Chitosan oligosaccharide improves ovarian granulosa cells inflammation and oxidative stress in patients with polycystic ovary syndrome.
Chitosan oligosaccharide improves ovarian granulosa cells inflammation and oxidative stress in patients with polycystic ovary syndrome.
复制标题
DOI：
10.3389/fimmu.2023.1086232
复制
发表时间：
2023
影响因子：
7.3
通讯作者：
Zheng, Yuehui
中科院分区：
文献类型：
--
作者：
Xie, Qi;Hong, Wenli;Li, Yuan;Ling, Shuyi;Zhou, Ziqiong;Dai, Yuqing;Wu, Wenbo;Weng, Ruoxin;Zhong, Zhisheng;Tan, Jun;Zheng, Yuehui
多囊卵巢综合征（Polycystic ovarian Syndrome， PCOS）是育龄妇女最常见的生殖内分泌疾病，是无排卵性不孕的主要原因之一。尽管快速发展的辅助生殖技术（ART）可以有效解决生育问题，但部分PCOS患者的临床效果仍不理想。PCOS患者卵泡发育异常导致的卵母细胞质量差可能直接导致ART治疗失败。卵巢颗粒细胞（GCs）是与卵母细胞关系最密切的细胞，其功能状态的改变直接影响卵母细胞的形成。既往研究表明，卵巢微环境的改变，如氧化应激、炎症等，可能通过损害GCs的生理状态，导致pcos相关的卵泡异常发育。因此，优化卵巢微环境是增强PCOS卵母细胞发育潜力的可行方法。在本研究中，我们首先检测了对照患者（非PCOS）和PCOS患者GCs中炎症相关因子（TGF-β1、IL-10、TNFα、IL-6）和氧化应激相关因子（HIF-1α、VEGFA）的表达，以及GCs的增殖能力和凋亡水平。随后，利用人卵巢颗粒细胞系（KGN）细胞验证壳寡糖（COS）对GCs的抗炎和抗氧化应激作用，并探讨COS的最佳培养时间和浓度。然后将最佳培养条件用于培养PCOS患者和对照患者的GCs。结果显示，PCOS患者的GCs表现出明显的炎症和氧化应激，细胞增殖明显减少，细胞凋亡明显增加。此外，COS可增加抗炎因子TGF-β1和IL-10的表达，降低促炎因子TNFα和IL-6的表达，促进GCs的增殖。此外，我们发现COS可以通过抑制HIF-1α和VEGFA的表达，抑制氧化应激诱导的GCs凋亡，从而降低氧化应激下GCs中活性氧的水平。我们发现PCOS患者的GCs中存在炎症和氧化应激，而COS可以降低这些因素，从而改善GCs的功能。
Polycystic Ovary Syndrome (PCOS) is the most common reproductive endocrine disorder among women of reproductive age, which is one of the main causes of anovulatory infertility. Even though the rapidly developed assisted reproductive technology (ART) could effectively solve fertility problems, some PCOS patients still have not obtained satisfactory clinical outcomes. The poor quality of oocytes caused by the abnormal follicular development of PCOS may directly contribute to the failure of ART treatment. Ovarian granulosa cells (GCs) are the most closely related cells to oocytes, and changes in their functional status have a direct impact on oocyte formation. Previous studies have shown that changes in the ovarian microenvironment, like oxidative stress and inflammation, may cause PCOS-related aberrant follicular development by impairing the physiological state of the GCs. Therefore, optimizing the ovarian microenvironment is a feasible method for enhancing the development potential of PCOS oocytes. In this study, we first detected the expression of inflammatory-related factors (TGF-β1, IL-10, TNFα, IL-6) and oxidative stress-related factors (HIF-1α and VEGFA), as well as the proliferation ability and apoptosis level of GCs, which were collected from control patients (non-PCOS) and PCOS patients, respectively. Subsequently, human ovarian granulosa cell line (KGN) cells were used to verify the anti-inflammatory and anti-oxidative stress effects of chitosan oligosaccharide (COS) on GCs, as well as to investigate the optimal culture time and concentration of COS. The optimal culture conditions were then used to culture GCs from PCOS patients and control patients. The results showed that GCs from PCOS patients exhibited obvious inflammation and oxidative stress and significantly reduced proliferation and increased apoptosis. Furthermore, COS can increase the expression of anti-inflammatory factors (TGF-β1 and IL-10) and decrease the expression of pro-inflammatory factors (TNFα and IL-6), as well as promote the proliferation of GCs. Moreover, we found that COS can reduce the level of reactive oxygen species in GCs under oxidative stress by inhibiting the expression of HIF-1α and VEGFA and by suppressing the apoptosis of GCs induced by oxidative stress. We find that inflammation and oxidative stress exist in the GCs of PCOS patients, and COS can reduce these factors, thereby improving the function of GCs.
登录
查看更多内容
影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
2.6
作者：
Alanbay, Ibrahim;Ercan, Cihangir Mutlu;Tapan, Serkan
通讯作者：
Tapan, Serkan
影响因子：
5.5
作者：
Tsvetkov YE;Paulovičová E;Paulovičová L;Farkaš P;Nifantiev NE
通讯作者：
Nifantiev NE
影响因子：
5.8
作者：
Jakimiuk, AJ;Weitsman, SR;Magoffin, DA
通讯作者：
Magoffin, DA
影响因子：
2.7
作者：
Su YQ;Sugiura K;Eppig JJ
通讯作者：
Eppig JJ