Increased Beta-Oxidation and Improved Oocyte Developmental Competence in Response to L-Carnitine During Ovarian In Vitro Follicle Development in Mice
Increased Beta-Oxidation and Improved Oocyte Developmental Competence in Response to L-Carnitine During Ovarian In Vitro Follicle Development in Mice
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DOI：
10.1095/biolreprod.110.090415
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发表时间：
2011-09-01
影响因子：
3.6
通讯作者：
Robker, Rebecca L.
中科院分区：
文献类型：
--
作者：
Dunning, Kylie R.;Akison, Lisa K.;Robker, Rebecca L.
卵母细胞的发育能力是在整个卵泡发生过程中获得的，与适当的分化和对黄体生成素(LH)激增的反应有关。一种在三维藻酸盐基质中培养卵巢卵泡的新系统最近的发展显示了在体内卵泡发生的表型复制方面的前景。然而，与体内成熟的卵母细胞相比，来自体外培养的卵泡的卵母细胞完成核成熟和受精的能力降低。卵母细胞的代谢与卵母细胞的质量密切相关，我们最近的研究表明，脂质的β-氧化对卵母细胞的发育能力是必不可少的。因此，我们研究了通过脂肪酸转运辅助因子L肉碱上调β-氧化是否能改善三维培养后小鼠卵泡的卵泡发生和发育能力。卵巢激素(雄烯二酮、雌二醇和孕酮)和卵丘基质蛋白(透明质酸和ADAMTS1)的诱导与体内卵泡相似，表明在黄体生成素/人绒毛膜促性腺激素(HCG)刺激下，培养的卵泡发生了适当的卵泡细胞分化。L-卡尼汀不改变卵泡的存活、生长或分化。而添加L肉碱则显著提高β-氧化水平，显著提高受精率和囊胚发育。综上所述，这些结果表明，在三维卵泡培养后，卵泡对促黄体生成素/人绒毛膜促性腺激素高峰有适当的反应，但关键代谢需求仍然存在限制。卵泡体外培养过程中补充L肉碱可促进卵泡的脂代谢，提高卵母细胞的发育能力。
Oocyte developmental competence is acquired throughout folliculogenesis and is associated with appropriate differentiation and responsiveness to the luteinizing hormone (LH) surge. The recent development of a novel system for culturing ovarian follicles in a three-dimensional alginate matrix shows promise in phenocopying in vivo folliculogenesis. However, oocytes from follicles grown in vitro have a reduced capacity to complete nuclear maturation and be fertilized compared to oocytes matured in vivo. Oocyte metabolism is closely linked with oocyte quality, and we have recently shown that beta-oxidation of lipids is essential for oocyte developmental competence. Thus we investigated whether upregulation of beta-oxidation by treatment with the fatty acid transport cofactor L-carnitine could improve folliculogenesis and developmental competence of mouse follicles following three-dimensional culture. Ovarian hormones (androstenedione, estradiol, and progesterone) and the induction of cumulus matrix proteins (hyaluronan and ADAMTS1) were similar to in vivo follicles, indicating that appropriate differentiation of follicular cells occurs in cultured follicles after an LH/human chorionic gonadotropin (hCG) stimulus. L-carnitine did not alter survival, growth, or differentiation of follicles. However, L-carnitine supplementation significantly increased beta-oxidation, and markedly improved both fertilization rate and blastocyst development. Together, these results show that appropriate responsiveness of the follicle to the LH/hCG surge occurs following three-dimensional follicle culture but limitations on key metabolic requirements remain. L-carnitine supplementation during in vitro follicle culture increased lipid metabolism and improved oocyte developmental competence.