Center for Reproductive MedicineRen Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive GeneticsShanghai, China.
Reproduction. 2017 Oct;154(4):355-362. doi: 10.1530/REP-17-0268. Epub 2017 Jul 4.
The aim of the present study was to elucidate the effects of kisspeptin-10 (Kp-10) on ovarian hyperstimulation syndrome (OHSS) and its related mechanism in OHSS rat models, human umbilical vein endothelial cells (HUVECs) and human luteinized granulosa cells. OHSS is a systemic disorder with high vascular permeability (VP) and ovarian enlargement. KISS1R (KISS1 receptor) is the specific receptor of kisspeptin. The kisspeptin/KISS1R system inhibits the expression of vascular endothelial growth factor (VEGF), which is the main regulator of VP. In our study, decreased expression of Kiss1r was observed in both ovaries and lung tissue of OHSS rats. Injection of exogenous Kp-10 inhibited the increase of VP and VEGF while promoting the expression of Kiss1r in both the ovarian and lung tissue of OHSS rats. Using HUVECs, we revealed that a high level of 17-β estradiol (E), a feature of OHSS, suppressed the expression of KISS1R and increased VEGF and nitric oxide (NO) through estrogen receptors (ESR2). Furthermore, mRNA also decreased in the luteinized human granulosa cells of high-risk OHSS patients, and was consistent with the results in rat models and HUVECs. In conclusion, Kp-10 prevents the increased VP of OHSS by the activation of KISS1R and the inhibition of VEGF.
本研究旨在阐明 kisspeptin-10 (Kp-10) 在卵巢过度刺激综合征 (OHSS) 及其相关机制中的作用，该机制涉及 OHSS 大鼠模型、人脐静脉内皮细胞 (HUVEC) 和人黄体化颗粒细胞。OHSS 是一种全身性疾病，具有高血管通透性 (VP) 和卵巢增大的特点。KISS1R（kisspeptin 受体 1）是 kisspeptin 的特异性受体。kisspeptin/KISS1R 系统抑制血管内皮生长因子 (VEGF) 的表达，而 VEGF 是 VP 的主要调节因子。在我们的研究中，OHSS 大鼠的卵巢和肺组织中观察到 Kiss1r 的表达减少。外源性 Kp-10 的注射抑制了 VP 和 VEGF 的增加，同时促进了 OHSS 大鼠卵巢和肺组织中 Kiss1r 的表达。使用 HUVEC，我们揭示了高水平的 17-β 雌二醇 (E)（OHSS 的特征）通过雌激素受体 (ESR2) 抑制 KISS1R 的表达，增加 VEGF 和一氧化氮 (NO)。此外，高风险 OHSS 患者的黄体化人颗粒细胞中的 mRNA 也减少，与大鼠模型和 HUVEC 的结果一致。总之，Kp-10 通过激活 KISS1R 和抑制 VEGF 来防止 OHSS 的 VP 增加。
