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Abstract：
Understanding how stress hormones induce apoptosis in oviductal epithelial cells (OECs) and mural granulosa cells (MGCs) can reveal the mechanisms by which female stress impairs embryonic development and oocyte competence. A recent study showed that tissue plasminogen activator (tPA) ameliorates corticosterone-induced apoptosis in MGCs and OECs by acting on its receptors low-density lipoprotein receptor-related protein 1 (LRP1) and Annexin A2 (ANXA2), respectively. However, whether tPA is involved in corticotropin-releasing hormone (CRH)-induced apoptosis and whether it uses the same or different receptors to inhibit apoptosis induced by different hormones in the same cell type remains unknown. This study showed that CRH triggered apoptosis in both OECs and MGCs and significantly downregulated tPA expression. Moreover, tPA inhibits CRH-induced apoptosis by acting on ANXA2 in both OECs and MGCs. While ANXA2 inhibits apoptosis via phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling, LRP1 reduces apoptosis via mitogen-activated protein kinase (MAPK) signaling. Thus, tPA used the same receptor to inhibit CRH-induced apoptosis in both OECs and MGCs, however used different receptors to inhibit corticosterone-induced apoptosis in MGCs and OECs. These data helps understand the mechanism by which female stress impairs embryo/oocyte competence and proapoptotic factors trigger apoptosis in different cell types.
摘要：
了解应激激素如何诱导输卵管上皮细胞（OEC）和壁颗粒细胞（MGC）凋亡，可以揭示雌性应激损害胚胎发育和卵母细胞能力的机制。最近的一项研究表明，组织纤溶酶原激活剂（tPA）通过作用于其受体低密度脂蛋白受体相关蛋白1（LRP1）和膜联蛋白A2（ANXA2）来改善皮质酮诱导的MGCs和OECs细胞凋亡，分别。然而,tPA是否参与促肾上腺皮质激素释放激素（CRH）诱导的细胞凋亡，以及它是否使用相同或不同的受体来抑制同一细胞类型中不同激素诱导的细胞凋亡，目前尚不清楚。这项研究表明，CRH触发了OECs和MGCs的凋亡，并显着下调了tPA的表达。此外，tPA通过作用于OECs和MGCs中的ANXA2来抑制CRH诱导的细胞凋亡。虽然ANXA2通过磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号抑制细胞凋亡，LRP1通过丝裂原活化蛋白激酶（MAPK）信号降低细胞凋亡。因此，tPA使用相同的受体来抑制CRH诱导的OECs和MGCs细胞凋亡，然而，在MGCs和OECs中使用不同的受体来抑制皮质酮诱导的凋亡。这些数据有助于了解女性压力损害胚胎/卵母细胞能力和促凋亡因子触发不同细胞类型凋亡的机制。
