PCOS患者卵泡液脂质谱改变对卵巢功能和辅助生殖结局的影响及机制的研究

Polycystic ovary syndrome (PCOS) is a common and complex multi-system syndrome in adolescent and reproductive age women. PCOS seriously affects the fertility of women of childbearing age. However, the understanding and intervention approaches of this disease are still limited. How to improve the embryos’ quality and to increase pregnancy rates in IVF procedure is an important issue. Our previous results indicated that serum and ovarian follicular fluid lipidomic profiles (phospholipids - free fatty acids - polyunsaturated fatty acid metabolites) of PCOS patients were quite different from those in control subjects. Especially, omega-3 PUFAs and prostaglandins, derived from arachidonic acid, were important lipid mediators in inflammation and reproductive regulation. Until now, there are no systematic study on lipidomic profiles, which has been reported in PCOS patients’ serum and ovarian follicular fluid. Furthermore, the potential mechanism is still not clear. This study will conduct via clinical interventions, animal models, and cellular biology experiments. The aims of the study include: 1) to investigate the changes of ovarian follicular fluid lipid profile in PCOS patients, and its relationship with ovarian function, embryo quality and IVF outcomes; 2) to screen the potential lipid markers of follicular development and embryo quality; 3) to investigate more effective interventions to relieve ovarian local inflammation, and improve ovarian function and ART outcomes. The results of this study will provide the new perspective approaches to improve pregnancy ability and IVF-ET outcomes.

多囊卵巢综合征（PCOS）是育龄妇女常见的一种复杂的多系统综合征，严重影响育龄女性的生育能力。但目前对本病的认识和干预手段仍很有限。对有生育要求的PCOS患者，如何提高自然受孕率或IVF-ET过程中的优胚率和成功率是当前的一个重要课题。在我们前期工作中发现PCOS患者血清和卵泡液的脂质谱（磷脂-游离脂肪酸-多不饱和脂肪酸代谢产物），尤其是花生四烯酸代谢产物前列腺素家族存在显著改变。虽然它们在炎症和生殖调节中均有重要作用，但目前在PCOS中尚未见报导。在本项目中，我们拟通过临床研究，动物和细胞实验，探索：1.PCOS患者卵泡液脂质谱的变化和机制，及其与卵巢功能、胚胎质量和辅助生殖结局之间的关系；2.筛查与卵泡发育、胚胎质量和IVF-ET结局相关的脂质标记物；3.探索缓解卵巢局部炎症，改善卵巢功能和ART结局的有效手段。为提高PCOS患者的受孕能力和IVF-ET的成功率提供新的策略。

多囊卵巢综合征（PCOS）是育龄妇女常见的一种复杂的多系统综合征，严重影响育龄女性的生育能力。但目前对本病的认识和干预手段仍很有限。对有生育要求的PCOS患者，如何提高自然受孕率或IVF-ET过程中的优胚率和成功率是当前的一个重要课题。通过临床和动物实验，我们按计划收集了肥胖伴糖耐量异常（IGT）的PCOS患者，分别经过生活方式干预、二甲双胍和阿卡波糖治疗，分析了PCOS 患者血清和卵泡液的脂质谱的变化，以及血清脂质谱与卵泡液脂质谱间的关联性，提示所有治疗方式均有效改善肥胖伴IGT的PCOS患者的代谢，血清游离脂肪酸及其代谢产物均有不同程度的降低。其次，观察了PCOS患者卵泡液中花生四烯酸（AA，C20:4）代谢产物的变化，及对胚胎质量、受孕率和活产率等指标的影响。P450epo、LOX途径和COX途径产生的代谢产物与优胚率、卵母细胞利用率的相关性均无统计学差异。但是，PGJ2，PGE2和PGF2a与睾酮和空腹胰岛素显著相关。我们进一步通过动物实验验证并深入分析了PCOS大鼠血清和卵巢组织脂质谱的差异，并进一步深入研究了产生上述变化的原因。在体外水平，进一步研究了睾酮和胰岛素对颗粒细胞功能的影响，尤其是对颗粒细胞COX2的影响。综上，为后续深入研究脂质谱对于PCOS致病机制和防治靶点做了良好的铺垫工作，为提高PCOS患者的受孕能力和IVF-ET的成功率提供新的策略。