The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.
Biol Reprod. 2011 Sep;85(3):548-55. doi: 10.1095/biolreprod.110.090415. Epub 2011 May 25.
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.
卵母细胞的发育能力是在卵泡发生过程中获得的，与适当的分化和对黄体生成素 (LH) 激增的反应能力有关。最近开发的一种在三维藻酸盐基质中培养卵巢卵泡的新系统有望在体内卵泡发生中进行表型复制。然而，与体内成熟的卵母细胞相比，体外培养的卵泡中的卵母细胞完成核成熟和受精的能力降低。卵母细胞代谢与卵母细胞质量密切相关，我们最近表明，脂质的β氧化对于卵母细胞的发育能力至关重要。因此，我们研究了通过用脂肪酸转运辅助因子 l-肉碱处理来上调β氧化是否可以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 LH/人绒毛膜促性腺激素 (hCG) 刺激后，培养的卵泡中适当分化了卵泡细胞。l-肉碱不会改变卵泡的存活、生长或分化。然而，l-肉碱补充显著增加了β氧化，并显著提高了受精率和囊胚发育。总之，这些结果表明，在三维卵泡培养后，卵泡对 LH/hCG 激增有适当的反应，但关键代谢要求仍然存在限制。在体外卵泡培养中补充 l-肉碱增加了脂代谢并提高了卵母细胞的发育能力。
