环境内分泌干扰物Parabens通过Hippo信号通路调控卵巢生殖干细胞功能的作用及其机制研究

卵巢衰老是严重危害女性健康的重要因素。卵巢生殖干细胞（oogonial stem cells, OSCs）的自我更新和分化参与了卵巢衰老的进程。我们前期研究发现环境内分泌干扰物对羟基苯甲酸酯（Parabens）通过抑制OSCs自我更新和分化加速卵巢衰老，对Parabens干预前后的OSCs进行转录组测序并验证，发现参与调控OSCs自我更新的Hippo信号通路有显著差异。我们推测Parabens可能是通过Hippo信号通路抑制OSCs自我更新与分化从而加速卵巢衰老，但其调控机制尚不清楚。本研究拟采用Ddx4-Cre、mT/mG转基因小鼠模型，联合生物信息学分析、染色质免疫沉淀技术（ChIP）、CRISPR/Cas9基因编辑技术等探讨Hippo信号通路下游关键基因及其调控分子，从而构建Parabens通过Hippo信号通路调控OSCs自我更新和分化的网络图，为卵巢衰老的防治提供分子靶点。

Ovarian aging is an important factor that seriously affects women’s health, but the mechanism is not yet clear. It is reported that the oogonial stem cells (OSCs),which have function of self-renewal and differentiation, take part in the process of ovarian aging. Our previous study found that the Parabens, a kind of environmental endocrine disruptors, can induce ovarian aging by inhibiting the self-renewal and differentiation of OSCs.We have done transcriptome high-throughput sequencing on the OSCs before and after the treatment of parabens,finding that the Hippo signaling pathway was significantly different. We speculated that parabens may inhibit the self-renewal and differentiation of OSCs through Hippo signaling pathway in ovarian aging, but the mechanism is still unclear. In this study, using Ddx4-Cre; mT / mG transgenic mice model, combined with biological information analysis prediction, chromatin immunoprecipitation assay (ChIP), CRISPR / Cas9 editing technology to explore the downstream key genes and molecular regulation of Hippo signaling pathway, so as to construct the network diagram about how Hippo signaling pathway regulates the self-renewal and differentiation of OSCs,thus providing molecular targets for delaying ovarian aging.