基于BDNF/TrkB淫羊藿苷调控PCOS大鼠卵母细胞体外成熟与胚胎发育潜能的机制研究

Polycystic ovary syndrome (PCOS) is the leading cause of dysfunctional ovulatory acyesis. Although assisted reproduction technology has been widely employed in the assisted reproductive treatment for PCOS, the decline of fertilization rate, cleavage rate and embryo implantation rate as well as the increase of abortion rate would generate due to the inferior quality of oocytes. Therefore, promoting the sufficient mature of PCOS oocytes plays an essential role in boosting pregnancy outcomes, increasing fecundity and facilitating aristogenesis. Brain derived neurotrophic factor (BDNF) and the receptor TrkB play an important role in the plasticity of neural mechanism and function. BDNF also expresses in ovary and is closely related with the dysmaturity of PCOS oocytes. Traditional Chinese Medicine holds that the root cause for PCOS lies in the deficiency of the kidney. As an effective medicine to tonify the kidney, Herba Epimedii is commonly employed in regulating menstruation and promoting pregnancy. Icariin, as a main ingredient, can promote the proliferation of granulosa cells, the maturation and fertilization of oocytes in vitro and reduce hyperandrogenism of PCOS. Early studies had found that icariin could improve the faculty of memory and the mitochondrial activity by up-regulating central BDNF. However, report on its function to BDNF/TrkB in ovary is rare. This study aims to discover the mechanism of icariin on regulating the maturity and embryonic development of PCOS oocytes based on BDNF/TrkB and further discovers the application and prospects of Chinese herb extracts on the excellent pregnancy and eugenics for PCOS.

多囊卵巢综合征（PCOS）是导致排卵障碍性不孕症的首要原因。辅助生殖技术已广泛用于PCOS助孕治疗，但往往因卵母细胞质量不佳，导致受精、卵裂、胚胎种植率下降而流产率升高。因此，PCOS卵母细胞充分成熟对改善妊娠结局、提高生育力、促进优生至关重要。脑源性神经营养因子（BDNF）及其受体TrkB在神经结构和功能可塑性中发挥重要作用。BDNF亦在卵巢组织表达，与PCOS卵母细胞成熟障碍密切相关。中医认为PCOS病本在肾虚，淫羊藿为补肾良药，常用于调经种子，其主成分淫羊藿苷可促进颗粒细胞增殖、卵母细胞体外成熟与受精，降低PCOS高雄。研究发现，淫羊藿苷可通过上调中枢BDNF改善记忆力、线粒体活性等，但其对卵巢组织BDNF/TrkB的作用鲜有报道。故本课题拟基于BDNF/TrkB挖掘淫羊藿苷调控PCOS卵母细胞成熟与胚胎发育潜能的机制，进一步探讨中药提取物在PCOS优孕优生中的应用价值与前景。

脑源性神经营养因子BDNF及受体TrkB在神经结构和功能可塑性中发挥重要作用。BDNF亦在卵巢表达，与PCOS卵母细胞成熟障碍密切相关。研究发现，BDNF在PCOS体外培养MII期卵母细胞中水平下降，TrKB表达抑制存在于PCOS卵母细胞体外培养从GV期至MII期，从受精至囊胚形成期。BDNF水平降低是PCOS MII卵母细胞形成障碍的重要因素，受体TrKBmRNA、DNA表达下调在促使PCOS MII卵母细胞受精、囊胚形成率下降中占据重要地位。补肾中药提取物淫羊藿苷干预后可通过激活p-MAPK信号通路不同程度地提高PCOS体外培养GV期、MII期卵母细胞、2细胞受精卵、囊胚BDNF/TrkBmRNA、DNA表达，促进高T诱导PCOS大鼠卵母细胞体外培养减数分裂进程，改善未成熟卵母细胞胞核胞质成熟，有助于受精卵向囊胚发育，籍此提高中医药在生殖助孕领域的应用。