinhib也能显著抑制甘油三酯积累(-47%,P = 0.01)、芳香化酶基因表达(-36%,P = 0.02)和雌二醇生成(-49%,P = 0.01)。将处于生发泡(GV)期的人未成熟卵母细胞与预处理的卵丘细胞共培养。与用SCDinhib处理的卵丘细胞共培养的卵母细胞达到减数分裂中期II期的比例显著低于与对照卵丘细胞共培养的情况(-18%,P < 0.01),补充油酸后可恢复。小鼠GV期卵母细胞的体外成熟率也得到了类似结果。结果表明,SCD1活性是卵丘细胞脂质储存和类固醇生成所必需的。此外,卵丘细胞中SCD1的抑制对卵母细胞成熟有负面影响,可能是由于脂质介导的旁分泌支持不足。