伊朗花剌子米大学Tahereh Foroutan教授：磁性氧化石墨烯调控卵母细胞成熟的在体研究

研究背景

当前全球不孕症患病率约为10%-15%，其中排卵障碍是导致不孕的主要原因之一。不孕症的常见治疗手段包括激素治疗、卵母细胞体外成熟技术(IVM)、体外受精技术(IVF)等。尽管这些治疗手段有效，但仍存在副作用大和成本高昂的问题。而且，相较于体内成熟，体外成熟的卵母细胞质量较低，进而影响了其发展为成功胚胎的概率。不仅如此，培养条件对卵母细胞的成熟与发育也至关重要。在缺少培养基营养液的情况下，相较于体内成熟，体外成熟的卵母细胞发育到囊胚期的成熟能力较弱。研究表明，磁性氧化石墨烯材料（即经纳米Fe₃O₄改性后的GO）具有良好的生物相容性。来自伊朗花剌子米大学Tahereh Foroutan教授团队通过对小鼠腹腔注射磁性氧化石墨烯(MGO) 探究了MGO对卵母细胞成熟的影响及其对胚胎发育潜力的提升，旨在为改善辅助生殖技术提供新思路。

原文信息

Rahimi M, Foroutan T, Eini F. The Effects of Nano Magnetic Graphene Oxide on In Vivo Maturation of Oocyte. Nano Biomedicine and Engineering, 2023, 15(4): 354-362.

研究摘要

Abstract

Graphene oxide (GO) and Fe₃O₄ super paramagnetic material are good candidate for some applications such as drug delivery. It has been shown that combining Fe₃O₄ with graphene oxide increases the biological efficiency of GO. The use of novel assisted reproductive technologies such as gonadotropins injection has been able to help the fertility of infertile people, but the side effects of these methods and high costs are still problems. The aim of the present study was to investigate the effect of magnetic graphene oxide (MGO) on the in vivo maturation of mouse oocytes. Thirty 6–8-week old female Naval Medical Research Institute (NMRI) mice were treated with intra peritoneal (I.P) injection of MGO mixed with hormones. 12 h after I.P. injection of MGO mixed with PMSG and HCG, the number of metaphase II (MII) oocytes obtained from the left fallopian tubes was counted in each group. Also, immuno-cytochemical staining of glutathione and morphometric analysis of ovaries were studied. The results of this study showed that the simultaneous use of MGO, pregnant mare serum gonadotropin (PMSG), and human chorionic gonadotrophin (HCG) increases the number of MII oocytes and helps to increase maturation of oocytes. It could be concluded that MGO can increase the efficiency of super ovulating hormones due to increase in adsorption of serum hormones and growth factors.

摘要

氧化石墨烯(GO)和Fe₃O₄超顺磁性材料广泛应用于药物传递、基因输运中。研究表明，将Fe₃O₄与氧化石墨烯结合可显著提高GO的生物效率。虽然目前注射促性腺激素等新型辅助生殖技术可提高不孕症人群的生育能力，但其副作用较大且成本高昂。本研究旨在探讨磁性氧化石墨烯(MGO)对小鼠卵母细胞体内成熟的影响。研究中对30只6-8周龄的雌性NMRI小鼠进行含激素的MGO腹腔注射，混合的激素包括孕马血清促性腺激素(PMSG)和人绒毛膜促性腺激素(HCG)。药物注射12小时后，计算每组左侧输卵管中期(MII)卵母细胞数量。此外，文章还利用免疫组织化学染色法研究分析了卵巢形态。结果显示，混合使用PMSG和HCG的MGO能够增加MII卵母细胞的数量，有助于促成卵母细胞的成熟，MGO能够提升血清中生殖激素类物质和生长因子的吸附能力，从而提高排卵激素的运作效率。

研究结论

(1) 小鼠体内注射的MGO显著增强了生殖激素PMSG和HCG向卵母细胞输送的能力。

(2) MGO提高了PMSG和HCG在卵巢组织中的作用效率，使MII卵母细胞的数量增加。

综上，使用MGO输送生殖激素具有促进卵母细胞成熟的能力，MGO可作为激素类药物递送的候选载体。