蔡氏育肾培元方通过促进细胞活化改善POR患者卵巢反应性的机制研究

Due to the few number of cyclic developmental ovarian follicle and viable embryos stimulated by the gonadotropin overstrain, which leads to low clinical pregnancy rate, poor ovarian response (POR) in the assisted reproduction, incidence of which presents a gradual upward trend, has become one of the most challenging clinical problems. Accordingly, how to increase the ovarian reserve and improve the ovarian response and pregnancy rate has become a hot and difficult problem to be solved urgently. Cai’s Gynaecology has developed over 200 years. Cai's Tonifying Kidney and Strengthening Vitals Recipe is Professor Cai Xiaosun's experience who is the 7th generation in the treatment of infertility and it has a significant clinical effect. Our previous clinical studies showed that the ovarian reserve and the number of top embryos in poor ovarian responders can be improved by Cai's Tonifying Kidney and Strengthening Vitals Recipe ,but so far there’s still no research which can clarify its mechanism.Our preliminary test initially found that the genes related to cell activation in ovarian granulosa cells were obviously increased. In this study we will expand the sample size to screen the expression of these cell activation related genes. The selected candidate genes will be treated with knockdown and overexpression. Through the study on granule cell proliferation, cell morphology, expression of cytokines and cytokine secretion ability etc, together with the impact of candidate genes on genes related to ovarian development, we will clarify the mechanism of Cai's Tonifying Kidney and Strengthening Vitals Recipe in improving the ovarian response of poor ovarian responders by promoting the cell activation.

卵巢低反应(poor ovarian response,POR)因其促性腺激素刺激周期发育卵泡少，可用胚胎少，临床妊娠率低，发病率逐年上升，已成为临床最具挑战性的问题之一。如何提高卵巢储备，改善卵巢反应性，提高妊娠率成为亟待解决的热点难点。蔡氏女科历经二百余载，育肾培元方是蔡氏七代蔡小荪教授治疗不孕症经验方，临床疗效显著。我们前期临床研究发现育肾培元方可改善POR患者卵巢储备，增加优质胚胎数，但尚无研究可阐明其机制。我们前期试验初步发现本方对卵巢颗粒细胞中细胞活化相关基因明显上调，本研究拟扩大样本量，对这些细胞活化相关基因的表达情况进行筛查，对筛选出的候选基因分别进行基因knockdown、基因过表达，通过对颗粒细胞增殖能力、细胞形态、细胞因子表达、细胞激素分泌能力等方面的研究，并结合候选基因对卵巢发育相关基因的影响，阐明育肾培元方通过促进细胞活化改善POR患者卵巢反应性的机制。

卵巢低反应(poor ovarian response POR)因其促性腺激素刺激周期发育卵泡少，可用胚胎少，临床妊娠率低，发病率逐年上升，已成为临床最具挑战性的问题之一。如何改善卵巢反应性，提高妊娠率成为辅助生殖领域亟待解决的热点和难点。蔡氏女科历经二百余载，育肾培元方是蔡小荪教授治疗不孕症经验方，临床疗效显著。我们前期临床研究发现育肾培元方可改善POR患者卵巢储备，增加优质胚胎数，但其作用机制尚不明确。本项目通过RNA-seq技术，筛选发现ARHGAP4是调控卵巢颗粒细胞活性的关键靶点，而且POR患者中高表达的ARHGAP4在蔡氏育肾培元方服用后显著降低。进一步通过细胞、分子、临床组织水平进行基因功能和机制研究，发现蔡氏育肾培元方抑制卵巢颗粒细胞中ARHGAP4表达后通过PI3K-AKT信号通路改善POR患者卵巢反应性的相关生物学机制，为中药治疗辅助生殖中卵巢低反应药理机制提供更充足的科学研究数据依据。